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Exploring the recent developments of alginate silk fibroin material for hydrogel wound dressing: A review
Abstract
Hydrogels, a type of polymeric material capable of retaining water within a three-dimensional network, have demonstrated their potential in wound healing, surpassing traditional wound dressings. These hydrogels possess remarkable mechanical, chemical, and biological properties, making them suitable scaffolds for tissue regeneration. This article aims to emphasize the advantages of alginate, silk fibroin, and hydrogel-based wound dressings, specifically highlighting their crucial functions that accelerate the healing process of skin wounds. Noteworthy functions include self-healing ability, water solubility, anti-inflammatory properties, adhesion, antimicrobial properties, drug delivery, conductivity, and responsiveness to stimuli. Moreover, recent advancements in hydrogel technology have resulted in the development of wound dressings with enhanced features for monitoring wound progression, further augmenting their effectiveness. This review emphasizes the utilization of hydrogel membranes for treating excisional and incisional wounds, while exploring recent breakthroughs in hydrogel wound dressings, including nanoparticle composite hydrogels, stem cell hydrogel composites, and curcumin-hydrogel composites. Additionally, the review focuses on diverse synthesis procedures, designs, and potential applications of hydrogels in wound healing dressings.
... The innovative strategy for enhancing this intricate process involves leveraging nanofiber matrices, proven to be effective in wound dressing applications. This holistic exploration of wound healing emphasizes the multifaceted role of nanofiber technology in both expediting tissue regeneration and providing a robust defense against bacterial challenges [2]. This dual functionality significantly contributes to the overall success of the wound-healing process. ...
In the field of biomedical engineering, nanofiber scaffolds have excellent biomaterial properties, making them highly suitable for superior wound dressing applications. This work presents the fabrication of a novel bimetal blend comprising palladium and platinum nanoparticles integrated with silk fibroin and collagen composite nanofibers through the electrospinning method. The fabricated composite nanofibrous scaffolds were investigated to analyze their chemical composition, surface morphology, thermal stability, porosity, hemocompatibility, mechanical strength, swelling, and degradation properties. The average diameter length of the SF/CL/Pd–Pt composite nanofiber scaffolds is 141.62 ± 33.03 nm, with Pd and Pt nanoparticle diameters measured at 8.64 and 7.36 nm, respectively. In vitro assessments of SF/CL and SF/CL/Pd–Pt composite nanofiber scaffolds demonstrated outstanding antibacterial efficacy against both gram-positive (S. aureus) and gram-negative (E. coli) bacteria. The antioxidant activity of SF/CL/Pd–Pt composite nanofibers exhibited a free radical scavenging percentage of 94.34%. Additionally, cell proliferation studies conducted on the fibroblast (NIH3T3) cell line, along with in vivo investigations on male Sprague–Dawley rats, underscored the remarkable wound-healing ability of the SF/CL/Pd–Pt composite nanofiber scaffolds. Furthermore, histopathological examination of wounded tissue samples using H&E and Masson trichrome staining revealed faster reepithelialization, granulation, angiogenesis, and reduced inflammatory response. These findings demonstrate that SF/CL/Pd–Pt composite nanofibrous scaffolds are excellent wound dressing materials for all biomedical applications.
Graphical Abstract
... Another advantage of nanohydrogel is its ability to retain moisture. 24 By keeping the wound moist, it can accelerate the healing process and reduce scarring. 25 Furthermore, nanohydrogel can conform to the shape of the wound, providing a comfortable and snug fit. ...
Nanohydrogel wound healing refers to the use of nanotechnology-based hydrogel materials to promote the healing of wounds. Hydrogel dressings are made up of a three-dimensional network of hydrophilic polymers that can absorb and retain large amounts of water or other fluids. Nanohydrogels take this concept further by incorporating nanoscale particles or structures into the hydrogel matrix. These nanoparticles can be made of various materials, such as silver, zinc oxide, or nanoparticles derived from natural substances like chitosan. The inclusion of nanoparticles can provide additional properties and benefits to the hydrogel dressings. Nanohydrogels can be designed to release bioactive substances, such as growth factors or drugs, in a controlled manner. This allows for targeted delivery of therapeutics to the wound site, promoting healing and reducing inflammation. Nanoparticles can reinforce the structure of hydrogels, improving their mechanical strength and stability. Nanohydrogels often incorporate antimicrobial nanoparticles, such as silver or zinc oxide. These nanoparticles have shown effective antimicrobial activity against a wide range of bacteria, fungi, and other pathogens. By incorporating them into hydrogel dressings, nanohydrogels can help prevent or reduce the risk of infection in wounds. Nanohydrogels can be designed to encapsulate and release bioactive substances, such as growth factors, peptides, or drugs, in a controlled and sustained manner. This targeted delivery of therapeutic agents promotes wound healing by facilitating cell proliferation, reducing inflammation, and supporting tissue regeneration. The unique properties of nanohydrogels, including their ability to maintain a moist environment and deliver bioactive agents, can help accelerate the wound healing process. By creating an optimal environment for cell growth and tissue repair, nanohydrogels can promote faster and more efficient healing of wounds.
... The result concluded that the produced hydrogel can provide a moist environment to accelerate the wound healing process by increasing the rate of mass transfer of biologic substances to the wound site. In addition, hydrogels with favourable swelling properties can absorb the wound exudates, which in turn, prevent infections [45]. ...
Hybrid structures made of natural-synthetic polymers have been interested due to high biological features combining promising physical-mechanical properties. In this research, a hybrid dressing consisting of a silk fibroin (SF)/polyvinyl alcohol (PVA) nanofibers and sodium alginate (SA)/gum tragacanth (GT) hydrogel incorporating cardamom extract as an antibacterial agent was prepared. Accordingly, SF was extracted from cocoons followed by electrospinning in blend form with PVA (SF/PVA ratio: 1:1) under the voltage of 18 kV and the distances of 15 cm. The SEM images confirmed the formation of uniform, bead free fibers with the average diameter of 199±28 nm. FTIR and XRD results revealed the successful extraction of SF and preparation of mixed fibrous mats. Next, cardamom oil extract-loaded SA/GT hydrogel was prepared and the nanofibrous structure was placed on the surface of hydrogel. SEM analysis depicted the uniform morphology of hybrid structure with desirable matching between two layers. TGA analysis showed desired thermal stability. The swelling ratio was found to be 1251% after 24 h for the hybrid structure and the drug was released without any initial burst. MTT assay and cell attachment results showed favorable biocompatibility and cell proliferation on samples containing extract, and antibacterial activity values of 85.35% against S. aureus and 75% against E. coli were obtained as well. The results showed that the engineered hybrid nanofibrous-hydrogel film structure incorporating cardamom oil extract could be a promising candidate for wound healing applications and skin tissue engineering.
... The society named as "wound medicine", acknowledge about skin injuries, 'bruises or abrasions' that interrupt the normal structures and functions of skin [1]. Skin performs its functions even during injured condition [2]. Human skin has large number of microorganisms on it and they belong to a varying and multiplex group of organisms. ...
Human skin has a major role in protecting several organs from various microbial attacks. It regulates the body’s temperature and its other normal functions. It is usually possessed by various microbes that may vary in different aspects and impacts on human dermal layer and may lead to serious infections in future. Encounter of human dermal layer to any injury or wound can be a forum for microbes to get entered and cause infection. Most of infections occur due to zoonosis. Anthropozoonosis, zooanthroponosis and amphixenoses are the terms acknowledged for transmit of disease or infections. Zoonosis has three major categories on the basis of type of host, etiological agents and life cycle of pathogens. Each category is further sub-categorized into various possible groups. Domestic animals are generally the primary source for humans to get infected. Human skin is affected by the virus, namely Orf zoonosis having corresponding to the genus Parapoxvirus. It is a major threat to human dermal layer.
Hybrid structures made of natural-synthetic polymers have been interested due to high biological features combining promising physical–mechanical properties. In this research, a hybrid dressing consisting of a silk fibroin (SF)/polyvinyl alcohol (PVA) nanofibers and sodium alginate (SA)/gum tragacanth (GT) hydrogel incorporating cardamom extract as an antibacterial agent was prepared. Accordingly, SF was extracted from cocoons followed by electrospinning in blend form with PVA (SF/PVA ratio: 1:1) under the voltage of 18 kV and the distances of 15 cm. The SEM images confirmed the formation of uniform, bead free fibers with the average diameter of 199 ± 28 nm. FTIR and XRD results revealed the successful extraction of SF and preparation of mixed fibrous mats. Next, cardamom oil extract-loaded SA/GT hydrogel was prepared and the nanofibrous structure was placed on the surface of hydrogel. SEM analysis depicted the uniform morphology of hybrid structure with desirable matching between two layers. TGA analysis showed desired thermal stability. The swelling ratio was found to be 1251% after 24 h for the hybrid structure and the drug was released without any initial burst. MTT assay and cell attachment results showed favorable biocompatibility and cell proliferation on samples containing extract, and antibacterial activity values of 85.35% against S. aureus and 75% against E. coli were obtained as well. The results showed that the engineered hybrid nanofibrous-hydrogel film structure incorporating cardamom oil extract could be a promising candidate for wound healing applications and skin tissue engineering.
