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A Review on Recent Advances in Polymer and Peptide Hydrogels
Abstract
In this review, we focus on the very recent progresses on the use of stimuli responsive property of the polymer hydrogels for targeted drug delivery, tissue engineering, biosensing utilizing their different optoelectronic properties. Besides, the stimuli-responsive hydrogels, the conducting polymer hydrogels are discussed giving specific attention to the energy generation and storage behaviour of the xerogel derived from the hydrogel. The electronic and ionic conducting gels have been discussed conferring their applications at various electronic devices eg. organic field effect transistor, soft robotic, ionic skin, sensor etc. The properties of polymer hybrid gels containing carbon nanomaterials have been embodied here giving attention to applications in supercapacitor, dye sensitized solar cell, photocurrent switching etc. Recent trends in the properties and applications of some natural polymer gels to produce thermal and acoustic insulating materials, drug delivery vehicles, self-healing material, tissue engineering etc are discussed. Besides the polymer gels, the peptide gels of different dipeptide, tripeptide, oligopeptides, polypeptides, cyclic peptides etc. are discussed giving attention mainly to biosensing, bioimaging and drug delivery applications. The properties of peptide based hybrid hydrogels with polymers, nanoparticles, nucleotides, fullerene etc are embodied giving specific attention to the drug delivery, cell culture, bio-sensing, and bioimaging properties. So the present review delineates in short, the preparation, properties and applications of different polymer and peptide hydrogels engrossed in past few years.
... Crosslinking agents for PCPHs not only affect the probity of the substances but can also produce some naturally toxic effects (Singhal, et al., 2020). Different methods involved in the synthesis of physically crosslinked hydrogels are shown in Figure 2, below: As shown in Figure 2, PCPHs are obtained from natural polysaccharides, poly(vinyl alcohol), poly(ethylene glycol), poly(N-isopropylacrylamide), poly(acrylic acid), poly(vinyl imidazole), and others (Mondal, et al., 2020). One of the advantages of PCPHs is that they avoid the potential toxicity produced by chemical crosslinkers (Liu, et al., 2018;Pita-López, 2021), so they are safer for applications in vivo assays, since chemical crosslinkers can leave toxic residues, resulting in damage to cells (Ahsan, et al., 2021). ...
... Ionic crosslinking has also been used to prepare hydrogels based on oxidized nanocellulose and alginate, using Ca 2+ as the crosslinking agent (Lin, et al., 2012;Mondal, et al., 2020). Carboxyl groups on the nanocellulose surface were induced by chemical oxidation via the 2,2,6,6-tetramethylpiperidin-1-oxyl radical (TEMPO). ...
... Carboxyl groups on the nanocellulose surface were induced by chemical oxidation via the 2,2,6,6-tetramethylpiperidin-1-oxyl radical (TEMPO). By the ion crosslinking process, hydrogel sponges were prepared and showed high porosity, promising water absorption and retention as well as compressive strength (Lin, et al., 2012, Mondal, et al., 2020. ...
Hydrogels are three-dimensional networks formulated from natural or synthetic polymers with a high capacity to absorb and transport water in their structure. Hydrogels are prepared from the crosslinking of their polymeric chains, which involves two basic mechanisms: chemical crosslinking and physical crosslinking. In chemical crosslinking, hydrogels are held together by covalent bonds; while physically cross-linked hydrogels are produced by non-covalent interactions, such as hydrogen bonds, electrostatic interactions, and hydrophobic forces, among others. Physically cross-linked hydrogels are more similar to biological systems due to their assembly dynamics, so they have wide biomedical applications. The most used approaches in the preparation of hydrogels by physical crosslinking include freeze-thaw, formation of stereocomplexes, ionic interaction, hydrogen bonding, crystallization, and crosslinking by hydrophobic interactions. These approaches are briefly discussed in this review. Some biomedical applications of these hydrogels will also be discussed.
... This paper provides an overview of the recent applications of hydrogels in drug delivery systems and the intelligent control of drug release, as illustrated in Figure 1 [24][25][26]. By summarizing the materials, characteristics, and application methods of hydrogels, they are categorized into injectable hydrogels, sprayable hydrogels, and implantable hydrogels [27][28][29][30]. Additionally, this article summarizes the specific applications of smart hydrogels in the treatment of brain tumors, including temperature-and pH-responsive hydrogels, photoresponsive hydrogels, and magneticresponsive hydrogels [31][32][33][34]. ...
... This paper provides an overview of the recent applications of hydrogels in drug delivery systems and the intelligent control of drug release, as illustrated in Figure 1 [24][25][26]. By summarizing the materials, characteristics, and application methods of hydrogels, they are categorized into injectable hydrogels, sprayable hydrogels, and implantable hydrogels [27][28][29][30]. Additionally, this article summarizes the specific applications of smart hydrogels in the treatment of brain tumors, including temperature-and pH-responsive hydrogels, photoresponsive hydrogels, and magnetic-responsive hydrogels [31][32][33][34]. ...
The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood–brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at the histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach to addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors.
... Polymeric gelators mainly include macromolecular compounds that are capable of inducing gel formation. 18 Such gelators usually establish their gel networks through either noncovalent or covalent forces with a wide range of applications. 19,20 Over the past few decades, there has been a growing fascination among researchers with reports on LMWGs and their associated gel formations. ...
... Derivatization of glycogen (C-derivatized or O-derivatized) to form an amphiphile is also an important principle while designing a glycolipid gelator. 23,93 Exploring the arena of monosaccharide-based glycolipid gelators, a deliberately synthesized gelator was studied for its gelation capacity in both organic solvents and water [ Figure 11, (18)]. 94 The work extended to identifying sugars and suitable hydrophobic groups to potentially uncover highly effective amphiphilic gelators. ...
Within the scope of this review, our exploration spans diverse facets of amphiphilic glycolipid-based low-molecular-weight gelators (LMWGs). This journey explores glycolipid synthesis, self-assembly, and gelation with tailorable properties. It begins by examining the design of glycolipids and their influence on gel formation. Following this, a brief exploration of several gel characterization techniques adds another layer to the understanding of these materials. The final section is dedicated to unraveling the various applications of these glycolipid-based supramolecular gels. A meticulous analysis of available glycolipid gelators and their correlations with desired properties for distinct applications is a pivotal aspect of their investigation. As of the present moment, there exists a notable absence of a review dedicated exclusively to glycolipid gelators. This study aims to bridge this critical gap by presenting an overview that provides novel insights into their unique properties and versatile applications. This holistic examination seeks to contribute to a deeper understanding of molecular design, structural characteristics, and functional applications of glycolipid gelators by offering insights that can propel advancements in these converging scientific disciplines. Overall, this review highlights the diverse classifications of glycolipid-derived gelators and particularly emphasizes their capacity to form gels.
... However, it remains challenging to fully decode the P-SA/PR since Nature can be highly complex. Interestingly, peptides could solve many current clinical, biological, chemical, pharmacological, and agrochemical issues 3,[61][62][63][64][65] For this reason, it is crucial to use novel approaches to quantify and understand their SA/PR studies. ...
... The idea of P-SA/PR has been used to discover and create lipopeptides and cyclic peptides 80,81 and decode the membranolytic mechanism of different peptides 82 . However, there are complex challenges to resolve towards consolidating the in silico peptide design area 17,[61][62][63][64]68 . Limited access to quality data and the balance of active and inactive reports make generating new information and knowledge challenging. ...
Peptide structure–activity/property relationship (P-SA/PR) studies focus on understanding how the structural variations of peptides influence their biological activities and other functional properties. This knowledge accelerates the rational design and optimisation of peptide-based drugs, biomaterials, or diagnostic agents. These studies examine peptide structures from their primary sequences, essentially encoded from the 20 amino acids. Current approaches often exclude peptide libraries with post-translational and synthetic modifications. The molecular fingerprint MAP4 was recently developed to map complex molecules' sequence/structure diversity, including peptides. This study used structure–activity landscape modelling to conduct the P-SA/PR studies of an exemplary dataset of 223 antimicrobial peptides against methicillin-resistant Staphylococcus aureus (MRSA). To this end, we employed the MAP4 fingerprint to represent the chemical structures of the peptides, study their relationship(s) with the antibacterial activity, and seek the potential activity cliff(s). We identified critical residues and structural motifs that play a crucial role in the anti-MRSA activity of the peptides. This is the first computational study to systematically explore the activity landscape of peptides with non-canonical residues, emphasising the quantification of structural similarity.
... As a reservoir for local delivery, hydrogels can be loaded with drugs or other therapeutic agents and slowly release these drugs over time to allow tumor targeting [11][12][13]. Hydrogels are highly biocompatible materials that will enable topical delivery of stimulus-responsive therapeutic agents with systemic effects [14][15][16][17]. Researchers are constantly exploring novel hydrogels with unique properties and exploring new applications. ...
The management of brain tumors presents numerous challenges, despite the employment of multimodal therapies including surgical intervention, radiotherapy, chemotherapy, and immunotherapy. Owing to the distinct location of brain tumors and the presence of the blood-brain barrier (BBB), these tumors exhibit considerable heterogeneity and invasiveness at a histological level. Recent advancements in hydrogel research for the local treatment of brain tumors have sought to overcome the primary challenge of delivering therapeutics past the BBB, thereby ensuring efficient accumulation within brain tumor tissues. This article elaborates on various hydrogel-based delivery vectors, examining their efficacy in the local treatment of brain tumors. Additionally, it reviews the fundamental principles involved in designing intelligent hydrogels that can circumvent the BBB and penetrate larger tumor areas, thereby facilitating precise, controlled drug release. Hydrogel-based drug delivery systems (DDSs) are posited to offer a groundbreaking approach in addressing the challenges and limitations inherent in traditional oncological therapies, which are significantly impeded by the unique structural and pathological characteristics of brain tumors.
... The self-assembly of small peptides has received great attention in nanoscience and nanotechnology [1][2][3]. These molecules can be easily produced at a large scale and their spontaneous assembly can lead to the formation of ordered architectures, from nanotubes to spheres, micelles, and fibers. ...
Supramolecular gels were developed by taking advantage of an assembly of small dipeptides containing pyrrolo-pyrazole scaffolds. The dipeptides were prepared through a robust and ecofriendly synthetic approach from the commercially available starting materials of diazoalkanes and maleimides. By playing with the functionalization of the scaffold, the choice of the natural amino acid, and the stereochemistry, we were able to obtain phase-selective gels. In particular, one peptidomimetic showed gelation ability and thermoreversibility in aromatic solvents at very low concentrations. Rheology tests showed a typical viscoelastic solid profile, indicating the formation of strong gels that were stable under high mechanical deformation. NMR studies were performed, allowing us to determine the conformational and stereochemical features at the base of the supramolecular interactions.
... Polymer chains covalently cross-link chemical nanogels and are permanent, while physically crosslinked nanogels are not permanent because they are formed through hydrogen bonds, entanglement of chains, hydrophobic interactions, crystal interactions, host-guest mechanisms, etc. Another type is double network nanogels, where the "first network" is usually rigid, closely cross-linked by covalent bonds, and the "second network" is typically soft, loosely cross-linked by supramolecular interactions (such as hydrogen bonds, ionic interactions, coordination interactions, etc.), and the combination of these chemical and physical cross-links ultimately forms the double network nanogels [80]. Yukun Wang et al. prepared a gelatin/hydrophobically modified polyacrylamide (HPAAm) double network (DN) nanogels, where the "first network" is formed by hydrogen bonds instead of covalent bonds, providing a new approach for the preparation of nanogel drug carriers with good stability [81]. ...
