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SEM images of different mass ratios of thiolated-gelatin: PA. (a) 1:3 mass ratio. (b) 1:1 mass ratio. (c) 3:1 mass ratio. (d) 1:0 mass ratio (pure thiolated-gelatin). All the scale bars are 2 μm.
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3D-printing has expanded our ability to produce reproducible and more complex scaffold architectures for tissue engineering applications. In order to enhance the biological response within these 3D printed scaffolds incorporating nanostructural features and/or specific biological signaling may be an effective means to optimize tissue regeneration....
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Bone is a highly vascularized tissue and one of the most dynamic tissues in terms of self-renewal throughout one’s life. It possesses a high regenerative capacity, which makes it possible that a majority of bone fractures will heal well without the need for major intervention. However, some large bone defects and fractures require medical intervent...
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... PAs have been extensively applied in tissue engineering, including angiogenesis, neurogenesis, and bone regeneration. Yan et al. 124 established a thiolated gelatin 3D-printable bioink augmented with PAs to modify its nanostructure and bioactivity, thereby facilitating cell incorporation. The bioink was developed through a double secondary crosslinking approach, involving homo-bi-functional maleimide PEG (MAL-PEG-MAL) and Ca 2+ . ...
... This method enabled multi-layered bioprinting, exemplified by the use of a laminin-mimetic IKVAV (CH 3 [CH 2 ] 15 VVAAEEIKVAV)-based PA system with biliary epithelial cells (SV40SM) that displayed remarkable rheological properties. 124 Additionally, Sather et al. 125 utilized supramolecular polymer aqueous inks, composed of PAs and chromophore amphiphile (CA), in direct ink writing (DIW) to construct macroscopic ionically crosslinked liquid crystalline hydrogels with modifiable nanoscale arrangement. Intermolecular interactions among the self-assembled structures were determined by the pH and salt concentrations in the system. ...
Supramolecular hydrogels have emerged as versatile bioinks in tissue engineering, providing a promising avenue for constructing intricate and functional biological structures. This paper explores the significance of employing supramolecular hydrogels as advanced bioinks for three-dimensional bioprinting and various biomedical applications. Supramolecular hydrogels possess distinct and tunable characteristics attributed to the dynamic nature of supramolecular host–guest interactions alongside interactions based on DNA and peptides, which increases their significance in tissue engineering. These interactions are essential for enhancing the mechanical properties, injectability, printability, post-printing stability, and biocompatibility of hydrogels. Gelation kinetics and rheological properties can also be manipulated to suit specific printing techniques. Furthermore, these supramolecular interactions facilitate the incorporation of bioactive molecules to regulate cellular behavior and tissue development. These diverse interactions observed in supramolecular hydrogels underscore their ability to emulate the dynamic and responsive nature of the cell’s extracellular matrix, which fosters cell growth, adherence, and differentiation. This review specifically highlights the cucurbit[n]uril and cyclodextrin-based host–guest supramolecular hydrogels, as well as peptide and DNA-based supramolecular structures as advanced bioinks and brief examples of their applications in various biomedical fields. These advanced bioinks would drive the development of intricate tissue constructs with enhanced biomimicry and therapeutic potential in regenerative medicine.
... [20][21][22][23][24] The alginate polymer chains can be modied directly with these celladhesive peptides or indirectly over modied polyethylene glycol (PEG) moieties, which are also widely used in hydrogel systems for biofabrication studies. [25][26][27] Until today various peptide sequences were used to specically modify natural inert biomaterials, such as ALG. 28,29 For example, the sequence tyrosine-isoleucine-glycine-serine-arginine (YIGSR, Peptide A), found in laminin, 30 was shown to promote neuronal cell adhesion and differentiation, 31 neuronal outgrowth 32 and nerve regeneration. ...
Alginate (ALG) and its oxidised form alginate-dialdehyde (ADA) are highly attractive materials for hydrogels used in 3D bioprinting as well as drop-on-demand (DoD) approaches. However, both polymers need to be modified using cell-adhesive peptide sequences, to obtain bioinks exhibiting promising cell-material interactions. Our study explores the modification of ALG- and ADA-based bioinks with the adhesive peptides YIGSR (derived from laminin), RRETEWA (derived from fibronectin) and IKVAV (derived from laminin) for 3D bioprinting. Two coupling methods, carbodiimide and Schiff base reactions, were employed to modify the polymers with peptides. Analytical techniques, including FTIR and NMR were used to assess the chemical composition, revealing challenges in confirming the presence of peptides. The modified bioinks exhibited decreased stability, viscosity, and stiffness, particularly-ADA-based bioinks in contrast to ALG. Sterile hydrogel capsules or droplets were produced using a manual manufacturing process and DoD printing. NIH/3T3 cell spreading analysis showed enhanced cell spreading in carbodiimide-modified ADA, Schiff base-modified ADA, and PEG-Mal-modified ADA. The carbodiimide coupling of peptides worked for ADA, however the same was not observed for ALG. Finally, a novel mixture of all used peptides was evaluated regarding synergistic effects on cell spreading which was found to be effective, showing higher aspect ratios compared to the single peptide coupled hydrogels in all cases. The study suggests potential applications of these modified bioinks in 3D bioprinting approaches and highlights the importance of peptide selection as well as their combination for improved cell–material interactions.