Bacterial infection, inflammation, and excessive oxidative stress are the primary factors that contribute to delayed healing of skin wounds. In this study, a multifunctional wound dressing (SF/Ag@rGO hydrogel) is developed to promote the healing of infected skin wounds by combining the inherent antibacterial activity of Ag nanoparticles (NPs) with near‐infrared (NIR)‐assisted antibacterial therapy. Initially, L‐ascorbic acid is used as a reducing agent and PVP‐K17 as a stabilizer and dispersant, this facilitates the synthesis of reduced graphene oxide loaded with Ag NPs (Ag@rGO). Ag@rGO is then blended with a silk fibroin (SF) solution to form an instantly gelling SF/Ag@rGO hydrogel that exhibits rapid self‐healing, injectability, shape adaptability, NIR responsiveness, antioxidant, high tissue adhesion, and robust mechanical properties. In vitro and in vivo experiments show that the SF/Ag@rGO hydrogel demonstrates strong antioxidant and photothermal antibacterial capabilities, promoting wound healing through angiogenesis, stimulating collagen generation, alleviating inflammation, antioxidant, and promoting cell proliferation, indicating that the SF/Ag@rGO hydrogel dressing is an ideal candidate for clinical treatment of full‐thickness bacterial‐stained wounds.
The development of innovative wound dressing materials is crucial for effective wound care. It’s an active area of research driven by a better understanding of chronic wound pathogenesis. Addressing wound care properly is a clinical challenge, but there is a growing demand for advancements in this field. The synergy of medicinal plants and nanotechnology offers a promising approach to expedite the healing process for both acute and chronic wounds by facilitating the appropriate progression through various healing phases. Metal nanoparticles play an increasingly pivotal role in promoting efficient wound healing and preventing secondary bacterial infections. Their small size and high surface area facilitate enhanced biological interaction and penetration at the wound site. Specifically designed for topical drug delivery, these nanoparticles enable the sustained release of therapeutic molecules, such as growth factors and antibiotics. This targeted approach ensures optimal cell-to-cell interactions, proliferation, and vascularization, fostering effective and controlled wound healing. Nanoscale scaffolds have significant attention due to their attractive properties, including delivery capacity, high porosity and high surface area. They mimic the Extracellular matrix (ECM) and hence biocompatible. In response to the alarming rise of antibiotic-resistant, biohybrid nanofibrous wound dressings are gradually replacing conventional antibiotic delivery systems. This emerging class of wound dressings comprises biopolymeric nanofibers with inherent antibacterial properties, nature-derived compounds, and biofunctional agents. Nanotechnology, diminutive nanomaterials, nanoscaffolds, nanofibers, and biomaterials are harnessed for targeted drug delivery aimed at wound healing. This review article discusses the effects of nanofibrous scaffolds loaded with nanoparticles on wound healing, including biological (in vivo and in vitro) and mechanical outcomes.
Graphical Abstract
The endometrium undergoes a series of precise monthly changes under the regulation of dynamic levels of ovarian hormones that are characterized by repeated shedding and subsequent regeneration without scarring. This provides the potential for wound healing during endometrial injuries. Bioengineering materials highlight the faithful replication of constitutive cells and the extracellular matrix that simulates the physical and biomechanical properties of the endometrium to a larger extent. Significant progress has been made in this field, and functional endometrial tissue bioengineering allows an in-depth investigation of regulatory factors for endometrial and myometrial defects in vitro and provides highly therapeutic methods to alleviate obstetric and gynecological complications. However, much remains to be learned about the latest progress in the application of bioengineering technologies to the human endometrium. Here, we summarize the existing developments in biomaterials and bioengineering models for endometrial regeneration and improving the female reproductive potential.
This review will present the latest research related to the production and application of spider silk and silk-based materials in reconstructive and regenerative medicine and tissue engineering, with a focus on musculoskeletal tissues, and including skin regeneration and tissue repair of bone and cartilage, ligaments, muscle tissue, peripheral nerves, and artificial blood vessels. Natural spider silk synthesis is reviewed, and the further recombinant production of spider silk proteins. Research insights into possible spider silk structures, like fibers (1D), coatings (2D), and 3D constructs, including porous structures, hydrogels, and organ-on-chip designs, have been reviewed considering a design of bioactive materials for smart medical implants and drug delivery systems. Silk is one of the toughest natural materials, with high strain at failure and mechanical strength. Novel biomaterials with silk fibroin can mimic the tissue structure and promote regeneration and new tissue growth. Silk proteins are important in designing tissue-on-chip or organ-on-chip technologies and micro devices for the precise engineering of artificial tissues and organs, disease modeling, and the further selection of adequate medical treatments. Recent research indicates that silk (films, hydrogels, capsules, or liposomes coated with silk proteins) has the potential to provide controlled drug release at the target destination. However, even with clear advantages, there are still challenges that need further research, including clinical trials.
Hydrogels are polymeric materials that possess a set of characteristics meeting various requirements of an ideal wound dressing, making them promising for wound care. These features include, among others, the ability to absorb and retain large amounts of water and the capacity to closely mimic native structures, such as the extracellular matrix, facilitating various cellular processes like proliferation and differentiation. The polymers used in hydrogel formulations exhibit a broad spectrum of properties, allowing them to be classified into two main categories: natural polymers like collagen and chitosan, and synthetic polymers such as polyurethane and polyethylene glycol. This review offers a comprehensive overview and critical analysis of the key polymers that can constitute hydrogels, beginning with a brief contextualization of the polymers. It delves into their function, origin, and chemical structure, highlighting key sources of extraction and obtaining. Additionally, this review encompasses the main intrinsic properties of these polymers and their roles in the wound healing process, accompanied, whenever available, by explanations of the underlying mechanisms of action. It also addresses limitations and describes some studies on the effectiveness of isolated polymers in promoting skin regeneration and wound healing. Subsequently, we briefly discuss some application strategies of hydrogels derived from their intrinsic potential to promote the wound healing process. This can be achieved due to their role in the stimulation of angiogenesis, for example, or through the incorporation of substances like growth factors or drugs, such as antimicrobials, imparting new properties to the hydrogels. In addition to substance incorporation, the potential of hydrogels is also related to their ability to serve as a three-dimensional matrix for cell culture, whether it involves loading cells into the hydrogel or recruiting cells to the wound site, where they proliferate on the scaffold to form new tissue. The latter strategy presupposes the incorporation of biosensors into the hydrogel for real-time monitoring of wound conditions, such as temperature and pH. Future prospects are then ultimately addressed. As far as we are aware, this manuscript represents the first comprehensive approach that brings together and critically analyzes fundamental aspects of both natural and synthetic polymers constituting hydrogels in the context of cutaneous wound healing. It will serve as a foundational point for future studies, aiming to contribute to the development of an effective and environmentally friendly dressing for wounds.
Wound infection is a major problem faced during wound healing. Therefore, it is necessary to develop wound dressings with excellent antimicrobial properties. Here, a smart response system of PVA-TPE/HA-AMP/SF/ALG wound dressing was prepared by a combination of chemical cross-linking and freeze-drying methods. We grafted AMP onto HA to endow the wound dressing with bacterial resistance and slow release of AMP. At the same time, the system detects bacterial activity in real time for precise antimicrobial activity (through the use of PVA-TPE) and modulates inflammation to reduce bacterial infection (through the use of AMP). In addition, the PVA-TPE/HA-AMP/SF/ALG wound dressing has a good three-dimensional mesh structure, which promotes cell proliferation, enhances collagen deposition and angiogenesis, and thus effectively promotes rapid healing of infected wounds. Moreover, it can induce the expression of inflammatory factors such as VEGF, TNF-α, IFN-γ, IL-4 and TGF-β1 in infected wounds through the Wnt/CAMK/p-PKC signaling pathway, inhibit inflammatory responses, promote wound healing and reduce scar formation. Therefore, the PVA-TPE/HA-AMP/SF/ALG wound dressing smart response system shows great promise in infected wound healing.