With the development of nanomedicine, nanomaterials have been widely used, offering specific drug delivery to target sites, minimal side effects, and significant therapeutic effects. The kidneys have filtration and reabsorption functions, with various potential target cell types and a complex structural environment, making the strategies for kidney function protection and recovery after injury complex. This also lays the foundation for the application of nanomedicine in kidney diseases. Currently, evidence in preclinical and clinical settings supports the feasibility of targeted therapy for kidney diseases using drug delivery based on nanomaterials. The prerequisite for nanomedicine in treating kidney diseases is the use of carriers with good biocompatibility, including nanoparticles, hydrogels, liposomes, micelles, dendrimer polymers, adenoviruses, lysozymes, and elastin-like polypeptides. These carriers have precise renal uptake, longer half-life, and targeted organ distribution, protecting and improving the efficacy of the drugs they carry. Additionally, attention should also be paid to the toxicity and solubility of the carriers. While the carriers mentioned above have been used in preclinical studies for targeted therapy of kidney diseases both in vivo and in vitro, extensive clinical trials are still needed to ensure the short-term and long-term effects of nano drugs in the human body. This review will discuss the advantages and limitations of nanoscale drug carrier materials in treating kidney diseases, provide a more comprehensive catalog of nanocarrier materials, and offer prospects for their drug-loading efficacy and clinical applications.
... Many types of hydrogels including environment-responsive, self-healing, self-assembled, conductive, shape-memory, and supermolecular, have been developed in recent years, tested, and applied in numerous biomedical and engineering applications, ranging from wastewater treatment, agriculture and controlled drug release to tissue engineering, regenerative medicine, and soft robotics (Dias-Ferreira and Teixeira, 2023;Kaith et al., 2021;Ma et al., 2021;Markovic et al., 2019;Sun et al., 2021;Yu et al., 2021;Zhao et al., 2023). Using relatively simple synthesis pathways, hydrogels could be prepared at various dimensions and shapes, which further contributed to their positioning as frontrunners in many fields (Amiryaghoubi et al., 2022;Khan et al., 2020;Mondal et al., 2020). ...
... Hydrogels have a high degree of porosity, which can be tuned through crosslinking of the constituting polymers, which additionally provides mechanical strength, adhesive properties, stability, and protection of the therapeutic agent. With a highly tunable physical structure, the applications of hydrogels are almost unlimited, rendering them a useful toolbox for biomedical applications and MN fabrication [10,11]. Regarding cancer research, HFMs are ideal substrates for the integration of diagnostics, therapy, and/or imaging into a single system, which is often referred to as a theranostic platform [12,13]. ...
Due to the severity and high prevalence of cancer, as well as its complex pathological condition, new strategies for cancer treatment and diagnostics are required. As such, it is important to design a toolbox that integrates multiple functions on a single smart platform. Theranostic hydrogels offer an innovative and personalized method to tackle cancer while also considering patient comfort, thereby facilitating future implementation and translation to the clinic. In terms of theranostic systems used in cancer therapy, nanoparticles are widely used as diagnostic and therapeutic tools. Nanoparticles can achieve systemic circulation, evade host defenses, and deliver drugs and signaling agents at the targeted site, to diagnose and treat the disease at a cellular and molecular level. In this context, hydrogel microneedles have a high potential for multifunctional operation in medical devices, while avoiding the complications associated with the systemic delivery of therapeutics. Compared with oral administration and subcutaneous injection, microneedles offer advantages such as better patient compliance, faster onset of action, and improved permeability and efficacy. In addition, they comprise highly biocompatible polymers with excellent degradability and tunable properties. Nanoparticles and microneedles thus offer the possibility to expand the theranostic potential through combined synergistic use of their respective features. We review herein recent advances concerning processing methods and material requirements within the realm of hydrogel microneedles as theranostic platforms, various approaches toward cancer therapy, and the incorporation of nanoparticles for added functionality.
Graphical Abstract
... However, bio-based, specifically protein-and peptide-based hydrogels may be viable alternatives. [8,[40][41][42][43] While less well-defined compared to synthetic hydrogels, naturally derived hydrogels have macromolecular properties that more closely resemble those of tissue extracellular matrix than polymer hydrogels do. Furthermore, successful cell growth and differentiation are often correlated with proper cell adhesion and signaling, which are much easier achieved with protein and peptide-based hydrogels. ...
Functional amyloid (FAs), particularly the bacterial proteins CsgA and FapC, have many useful properties as biomaterials: high stability, efficient, and controllable formation of a single type of amyloid, easy availability as extracellular material in bacterial biofilm and flexible engineering to introduce new properties. CsgA in particular has already demonstrated its worth in hydrogels for stable gastrointestinal colonization and regenerative tissue engineering, cell‐specific drug release, water‐purification filters, and different biosensors. It also holds promise as catalytic amyloid; existing weak and unspecific activity can undoubtedly be improved by targeted engineering and benefit from the repetitive display of active sites on a surface. Unfortunately, FapC remains largely unexplored and no application is described so far. Since FapC shares many common features with CsgA, this opens the window to its development as a functional scaffold. The multiple imperfect repeats in CsgA and FapC form a platform to introduce novel properties, e.g., in connecting linkers of variable lengths. While exploitation of this potential is still at an early stage, particularly for FapC, a thorough understanding of their molecular properties will pave the way for multifunctional fibrils which can contribute toward solving many different societal challenges, ranging from CO2 fixation to hydrolysis of plastic nanoparticles.
... [4][5][6] Similarly, plants leverage this trait to adapt to varying environmental conditions. [6][7][8] With recent scientific advances in the fields of gels and polymers, [9][10][11] engineers have achieved significant progress in the manufacturing of versatile, biocompatible and durable soft structures. This has led to the development of soft robots, [12][13][14][15] medical devices, [16][17][18] and inflatable structures, 19-21 among others. ...
To produce sounds, we adjust the tension of our vocal folds to shape their properties and control the pitch. This efficient mechanism offers inspiration for designing reconfigurable materials and adaptable soft robots. However, understanding how flexible structures respond to a significant static strain is not straightforward. This complexity also limits the precision of medical imaging when applied to tensioned organs like muscles, tendons, ligaments and blood vessels among others. In this article, we experimentally and theoretically explore the dynamics of a soft strip subject to a substantial static extension, up to 180%. Our observations reveal a few intriguing effects, such as the resilience of certain vibrational modes to a static deformation. These observations are supported by a model based on the incremental displacement theory. This has promising practical implications for characterizing soft materials but also for scenarios where external actions can be used to tune properties.
... Sonication, heating-cooling, and solution pH adjustments are further techniques for creating hydrogels. Peptide characteristics are mostly determined by their molecular structures [15]. Peptide gels have the ability to act quickly against stimuli, and entrap drugs with the physiological or chemical linkages. ...
Diabetes is a widespread epidemic that includes a number of comorbid conditions that greatly increase the chance of acquiring other chronic illnesses. Every year, there are significantly more people with diabetes because of the rise in type-2 diabetes prevalence. The primary causes of illness and mortality worldwide are, among these, hyperglycemia and its comorbidities. There has been a lot of interest in the creation of peptide-based hydrogels as a potentially effective platform for the treatment of diabetes and its consequences. Here, we emphasize the use of self-assembled hydrogel formulations and their unique potential for the treatment/management of type-2 diabetes and its consequences. (i.e., wounds). Key aspects covered include the characteristics of self-assembled peptide hydrogels, methods for their preparation, and their pre-clinical and clinical applications in addressing metabolic disorders such as type-2 diabetes.
... The excellent physical and chemical properties of hydrogel make them the preferred material for many applications such as medical excipients, drug sustained release, cartilage and bone tissue engineering, biofertilizers, and environmentally friendly coatings. [10][11][12][13][14] Hydrogels can be used in flexible sensors to transmit electrical signals through both electrical and ionic conduction [15,16]. The biological adjustable sensor should have high ionic conductivity, fracture strength, and sensitive electrical signal responseability to be suitable for human skin. ...
The development of advanced hydrogels with exceptional fracture strength and ionic conductivity is critical and challenging for the progress of flexible biological sensors. This study presents a novel PVA/CS/MOP ionic conductive hydrogel, which stands out due to its unique combination of remarkable fracture strength and enhanced ionic conductivity. While chitosan/PVA hydrogels have been previously established, this work focuses on a distinct fabrication method. It addresses the main scientific problem of achieving optimal fracture strength and ionic conductivity simultaneously. Chitosan (CS) is incorporated within a biocompatible polyvinyl alcohol (PVA) matrix, and subsequently, the hydrogel is immersed in muriate of potash (MOP) solution, resulting in a hydrogel with outstanding fracture strength (0.39 MPa) and stretchability (265% fracture strain). The salt soaking process effectively enhances the ionic conductivity of the hydrogel, achieving a maximum of 4.5 S m⁻¹. Additionally, the hydrogel serves as a flexible sensor, capable of monitoring stable electrical signals and recovering after deformation, making it a promising candidate for various applications in flexible electronics and human health monitoring. This study highlights the novelty of achieving an optimized combination of fracture strength and ionic conductivity in the PVA/CS/MOP hydrogel, contributing to the advancement of flexible sensor technologies.
Graphical abstract
... LiCl acts as an "initiator" during the formation of supramolecular gels, and the chloride ions in it could break the hydrogen bond structure in β-CD; meanwhile, lithium ions drive the cage structure into a compact rodlike structure and finally form a temperature-responsive supramolecular gel. 28 Figure 5c shows that as the concentration of LiCl increased, the gelation temperature of the supramolecular gel first decreased and then increased. When the concentration was 0.7 wt%, the gelation temperature possessed a minimum value, and the gelation strength first increasing and then decreasing. ...
In this study, response surface methodology (RSM) was applied to optimize the preparation of a supramolecular gel temporary plugging agent. According to single‐factor experiments, results showed that the gelling temperature was preset at 100°C, and the gelling strength reached the maximum. Three‐factor RSM model prediction was carried out to explore the determination coefficient (R²) of the gelling temperature and strength and their degree of influence, and the predicted results were verified by experiments. No difference was found between the experimental results and the predicted results, indicating that this model could be used to optimize the preparation of DMF supramolecular gels. DSC, FT‐IR, XRD, and SEM were used to investigate the formation mechanism of the optimized supramolecular gel temporary plugging agent (CD‐Da), and its compatibility, stability, rheology, and plugging performance were evaluated. Experimental results showed that CD‐Da has the characteristics of good injectability in low‐permeability rock cores, strong plugging capacity, self‐breaking, and less damage to the formation. Therefore, this study not only provides a stable and efficient supramolecular gel plugging agent for tight oil and gas reservoirs, but also establishes a prediction model between each component and supramolecular gel, providing a new optimization method for the preparation of supramolecular gel.
... Although, because of its high cost, scientists and engineers have studied many alternatives, like manganese (III) oxide, magnesium oxide (Fe 2 O 3 ), and graphite carbonaceous materials. The fecal wastewater from the septic tank also undergoes MFC biological power generation through the microbial community in the anode chamber (Mondal et al., 2020). Applying natural microbial populations as anodes and Psathyrella candolleana in the cathode chamber promotes bioelectricity production with a 147 mW/m 2 maximum power density. ...