... Other peptide amphiphiles (PAs) were also reported to serve as supramolecular hydrogel biomaterial with tailored nanostructures and biochemical cues to stimulate cholangioctyes and formed functional tubular structures for bile duct formation in animal model. [248] In fact, to develop next-generation medical technologies, [249] dSAP hydrogel biomaterial is an useful platform at the proper intensity and extension through molecular biofabrication of scaffold material, including stretchable 3D cell culture or microfluidic platform with shear stress and hydrostatic pressure. [250] To deeply excavate dSAP biomaterial-based endoscopic techniques, Yuki Uba and co-workers evidenced the safety and hemostatic efficacy of PuraStat dSAP hydrogel in oozing, pulsatile, and projectile bleeding scenarios in EST procedures under ERCP guidance (IRB No. 2021-019) ( Figure 10D), [251] in which dSAP biomaterials had much higher technical success rate than conventional endoscopic hemostatic techniques such as balloon tamponade, coagulation, and self-expandable metal stent. ...
Short designer self-assembling peptide (dSAP) biomaterials are a new addition to hemostat group. It may provide diverse and robust toolboxes for surgeon to integrate wound microenvironment with much safer and stronger hemostatic capacity than conventional materials and hemostatic agents. Especially in noncompressible torso hemorrhage (NCTH), diffuse mucosal surface bleeding, and internal medical bleeding (IMB), et al., with respect to the optimal hemostatic formulation, dSAP biomaterials are the ingenious nanofiber alternatives to make bioactive neural scaffold, nasal packing, large mucosal surface coverage in gastrointestinal surgery (esophagus, gastric lesion, duodenum, and lower digestive tract), epicardiac cell delivery carrier, transparent matrix barrier, et al. Herein, in multiple surgical specialties, dSAP biomaterials-based nano hemostats achieve safe, effective and immediate hemostasis, facile wound healing, and potentially reduce the risks in delayed bleeding, rebleeding, postoperative bleeding or related complications. The biosafety in vivo, bleeding indications, tissue-sealing quality, surgical feasibility, and local usability are addressed comprehensively and sequentially and pursued to develop useful surgical techniques with better hemostatic performance. This article provides the state of art and all-round advancements of nano hemostatic approaches in surgery. Relevant critical insights will inspire exciting investigations on peptide nanotechnology, next-generation biomaterials, and better promising prospects in clinics. This article is protected by copyright. All rights reserved.
... Especially in the process of vascular and nerve cell regeneration in the spinal cord, the good coating of hydrogels can guide the differentiation and regeneration of nerve cells in all directions. Because of its good infiltration, permeability, and biocompatibility, hydrogel plays an important role in the vascular regeneration, guiding the nerve differentiation, and promoting the cartilage formation [97,98]. ...
Functional hydrogels show potential application in repairing spinal cord injury (SCI) due to their unique chemical, physical, and biological properties and functions. In this comprehensive review, we present recent advance in the material design, functional regulation, and SCI repair applications of bioactive hydrogels. Different from previously released reviews on hydrogels and three-dimensional scaffolds for the SCI repair, this work focuses on the strategies for material design and biologically functional regulation of hydrogels, specifically aiming to show how these significant efforts can promoting the repairing performance of SCI. We demonstrate various methods and techniques for the fabrication of bioactive hydrogels with the biological components such as DNA, proteins, peptides, biomass polysaccharides, and biopolymers to obtain unique biological properties of hydrogels, including the cell biocompatibility, self-healing, anti-bacterial activity, injectability, bio-adhesion, bio-degradation, and other multi-functions for repairing SCI. The functional regulation of bioactive hydrogels with drugs/growth factors, polymers, nanoparticles, one-dimensional materials, and two-dimensional materials for highly effective treating SCI are introduced and discussed in detail. This work shows new viewpoints and ideas on the design and synthesis of bioactive hydrogels with the state-of-the-art knowledges of materials science and nanotechnology, and will bridge the connection of materials science and biomedicine, and further inspire clinical potential of bioactive hydrogels in biomedical fields.