The aim of this study was to provide a comparative analysis of chitosan (CH), copper oxide (CuO), and chitosan-based copper oxide (CH-CuO) nanoparticles for their application in the healthcare sector. The nanoparticles were synthesized by a green approach using the extract of Trianthema portulacastrum. The synthesized nanoparticles were characterized using different techniques, such as the synthesis of the particles, which was confirmed by UV–visible spectrometry that showed absorbance at 300 nm, 255 nm, and 275 nm for the CH, CuO, and CH-CuO nanoparticles, respectively. The spherical morphology of the nanoparticles and the presence of active functional groups was validated by SEM, TEM, and FTIR analysis. The crystalline nature of the particles was verified by XRD spectrum, and the average crystallite sizes of 33.54 nm, 20.13 nm, and 24.14 nm were obtained, respectively. The characterized nanoparticles were evaluated for their in vitro antibacterial and antibiofilm potential against Acinetobacter baumannii isolates, where potent activities were exhibited by the nanoparticles. The bioassay for antioxidant activity also confirmed DPPH scavenging activity for all the nanoparticles. This study also evaluated anticancer activities of the CH, CuO, and CH-CuO nanoparticles against HepG2 cell lines, where maximum inhibitions of 54, 75, and 84% were recorded, respectively. The anticancer activity was also confirmed by phase contrast microscopy, where the treated cells exhibited deformed morphologies. This study demonstrates the potential of the CH-CuO nanoparticle as an effective antibacterial agent, having with its antibiofilm activity, and in cancer treatment.
One of the most advanced, promising, and commercially viable research issues in the world of hydrogel dressing is gaining functionality to achieve improved therapeutic impact or even intelligent wound repair. In addition to the merits of ordinary hydrogel dressings, functional hydrogel dressings can adjust their chemical/physical properties to satisfy different wound types, carry out the corresponding reactions to actively create a healing environment conducive to wound repair, and can also control drug release to provide a long-lasting benefit. Although a lot of in-depth research has been conducted over the last few decades, very few studies have been properly summarized. In order to give researchers a basic blueprint for designing functional hydrogel dressings and to motivate them to develop ever-more intelligent wound dressings, we summarized the development of functional hydrogel dressings in recent years, as well as the current situation and future trends, in light of their preparation mechanisms and functional effects.
Wounds are alterations in skin integrity resulting from any type of trauma. The healing process is complex, involving inflammation and reactive oxygen species formation. Therapeutic approaches for the wound healing process are diverse, associating dressings and topical pharmacological agents with antiseptics, anti-inflammatory, and antibacterial actions. Effective treatment must maintain occlusion and moisture in the wound site, suitable capacity for the absorption of exudates, gas exchange, and the release of bioactives, thus stimulating healing. However, conventional treatments have some limitations regarding the technological properties of formulations, such as sensory characteristics, ease of application, residence time, and low active penetration in the skin. Particularly, the available treatments may have low efficacy, unsatisfactory hemostatic performance, prolonged duration, and adverse effects. In this sense, there is significant growth in research focusing on improving the treatment of wounds. Thus, soft nanoparticles-based hydrogels emerge as promising alternatives to accelerate the healing process due to their improved rheological characteristics, increased occlusion and bioadhesiveness, greater skin permeation, controlled drug release, and a more pleasant sensory aspect in comparison to conventional forms. Soft nanoparticles are based on organic material from a natural or synthetic source and include liposomes, micelles, nanoemulsions, and polymeric nanoparticles. This scoping review describes and discusses the main advantages of soft nanoparticle-based hydrogels in the wound healing process. Herein, a state-of-the-art is presented by addressing general aspects of the healing process, current status and limitations of non-encapsulated drug-based hydrogels, and hydrogels formed by different polymers containing soft nanostructures for wound healing. Collectively, the presence of soft nanoparticles improved the performance of natural and synthetic bioactive compounds in hydrogels employed for wound healing, demonstrating the scientific advances obtained so far.
In this study, electrospun nanofibers (NFs) used in trauma dressings were prepared using silk fibroin (SF) and gelatin (GT) as materials and highly volatile formic acid as the solvent, with three different concentrations of propolis extracts (EP), which were loaded through a simple process. The resulting samples were characterized by surface morphology, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), contact angle meter, water absorption, degradation rate, and mechanical property tests. The incorporation of propolis improved its antibacterial properties against Escherichia coli, and Staphylococcus aureus, compared to those of the silk gelatin nanofiber material (SF/GT) alone. In vitro biocompatibility assays showed that SF/GT-1%EP had good cytocompatibility and hemocompatibility. In addition, it can also significantly promote the migration of L929 cells. SF/GT-1%EP was applied to a mouse model of full thickness skin defects, and it was found to significantly promote wound healing. These results indicate that the SF/GT-EP nanofiber material has good biocompatibility, migrating-promoting capability, antibacterial properties, and healing-promoting ability, providing a new idea for the treatment of full thickness skin defects.
The skin, acting as the outer protection of the human body, is most vulnerable to injury. Wound healing can often be impaired, leading to chronic, hard-to-heal wounds. For this reason, searching for the most effective dressings that can significantly enhance the wound healing process is necessary. In this regard, silk fibroin, a protein derived from silk fibres that has excellent properties, is noteworthy. Silk fibroin is highly biocompatible and biodegradable. It can easily make various dressings, which can be loaded with additional substances to improve healing. Dressings based on silk fibroin have anti-inflammatory, pro-angiogenic properties and significantly accelerate skin wound healing, even compared to commercially available wound dressings. Animal studies confirm the beneficial influence of silk fibroin in wound healing. Clinical research focusing on fibroin dressings is also promising. These properties make silk fibroin a remarkable natural material for creating innovative, simple, and effective dressings for skin wound healing. In this review, we summarise the application of silk fibroin biomaterials as wound dressings in full-thickness, burn, and diabetic wounds in preclinical and clinical settings.
Hydrogels are promising and widely utilized in the biomedical field. In recent years, the anti‐inflammatory function of hydrogel dressings has been significantly improved, addressing many clinical challenges presented in ongoing endeavours to promote wound healing. Wound healing is a cascaded and highly complex process, especially in chronic wounds, such as diabetic and severe burn wounds, in which adverse endogenous or exogenous factors can interfere with inflammatory regulation, leading to the disruption of the healing process. Although insufficient wound inflammation is uncommon, excessive inflammatory infiltration is an almost universal feature of chronic wounds, which impedes a histological repair of the wound in a predictable biological step and chronological order. Therefore, resolving excessive inflammation in wound healing is essential. In the past 5 years, extensive research has been conducted on hydrogel dressings to address excessive inflammation in wound healing, specifically by efficiently scavenging excessive free radicals, sequestering chemokines and promoting M1‐to‐M2 polarization of macrophages, thereby regulating inflammation and promoting wound healing. In this study, we introduced novel anti‐inflammatory hydrogel dressings and demonstrated innovative methods for their preparation and application to achieve enhanced healing. In addition, we summarize the most important properties required for wound healing and discuss our analysis of potential challenges yet to be addressed. We present an overview highlighting the recent achievements in anti‐inflammatory hydrogel dressings, from preparation mechanisms to application methods in wound healing. Categories of anti‐inflammatory hydrogel dressings are based on the specific mechanisms of anti‐inflammatory activities for which hydrogel dressings are created, for example scavenging excessive ROS, sequestering chemokines and promoting M1‐to‐M2 polarization of macrophages.
Chronic wounds severely affect 1–2% of the population in developed countries. It has been reported that nearly 6.5 million people in the United States suffer from at least one chronic wound in their lifetime. The treatment of chronic wounds is critical for maintaining the physical and mental well-being of patients and improving their quality of life. There are a host of methods for the treatment of chronic wounds, including debridement, hyperbaric oxygen therapy, ultrasound, and electromagnetic therapies, negative pressure wound therapy, skin grafts, and hydrogel dressings. Among these, hydrogel dressings represent a promising and viable choice because their tunable functional properties, such as biodegradability, adhesivity, and antimicrobial, anti-inflammatory, and pre-angiogenic bioactivities, can accelerate the healing of chronic wounds. This review summarizes the types of chronic wounds, phases of the healing process, and key therapeutic approaches. Hydrogel-based dressings are reviewed for their multifunctional properties and their advantages for the treatment of chronic wounds. Examples of commercially available hydrogel dressings are also provided to demonstrate their effectiveness over other types of wound dressings for chronic wound healing.
Hemorrhage, as a common trauma injury and clinical postoperative complication, may cause serious damage to the body, especially for patients with huge blood loss and coagulation dysfunction. Timely and effective hemostasis and avoidance of bleeding are of great significance for reducing body damage and improving the survival rate and quality of life of patients. Alginate is considered to be an excellent hemostatic polymer-based biomaterial due to its excellent biocompatibility, biodegradability, non-toxicity, non-immunogenicity, easy gelation and easy availability. In recent years, alginate hydrogels have been more and more widely used in the medical field, and a series of hemostatic related products have been developed such as medical dressings, hemostatic needles, transcatheter interventional embolization preparations, microneedles, injectable hydrogels, and hemostatic powders. The development and application prospects are extremely broad. This manuscript reviews the structure, properties and history of alginate, as well as the research progress of alginate hydrogels in clinical applications related to hemostasis. This review also discusses the current limitations and possible future development prospects of alginate hydrogels in hemostatic applications.