The growing global concern regarding plastic waste pollution and its detrimental environmental impact has prompted significant research and innovation in waste management and energy generation. This comprehensive review explores the current state of handling plastic waste for energy generation, encompassing various technologies and approaches. It also identifies and addresses the imminent challenges facing pursuing sustainable and efficient plastic waste-to-energy solutions. The review discusses the alarming rise in plastic waste production, emphasizing the critical need for sustainable waste management strategies. It provides an overview of the existing methods for handling plastic waste, including mechanical recycling, chemical recycling, and landfill disposal. Special attention is given to emerging technologies such as pyrolysis, gasification, and waste-to-energy incineration, which offer promising avenues for converting plastic waste into valuable energy resources. This comprehensive review provides a valuable overview of the current state of handling plastic waste for energy generation. It underscores the significance of sustainable waste management practices and outlines the potential benefits and challenges associated with various plastic-to-energy technologies. By addressing these challenges and embracing a holistic approach, society can move closer to a sustainable future where plastic waste is managed effectively and contributes to generating clean and renewable energy.
... Hydrogels, consisting of polymer network and large amount of water, are now intensively studied due to its huge application potential in tissue engineering, drug delivery, soft electronics, smart devices and energy saving because of they are soft, flexible, hydrophilic, biocompatible and quasi-solid [1][2][3][4][5]. Generally, polymers used in hydrogels include natural ones such as gelatin, bacterial cellulose, alginate, agar, chitosan, ferritin, polypeptoid [6][7][8][9][10], and synthetic ones such as polyvinyl alcohol, poly(methacrylic acid), polyacrylonitrile, polyethylene glycol and polyacrylamide [1,[11][12][13]. ...
... Peptide hydrogels, serving as drug-delivery systems, possess the ability to encapsulate drugs and release them by the modulating their structure and composition. Additionally, they exhibit excellent biocompatibility and can be easily synthesized [141]. Moreover, peptide hydrogels display various responsiveness, allowing for precise regulation of drug release in response to external environmental factors [142]. ...
Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest malignancies worldwide, is characteristic of the tumor microenvironments (TME) comprising numerous fibroblasts and immunosuppressive cells. Conventional therapies for PDAC are often restricted by limited drug delivery efficiency, immunosuppressive TME, and adverse effects. Thus, effective and safe therapeutics are urgently required for PDAC treatment. In recent years, hydrogels, with their excellent biocompatibility, high drug load capacity, and sustainable release profiles, have been developed as effective drug-delivery systems, offering potential therapeutic options for PDAC. This review summarizes the distinctive features of the immunosuppressive TME of PDAC and discusses the application of hydrogel-based therapies in PDAC, with a focus on how these hydrogels remodel the TME and deliver different types of cargoes in a controlled manner. Furthermore, we also discuss potential drug candidates and the challenges and prospects for hydrogel-based therapeutics for PDAC. By providing a comprehensive overview of hydrogel-based therapeutics for PDAC treatment, this review seeks to serve as a reference for researchers and clinicians involved in developing therapeutic strategies targeting the PDAC microenvironment.
... Recent research has revealed that incorporating natural polymers into keratin could create hybrid hydrogels with excellent cell adhesion and cell-cell interactions, ultimately producing tissue constructs with enhanced mechanical integrity [31]. These hybrid hydrogels, which were composed of a diverse range of natural components, could combine the best features of biologically active proteins with structurally stable polymers such as polysaccharides, resulting in hydrogels with more well-defined structures and functions [32,33]. The composite hydrogel that combines keratin and chitosan demonstrated remarkable advantages that stem from the synergistic effects of both [34][35][36]. ...
... Hybrid dual-network polymer hydrogels (HDNPH) consist of two crosslinked, interwoven networks. The first is generally rigid and strongly crosslinked through covalent bonds; the second is soft and weakly crosslinked through supramolecular interactions such as hydrogen bonds, ionic interactions, or coordination interactions (Figure 1.C) (Mondal, et al., 2020). ...
Hydrogels are three-dimensional polymer matrices with recognized biomedical applications. Chemically crosslinked hydrogels offer greater mechanical stability than physically crosslinked hydrogels due to the covalent bonds between their polymeric chains. The preparation of hydrogels by chemical crosslinking involves three basic components: monomer, initiator and crosslinking agent, which must be present in proportions that do not alter the integrity of the hydrogel. The chemical crosslinking mechanism can be designed from reactions between complementary functional groups, ultraviolet light reactions, radical polymerization, high energy irradiation, among others. In this review, we revisit the chemical crosslinking mechanisms involving synthetic or natural polymers. Finally, biomedical applications of hydrogels are discussed, such as drug delivery, cell culture, tissue engineering, cancer therapy, among others.
Hydrocarboxylation of methyl 2‐octynoate, a chemical commercially available at a low cost, with N‐protected amino acids was developed with a gold‐zinc cooperative catalyst constructed with a 5‐[(2,2′‐bipyridin)‐5‐yl]imidazo[1,5‐a]pyridin‐3‐ylidene to prepare α‐methoxycarbonyl enol esters as acylating reagents. The α‐methoxycarbonyl enol esters were isolable through silica‐gel column chromatography and storable without precautions regarding moisture. Acylation of free amines with the α‐methoxycarbonyl enol esters proceeded without epimerization of the stereogenic center derived from the enol esters, affording analytically pure dipeptide compounds through filtration and hexane‐washing.
A strategy is developed for fabricating liquid crystalline elastomer self-oscillators by using soft tubes as molds. Through different soft tube configurations, the prepared oscillators perform different self-oscillation modes under light stimuli.
The gallbladder is a small, pear-shaped organ located beneath the liver. It plays a role in the digestive system by storing and concentrating bile, a digestive fluid produced by the liver. When you eat, the gallbladder releases bile into the small intestine to help emulsify and break down fats. Gallbladder tissue is composed of various cell types and structures that contribute to its function. The inner lining of the gallbladder is made up of epithelial cells, which form a mucous membrane. These cells are responsible for the secretion of mucus and help prevent the bile from damaging the gallbladder walls. The gallbladder has a muscular wall made of smooth muscle tissue. This muscular layer contracts to expel bile into the small intestine when needed for digestion. The contraction is triggered by the hormone cholecystokinin (CCK), which is released in response to the presence of fats in the small intestine. Connective tissue provides structural support to the gallbladder and helps maintain its shape and integrity. Like any organ, the gallbladder is supplied with blood vessels and innervated by nerves. Blood vessels deliver nutrients and oxygen, while nerves help regulate the contraction and relaxation of the gallbladder muscles.
This review aims to capture the current state of electrochemical actuators and set a trajectory for future innovation in this field.
Peptide-based molecules and their hydrogels are useful materials for biomedical applications due to the reversible nature of their self-assembly as well as the diversity of nanostructures that can be created starting from low-molecular weight compounds. In this study, we have focused on comprehending the characteristics of fibrillar networks of l-lysine-based self-assembled dipeptide hydrogels with a focus on their antibacterial properties. For that purpose, l-lysine has been complemented with hydrophobic aromatic moieties coming from l-phenylalanine and benzyloxyxarbonyl N-capping. In addition, the peptide C-terminus is blocked with alkylamides of different chain lengths which introduces additional dispersive interactions and hydrophobicity. These materials were well characterized by transmission electron microscopy, scanning electron microscopy, wide-angle powder X-ray diffraction and oscillatory rheology. Finally, biocompatibility and antimicrobial tests were performed showing that these hydrogels are compatible with HEK 293 cells and present a remarkable antibacterial activity against both Gram positive (S. aureus) and Gram negative (E. coli) bacteria.
Naturally-derived biomaterials invite immense interest from diverse segments of science and engineering. Recent decades have witnessed a leap in knowledge and efforts in ongoing research with biomaterials as synthons, yet biomaterial research never fails to create surprises. This book summarizes modern knowledge of bioderived materials for beginners in research and advanced readers in materials science.
The book lays the foundations of understanding the design and development of mimetic peptides and enzyme mimetic bioinorganic catalysts, including the toolsets used in the process. Next, the book demonstrates different approaches for obtaining task-specific designer hydrogels. Additional topics covered in the book are tissue engineering and regenerative medicine. From this point, the book presents information on complex biomaterials systems: bacterial cellulose, cell membrane architecture for nanocomposite material design, and whole cellular microorganisms. Chapters provide applied knowledge with information on the strategies used to design novel biomaterials for applications such as drug delivery, therapy and controlled chemical synthesis.
In summary, this book brings together a wealth of information on bioderived materials with versatile applications, derived from different sources, such as plant derivatives and microorganisms (in part or whole as synthons), benefitting readers from multidisciplinary backgrounds.
Flexible hydrogel polymers with excellent stretchability, high conductivity, and biocompatibility are widely used to prepare flexible sensing devices. However, it remains difficult to simultaneously combine excellent tensile capacity and high ion conducting ability into a simple hydrogel material. While PVA‐based hydrogels have been developed before, this work focuses on a unique preparation method. It solves the engineering problem of making hydrogels that have both high elongation at break and high ionic conductivity. In the study, we introduced cellulose nanofibers (CNFs) into polyvinyl alcohol (PVA)/chitosan (CS) cross‐linked polymer networks to form triple network (TN) composite hydrogel. The labyrinthine three‐dimensional (3D) honeycomb through‐hole network nanostructure generated by the addition of CNF provides the hydrogel with excellent mechanical properties. Then, the simple salting‐out strategy of muriate of potash (MOP) solution gives the hydrogel superior mechanical properties and high ionic conductivity. The prepared PVA/CS/CNF/MOP TN ionic conductive hydrogel not only exhibits excellent mechanical properties (toughness up to 2.39 MJ m ⁻³ , fracture strength up to 1.78 MPa, fracture strain up to 350%) but also has impressive ionic conductivity (highest to 8.4 S m ⁻¹ ). The flexible hydrogel strain sensor assembled from the PVA/CS/CNF/MOP TN ionic conductive hydrogel showed remarkable sensitivity (gauge factor for 6.9) and the ability to detect human motions reliably. Besides, the hydrogel also has maintained long‐term antimicrobial and antioxidant properties. The study provided a new perspective on designing multifunctional materials featuring strong mechanical properties and high ionic conductivity, contributing to the advancement of flexible sensor technologies.
As adaptable biomaterials, hydrogels have shown great promise in several industries, which include the delivery of drugs, engineering of tissues, biosensing, and regenerative medicine. These hydrophilic polymer three-dimensional networks have special qualities like increased content of water, soft, flexible nature, as well as biocompatibility, which makes it excellent candidates for simulating the extracellular matrix and promoting cell development and tissue regeneration. With an emphasis on their design concepts, synthesis processes, and characterization procedures, this review paper offers a thorough overview of hydrogels. It covers the various hydrogel material types, such as natural polymers, synthetic polymers, and hybrid hydrogels, as well as their unique characteristics and uses. The improvements in hydrogel-based platforms for controlled drug delivery are examined. It also looks at recent advances in bioprinting methods that use hydrogels to create intricate tissue constructions with exquisite spatial control. The performance of hydrogels is explored through several variables, including mechanical properties, degradation behaviour, and biological interactions, with a focus on the significance of customizing hydrogel qualities for particular applications. This review paper also offers insights into future directions in hydrogel research, including those that promise to advance the discipline, such as stimuli-responsive hydrogels, self-healing hydrogels, and bioactive hydrogels. Generally, the objective of this review paper is to provide readers with a detailed grasp of hydrogels and all of their potential uses, making it an invaluable tool for scientists and researchers studying biomaterials and tissue engineering.
Long‐term in vivo monitoring of chemicals with implantable sensors has garnered significant interest in recent decades due to their profound impact on reflecting health conditions and aiding in disease diagnosis. Hydrogel‐based sensors have emerged as a promising choice for such applications, owing to their swellable, nano‐/microporous, and aqueous 3D structures, as well as their ability to maintain adjustable mechanical properties in wearable and implantable devices. This article presents a comprehensive review of the advancements in hydrogel‐based sensors for living biosystems, encompassing hydrogel synthesis, functionalization, and sensing properties, along with their in vivo applications. Additionally, the article explores key challenges, implementable strategies, and future design possibilities that hold potential for researchers seeking to develop innovative, multifunctional smart sensors. image
Proteins have great importance for medicine and the pharmaceutical and food industries. However, proteins need to be purified prior to their application. This work investigated the application of a hydrogel...