... Yan et al. printed models with ink containing cholangiocytes and laminin-like amphiphiles that comprise the base membrane. They found that the cells could organize and develop tubular structures with branches [94] . Boyer et al. also invented a 3D bioprinted biliary stent infused with collagen, human placental MSCs, and cholangiocytes, aiming to improve biliary stent patency and patient care [95] . ...
Gastrointestinal (GI) system comprises a great number of organs and tissues of various functions, both hollow and solid. However, it is still a less well-developed area for three-dimensional (3D) printing (3DP) applications compared to orthopedics. Clinical applications of 3DP in the GI system are presently restricted to preoperative planning, surgical guidance, and education for students, residents, and patients, either for laparoscopy or endoscopy. Several surgery-related accessories have been designed to facilitate surgical procedures. The results are promising but not adequately proven due to a lack of reasonable study design and proper comparisons. Other important requirements for GI systems in clinical scenarios are structural reconstruction, replacement, defect repair, drug screening, and delivery. Many 3D-printed decellularized, cell-seeded, or even bioprinted scaffolds have been studied; however, most studies were conducted on small animal or in vitro models. Although encouraging results have been obtained, there is still a long way to go before products compatible with humans in size, histology, and functions can be printed. The key points to achieving this goal are the printing material, cell type and source, and printing technology. The ultimate goal is to print tissue and organ substitutes with physiological functions for clinical purposes in both time- and cost-effective ways.
... In another example Dubbin et al. 159 designed gel-phase inks, containing proline-rich peptide domains, which were shown to increase mechanical support in the 3D environment via a dual-stage crosslinking and prevented dehydration during printing. Yan et al. 160 reported IKVAV-based PAs integrated within a thiolated-gelatin bioink which was successfully 3D ...
Peptide amphiphiles (PAs) are peptide-based molecules that contain a peptide sequence as a head group covalently conjugated to a hydrophobic segment, such as lipid tails. They can self-assemble into well-ordered supramolecular nanostructures such as micelles, vesicles, twisted ribbons and nanofibers. In addition, the diversity of natural amino acids gives the possibility to produce PAs with different sequences. These properties along with their biocompatibility, biodegradability and a high resemblance to native extracellular matrix (ECM) have resulted in PAs being considered as ideal scaffold materials for tissue engineering (TE) applications. This review introduces the 20 natural canonical amino acids as building blocks followed by highlighting the three categories of PAs: amphiphilic peptides, lipidated peptide amphiphiles and supramolecular peptide amphiphile conjugates, as well as their design rules that dictate the peptide self-assembly process. Furthermore, 3D bio-fabrication strategies of PAs hydrogels are discussed and the recent advances of PA-based scaffolds in TE with the emphasis on bone, cartilage and neural tissue regeneration both in vitro and in vivo are considered. Finally, future prospects and challenges are discussed.
... These motifs can be obtained from the vast literature, through protein docking analysis in silico, through screening of synthesized peptide libraries, and by screening phage display against a specific target (e.g., cell, drug) [130,131]. RGD from fibronectin and IKAV from laminin are among the most used functional motifs in SAP applications, owing to their short length, simple synthesis and ubiquitous distribution in the ECM of living tissues [132][133][134]. ...
Supramolecular peptide hydrogels have many important applications in biomedicine, including drug delivery applications for the sustained release of therapeutic molecules. Targeted and selective drug administration is often preferential to systemic drug delivery, as it can allow reduced doses and can avoid the toxicity and side-effects caused by off-target binding. New discoveries are continually being reported in this rapidly developing field. In this review, we report the latest developments in supramolecular peptide-based hydrogels for drug delivery, focusing primarily on discoveries that have been reported in the last four years (2018–present). We address clinical points, such as peptide self-assembly and drug release, mechanical properties in drug delivery, peptide functionalization, bioadhesive properties and drug delivery enhancement strategies, drug release profiles, and different hydrogel matrices for anticancer drug loading and release.
... For instance, Yan et al. described a bioink based on thiolated gelatin crosslinked with a bifunctional maleimide polyethylene glycol (PEG). (Yan et al., 2018). Noteworthy, their network was further stabilized by the introduction of amphiphilic peptides. ...