Hydrogels from biopolymers are readily synthesized, can possess various characteristics for different applications, and have been widely used in biomedicine to help with patient treatments and outcomes. Polysaccharides, polypeptides, and nucleic acids can be produced into hydrogels, each for unique purposes depending on their qualities. Examples of polypeptide hydrogels include collagen, gelatin, and elastin, and polysaccharide hydrogels include alginate, cellulose, and glycosaminoglycan. Many different theories have been formulated to research hydrogels, which include Flory-Rehner theory, Rubber Elasticity Theory, and the calculation of porosity and pore size. All these theories take into consideration enthalpy, entropy, and other thermodynamic variables so that the structure and pore sizes of hydrogels can be formulated. Hydrogels can be fabricated in a straightforward process using a homogeneous mixture of different chemicals, depending on the intended purpose of the gel. Different types of hydrogels exist which include pH-sensitive gels, thermogels, electro-sensitive gels, and light-sensitive gels and each has its unique biomedical applications including structural capabilities, regenerative repair, or drug delivery. Major biopolymer-based hydrogels used for cell delivery include encapsulated skeletal muscle cells, osteochondral muscle cells, and stem cells being delivered to desired locations for tissue regeneration. Some examples of hydrogels used for drug and biomolecule delivery include insulin encapsulated hydrogels and hydrogels that encompass cancer drugs for desired controlled release. This review summarizes these newly developed biopolymer-based hydrogel materials that have been mainly made since 2015 and have shown to work and present more avenues for advanced medical applications.
At present, food security is a matter of debate of global magnitude and fulfilling the feeding requirement of > 8 billion human populations by 2030 is one of the major concerns of the globe. Aquaculture plays a significant role to meet the global food requirement. Shrimp species such as Litopenaeus vannamei, Penaeus monodon, and Macrobrachium rosenbergii are among the most popular food commodities worldwide. As per Global Outlook for Aquaculture Leadership survey, disease outbreaks have been a matter of concern from the past many decades regarding the shrimp aquaculture production. Among the past disease outbreaks, white spot disease caused by the white spot syndrome virus is considered to be one of the most devastating ones that caused colossal losses to the shrimp industry. Since the virus is highly contagious, it spreads gregariously among the shrimp population; hence, practicing proper sanitization practices is crucial in order to have disease-free shrimps. Additionally, in order to control the disease, antibiotics were used that further leads to bioaccumulation and biomagnification of antibiotics in several food webs. The bioaccumulation of the toxic residues in the food webs further adversely affected human too. Recently, immunostimulants/antivirals were used as an alternative to antibiotics. They were found to enhance the immune system of shrimps in eco-friendly manner. In context to this, the present paper presents a critical review on the immunostimulants available from plants, animals, and chemicals against WSSV in shrimps. Looking into this scenario, maintaining proper sanitation procedures in conjunction with the employment of immunostimulants may be a viable approach for preserving shrimp aquaculture across the globe.
The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seriously affected public health and social stability. The main route of the transmission is droplet transmission, where the oral cavity is the most important entry point to the body. Due to both the direct harmful effects of SARS-CoV-2 and disordered immune responses, some COVID-19 patients may progress to acute respiratory distress syndrome or even multiple organ failure. Genetic variants of SARS-CoV-2 have been emerging and circulating around the world. Currently, there is no internationally approved precise treatment for COVID-19. Mesenchymal stem cells (MSCs) can traffic and migrate towards the affected tissue, regulate both the innate and acquired immune systems, and participate in the process of healing. Here, we will discuss and investigate the mechanisms of immune disorder in COVID-19 and the therapeutic activity of MSCs, in particular human gingiva mesenchymal stem cells.
Hydrogels are known for their leading role in biomaterial systems involving pharmaceuticals that fascinate material scientists to work on the wide variety of biomedical applications. The physical and mechanical properties of hydrogels, along with their biodegradability and biocompatibility characteristics, have made them an attractive and flexible tool with various applications such as imaging, diagnosis and treatment. The water-cherishing nature of hydrogels and their capacity to swell—contingent upon a few ecological signals or the simple presence of water—is alluring for drug conveyance applications. Currently, there are several problems relating to drug delivery, to which hydrogel may provide a possible solution. Hence, it is pertinent to collate updates on hydrogels pertaining to biomedical applications. The primary objective of this review article is to garner information regarding classification, properties, methods of preparations, and of the polymers used with particular emphasis on injectable hydrogels. This review also covers the regulatory and other commerce specific information. Further, it enlists several patents and clinical trials of hydrogels with related indications and offers a consolidated resource for all facets associated with the biomedical hydrogels.
Tissue engineering is a novel regenerative approach in the medicinal field that promises the regeneration of damaged tissues. Moreover, tissue engineering involves synthetic and natural biomaterials that facilitate tissue or organ growth outside the body. Not surprisingly, the demand for polymer-based therapeutical approaches in skin tissue defects has increased at an effective rate, despite the pressing clinical need. Among the 3D scaffolds for tissue engineering and regeneration approaches, hydrogel scaffolds have shown significant importance for their use as 3D cross-linked scaffolds in skin tissue regeneration due to their ideal moisture retention property and porosity biocompatibility, biodegradable, and biomimetic characteristics. In this review, we demonstrated the choice of ideal biomaterials to fabricate the novel hydrogel scaffolds for skin tissue engineering. After a short introduction to the bioactive and drug-loaded polymeric hydrogels, the discussion turns to fabrication and characterisation techniques of the polymeric hydrogel scaffolds. In conclusion, we discuss the excellent wound healing potential of stem cell-loaded hydrogels and Nano-based approaches to designing hydrogel scaffolds for skin tissue engineering.
Wounds have become one of the causes of death worldwide. The metabolic disorder of the wound microenvironment can lead to a series of serious symptoms, especially chronic wounds that bring great pain to patients, and there is currently no effective and widely used wound dressing. Therefore, it is important to develop new multifunctional wound dressings. Hydrogel is an ideal dressing candidate because of its 3D structure, good permeability, excellent biocompatibility, and ability to provide a moist environment for wound repair, which overcomes the shortcomings of traditional dressings. This article first briefly introduces the skin wound healing process, then the preparation methods of hydrogel dressings and the characteristics of hydrogel wound dressings made of natural biomaterials and synthetic materials are introduced. Finally, the development prospects and challenges of hydrogel wound dressings are discussed.
Chronic wounds do not progress through the wound healing process in a timely manner and are considered a burden for healthcare system; they are also the most common reason for decrease in patient quality of life. Traditional wound dressings e.g., bandages and gauzes, although highly absorbent and effective for dry to mild, exudating wounds, require regular application, which therefore can cause pain upon dressing change. In addition, they have poor adhesional properties and cannot provide enough drainage for the wound. In this regard, the normalization of the healing process in chronic wounds is an extremely urgent task of public health and requires the creation and implementation of affordable dressings for patients with chronic wounds. Modern wound dressings (WDs) are aimed to solve these issues. At the same time, hydrogels, unlike other types of modern WDs (foam, films, hydrocolloids), have positive degradation properties that makes them the perfect choice in applications where a targeted delivery of bioactive substances to the wound is required. This mini review is focused on different types of traditional and modern WDs with an emphasis on hydrogels. Advantages and disadvantages of traditional and modern WDs as well as their applicability to different chronic wounds are elucidated. Furthermore, an effectiveness comparison between hydrogel WDs and the some of the frequently used biotechnologies in the field of regenerative medicine (adipose-derived mesenchymal stem cells (ADMSCs), mesenchymal stem cells, conditioned media, platelet-rich plasma (PRP)) is provided.
Background
Wound is an anatomical and functional disruption of the skin following an injury. In response to the injury, wound healing is a complex process of tissue repair or remodeling. Historically, plants and plant-based constituents have been extensively used for the treatment and management of different types of wounds. In the current times, different types of biopolymers are being researched for developing economical, sustainable, stable, and effective delivery system for the treatment of wounds.
Main text
The present review article attempts to enlist medicinal plants which have been reported to be effective in the treatment of wounds. Plant constituent-based wound dressings have also been discussed systematically including patented formulations reported by different inventors.
Conclusion
The compiled data aims to update the researchers/scientists which will be helpful in providing them a directional view in understanding the role and importance of plant-based components for the treatment and management of wounds.
Over the past decade, the hydrogels prepared from silk fibroin have received immense research attention due to the advantages of safe nature, biocompatibility, controllable degradation and capability to combine with...