The structures of gels synthesized by controlled radical copolymerization (CRP) and conventional free radical copolymerization (FRP) were studied by a coarse-grained molecular dynamics simulation. It was confirmed that the CRP...
Spontaneous formation of supramolecular metal-organic hydrogel using unsubstituted guanosine as ligand and Zn2+ ions is reported. Guanosine, in the presence of NaOH self-assembled into a stable G-quadruplex structure, which underwent...
Nature materials (skin, tissue, plant fiber, and nacre) exhibit super strength and toughness attributed to their unique multiscale hierarchical anisotropic structure. Hydrogels with excellent flexibility, adjustability, and good biocompatibility have become the exciting frontiers in soft electronics, while anisotropic hydrogels that mimic natural materials still face challenges. Herein, we fabricated an anisotropic poly(vinyl alcohol) hydrogel (DS-PVA) with a multiscale hierarchical structure (micro, submicron, and nano) by directional freezing versus salting out, which differs from isotropic hydrogel mechanical performance and force stimuli electrical response behavior. The PVA hydrogel parallel to the freezing direction (DS-PVA∥) showed excellent strength 2.35 MPa (about five times DS-PVA⊥), toughness 1712 KJ/M3 (9.4 times DS-PVA⊥), stability, and antifatigue characteristics, while the DS-PVA⊥ indicated a higher sensitivity (GF = 4.4, ε = 5%) and a faster response/recovery time (127 ms/63 ms). These hydrogels, similar to natural materials with anisotropic mechanical properties, asymmetric sensing properties, and directional recognition, will provide a strategy for flexible sensor applications.
Peptides are functional biomolecules that hold great potential for the discovery of new therapeutics and drug delivery systems. Structurally, these are short molecules, but they possess similar functionality of large proteins. Peptides can overcome the physiological barriers posed by the diseases due to their intrinsic properties. In recent years, bioactive peptides such as antimicrobial, anticancer, antithrombotic, antidiabetic, and anti-Alzheimer effects have been successfully identified, and many of them are in clinical trials. Apart from that, peptides are also reported for the drug delivery applications as targeting molecules or as self-assembling soft nano-materials. This chapter offers a brief introduction to peptides as therapeutics and drug delivery agents and their application in the management of different diseases through targeted therapy. Here, we discuss the recent development on peptides as carriers to penetrate different physiological barriers such as gastrointestinal (GI) tract and blood-brain barriers.
Self-assembled peptide-based hydrogels have shown great potential in bio-related applications due to their porous structure, strong mechanical stability, high biocompatibility, and easy functionalization. Herein, the structure and characteristics of hydrogels and the mechanism of action of several regular secondary structures during gelation are investigated. The factors influencing the formation of peptide hydrogels, especially the pH responsiveness and salt ion induction are analyzed and summarized. Finally, the biomedical applications of peptide hydrogels, such as bone tissue engineering, cell culture, antigen presentation, antibacterial materials, and drug delivery are reviewed.
The magnetic nanocarriers containing chitosan/hyaluronic acid complexed with κ-carrageenan were synthesized by solution method, as the drug delivery system. Doxorubicin (DOX) was used as the model drug. Characterization assessments were performed to identify the functional groups, determine the structure and morphology, and magnetic properties of nanodelivery system. Furthermore, their impacts on MCF-7 and MDA-MB-237 cell lines were evaluated by MTT assay. Analyses confirm polymers physical interaction, chemical bonding in the structure, moreover presence of spherical shape magnetic nanoparticles in the 100-150 nm range. The DOX loading was 74.1 ± 2.5 %. Results indicate that the drug loading was raised to 83.0±2.2 % by increasing the amount of κ-carrageenan in specimens. The swelling of samples in the acidic environment (e.g. pH 5.5) was verified by the Dynamic Light Scattering analysis. Consequently, pH stimulus-responsive drug release in the sustained stream and a considerable amount of DOX release (84±3.1 %) was detected as compared to a higher pH medium (27±1.5 % at pH 7.4). According to the MTT assay results, MNPs showed no inhibitory effect on both cell lines. Also, 10 and 15 μg/ml of MNPs-DOX was considered as IC50 value on MDA-MB-237 and MCF-7 cells, respectively. The DOX 25 μg/ml caused 50 % antiproliferative activity in both cell lines.
Deciphering the most promising strategy for the evolution of potential wound-healing therapeutics is one of the greatest challenging affairs to date. The development of peptide-based smart scaffolds with innate antimicrobial, anti-inflammatory, and antioxidant properties is an appealing way out. Aligned to the goal a set of Hydrogelators I - IV were developed utilizing the concept of chiral orchestration in diphenylalanine fragment, such that the most potent construct with all the bench marks namely mechanoresponsiveness, biocompatibility, consistent antimicrobial and antioxidant properties, could be fished out from the design. Interestingly, our invitro Antifungal and Lipid peroxidation analysis identified the homochiral isomer (Hydrogelator I), as an ideal candidate for the wound healing experiment. So we proceeded for the invivo measurements in Wister rats. Indeed the wound images demonstrated that with increased recovery time, hydrogelator I displayed a significant reduction in the lesion diameter compared to the marketed drug, and negative control. Even the histopathological measurements using H & E staining demonstrated diminished tissue destruction, neutrophil infiltration necrosis, and lymphatic proliferation in the hydrogelators, incomparison to others, backed by invivo lipid peroxidation data. Overall our investigation certifies hydrogelator I as an effective therapeutic for managing the wound healing complication.
Hydrogels based on polysaccharide and protein natural polymers are of great interest in biomedical applications and more specifically for tissue regeneration and drug delivery. Cellulose, chitosan (a chitin derivative), and collagen are probably the most important components since they are the most abundant natural polymers on earth (cellulose and chitin) and in the human body (collagen). Peptides also merit attention because their self-assembling properties mimic the proteins that are present in the extracellular matrix. The present review is mainly focused on explaining the recent advances on hydrogels derived from the indicated polymers or their combinations. Attention has also been paid to the development of hydrogels for innovative biomedical uses. Therefore, smart materials displaying stimuli responsiveness and having shape memory properties are considered. The use of micro- and nanogels for drug delivery applications is also discussed, as well as the high potential of protein-based hydrogels in the production of bioactive matrices with recognition ability (molecular imprinting). Finally, mention is also given to the development of 3D bioprinting technologies.
The lower conductivity of MoS2 sheet presents a huge barrier for the exploitation of its supercapaciator electrode application. To alleviate this difficulty, MoS2 quantum dots (QDs) having high surface area is prepared. The synthesized MoS2 QDs are embedded into polyaniline (PANI)‐N,N‐dibenzoyl‐L‐cystine (D) aerogel matrix for application in high performance supercapaciator. Here, conductive PANI hydrogel are prepared by in situ polymerization of aniline where D acts as a gelator, dopant, and cross‐linker. The D‐PANI aerogel shows conductivity of 0.02 S cm−1, specific capacitance of 278 F g−1 at a current density of 1 A g−1. The optimal MoS2 QDs in D‐PANI aeogel improves specific capacitance up to 796.2 F g−1 at 1 A g−1 showing long cycling stability (86% after 5000 cycles).
DNA and RNA biomarkers have not progressed beyond the automated specialized clinic due to failure in the reproducibility necessary to standardize robust and rapid nucleic acid detection at the point of care, where health outcomes can be most improved by early-stage diagnosis and precise monitoring of therapy and disease prognosis. We demonstrate here a new analytical platform to meet this challenge using functional 3D hydrogels engineered from peptide and oligonucleotide build-ing blocks to provide sequence-specific, PCR-free fluorescent detection of un-labelled nucleic acid sequences. We discrimi-nated at picomolar detection limits (<7 pM) ‘perfect-match’ from mismatched sequences, down to a single nucleotide muta-tion, buried within longer lengths of target. Detailed characterisation by NMR, TEM, mass spectrometry and rheology pro-vided the structural understanding to design these hybrid peptide-oligonucleotide biomaterials with the desired sequence sen-sitivity and detection limit. We discuss the generic design, which is based on a highly-predictable secondary structure of the oligonucleotide components, as a platform to detect genetic abnormalities and to screen for pathogenic conditions at the level of both DNA (e.g. SNPs) and RNA (messenger, micro and viral genomic RNA).
Conductive polymer hydrogels are emerging as an advanced electronic platform for sensors by synergizing the advantageous features of soft materials and organic conductors. Doping provides a simple yet effective methodology for the synthesis and modulation of conductive polymer hydrogels. By utilizing different dopants and levels of doping, conductive polymer hydrogels show a highly flexible tunability for controllable electronic properties, microstructures, and structure-derived mechanical properties. By rationally tailoring these properties, conductive polymer hydrogels are engineered to allow sensitive responses to external stimuli and exhibit the potential for application in various sensor technologies. The doping methods for the controllable structures and tunable properties of conductive polymer hydrogels are beneficial to improving a variety of sensing performances including sensitivity, stability, selectivity, and new functions. With this perspective, we review recent progress in the synthesis and performance of conductive polymer hydrogels with an emphasis on the utilization of doping principles. Several prototype sensor designs based on conductive polymer hydrogels are presented. Furthermore, the main challenges and future research are also discussed.
The development of stretchable supercapacitors (SSCs) is heading to compact and robust devices with higher capacitance and simpler preparation process. Herein, a new strategy is reported to prepare a highly stretchable and conductive polypyrrole hydrogel with a unique biphase microstructure (loose phase and dense phase), which is formed by the supramolecular assembly of polypyrrole (PPy), poly(vinyl alcohol), and anionic micelles. The loose phase enables the PPy hydrogel large stretchability (elongation at a break of 500%) and good electrochemical capacitive behavior, while the dense phase enables the PPy hydrogel high tensile strength (2 MPa) and good conductivity (0.8 S cm−1). Without using any substrate, the SSC made of this polypyrrole hydrogel provides an areal capacitance of 950 mF cm−2 at a current density of 1.6 mA cm−2, exceeding most of reported SSCs. This SSC can withstand repeated deformation and retain 81% capacitance after 500 stretching–releasing cycles. Besides, at subzero temperature down to −20 °C, this SSC can still retain its good stretchability and capacitance. The combination of high areal capacitance, good stretchability, and high retention of capacitance under various circumstances enables the polypyrrole hydrogel–based SSC an economical and robust SSC for stretchable electronics. Strong and stretchable conductive polypyrrole hydrogels with a unique spongy biphase microstructure are facilely prepared. Without any substrate, the supercapacitor assembled with this hydrogel as electrode demonstrates high areal capacitance, good stretchability and high retention of capacitance under large deformation and subzero temperature environment, which enable this supercapactor a high‐performance and low‐cost stretchable energy supply for flexible electronics.
Low cell survival after syringe injection hampers the success of preclinical and clinical cell transplantation trials. During syringe injection cells experience mechanical forces that lead to cell-membrane disruption and decreased viability. To improve cell surviv-al, we designed Rapidly Assembling Pentapeptides for Injectable Delivery (RAPID) hydrogels that shear-thin, protect cells from extensional flow, form fibers, and provide mechanical properties similar to native tissue. We found that 1.5 wt % RAPID hydrogels mitigate the damaging effects of extensional flow resulting in significantly greater cell viability (of common laboratory cell lines, primary cells, and human cells) than cells injected in PBS.