Physical hydrogels prepared from natural biopolymers are the most popular components for bioinks. However, to improve the mechanical properties of the network, in particular its durability for long-lasting tissue engineering applications or its stiffness for bone/cartilage applications, covalent chemical hydrogels have to be considered. For that purpose, biorthogonal reactions are required to allow the inclusion of living cells within the bioink reservoir before the 3D printing procedure. Interestingly, such reactions also unlock the possibility to further multifunctionalize the network, adding bioactive moieties to tune the biological properties of the resulting printed biomaterial. Surprisingly, compared to the huge number of studies disclosing novel bioink compositions, no extensive efforts have been made by the scientific community to develop new chemical reactions meeting the requirements of both cell encapsulation, chemical orthogonality and versatile enough to be applied to a wide range of molecular components, including fragile biomolecules. That could be explained by the domination of acrylate photocrosslinking in the bioprinting field. On the other hand, proceeding chemoselectively and allowing the polymerization of any type of silylated molecules, the sol-gel inorganic polymerization was used as a crosslinking reaction to prepare hydrogels. Recent development of this strategy includes the optimization of biocompatible catalytic conditions and the silylation of highly attractive biomolecules such as amino acids, bioactive peptides, proteins and oligosaccharides. When one combines the simplicity and the versatility of the process, with the ease of functionalization of any type of relevant silylated molecules that can be combined in an infinite manner, it was obvious that a family of bioinks could emerge quickly. This review presents the sol-gel process in biocompatible conditions and the various classes of relevant silylated molecules that can be used as bioink components. The preparation of hydrogels and the kinetic considerations of the sol-gel chemistry which at least allowed cell encapsulation and extrusion-based bioprinting are discussed.
... Many bioprinting techniques have been introduced in the last decade based on extrusion, inkjet, and laser techniques, which provide a wide range of cell-friendly processes, adjustable precision, and compatible crosslinking methods. These techniques have advantages and disadvantages for any specific bioinks and crosslinking procedures, making the selection of the method extremely important [4,10,[14][15][16][17][18][19][20][21]. ...
... However, the lack of extensively discussed printability parameters (e.g., viscosity, shear-thinning, and filament analysis) has restricted the wide application of SAPs. This is why to increase the printability and shape fidelity of these peptides, a combination with other molecular structures as hybrid bioinks are used and the formation of complementary interaction in between is mostly responsible for the improved rheological behavior [14,17]. ...
... Despite having some intrinsic challenges in their current state, the potential properties that this class of materials suggests have made a great incentive toward increasing study over their translation into bioinks. Among the ranges of advantages they exhibit, the mimicking of native ECM structure and function coupled with the bioactivity can be highlighted [14,17]. ...
Cardiovascular diseases such as myocardial infarction account for millions of worldwide deaths annually. Cardiovascular tissues constitute a highly organized and complex three-dimensional (3D) structure that makes them hard to fabricate in a biomimetic manner by conventional scaffold fabrication methods. 3D bioprinting has been
introduced as a novel cell-based method in the last two decades due to its ability to recapitulate cell density, multicellular architecture, physiochemical environment, and vascularization of biological constructs with accurate designs. This review article aims to provide a comprehensive outlook to obtain cardiovascular functional tissues from the engineering of bioinks comprising cells, hydrogels, and biofactors to bioprinting techniques and
relevant biophysical stimulations responsible for maturation and tissue-level functions. Also, cardiac tissue 3D bioprinting investigations and further discussion over its challenges and perspectives are highlighted in this review article.
... Other hollow GIT structures, such as the gallbladder and bile ducts, have similar general structures: a simple columnar epithelium-lined central lumen that is bordered by smooth muscle layers. Yan et al. (2018) demonstrated that bioprinted cholangiocytes may selforganize into branching tubular structures using a bioink made of cholangiocytes, self-assembled nanofibers, and gelatin (93). ...
... Other hollow GIT structures, such as the gallbladder and bile ducts, have similar general structures: a simple columnar epithelium-lined central lumen that is bordered by smooth muscle layers. Yan et al. (2018) demonstrated that bioprinted cholangiocytes may selforganize into branching tubular structures using a bioink made of cholangiocytes, self-assembled nanofibers, and gelatin (93). ...
3D bioprinting is a rapidly evolving technique that has been found to have extensive applications in disease research, tissue engineering, and regenerative medicine. 3D bioprinting might be a solution to global organ shortages and the growing aversion to testing cell patterning for novel tissue fabrication and building superior disease models. It has the unrivaled capability of layer-by-layer deposition using different types of biomaterials, stem cells, and biomolecules with a perfectly regulated spatial distribution. The tissue regeneration of hollow organs has always been a challenge for medical science because of the complexities of their cell structures. In this mini review, we will address the status of the science behind tissue engineering and 3D bioprinting of epithelialized tubular hollow organs. This review will also cover the current challenges and prospects, as well as the application of these complicated 3D-printed organs.