Due to their high mechanical properties and recoverability, hybrid double-network (DN) hydrogels composed with a physically cross-linked network (the first network) and a chemically cross-linked network (the second network) arouse researchers’ interest and attention in various fields. In this work, we have fabricated hybrid double-network hydrogels with ionically cross-linked κ-carrageenan as the first network and covalently cross-linked poly(N-acryloyl glycinamide) (PNAGA) as the second network by using an one-pot method. Because of synergistic interaction between κ-carrageenan and PNAGA polymer chains, the hybrid DN hydrogels exhibit excellent mechanical properties with a breaking stress of 1.7 MPa and a breaking strain of 250%, which are much better than their parent single-network hydrogels. In addition, due to the physical cross-links among κ-carrageenan and PNAGA, the hybrid DN hydrogels show good self-healing ability; and due to the biocompatibility of all components, the hybrid DN hydrogels show low cytotoxicity. All those properties endow the potential application of κ-carrageenan/PNAGA DN hydrogel in bioengineering.
Hydrogels are polymeric networks having the ability to absorb a large volume of water. Flexibility, versatility, stimuli-responsive, soft structure are the advantages of hydrogels. It is classified based on its source, preparation, ionic charge, response, crosslinking and physical properties. Hydrogels are used in various fields like agriculture, food industry, biosensor, biomedical, etc. Even though hydrogels are used in various industries, more researches are going in the field of biomedical applications because of its resembles to living tissue, biocompatibility, and biodegradability. Here, we are mainly focused on the commercially available hydrogels used for biomedical applications like wound dressings, contact lenses, cosmetic applications, tissue engineering, and drug delivery.
Mesenchymal stem cells are culture-derived mesodermal progenitors isolatable from all vascularized tissues. In spite of multiple fundamental, pre-clinical and clinical studies, the native identity and role in tissue repair of MSCs have long remained elusive, with MSC selection in vitro from total cell suspensions essentially unchanged as a mere primary culture for half a century. Recent investigations have helped understand the tissue origin of these progenitor cells, and uncover alternative effects of MSCs on tissue healing via growth factor secretion and interaction with the immune system. In this review, we describe current trends in MSC biology and discuss how these may improve the use of these therapeutic cells in tissue engineering and regenerative medicine.
Developing physical double‐network (DN) removable hydrogel adhesives with both high healing efficiency and photothermal antibacterial activities to cope with multidrug‐resistant bacterial infection, wound closure, and wound healing remains an ongoing challenge. An injectable physical DN self‐healing hydrogel adhesive under physiological conditions is designed to treat multidrug‐resistant bacteria infection and full‐thickness skin incision/defect repair. The hydrogel adhesive consists of catechol–Fe³⁺ coordination cross‐linked poly(glycerol sebacate)‐co‐poly(ethylene glycol)‐g‐catechol and quadruple hydrogen bonding cross‐linked ureido‐pyrimidinone modified gelatin. It possesses excellent anti‐oxidation, NIR/pH responsiveness, and shape adaptation. Additionally, the hydrogel presents rapid self‐healing, good tissue adhesion, degradability, photothermal antibacterial activity, and NIR irradiation and/or acidic solution washing‐assisted removability. In vivo experiments prove that the hydrogels have good hemostasis of skin trauma and high killing ratio for methicillin‐resistant staphylococcus aureus (MRSA) and achieve better wound closure and healing of skin incision than medical glue and surgical suture. In particular, they can significantly promote full‐thickness skin defect wound healing by regulating inflammation, accelerating collagen deposition, promoting granulation tissue formation, and vascularization. These on‐demand dissolvable and antioxidant physical double‐network hydrogel adhesives are excellent multifunctional dressings for treating in vivo MRSA infection, wound closure, and wound healing.
In line with experiments showing that implanted hydrogels are promising tools, we designed and injected, after a C2 spinal cord hemisection, a thermoresponsive and thermoreversible physically cross-linked poly(N-isopropylacrylamide)-poly(ethylene glycol) copolymer in order to reduce functional deficits and provide a favorable environment to axotomized axons.
Nasal olfactory ecto-mesenchymal stem cells were cultured on the hydrogel in order to verify its biocompatibility. Then, inflammatory reaction (Interleukin-1β and 6, Tumor Necrosis Factor-α) was examined 15 days post-hydrogel injection. Functional recovery (postural and locomotor activities, muscle strength and tactile sensitivity) was assessed once a week, during 12 weeks. Finally, at 12 weeks post-injection, spinal reflexivity and ventilatory adjustments were measured, and the presence of glial cells and regenerated axons were determined in the injured area.
Our results indicate that cells survived and proliferated on the hydrogel which, itself, did not induce an enhanced inflammation. Furthermore, we observed significant motor and sensitive improvements in hydrogel-injected animals. Hydrogel also induced H-reflex recovery close to control animals but no improved ventilatory adjustment to electrically-evoked isometric contractions. Finally, regrowing axons were visualized within the hydrogel with no glial cells colonization.
Our results emphasize the effectiveness of our copolymer and its high therapeutic potential to repair the spinal cord after injury.
The field of regenerative medicine has tremendous potential for improved treatment outcomes and has been stimulated by advances made in bioengineering over the last few decades. The strategies of engineering tissues and assembling functional constructs that are capable of restoring, retaining, and revitalizing lost tissues and organs have impacted the whole spectrum of medicine and health care. Techniques to combine biomimetic materials, cells, and bioactive molecules play a decisive role in promoting the regeneration of damaged tissues or as therapeutic systems. Hydrogels have been used as one of the most common tissue engineering scaffolds over the past two decades due to their ability to maintain a distinct 3D structure, to provide mechanical support for the cells in the engineered tissues, and to simulate the native extracellular matrix. The high water content of hydrogels can provide an ideal environment for cell survival, and structure which mimics the native tissues. Hydrogel systems have been serving as a supportive matrix for cell immobilization and growth factor delivery. This review outlines a brief description of the properties, structure, synthesis and fabrication methods, applications, and future perspectives of smart hydrogels in tissue engineering.
Exploration on hydrogel fibres concerning about smart based application in the medical sector has stimulated great interests for the last couple of years due to its wide range of purposes that include actuators, artificial adhesives, transplantable tissue organs, cell scaffolds, cell therapeutics, wound healing, cartilage or bone regeneration. Nevertheless, recently hydrogel fibre based biomaterials have drawn great concentration for use in a wide variety of biomedical applications like the sustained release of drugs. This is due to the fact that, hydrogel fibers are biocompatible and their similarity about physical properties is in relation with natural tissue. This review article prescribes about the application of hydrogels with diversified prospects in tissue engineering, wound care dressings, soft tissue recovery and plastic surgery. As the products of hydrogels are composed with a group of polymeric materials, the hydrophilic network structure makes them competent for holding an immense quantity of water in their three-dimensional polymer network structure. A wide-ranging application of these products in modern industrial and environmental areas has already taken into account to be of prime importance. Inevitably, natural hydrogels right is now gradually replaced by synthetic types due to their larger amount of water absorption capacity, durability alongside with wide ranges of raw chemical resources.
Biopolymer based metal oxide nanoparticles, prepared by eco-friendly approach, are gaining interest owing to their wide range of applications. In this study, aqueous extract of Trianthema portulacastrum was used for the green synthesis of chitosan base copper oxide (CH-CuO) nanoparticles. The nanoparticles were characterized through UV-Vis Spectrophotometry, SEM, TEM, FTIR and XRD analysis. These techniques provided evidence for the successful synthesis of the nanoparticles, having poly-dispersed spherical shaped morphology with average crystallite size of 17.37 nm. The antibacterial activity for the CH-CuO nanoparticles was determined against multi-drug resistant (MDR), Escherichia coli, Pseudomonas aeruginosa (gram-negative), Enterococcus faecium and Staphylococcus aureus (gram-positive). Maximum activity was obtained against Escherichia coli (24 ± 1.99 mm) while least activity was observed against Staphylococcus aureus (17 ± 1.54 mm). In-vitro analysis for biofilm inhibition, EPS and cell surface hydrophobicity showed >60 % inhibitions for all the bacterial isolates. Antioxidant and photocatalytic assays for the nanoparticles showed significant activities of radical scavenging (81 ± 4.32 %) and dye degradation (88 %), respectively. Antidiabetic activity for the nanoparticles, determined by in-vitro analysis of alpha amylase inhibition, showed enzyme inhibition of 47 ± 3.29 %. The study signifies the potential of CH-CuO nanoparticle as an effective antimicrobial agent against MDR bacteria along with the antidiabetic and photocatalytic activities.