Since the traditional 2D surface for cell growth has been shown to be increasingly insufficient in contemporary cell biology, more and more research is performed on 3D matrices that can better represent the natural extracellular matrix (ECM) in many aspects. To create such a complex nonuniform 3D matrix, four‐armed polyethylene glycol with azides and (1R,8S,9S)‐bicyclo[6.1.0]non‐4‐yn‐9‐yl groups is functionalized to form the hydrogel basis. Together with these, a matrix metalloproteinase cleavable peptide sequence as a functional motif is also built in to add degradability to the hydrogel. In addition, self‐assembled peptide amphiphile (PA) fibers containing a cellular binding peptide sequence (RGDS) are encapsulated in the hydrogel to mimic the natural fibrous structure of the ECM and to stimulate cell adhesion. Rheology studies confirm that the polymer dissolved in the PA fiber solution forms a stable hydrogel with acceptable mechanical properties (G′ = 3.8 kPa). In addition, it is shown that this hydrogel network is degradable under the action of a metalloproteinase enzyme. Finally, the hybrid hydrogel is used to culture and it is demonstrated that both HeLa cells and human mesenchymal stem cells show adherence, good viability, and a well‐spread shape inside the hybrid hydrogel after 5 days of incubation when all components are present.
Amino acid chirality has been recognized as an important driving force in constructing peptide architectures, via interactions such as chirality-induced stereochemical effect. The introduction of site-specific chiral conversion of L- and D-amino acids in peptide sequences could enable the pursuit of the chirality effects in peptide assembly. In this work, we characterized the assemblies of heptapeptides with various side chain moieties and their chiral variants using STM. Specifically, two pairs of amino acids, Gln (Q) and Asn (N), Glu (E) and Asp (D), having one methylene difference in their side chains, are selected to elucidate the steric dependence of amino acid chiral effects on surface-bound peptide assemblies. The observed heptapeptide assembly structures reveal that chirality switching of single amino acid is able to destabilize the surface-mediated peptide assemblies and this disturbance effect can be positively correlated with the steric hindrance of amino acid side chains. Furthermore, the strength of the impact due to chiral conversion on heptapeptide assembly structure is noticeably dependent on the mutation sites, indicative of structural heterogeneity of chiral effects. These results could contribute to the molecular insights of chirality-induced stereochemical interactions in peptide assembly.
The engineering of natural protein-based hydrogels with outstanding mechanics and functionalities is an eternal pursuit in biomaterial science. Soaking methods have recently been used to simply and efficiently tune the macroscopic mechanical properties of hydrogels consisting of natural polymers (protein or polysaccharide). However, the high concentration of salts or organic solvent within the soaked hydrogels is harmful to cells. Once eliminating the salts, however, these hydrogels experience mechanics attenuation and swelling, limiting their applications as biomaterials. Here we utilize dual crosslink networks to address these problems by preserving the physical interactions formed during soaking treatment. As an example, a dual crosslink gelatin-chitosan hydrogel is prepared by click reaction and hydrophobic interactions, which achieve an unusual combination of abundant water content (>87%), strong mechanics (ultimate strength ~ 1.8 MPa), antiswelling property (swelling ratio of 11.25% in PBS for 7 days), thermal stability, and biocompatibility. We expect that this strategy can be generalized for the development of tough, biocompatible and environmentally stable protein-based hydrogels.
The development of silk fibroin hydrogels with a suitable gelation rate and mechanical strength, as well as multifunctional properties including injectability, antibacterial activity, and adhesiveness, is of importance for wound healing and skin infection treatment, yet their design remains challenging. Herein, a multifunctional hydrogel from silk fibroin and tannic acid is developed, relying on the favorable interactions between them. The hybrid hydrogel (SF-TA) exhibits numerous advantages, such as short gelation time, low gelation concentrations, good adhesiveness, and shear-thinning and self-recovery properties. Moreover, the incorporation of tannic acid endows the hybrid hydrogel with remarkable bioactivity, including antimicrobial and antioxidant activities, beneficial to improving wound healing. In vivo experiments verify that the designed hybrid hydrogel can significantly accelerate the wound healing process in a full-thickness skin defect model on mice.
Peptide based hydrogels are highly promising for various biomedical applications owing to their precise self-assembly, biocompatibility and sensitivity towards biologically relevant external stimuli. Herein, we report pH-responsive self-assembly and gelation of a highly biocompatible amphiphilic peptide PEP-1. This is an octa-peptide and double mutant of a naturally occurring β-strand peptide fragment of the protein Galectin-1, available in bovine spleen. PEP-1 was synthesized by using the Rink amide resin as the solid support in a home-made apparatus. At pH 7.4, it exhibits spontaneous gelation with very high yield stress of 88.0 Pa and gel-to-sol temperature of 84 °C at C = 2.0 wt %. Microscopy studies revealed entangled fibrillar morphology while CD, FT-IR and Thioflavin T assay indicated formation of β-sheet rich secondary structure. The assembled state was found to be stable in neutral pH while either decrease or increase in the pH resulted in disassembly owing to presence of the pH responsive Asp and Lys residues. The gel network showed ability to entrap water soluble guest molecules such as Calcein which could be selectively released at acidic pH while under neutral condition the release was negligible. MTT assay revealed remarkable biocompatibility of the PEP-1 gel as almost 100 % cells were alive after 48 h incubation in presence of PEP-1 (2.0 mg/ mL).
The discovery of potent stimuli-responsive hydrogels have rapidly expanded in the last decades due to their diversified applications in the field of biomedicines. In accordance to this drift, herein our...
Controlling the self-assembly pathways can be an effective means to create complex multifunctional structures based on a single gelator design. To this direction, ion mediated approach to control and direct supramolecular structure of the low molecular weight peptide hydrogelator (LMWH) would be an excellent methodology for bottom-up nanofabrication of these advanced functional materials. Our work primarily aims to understand the role of different metal ions as well as anions in modulating the self-assembly of the peptide amphiphiles. Our approach relies on rational incorporation of histidine in the peptide amphiphile, which can impart ion responsive behavior to the hydrogels. Interestingly, the self-assembly pathway of histidine based dipeptide amphiphile was found to be largely influenced by various metal salts. A gel to sol transition occurred at physiological pH in the presence of Cu2+, Ni2+ and Co2+ ions, owing to their strong interactions with the histidine thus shifting the gelation to pH 3.0. However, in case of Fe2+ and Mn2+, the weak interactions of histidine-metal ion can still hold the gel at physiological pH but gel strength was significantly decreased. Our studies provide a clear insight into this ion-responsive behavior across the wide pH range, which is mainly governed by the stability of peptide-metal ion complex as per Irving-Williams series. Moreover, anions also influenced the mechanical strength as well as morphology of the nanostructures owing to their differential interaction with water as depicted in Hofmeister series of anions. This bioinspired approach will provide an elegant strategy for accessing diverse structures, which are ‘out of equilibrium’ and otherwise are only accessible through differential molecular design. We envisage that our systematic studies on histidine-metal ion interaction can be an extremely useful methodology, which will pave a way to design and develop the stimuli responsive biomaterials.
Although assembly of recombinant proteins by SpyTag/SpyCatcher chemistry has proven to be a versatile approach for creating bioactive hydrogels, the resulting Spy networks often exhibit weak mechanics due to the poor efficiency of interchain cross-linking. Here we leverage metal/ligand (i.e., cobalt/His6-tag) coordination interactions to modulate the bulk mechanics of the protein networks. The drastic difference between the Co2+ and Co3+ complexes in thermodynamic and kinetic properties enabled us to regulate the materials’ properties and to immobilize and release recombinant proteins in a redox-dependent manner. The resulting hydrogels are capable of not only supporting cell growth and proliferation, but also influencing specific cell signaling via immobilized growth factors such as leukemia inhibitory factor (LIF). The integrated use of stimuli-responsive metal coordination and SpyTag/SpyCatcher chemistry opens up a new dimension for designing bioactive protein materials.
The misfolding of proteins and peptides potentially leads to a conformation transition from an α-helix or random coil to β-sheet-rich fibril structures, which are associated with various amyloid degenerative disorders. Inhibition of the β-sheet aggregate formation and control of the structural transition could therefore attenuate the development of amyloid-associated diseases. However, the structural transitions of proteins and peptides are extraordinarily complex processes that are still not fully understood and thus challenging to manipulate. To simplify this complexity, herein, the effect of metal ions on the inhibition of amyloid-like β-sheet dipeptide self-assembly is investigated. By changing the type and ratio of metal ion/dipeptide mixture, structural transformation is achieved from a β-sheet to a super-helix or random coil, as confirmed by experimental results and computational studies. Furthermore, the obtained supramolecular metallogel exhibits excellent in vitro DNA binding and diffusion capability due to the positive charge of the metal/dipeptide complex. This work may facilitate the understanding of the role of metal ions in inhibiting amyloid formation and broaden the future applications of supramolecular metallogels in three-dimensional (3D) DNA biochip, cell culture, and drug delivery.
The emergence of hydrogel ionotronics has significantly extended the applications of soft electronics by allowing intimate interfaces between electronic components and biological/engineered surfaces for improved sensing and communication with surrounding stimuli. However, hydrogel ionotronic devices that combine high stretchability, self-healing, good water-retention and biocompatibility are still needed. Here, we report a biocompatible ionic hydrogel prepared from polyvinyl alcohol, silk fibroin, and borax. In this ionic hydrogel, polyvinyl alcohol and borax offer high stretchability and conductivity, respectively, while silk fibroin improves the stability of the hydrogel and increases water uptake by the gels. The hydrogels feature strains larger than 5,000%, good water retention, self-healing and tunable conductivity and adhesive capabilities. We also demonstrate the utility of the hydrogel as a sensing platform to monitor human body motion for applications in health management, soft robotics, and human-machine interfaces.
One key design feature in the development of any local drug delivery system is the controlled release of therapeutic agents over a certain period of time. In this context, we report the characteristic feature of a supramolecular filament hydrogel system that enables a linear and sustainable drug release over the period of several months. Through covalent linkage with a short peptide sequence, we are able to convert an anticancer drug, paclitaxel (PTX), to a class of prodrug hydrogelators with varying critical gelation concentrations. These self-assembling PTX prodrugs associate into filamentous nanostructures in aqueous conditions and consequently percolate into a supramolecular filament network in the presence of appropriate counterions. The intriguing linear drug release profile is rooted in the supramolecular nature of the self-assembling filaments which maintain a constant monomer concentration at the gelation conditions. We found that molecular engineering of the prodrug design, such as varying the number of oppositely charged amino acids or through the incorporation of hydrophobic segments, allows for the fine-tuning of the PTX linear release rate. In cell studies, these PTX prodrugs can exert effective cytotoxicity against glioblastoma cell lines and also primary brain cancer cells derived from patients and show enhanced tumor penetration in a cancer spheroid model. We believe this drug-bearing hydrogel platform offers an exciting opportunity for the local treatment of human diseases.
We report that the helical coiling of micelles induced by disulfide crosslinking in a lyotropic peptide liquid crystal leads to the formation of a printable hydrogel. The (9-fluorenylmethyloxycarbonyl)-protected phenylalanine-phenylalanine-cysteine tripeptide could firstly self-assemble into aligned micelles at high pH values via noncovalent interactions, leading to the formation of a viscous solution. Intriguingly, the cross-linking of the sulfhydryl group between the peptides changed greatly the rheological properties of the peptide solutions, leading to a 6500-fold increase of the storage modulus to 39 kPa. This led to the formation of a self-supporting peptide hydrogel with a series of improved physical properties, including shear-thinning and thixotropy. The formation of the peptide hydrogels with enhanced physical properties can be attributed to the structural transition of the parallelly aligned worm-like micelles into coiled nanohelices induced by the cross-linking of disulfide bonding. The findings deepen our understanding on the relationship between micelle chirality and gel properties, and provide a strategy to fabricate highly functional materials via simultaneous noncovalent and covalent polymerizations.