Hydrogels which become increasingly important in the biomedical field are composed of a three-dimensional hydrophilic network. Pure hydrogels are usually weak and brittle; therefore, reinforcements are assimilated into the hydrogel structure to improve the mechanical strength of the hydrogels. However, even if mechanical properties are enhanced, drapability remains an issue. In that regard, natural fiber-reinforced composite hydrogel fibers for wound dressing application are investigated in this study. Kapok and hemp fibers were used as reinforcement to improve the strength of hydrogel fibers. The properties of the prepared composite hydrogel fibers were studied with Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and differential scanning calorimeter (DSC). The effect of alginate concentration and fiber weight percent on the mechanical characteristics and water absorbency was studied. Diclofenac sodium drug was loaded in the hydrogel fibers and investigated the drug release as well as antibacterial characteristics. Both fibers' reinforcement enhanced the strength of the alginate hydrogel fiber, but hemp reinforcement showed better mechanical properties. Kapok reinforcement resulted in a maximum tensile strength of 174 cN (1.24 % elongation) and 432 % exudate absorbency, while hemp reinforcement resulted in 185 cN (1.48 % elongation) and 435 % exudate absorbency. Statistical analysis revealed significant effects of sodium alginate concentration on tensile strength (p-value 0.042) and exudate absorbency (p-value 0.020) and of reinforcement (wt%) on exudate absorbency (p-value 0.043). Therefore, these composite hydrogel fibers with improved mechanical properties are capable of drug release and exhibit antibacterial effectiveness, making them a promising option for use as wound dressings.
Recently, significant attention has been focused on the progression of skin equivalents to facilitate faster wound healing and thereby skin restoration. The main aim of this study was the design and characterization of a novel polysaccharide-based hydrogel scaffold by using alginate, pullulan, and hyaluronic acid polymers to provide an appropriate microenvironment to deliver Adipose-derived mesenchymal Stem Cells (ASC) in order to promote wound healing in an animal model. Characterization of synthesized hydrogel was done by using a field emission scanning electron microscope (FE-SEM), Fourier Transform-Infrared spectroscopy (FT-IR), and Differential Scanning Calorimetry (DSC). Also, contact angle analysis, the swelling and mechanical tests were performed. As a result of in vitro studies, cells can be attached, alive, and migrate through the prepared hydrogel scaffold. Finally, the therapeutic effect of the cell-seeded hydrogels was tested in the full-thickness animal wound model. Based on obtained results, the hydrogel-ASC treatment improved the healing process and accelerated wound closure.
It is important to treat a bacterial-infected wound with a hydrogel dressing due to its excellent biocompatibility and extracellular matrix mimicking structure. In this work, the antibacterial curcumin nanoparticles (Cur-NPs) loaded silk fibroin and sodium alginate (SF/SA) composite hydrogels have been developed as dressings for bacterial-infected wound closure. The as-prepared composite hydrogel dressings exhibited excellent biocompatibility and antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in vitro. In addition, the composite hydrogel dressings showed good tissue adhesive strength because of their high viscosity and abundance of amino groups distributed on SF, which can form multi-aldehyde polysaccharides with the tissue surface. The porous 3D structure of the composite hydrogel dressings facilitated the absorption of exudate from the wound site and promoted the fusion of cellular nutrients and metabolites. In the full-thickness skin defect model with and without bacterial infection, the Cur-NPs loaded SF/SA composite hydrogel dressings prominently improves the closure of bacterial-infected wounds by improving cell proliferation, anti-inflammatory properties, vascular remodeling, and collagen deposition.
Gelatin hydrogel is widely employed in various fields, however, commercially available gelatin hydrogels are mostly derived from mammalian which has many disadvantages due to the supply and ethical issues. In this study, the properties of hydrogels from fish-derived collagen fabricated with varying Glutaraldehyde (GA) determined. The antidiabetic properties of salmon gelatin (SG) and tilapia gelatin (TG) was also evaluated against α-glucosidase. Glutaraldehyde-crosslinked salmon gelatin and tilapia gelatin were used, and compared with different concentrations of GA by 0.05 %, 0.1 %, and 0.15 %. Water absorbency, swelling, porosity, pore size and water retention of the hydrogels were dependent on the degree of crosslinking. The synthesis of hydrogels was confirmed by FTIR study. Scanning electron microscope (SEM) observation showed that all hydrogels have a porous structure with irregular shapes and heterogeneous morphology. Performance tests showed that gelatin-GA 0.05 % mixture had the best performance. Antidiabetic bioactivity in vitro and in silico tests showed that the active peptides of SG and TG showed a high binding affinity to α-glucosidase enzyme. In conclusion, SG and TG cross-linked GA 0.05 % have the potential as an antidiabetic agent and as a useful option over mammalian-derived gelatin.
Significance:
Nowadays, the wound dressing is no longer limited to its primary wound protection ability. Hydrogel, sponge-like material, three-dimensional (3D)-printed mesh, and nanofiber-based dressings with incorporation of functional components, such as nanomaterials, growth factors, enzymes, antimicrobial agents, and electronics, are able to not only prevent/treat infection but also accelerate the wound healing and monitor the wound healing status.
Recent advances:
The advances in nanotechnologies and materials science have paved the way to incorporate various functional components into the dressings, which can facilitate wound healing and monitor different biological parameters in the wound area. In this review, we mainly focus on the discussion of recently developed functional wound dressings.
Critical issues:
Understanding the structure and composition of wound dressings is important to correlate their functions with the outcome of wound management.
Future directions:
"All-in-one" dressings that integrate multiple functions (e.g., monitoring, antimicrobial, pain relief, immune modulation, and regeneration) could be effective for wound repair and regeneration.
Infection is a huge obstacle to wound healing. Thus, to enhance the healing of infected wounds, wound dressings that permit the dual delivery of antimicrobials and antioxidants are highly desirable. In this study, a series of gelatin-based nanofiber membranes with different curcumin contents were fabricated via solution electrospinning. The obtained membranes were characterized in terms of their morphologies, in addition to their physical, mechanical, and in vitro properties. The results showed that the membranes maintained an integrated morphology, excellent water absorption capability, satisfactory mechanical properties, and a high dissolution rate of curcumin. The addition of curcumin and borneol conferred the membranes the ability to inhibit Staphylococcus aureus and eliminate free radicals. Furthermore, cytocompatibility testing using the L929 cell line confirmed the excellent biocompatibility of the membranes. These gelatin-based nanofiber membranes loaded with curcumin and borneol can therefore be considered as promising materials for dressing wounds. Moreover, the use of biodegradable polymers and environmentally sustainable production techniques in this system render it suitable for the commercial manufacture of composite membranes.
Hydrogels have attracted extensive attention as wound dressing because they can provide a moist microenvironment to accelerate wound healing. However, simple physical coverage of wound cannot satisfy the complicated process of wound repair. Here, we report an injectable multifunctional hydrogel (CMCS-brZnO) synthesized by incorporating fusiform-like zinc oxide nanorods (brZnO) into carboxymethyl chitosan (CMCS), in which the brZnO works dually as crosslinker and nano-filler. The hydrogel possesses controllable gelation time, quick self-healing, good tissue adhesion and fast hemostasis capability. Further, the CMCS-brZnO hydrogel presents excellent antibacterial properties with minimal inhibitory concentration (MIC) for E.coli and S.aureus of 0.0125 and 0.025 mg mL⁻¹, respectively. The hydrogel could be injected directly into the irregular-shaped wounds in a full-thickness skin defect experiment, and the good fitting of the gel to the wound geometries together with the slow and sustainable release of antibacterial Zn²⁺ significantly promoted wound healing and reduced the inflammatory response. This study illustrates that the CMCS-brZnO hydrogels with an organic-inorganic micro-structure have great potential in accelerating wound healing.
Natural wound healing is a highly complex and regulated process. Disruption and barriers to cellular and tissue repair processes contributes to impaired wound healing, including sustained infections. Superficial wound healing requires many factors to work in concrete at the wound site, and thus many treatment options and wound dressings have evolved to address the barriers to wound healing. Biomaterials are proven to encourage the wound healing process by stimulating repair and regeneration of injured tissues and preventing wound infections. A wide range of natural and synthetic hydrophilic and porous formulations such as foams, films, fibers, and hydrogels have been examined for these applications. Among these formulations, polymeric hydrogels have gained considerable interest in the medical applications. They effectively absorb wound exudates and provide a moist environment for aiding the wound healing process. However, chronic wounds that are sustained longer might need supplementary healing features as addendums such as antimicrobials, stem cells, growth factors, peptides, vitamins, and natural compounds. Therefore, when combined with hydrogels healing supporting addendums promote rapid and effective wound healing. Although there have been several advancements in biopolymer‐based hydrogel systems, only limited reviews on various management strategies in wound healing are available in medical research and applications. Therefore, in this review, we have compiled and integrated various hydrogel‐based approaches with the potential to improve chronic wound healing and advance important outcomes. In addition, in‐situ injectable hydrogel preparation that have the advantage of packing patient wounds of different sizes and using 3D printing based tailor‐made hydrogels, and bio‐inks for wound closure applications are also highlighted.
Chronic wound remains a significant challenge in clinical care due to the long treatment process and the poor quality of tissue regeneration affected by bacterial infection, calling timely and effective wound management approach to achieve real-time intelligent wound monitoring and promote wound healing. In this work, a multifunctional hydrogel is employed as wound dressing for intelligent wound monitoring, which not only have the functions of antibacterial, hemostatic and adhesive properties for effectively promoting wound healing, but also can realize real-time wound status monitoring (e.g., pH). The whole intelligent wound monitoring process mainly includes three parts: wound recognition, real-time status monitoring and personalized wound management. Among them, the customized hydrogel wound dressing can accurately match the contour of the wound for precise treatment. Moreover, the personalized wound management model with high accuracy (94.47%) based on the convolutional neural network (CNN) machine learning algorithm can analyze and evaluate the wound healing and infection status through the colorimetric signal of the hydrogel dressing. This multifunctional hydrogel wound dressing, which integrates precise treatment, real-time monitoring and personalized management for intelligent wound monitoring, provides an advanced solution to accelerate wound healing and reduce bacterial infections and plays an inestimable step for future intelligent wound management.
Advanced dressings that can simultaneously prevent bacterial colonization/infection and reduce inflammation are highly desired. A simple strategy was developed to incorporate an anti-inflammatory and antibacterial drug rhein into the structure of silk fibroin (SF) matrix to fabricate a hydrogel dressing. The SF/Rhein hydrogels showed fibrous network nanostructure, high water content (~90%), high water adsorption ability (>2 folds of its own weight), acceptable mechanical strength, biocompatibility and antibacterial properties, suitable as dressings for the treatment of bacterial infected wounds. The SF/Rhein hydrogels enhanced the healing rate of burn wounds by reducing inflammation, expediting angiogenesis, and promoting skin appendages formation, being a promising candidate as wound dressings.
The wound healing process of the diabetic wound is often hindered by excessive oxygen free radicals and infection. An ideal wound dressing should possess great reactive oxygen species (ROS) scavenging property and considerable antibacterial ability. In this study, we facilely constructed a novel hydrogel dressing with excellent ROS scavenging property and outstanding antibacterial performance by introducing tannic acid (TA) into quaternized chitosan (QCS) matrix. Attributing to the suitable physical crosslinking between TA and QCS, this QCS/TA hydrogel was endowed with injectable and self-healing properties, which could avoid the various external squeezing on the irregular shape by wound dressing. The results showed that it could promote coagulation, suppress inflammation and expedite collagen deposition in the skin defect model of diabetic rats. This study provides a facile and convenient method for constructing injectable hydrogel dressing, which has application potentials in the clinical management of diabetic wounds.
The potential of berberine loaded in chitosan nanoparticles (BerNChs) within a hybrid of alginate (Alg) and chitosan (Ch) hydrogel was investigated for the substrate which is known as an inhibit activator proteins. The physicochemical properties of the developed Alg-Ch hydrogel were investigated by fourier-transform infrared spectroscopy. The swelling ability and degradation rate of hydrogels were also analyzed in a phosphate-buffered saline solution at physiological pH. The seeded scaffolds with endometrial stem cells as well as scaffolds alone were then transplanted into hemisected SCI rats. The SEM images displayed the favorable seeding and survival of the cells on the Alg-Ch/BerNChs hydrogel scaffold. The obtained data from immunostining of neuroflilament (NF), as a neuronal growth marker, in the various groups showed that the lowest and highest immunoractivity was belonged to the control and Alg-Ch/BerNCh seeded with ESCs groups, respectively. Finally, the Basso, Beattie, and Bresnahan (BBB) test confirmed the recovery of sensory and motor functions, clinically. The results suggested that combination therapy using the endometrial stem cells seeded on Alg-Ch/BerNChs hydrogel scaffold has the potential to regenerate the injured spinal cord and to limit the secondary damage.
Developing a new family of hydrogel-based wound dressings that could have a dual biofunctionality of antibacterial and biological responses is highly desirable. In this study, an inherently effective antibacterial and biodegradable hydrogel dressing without the need for impregnated antibiotics was designed, synthesized, characterized, and examined for its effect on macrophages, which initiated inflammatory activity and activated both NO and TNF-α production for the purpose of achieving a better and faster wound healing. The purposes of this research was to develop a novel family of cationic biodegradable hydrogels based on arginine-based poly(ester urea urethane) (Arg-PEUU) and glycidyl methacrylate-modified chitosan (CS-GMA) that has both inherent antibacterial and bioactive functionality as a wound healing dressing for accelerated healing of contaminated or infected wounds. These hybrid hydrogels present a well-defined three-dimensional microporous network structure and have a high water absorption ability, and their biodegradation is effectively accelerated in the presence of lysozymes. The hemolytic activity test, MTT assay, and live/dead assay of these hybrid hydrogels indicated that they had no cytotoxicity toward red blood cells, NIH-3T3 fibroblast cells, and human vascular endothelial cells, thus corroborating their cytocompatibility. Furthermore, these hybrid hydrogels could elevate the release of both produced NO and TNF-α by stimulating and activating RAW 264.7 macrophages, augmenting their antibacterial biological response. The antibacterial assay of these hybrid hydrogels demonstrated their excellent antibacterial activity without the need for impregnated antibacterial agents. Taken together, this new family of biodegradable, antibacterial, and biologically responsive hybrid hydrogels exhibits great potential as biofunctional antibacterial wound dressing candidates for wound healing.
Hydrogels are important biomaterials that have several applications in drug and cell delivery, tissue engineering, three-dimensional (3D) printing and more recently, in sensing and actuating applications. With the advent of self-healing hydrogels, it is becoming possible to have smarter materials with sustainable mechanical properties under stress and also added functionalities. The mechanisms responsible for the self-healing behavior of these materials are related to their internal structure and processes triggered by damage they may sustain. These mechanisms rely on either chemical bonding or physical interactions of the structural components of hydrogels, or on both. Many self-healing hydrogels have been developed and tested in vitro and in animals. However, there are still challenges, especially with healing characteristics that need to be addressed and investigated in animal experiments before their clinical applications can be initiated, for which a multidisciplinary approach is required. In the current paper, various biomedical applications of self-healing hydrogels are discussed in detail, highlighting current challenges and future prospects.
With the changes in the modern disease spectrum, pressure ulcers, diabetic feet, and vascular-derived diseases caused refractory wounds is increasing rapidly. The development of wound dressings has partly improved the effect of wound management. However, traditional wound dressings can only cover the wound and block bacteria, but are generally powerless to recurrent wound infection and tissue healing. There is an urgent need to develop a new type of wound dressing with comprehensive performance to achieve multiple effects such as protecting the wound site from the external environment, absorbing wound exudate, anti-inflammatory, antibacterial, and accelerating wound healing process. Hydrogel wound dressings have the aforementioned characteristics, and can keep the wound in a moist environment because of the high water content, which is an ideal choice for wound treatment. This review introduces the wound healing process and the development and performance advantages of hydrogel wound dressings. The choice of different preparation materials gives the particularities of different hydrogel wound dressings. It also systematically explains the main physical and chemical crosslinking methods for hydrogel synthesis. Besides, in-depth discussion of four typical hydrogel wound dressings including double network hydrogels, nanocomposite hydrogels, drug-loaded hydrogels and smart hydrogels fully demonstrates the feasibility of developing hydrogels as wound dressing products and their future development trends.
Silk fibroin (SF) based hydrogels possess great potential in wound healing. However, they have limitations as wound dressings, such as long-gelation time, high temperature or organic solvent-assisted treatment, and lack of self-healing property. In this study, a supramolecular hydrogel based on SF, acryloyl-β-cyclodextrin (Ac-CD) and 2-hydroxyethyl acrylate was developed through a facile method by photo-polymerization of acrylate under UV irradiation, and showed enhanced performance as wound dressing than commercial dressing. This SF based hydrogel was confirmed to be dually crosslinked by host-guest interaction and hydrophobic β-sheet conformation, and demonstrated improved mechanical properties, long-term stability, rapid self-healing behavior, injectability, and good biocompatibility, benefiting its application as wound dressing. Moreover, as a drug carrier owing abundant CDs, the hydrophobic drug curcumin with antioxidant and anti-inflammatory activity was loaded in SF-based hydrogel, accompanying with a controlled and sustained release profile, therewith boosting better wound healing performance with generating higher granulation tissue thickness, collagen disposition, upregulating vascular endothelial growth factor (VEGF), and decreasing inflammatory response in a full-thickness skin defect model. In conclusion, this novel self-healing SF-based hydrogel is of great value in wound healing and enriches the fabrication methodology of SF-based self-healing biomaterials as well.
Wounds are often recalcitrant to traditional wound dressings and a bioactive and biodegradable wound dressing using hydrogel membranes can be a promising approach for wound healing applications. The present research aimed to design hydrogel membranes based on hyaluronic acid, pullulan and polyvinyl alcohol and loaded with chitosan based cefepime nanoparticles for potential use in cutaneous wound healing. The developed membranes were evaluated using dynamic light scattering, proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. The results indicated the novel crosslinking and thermal stability of the fabricated hydrogel membrane. The in vitro analysis demonstrates that the developed membrane has water vapors transmission rate (WVTR) between 2000 and 2500 g/m2/day and oxygen permeability between 7 and 14 mg/L, which lies in the range of an ideal dressing. The swelling capacity and surface porosity to liberate encapsulated drug (cefepime) in a sustained manner and 88% of drug release was observed. The cefepime loaded hydrogel membrane demonstrated a higher zone of inhibition against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli and excisional rat model exhibit expeditious recovery rate. The developed hydrogel membrane loaded with cefepime nanoparticles is a promising approach for topical application and has greater potential for an accelerated wound healing process.