Self-assembling peptides can be used in a bottom-up approach to build hydrogels that are similar to the extracellular matrix at both structural and functional levels. In this study, a nucleo-tripeptide library was constructed to identify molecules that form hydrogels under physiological conditions. We used both experimental and computational approaches to study these self-assembled structures. Circular dichroism spectroscopy, transmission electron microscopy, and rheometry were utilized to support and supplement molecular dynamics simulations. Our data demonstrate that nucleo-tripeptides can form nano-fibrous hydrogels through Watson-Crick base pairing and π-π stacking interactions. Self-assembly conditions are mediated by nucleo-tripeptide hydrophobicity and amphiphilicity and can therefore be regulated by rational molecular design. We have found that structures derived from specific peptide and nucleobase conjugations form hydrogels under physiologic conditions, making them promising candidates for biomedical applications.
Supramolecular polymer-based biomaterials play a significant role in current biomedical research. In particular, peptide amphiphiles (PAs) represent a promising material platform for biomedical applications given their modular assembly, tunability, and capacity to render materials with structural and molecular precision. However, the possibility to provide dynamic cues within PA-based materials would increase the capacity to modulate their mechanical and physical properties and consequently enhance their functionality and broader use. In this study, we report on the synthesis of a cationic PA pair bearing complementary adamantane and β-cyclodextrin host-guest cues and their capacity to be further incorporated into self-assembled nanostructures. We demonstrate the possibility of these recognition motifs to selectively bind, enabling noncovalent cross-linking between PA nanofibers, and endowing the resulting low weight (1 wt%) supramolecular hydrogels with enhanced mechanical properties, including stiffness and resistance to degradation, while retaining in vitro biocompatibility. The incorporation of the host-guest PA pairs in the resulting hydrogels allowed not only for macroscopic mechanical control from the molecular scale but also for the possibility to engineer further spatiotemporal dynamic properties, opening opportunities for broader potential applications of PA-based materials.
Intact and stable bone reconstruction is ideal for the treatment of periodontal bone destructions but remains challenging. In research, biomaterials are used to encapsulate stem cell or bioactive factor for periodontal bone regeneration but, to the best of our knowledge, using supramolecular hydrogel to encapsulate bioactive factors for their sustained release in bone defect area to promote periodontal bone regeneration has not been reported. Herein, we used a well studied hydrogelator NapFFY to coassemble with SDF-1 and BMP-2 to prepare a new supramolecular hydrogel SDF-1/BMP-2/NapFFY. In vitro and in vivo results indicated that these two bioactive factors were ideally, synchronously, sustained released from the hydrogel to effectively promote the regeneration and reconstruction of periodontal bone tissues. Specifically, after the bone defect areas were treated with our SDF-1/BMP-2/NapFFY hydrogel for 8 weeks using maxillary critical-sized periodontal bone defect model rats, a superior bone regeneration rate of 56.7% bone volume (BV) fraction was achieved in these rats. We anticipate that our SDF-1/BMP-2/NapFFY hydrogel could replace bone transplantation in clinic for the repair of periodontal bone defect and periodontally accelerated osteogenic orthodontics (PAOO) in near future.
Although recent years have witnessed intense efforts and innovations in the design of flexible conductive materials for the development of next-generation electronic devices, it remains a great challenge to integrate multifunctionalities such as stretchability, self-healing, adhesiveness and sensing capability into one conductive system for practical applications. In this work, for the first time, we have prepared a new electrically conductive elastomer composite which combines all these functionalities, by triggering in situ polymerization of pyrrole in a supramolecular polymer matrix crosslinked by multiple hydrogen-bonding 2-ureido-4[1H]-pyrimidinone (UPy) groups. The polypyrrole (PPy) particles were uniformly dispersed and imparted the composite desirable conductive properties, while the reversible nature of the dynamic multiple hydrogen bonds in the polymer matrix allowed excellent stretchability, fast self-healing ability and adhesiveness under ambient condition. The elastomer composite with incorporation of 7.5 wt% PPy displayed a mechanical strength of 0.72 MPa with an elongation over 300%, where the rapid self-healing of the mechanical and electrical properties was achieved within 5 min. The elastic material also exhibited strong adhesiveness to a broad range of inorganic and organic substrates, and it was further fabricated as a strain sensor for the detection of both large and subtle human motions (i.e., finger bending, pulse beating). The novel PPy-doped conductive elastomer has demonstrated great potential as functional sensors for wearable electronics, which provides a facile and promising approach to the development of various flexible electronic materials with multifunctionalities by combining conductive components with supramolecular polymers.
Stem cell-derived exosomes have been recognized as a potential therapy for cardiovascular diseases. However, low retention rate of exosomes after transplantation in vivo remains a major challenge in clinical application. The aim of this study is to investigate whether human umbilical cord mesenchymal stem cell derived exosomes (UMSC-Exo) encapsulated in functional peptide hydrogel could increase the retention and stability of exosomes and improve heart function in a rat myocardial infarction model. Our results demonstrated that the PA-GHRPS peptide protected H9C2 cells from H2O2-induced oxidative stress. The gelatinization ability of PA-GHRPS can be enhanced by peptide NapFF. Therefore, these two peptides were mixed to form the PGN hydrogel, which was used to encapsulate exosomes. Our data showed that PGN hydrogel was able to encapsulate exosomes effectively and ensured a stable and sustained release of exosomes. The exosomes/PGN hydrogel mixture was injected into the infarct border zone of rat heart. Compared to exosome treatment alone, the mixture improved myocardial function by reducing inflammation, fibrosis, apoptosis, and by promoting angiogenesis. The strategy used in this study provided a practical and effective method to harness exosome for myocardial regeneration. Keywords: Self assembly, Peptide hydrogel, Exosomes, Myocardial infarction, Cell-free therapy
Combination therapy has been conferred with manifold assets leveraging the synergy of different agents to achieve sufficient therapeutic outcome with lower administered drug doses and reduced side effects. The therapeutic potency of a self-assembling peptide hydrogel for the co-delivery of doxorubicin (DOX) and curcumin (CUR) combination was evaluated against head and neck cancer cells. The dual loaded peptide hydrogel enabled control over the rate of drug release based on drug’s aqueous solubility. A significantly enhanced cell growth inhibitory effect was observed after treatment with the combination drug loaded hydrogel formulations compared to the respective combination drug solution. The synergistic pharmacological effect of selected hydrogel formulations was further confirmed with enhanced apoptotic cell response, interference in cell cycle progression and significantly altered apoptotic/anti-apoptotic gene expression profiles obtained in dose levels well below the half-maximal inhibitory concentrations of both drugs. The in vivo antitumour efficacy of the drug loaded peptide hydrogel formulation was confirmed in HSC-3 cell-xenografted SCID mice and visualized with μCT imaging. Histological and TUNEL assay analyses of major organs were implemented to assess the safety of the topically administered hydrogel formulation. Overall, results demonstrated the therapeutic utility of the dual drug-loaded peptide hydrogel as a promising approach for the local treatment of head and neck cancer.
Novel dehydropeptide-based magnetogels, based on the hydrogelators Npx-L-Phe-Z-ΔAbu-OH, Npx-L-Trp-Z-ΔPhe-OH and Npx-L-Ala-Z-ΔPhe-Gly-L-Arg-Gly-L-Asp-Gly-OH and containing manganese ferrite nanoparticles (diameter around 20 nm), were prepared and characterized. TEM and FTIR measurements showed that the magnetogels maintain the fibrous structure of the neat hydrogels, with fibres of ca. 20 nm average width (generally in the range 10 – 30 nm) and a few conformational changes relative to the neat hydrogels. The magnetogels were tested as nanocarriers for two potential fluorescent antitumor drugs, a thienopyridine derivative and the natural compound curcumin. FRET (Förster Resonance Energy Transfer) from the gels aromatic moieties (energy donors) to the fluorescent drugs (energy acceptors) and fluorescence anisotropy measurements confirmed the incorporation of both drugs in the magnetogels matrices. The transport of both drugs loaded in the magnetogels into membrane models (small unilamellar vesicles) was assessed by FRET between the fluorescent drugs and the dye Nile Red. The magnetogel possessing the RGD sequence was the most promising for delivery of the thienopyridine derivative, while the three magnetogels showed to be suitable for the delivery of curcumin.
Soy protein isolate (SPI), a plant derived protein, is emerging as a potential material for biomedical applications because of its abundance in nature, ease of isolation and processing, tailorable biodegradability, low cost and low immunogenicity. Herein we report the development and structure-property relationship of photocrosslinked SPI and SPI/silk fibroin (SF) hybrid hydrogels for the first time. The pristine SPI hydrogels were crosslinked at two different structural conformations (i.e. closed at pH 7, and open at pH 12), and SPI/SF hybrid hydrogels were co-crosslinked at pH 7 in three different weight ratios (3:1, 1:1 and 1:3). The fabricated hydrogels were characterized using electron microscopy, X-ray diffraction, Raman and infrared spectroscopy, thermal analysis, small and ultra-small angle neutron scattering, rheology, water uptake and in vitro degradation studies. The equilibrium water swollen SPI hydrogel crosslinked at pH 7 exhibited a specific microstructure, controlled degradation in phosphate buffered saline, and a shear storage modulus of ~7.7 kPa, which is in the range of human lumbar nucleus pulposus, and significantly higher than soy hydrogels reported by thermal treatment, pressure treatment, salt-induced cold-setting and enzymatic crosslinking. Conversely, the SPI hydrogel crosslinked at pH 12 exhibited ordered porous microstructure, higher water uptake of ~1946%, poor water-resistant and mechanical properties. Increase in SF content of the SPI/SF hybrid hydrogels demonstrated improved porosity, swelling, molecular chain mobility, elastic and water-resistant properties. An in-depth understanding of the effect of pH and composition on the hierarchical structure and physicochemical properties of the fabricated hydrogels was established. Moreover, the pristine SPI and SPI/SF hybrid inks used for hydrogel fabrication exhibited flow properties highly suitable for 3D-printing scaffolds for tissue engineering applications. The presented results contribute to a facile fabrication and fundamental understanding of the structure–property relationship of SPI-based hybrid hydrogels.
We investigate the self-assembly of a palmitoylated (C16-chain at the N terminus) peptide fragment in comparison to the unlipidated peptide EELNRYY based on a fragment of the gut hormone peptide PYY3-36. The lipopeptide C16-EELNRYY shows remarkable pH-dependent self-assembly above measured critical aggregation concentrations, forming fibrils at pH 7, but micelles at pH 10. The parent peptide does not show self-assembly behaviour. The lipopeptide forms hydrogels at sufficiently high concentration at pH 7, the dynamic mechanical properties of which were measured. We also show that the tyrosine functionality at the C terminus of EELNRYY can be used to enzymatically produce the pigment melanin. The enzyme tyrosinase oxidises tyrosine into 3,4-dihydroxyphenylalanine (DOPA), DOPA-quinone and further products, eventually forming eumelanin. This is a mechanism of photo-protection in the skin, for this reason controlling tyrosinase activity is a major target for skin care applications and EELNRYY has potential to be developed for such uses.
A biocompatible hydrogel containing hexa-peptide as key unit has been designed and fabricated. Our design construct comprises a β-sheet rich short hexa-peptide in the centre with a hydrophobic long chain and hydrophilic triple lysine unit attached at the N- and C- terminals respectively. Thus, it is this amphiphilic nature of the molecule that facilitates the gelation. It can capture solvent molecules in the three dimensional cross-linked fibrillary networks. The amphiphilic character of the construct has been modulated to produce an excellent biocompatible soft-material for the inhibition of bacterial growth by rupturing the bacterial cell membrane. This hydrogel is also stable against the enzymatic degradation (Proteinase K) and most importantly offers a bio-compatible environment for the growth of normal mammalian cells due to its non-cytotoxic nature as observed through the cell viability assay. From the haemolytic assay, the morphology of the hRBCs is found to be almost intact, which suggests that the hydrogel can be used in biomedical applications. Thus, this newly designed anti-bacterial hydrogel can be used both as antibacterial biomaterials and biocompatible scaffolds for mammalian cell culture.
Supramolecular hydrogels are emerging as next-generation alternatives to synthetic polymers for drug delivery applications. Self-assembling peptides are a promising class of supramolecular gelator for in vivo drug delivery that have been slow to be adopted despite advantages in biocompatibility due to the relatively high cost of producing synthetic peptide hydrogels compared to synthetic polymer gels. Herein we describe the development and use of inexpensive low molecular weight cationic derivatives of phenylalanine (Phe) as injectable hydrogels for in vivo delivery of an anti-inflammatory drug, diclofenac, for pain mitigation in a mouse model. N-Fluorenylmethoxycarbonyl phenylalanine (Fmoc-Phe) derivatives were modified at the carboxylic acid with diaminopropane (DAP) to provide Fmoc-Phe-DAP molecules that spontaneously and rapidly self-assemble in aqueous solutions upon addition of physiologically relevant sodium chloride concentrations to give hydrogels. When self-assembly occurs in the presence of diclofenac, the drug molecule is efficiently encapsulated within the hydrogel network. These hydrogels exhibit robust shear-thinning behavior, mechanical stability, and drug release profiles to enable application as injectable hydrogels for in vivo drug delivery. Delivery of diclofenac in vivo was demonstrated by a localized injection of an Fmoc-F<sup>5</sup>-Phe-DAP/diclofenac hydrogel into the ankle joint of mice with induced ankle injury and associated inflammation-induced pain. Remediation of pain in the ankle joint was observed immediately after initial injection and was sustained for a period of nearly two weeks while diclofenac controls remediated pain for less than one day. This data demonstrates the promise of these supramolecular hydrogels as inexpensive next-generation materials for sustained and localized drug delivery in vivo .
Functional hydrogels are an attractive material platform for energy-storage technologies. Thus, the development of hydrogels with enhanced physicochemical properties (e.g., improved mechanical strength, flexibility, and charge transport) offers new opportunities for next-generation batteries and supercapacitors. Armed with a deeper understanding of gelation chemistry, researchers have made significant strides toward fabricating hydrogels that are stimulus responsive, self-healing, and highly stretchable. In this short review, we highlight how hydrogels have been integrated into batteries and supercapacitors and provide exciting examples that demonstrate the versatility of hydrogels; namely, tailorable architectures, conductive nanostructures, 3D frameworks, and multifunctionalities. It is anticipated that creative and combinatorial approaches used in the design of functional hydrogels will continue to yield materials with great potential in the field of energy storage.
The design of light-responsive peptide hydrogel with controllable drug release characteristics is still a challenge. Here, we fabricated a NIR light-responsive short peptide hydrogel by using a thermo-responsive short peptide hydrogel and PEGylated NbSe2 nanosheets, namely NbSe2-PEG@YD hydrogel. Under NIR light irradiation, the hydrogel began to collapse owing to the local heating, leading to release of the cargos. The hydrogel exhibited recoverability and the release rate of the cargos could be accurately modulated by the NIR light irradiation according to the requirement. The excellent biocompatibility of this hydrogel ensured that it could be further developed as a drug carrier for clinical application.
The fundamental understanding of the detailed relationship between molecular structure and material function re-mains a challenging task, till date. In order to understand the relative contribution of aromatic moieties and hydro-phobicity of amino acid chain, we designed a library of ultra short amyloid-like peptides based on Ar-Phe-X (where ‘Ar’ represents different aromatic moieties and ‘X’ represents amino acids having varied side chain functionalities). Our research clearly indicated that alteration in the size and hydrophobicity of the aromatic capping play a crucial role compared to the subtle change in amino acid sequence of the dipeptide in dictating the final self-assembled structure and properties of these short peptide amphiphiles. Further, we explored our detailed understanding towards the controlled synthesis of bioinspired organic-inorganic hybrids. For the first time, we established the differential role of aliphatic and aromatic hydroxyl moiety towards the in situ shape-controlled synthesis of gold nanoparticles in 3D nanostructures of hydrogels. To the best of our knowledge, it is the first report which demonstrated the formation of rectangular platonic gold nanoparticles using simple dipeptide hydrogels, exhibiting pH dependent size control. Our study shows promising implications in bottom-up nanofabrication of next-generation nanomaterials with emergent properties.
An injectable hydrogel based drug delivery carrier has been developed for long term drug release by assembling various generation of cyclodextrin (CD) followed by hydrophobic layers to sustain the drug delivery rate for better cancer treatment. Three generations of CD are designed through urethane linkages using small spacer to create a large hydrophilic core which is covered with hydrophobic layers of polyurethane through grafting to maintain the hydrophilic hydrophobic balance of the whole superstructure. Drug release becomes sustained from the intricate superstructure following the non-Fickian diffusion process resulting massive cancer cell killing as compared to low killing rate from the pure drug/material arising from its burst release. The superstructure is found to be a good biomaterial and its drug loaded conjugate as carrier is applied to albino mice to treat their tumor, generated through melanoma cell line. Drug embedded superstructure is inoculated in injectable hydrogel and is placed in subcutaneous, below the tumor site, which completely heal the melanoma. No side effect is observed, as opposed to conventional/control system, arising from the sustained release of drug from the superstructure as evident from histopathological studies of sensitive body organs and biochemical parameters. Thus, new design of vehicle heals the melanoma tumor by enhancing the bioavailability of drug and specific interaction without having any side effects as opposed to conventional chemotherapeutic treatment.
The surface bioinspired modification of particles and films is a mainstream direction in biomaterial design and application. The interfacial coating of extracellular-matrix-like hydrogel can endow functional inorganic nanoparticles high circulation stability and biocompatibility but remains challenging due to large surface tension difference between organic gelators and solid nanosurfaces. Herein, the supramolecular hydrogel of NapGDFDFDK around gold nanorods (Au NRs-Gel) has been constructed by the amidation-grafting modification and the protonation-induced interface-assistant assembly of peptide precursors. As a proof of concept study, the acoustic cavitation experiments and in vitro ultrasound imaging have proved that the abundant hydrophobic microdomains as well as the water-rich network in the supramolecular hydrogel can served as valid sites to efficiently generate and stabilize nanobubbles as cavitation seeds to realize bubble-free ultrasound imaging. In vivo augmented ultrasound imaging and imaging-guided high intensity focused ultrasound (HIFU) therapy based on the Balb/c mice bearing Hela tumor model have been conducted. As the first example of using nanosurface hydrogelation to endow nanoparticles with bubble-free ultrasound theranostic ability, this work offers a simple approach to design multifunctional nanovehicles for ultrasound-guided drug/protein/gene delivery.
Developing multifunctional hydrogels that own expected functionality and excellent mechanical properties simultaneously is still challenging. Herein, we have successfully fabricated a self-healing conductive Boran Nitrogen nanosheets(f-BNNS)/PEDOT:PSS/PNIPAM hydrogel with compressive strength of 700 KPa, stretchability of 2666%, high adhesion and photothermal conversion capability using commercial PEDOT:PSS suspension and functionalized f-BNNS. The key in this material’s design is that ample dynamic hydrogen bonding cross-linking points can be formed between PSS and f-BNNS as well as PSS and PNIPAM, both of which not only improve the mechanical properties of the gel, but also ensure self-healing and adhesion. More importantly, for the first time we find that the hydrogen bonding of NIPAM and PSS can contribute to the enhanced conductivity of PEDOT:PSS for the reason that it can weaken the Coulomb interaction between PEDOT and PSS chains.
Short peptides are uniquely versatile building blocks for self-assembly. Supramolecular peptide assemblies can be used to construct functional hydrogel biomaterials—an attractive approach for neural tissue engineering. Here, we report a new class of short, five-residue peptides that form hydrogels with nanofiber structures. Using rheology and spectroscopy, we describe how sequence variations, pH, and peptide concentration alter the mechanical properties of our pentapeptide hydrogels. We find that this class of seven unmodified peptides forms robust hydrogels from 0.2–20 kPa at low weight percent (less than 3 wt. %) in cell culture media, and undergoes shear-thinning and rapid self-healing. The peptides self-assemble into long fibrils with sequence-dependent fibrillar morphologies. These fibrils exhibit a unique twisted ribbon shape, as visualized by TEM and Cryo-EM imaging, with diameters in the low tens of nanometers and periodicities similar to amyloid fibrils. Experimental gelation behavior corroborates our molecular dynamics simulations, which demonstrate peptide assembly behavior, an increase in beta-sheet content, and patterns of variation in solvent accessibility. Our Rapidly Assembling Pentapeptides for Injectable Delivery (RAPID) hydrogels are syringe-injectable and support cytocompatible encapsulation of oligodendrocyte progenitor cells (OPCs), as well as their proliferation and three-dimensional process extension. Furthermore, RAPID gels protect OPCs from mechanical membrane disruption and acute loss of viability when ejected from a syringe needle, highlighting the protective capability of the hydrogel as potential cell carriers for transplantation therapies. The tunable mechanical and structural properties of these supramolecular assemblies are shown to be permissive to cell expansion and remodeling, making this hydrogel system suitable as an injectable material for cell delivery and tissue engineering applications.
Tissue-specific self-assemblies of supramolecular hydrogels have attracted great interest in materials design and biomedic- al applications, for in situ-formed hydrogels serve as excellent local depot with tunable release of drug therapeutics. Here we report the design and syntheses of a novel class of histidine-containing hexapeptide derivatives (Nap-1 and ID-1) for in situ hydrogelation at the zinc ion-rich prostate tissue. Thanks to the efficient co-ordination between zinc and histindine, both Nap-1 and ID-1 displayed excellent self-assembling capability with a high sensitivity to zinc ions at ~ 0.1 equivalency. To foster a prostate-specific drug delivery system (DDS), ID-1 was chosen for further conjugation with bicalutamide (BLT), a clinically used drug for prostate cancer. As-synthesized ID-1-BLT retained the self-assembling capability with zinc ions, and conferred supramoelcular hydrogels at the prostate site. Interestingly, ID-1-BLT hydrogels demonstrated tunable drug release profiles in a typical tumor microenvironment, with acidic pH and esterase activity regulating the drug release in a dose dependent manner. Consequently, the hydrogel-based DDS demonstrated enhanced potency and selective cytotoxic- ity against prostate cancer cell DU145 over normal fibroblast cell NIH3T3, plausibly due to differential cellular uptake of drugs as well as the elevated esterase activities in cancer cells. Finally, the biocompatible hydrogel system demonstrated sustained delivery of drugs at the prostate gland of rats, with a superior in situ drug distribution profile comparing to that of aqueous solution of BLT alone.
Intratumoral delivery of chemotherapeutic agents may permit the localization of drug in tumors, decrease nonspecific targeting and increase efficacy. The pH-responsive peptide hydrogel is considered a suitable carrier for chemotherapeutics...
Peptide-based supramolecular hydrogels are promising scaffold materials and have been utilized in many fields. The mechanical properties of peptide hdyrogels are usually enhanced by synthetic or natural polymers to expand their application scope. In this study, antioxidant supramolecular hydrogels based on feruloyl-modified peptide and glycol chitosan are fabricated via mild laccase-mediated crosslinking reaction. Natural polysaccharide derivative—feruloyl glycol chitosan (GC-Fer) was used to enhance the mechanical properties of peptide hydrogels. Feruloyl groups are introduced into gel matrix via covalent bonds, which endows hydrogel inherent antioxidant properties. This is benifical for their in vivo application via scavenging harmful free radicals existed in the cutaneous wound. The further in vivo experiments demonstrated that the feruloyl-containing antioxidant hydrogel can improve cutaneous wound healing process. Regeneration process of mature epithelium and connective tissue were accelerated in a full-thick skin defect model.
Study of cells responding to an electroconductive environment is impeded by the lack of method, which would allow the encapsulation of cells in an ECM-like 3D electroactive matrix, and more challengingly, permit a simple mechanism to re-lease cells for further characterization. Herein we report a polysaccharide-based conductive hydrogel system formed via cyclodextrin-adamantane host-guest interaction. Oxidative polymerization of 3,4-ethylenedioxythiophene (EDOT) in the presence of adamantyl modified sulfated alginate (S-Alg-Ad) results in bio-electroconductive polymer PEDOT:S-Alg-Ad, which can form hydrogel with poly-β-Cyclodextrin (pβ-CD). The PEDOT:S-Alg-Ad/ pβ-CD hydrogels can be tuned on aspects of mechanical and electrical properties, exhibit self-healing feature and are injectable. Electron microscopy suggested that the difference in stiffness and conductivity is associated with the nacre-like layered nano-structures when different sizes of PEDOT:S-Alg-Ad nanoparticles were used. Myoblasts C2C12 cells were encapsulated in the conductive hydrogel and exhibited proliferation rate comparable to that in non-conductive S-Alg-Ad/pβ-CD hydrogel. The cells could be released from the hydrogels by adding β-CD monomer, and the upregulations of most myogenic marker genes under differentiation condition were more remarkable than the non-conductive counterpart. Astonishingly, the conductive hydrogel can dramatically promote myotube-like structure formation, while the myocytes grow into large clusters in the non-electroconductive hydrogel. The ability to embed and release cells in an electroconductive environment will open new doors for cell culture and tissue engineering.
Technological advances in protein biochemistry now enable researchers to modify the structure of peptides to enable them to possess self-assembling properties, forming hydrogels at low concentrations. Peptides can be altered further to provide multifunctional characteristics, for example, to demonstrate antimicrobial properties. The aim of this article is to investigate the in vivo toxicity and antimicrobial properties of a low molecular weight (naphthalene-2-ly)-acetyl-diphenylalanine-dilysine-OH (NapFFKK-OH) peptide hydrogel using an innovative waxworm (Galleria mellonella) model, as an alternative to mammalian/vertebrate testing. NapFFKK-OH hydrogels did not demonstrate any observable in vivo toxicity or death in G. mellonella larvae over 5 days at concentrations studied (≤2% w/v). A dose-dependent log10 reduction in viable (CFU/mL) Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria implicated in nosocomial infections was observed over 72 h. NapFFKK-OH was especially effective against in vivo infection models of S. aureus with a significant 4.4 log10 CFU/mL reduction in viable bacteria at 2% w/v after 72 h. Our results show G. mellonella to be a useful model for preliminary determination of in vivo toxicity and antimicrobial efficacy profiles of novel nanomaterials, including peptide-based hydrogels. This contributes to the 3R principles of animal testing, reduction, refinement, and replacement. The results also show NapFFKK-OH to be a promising alternative to standardly employed antimicrobials with the potential to be utilized as a novel therapeutic in the treatment and prevention of hospital infections.
H2S is a gasotransmitter with several physiological roles, but its reactivity and short half-life in biological media make its controlled delivery difficult. For biological applications of the gas, hydrogels have the potential to deliver H2S with several advantages over other donor systems, including localized delivery, controlled release rates, biodegradation, and variable mechanical properties. In this study, we designed and evaluated peptide-based H2S-releasing hydrogels with controllable H2S delivery. The hydrogels were prepared from short, self-assembling aromatic peptide amphiphiles (APAs), functionalized on their N-terminus with S-aroylthiooximes (SATOs), which release H2S in response to a thiol trigger. The APAs were studied both in solution and in gel forms, with gelation initiated by addition of CaCl2. Various substituents were included on the SATO component of the APAs in order to evaluate their effects on self-assembled morphology and H2S release rate in both the solution and gel phases. Transmission electron microscopy (TEM) images confirmed that all H2S-releasing APAs self-assembled into nanofibers above a critical aggregation concentration (CAC) of ∼0.5 mg/mL. Below the CAC, substituents on the SATO group affected H2S release rates predictably in line with electronic effects (Hammett σ values) according to a linear free energy relationship. Above the CAC, circular dichroism, infrared, and fluorescence spectroscopies demonstrated that substituents influenced the self-assembled structures by affecting hydrogen bonding (β-sheet formation) and π-π stacking. At these concentrations, electronic control over release rates diminished, both in solution and in the gel form. Rather, the release rate depended primarily on the degree of organization in the β-sheets and the amount of π-π stacking. This supramolecular control over release rate may enable the evaluation of H2S-releasing hydrogels with different release rates in biological applications.
Nowdays, how to improve the selectivity of chemotherapy drugs and reduce their side effects is still a significant challenge for cancer research. Although enzyme-instructed self-assembly (EISA) has provided a promising approach for selective cancer therapy, the application of EISA is still suffer from requiring much higher concentrations for inhibiting cancer cells. Therefore, new strategies are needed to maximize the anticancer efficacy as well as preserve the selectivity of EISA. In this study, we rationally designed and synthesised a novel peptide-based prodrug molecule， NapGDFDFpYSV， combining enzyme-instructed self-assembly (EISA) with the YSV anticancer peptide. The activity of the prodrug molecule was remarkably reduced by masking “Y” with a phosphoryl (-PO3) group and was recovered through dephosphorylation in situ by ALP catalysis. The resulting monomer, NapGDFDFYSV, as a hydrogelator further self-assembled into the nanodrug on the cell surface, resulting in enhanced cellular uptake and selective high cytotoxicity to cells overexpressing ALP via action on histone deacetylase. Moreover, the required cell inhibition concentration of NapGDFDFpYSV was much lower than its critical micelle concentration (CMC), exhibiting outstanding advantages compared with separately used EISA without the anticancer peptide. Our study provides a new strategy to improve the cytotoxicity selectivity and bioactivity of chemotherapy drugs as well as the anticancer efficiency of EISA.
Chirality is the intrinsic property of a molecule which can be tuned by the change in chirality of a molecule or by the addition of a chiral component as an external stimulus. An L-leucine based dipeptide appended succinic acid based bolaamphiphile co-assembled with D-tartaric acid to form supramolecular right handed nanostructured hydrogel whereas L-tartaric acid co-assembled to form supramolecular left handed nanostructured hydrogel. SEM and TEM experiments revealed the right and left handed helical nanofibers, which are responsible for the formation of supramolecular nanostructured hydrogels. The synergistic chiral effect of L-leucine in peptide bolaamphiphile and D/L-tartaric acid plays significant role in bicomponent gelation with helical nanofibers. The first two amino acids attached both the sides of succinic acid moiety act as a tuning button for supramolecular chirality of amino acids/peptides attached with succinic acid based bolaamphiphiles. The second amino acids play role to modulate supramolecular chirality if the first two amino acids act neutrally to the chirality of bolaamphiphiles which were confirmed by CD spectroscopy.
We report the ultrastiff and tough poly(acrylamide-co-acrylic acid)/Na-alginate/Fe3+ (P(AM-co-AA)/Na-alginate/Fe3+) hydrogel via the formation of hybrid ionic-hydrogen bond cross-linking networks. The optimal P(AM-co-AA)/Na-alginate/Fe3+ hydrogel possessed super high elastic modulus (~24.6 MPa), tensile strength (~10.4 MPa), compression strength (~44 MPa), and toughness (~4800 J/m2). The P(AM-co-AA)/Na-alginate/Fe3+ hydrogel was highly stable and maintained its superior mechanical properties in 0.5-2 M NaCl solution, aqueous solution with pH ranging from 4 to 10. The ionic cross-linking networks of the P(AM-co-AA)/Na-alginate/Fe3+ hydrogels can be locally and selectively dissociated by treating with NaOH aqueous solution with pH of 13 for 1 min and reformed by locally adding the additional Fe3+ solutions, making the hydrogels healable and cohesive. The healed hydrogels from the cutting surfaces can bear a tensile strength up to 7.1 MPa. Various complex hydrogel structures can be post constructed by using the P(AM-co-AA)/Na-alginate/Fe3+ hydrogels as building blocks via the adhesion of virgin prepared hydrogels.
We report the synthesis and self-assembly of fluorescent peptide amphiphiles (NBD-PA) comprised of a fluorescent NBD probe and a peptide derivative VVAADD with a C12-alkyl-chain as the linker (NBD-C12-VVAADD). The self-assembly of NBD-PA formed beta-sheet structures at neutral pH in aqueous solution, contributed to ~10-fold increase in the fluorescence and quantum yield of NBD molecules, and conferred a supramolecular hydrogel with excellect viscoelastic properties, while gel-to-sol transition of NBD-PA occurred rapidly when pH value was adjusted to strongly alkaline (e.g. pH 11). Through the pH-responsive self-assembly behavior, we further explored the relationship between fluorescence of NBD-PA and pH values. Interestingly, the fluorescence of NBD-PA system exhibited an excellent sigmoidal function relationship (R2=0.9999) with the alkaline pH values, which enabled accurate pH measurement regardless of salt types and inoinc strength of solvents. Furthermore, the fluorescence of NBD-PA was fully reversbile upon cycles of pH shifts, with chemical structure of NBD-PA well-maintained throughout the process. These features of NBD-PA would facilitate the design of in-situ pH detection systems as well as pH-responsive actuators for various apllications in future.
Conducting polymer hydrogels (CPHs) emerge as excellent functional materials, as they harness the advantages of conducting polymers with the mechanical properties and continuous 3D nanostructures of hydrogels. This bi-component organization results in soft, all-organic, conducting micro/nanostructures with multifarious material applications. However, the application of CPHs as functional materials for biomedical applications is currently limited due to the necessity to combine the features of biocompatibility, self-healing, and fine-tuning of the mechanical properties. To overcome this issue, we choose to combine, a protected dipeptide as the supramolecular gelator, owing to its intrinsic biocompatibility and excellent gelation ability, with the conductive polymer polyaniline (PAni), which was polymerized in situ. Thus, a two-component, all-organic, conducting, hydrogel was formed. Spectroscopic evidence reveals the formation of emeraldine salt form of PAni by intrinsic doping. The composite hydrogel is mechanically rigid with a very high storage modulus (G’) value of ~ 2 MPa and the rigidity was tuned by changing the peptide concentration. The hydrogel exhibits ohmic conductivity, pressure sensitivity, and, importantly, self-healing features. By virtue of its self-healing property, the hydrogel can reinstate its intrinsic conductivity when two macroscopically separated blocks are rejoined owing to its polymeric non-metallic composition. High cell viability of cardiomyocytes grown on the composite hydrogel demonstrates its non-cytotoxicity. These combined attributes of the hydrogel allowed its utilization for dynamic range pressure sensing and as conductive interface for electrogenic cardiac cells. The composite hydrogel supports cardiomyocyte organization into a spontaneously contracting system. The composite hydrogel thus has considerable potential for various applications.