The application of modern nanomedicines to enhance wound healing is growing due to their simplicity for topical organization and fast flexibility with molecules that can boost and reinforce the process of healing even in patients with diabetes. The point of the present investigation was to synthesize effective Pterocarpus marsupium heartwood extract/chitosan nanoparticles (PM-CNPs) loaded hydrogel (PM-CNPsH) and evaluate its drug release efficiency, in-vitro anti-microbial activity and wound healing action in streptozotocin administered diabetic rat models. The prepared PM-CNPs further utilized for the preparation of various carbopol hydrogel formulations. Hence, prepared hydrogels are characterized for pH, morphology, consistency, and spreadability; thus, PM-CNPsH-1 is found to be the optimized formulation. In-vivo rats treated with PM-CNPsH-1 displayed significantly much quicker healing of wounds in diabetic and non-diabetic rats. The histological examination revealed re-epithelization and growth of granular tissue and an improvement in collagen deposition. These results indicate the effectiveness of optimized nanocomposites as a potential treatment for curing diabetic wounds.
Easy and rapid continuous large-scale industrial production of transparent visualized cutaneous wound healing dressing from normal nature polymers is very worth studying in medical natural polymer materials and multifunction gauze dressing design fields. In this work, a super clear, porous cellulose membranes with chitosan-coated nanofiber were fabricated by using a simple, one-step electrostatic spinning (ES) technology and evaluated as potential wound dressings. Firstly, the pure cellulose membranes (CM) were dissolved by a simple physical method, and then the membranes were regenerated in the acidic coagulation bath by the casting method. The chitosan solution was polarized into nanofiber and formed a continuous fiber mat on cellulose membranes due to the charge repulsion between molecules. The prepared chitosan-coated cellulose membranes (CM-CS) were characterized by SEM, FT-IR, XRD, DSC and Tensile tests, etc. The results indicated that CM-CS showed high wettability, hydrophilicity, and gas permeability, in addition to excellent light transmittance and mechanical compliance. Cell cytotoxicity and morphology assay, and antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were also studied. It exhibited a good biocompatibility and antibacterial activity of CM-CS. Moreover, evaluation of an in vivo wound healing model in mice revealed that CM-CS had a good effect in promoting wound healing. This work provided an easy and rapid continuous large-scale industrial design strategy for nature bioresource-based wound dressing materials, which could act the potential wound dressings for clinical use. Keywords: Cellulose/chitosan membrane; electrostatic spinning technology; visualization; antibacterial activity; wound dressing.
The hydrogel wound dressing is an ideal wound treatment because of its excellent biocompatibility, high moisture resistance and the ability to activate immune cells to speed wound healing. However, the biomedical applications of hydrogels are limited currently, due to their poor mechanical properties and insufficient adhesion. In order to expand the scope of its application, people have explored new methods of chemical and physical cross-linking, designed new composite hydrogels, and introduced effective energy dissipation mechanisms. In this review, we also discuss materials used to produce hydrogels, focused on TCM-based hydrogel materials with bioactive properties that promote healing. Moreover, methods for evaluating hydrogel wound dressings are discussed to guide the preparation of new hydrogels.
Hydrogels with controlled degradation and sustained bactericidal activities are promising biomaterial substrates to repair or regenerate the injured tissue. In this work, we present a unique pair of lysozyme and chitosan as a hydrogel that can promote cell growth and proliferation while concomitantly preventing infection during the gradual process of hydrogel degradation and tissue ingrowth. Lysozyme and chitosan containing cell adhesion motifs are chemically modified with photoreactive methacrylate moieties to obtain a crosslinked hydrogel network by visible light irradiation. The resulting lysozyme-chitosan conjugate successfully modulates the degradation rate of hydrogels while promoting cell adhesion, proliferation, and matrix formation with no cytotoxicity. The hydrogel also exerts an intrinsic antibacterial effect by combining antimicrobial features of chitosan and lysozyme. This work demonstrates an advanced hydrogel platform with dual function of tunable degradation and infection control for tissue engineering and wound healing applications.
In this study, an optimal combination of sodium alginate (SA)/polyvinyl alcohol (PVA) hydrogel containing Rosuvastatin-loaded chitosan (CS) nanoparticles was fabricated as the drug delivery system (DDS). First, the drug-loaded nanoparticles were synthesized by the ionic gelation method. Then, several hydrogel films with different ratios of SA:PVA were prepared. Subsequently, different concentrations of drug-loaded CS nanoparticles were added to a hydrogel with an optimal SA:PVA ratio. The results of the tensile test showed that in the SA:PVA ratio of 7:3 and 3 wt. % of drug-loaded CS nanoparticles, the hydrogel film was achieved with optimal mechanical properties. The mean size of drug-loaded CS nanoparticles determined by the AFM and DLS methods was in the range of approximately 100-150 nm. The release profile of the Rosuvastatin drug from the fabricated DDS illustrated that all the loaded drug was released within 24 h, and the CS nanoparticles had a significant effect on the release behavior. Also, the cytotoxicity of the fabricated DDS on the human fibroblast cells demonstrated a high cell viability after 72 h of incubation. Therefore, the fabricated SA/PVA hydrogel containing drug-loaded CS nanoparticles depicted a great potential as the delivery system for the controlled release of the Rosuvastatin drug.
We report a water-soluble and non-toxic method to incorporate additional extracellular matrix proteins into gelatin hydrogels, while obviating the use of chemical crosslinkers such as glutaraldehyde. Gelatin hydrogels were fabricated using a range of gelatin concentrations (4%-10%) that corresponded to elastic moduli of approximately 1 kPa-25 kPa, respectively; a substrate stiffness relevant for multiple cell types. Microbial transglutaminase was then used to enzymatically crosslink a layer of laminin on top of gelatin hydrogels, resulting in 2-component gelatin-laminin hydrogels. Human induced pluripotent stem cell derived-neurospheres readily adhered and rapidly extended axons on GEL-LN hydrogels. Axons displayed a more mature morphology and superior electrophysiological properties on GEL-LN hydrogels compared to controls. Schwann cells on GEL-LN hydrogels adhered and proliferated normally, displayed a healthy morphology, and maintained expression of Schwann cell specific markers. Lastly, skeletal muscle cells on GEL-LN hydrogels achieved long-term culture for up to 28 days without delamination, while expressing higher levels of terminal genes including myosin heavy chain, MyoD, MuSK, and M-Cadherin suggesting enhanced maturation potential and myotube formation compared to controls. Future studies will employ the superior culture outcomes of this hybrid substrate for engineering functional neuromuscular junctions and related organ on a chip applications.
Excessive inflammation and reduced angiogenesis are two major obstacles in burn wound healing and skin regeneration. Here we report the fabrication and application of a sophisticated hydrogel from chemically modified hyaluronic acid (HA), dextran (Dex), and β-cyclodextrin (β-CD) integrating resveratrol (Res) and vascular endothelial growth factor (VEGF) plasmid as the anti-inflammatory and pro-angiogenic components for burn wounds. Firstly, covalent alterations were conducted to obtain methacrylic acid anhydride modified HA (HAMA), N-hydroxyethylacrylamide (HEAA) modified Dex (Dex-HEAA), and poly(ethylene glycol) methyl acrylate (526) modified β-CD (526-β-CD), respectively. Secondly, anti-inflammatory substance Res was embedded into the lipophilic central cavity of 526-β-CD to achieve a complex of 526-β-CD-Res. Then hydrogels with different HAMA, Dex-HEAA, and 526-β-CD-Res ratios were generated via UV irradiation. Lastly, plasmid DNA encoded with vascular endothelial growth factor (pDNA-VEGF) conjugating with polyethylenimine was loaded into the hydrogel scaffold. Combining the benefits of all components of the scaffold, the hydrogel embedded with Res and VEGF (Gel-Res/pDNA-VEGF) accelerated the splinted excisional burn wound healing, particularly by inhibiting inflammation response and promoting microvascular formation while being biocompatible. The Res and VEGF gene loaded hydrogel system can be considered as a promising wound dressing for the treatment of various types of wounds.
Statement of significance
Combining the benefits of all components of the scaffold, the hydrogel embedded with Res and VEGF (Gel-Res/pDNA-VEGF) accelerated the splinted excisional burn wound healing, particularly by inhibiting inflammation response and promoting microvascular formation while being biocompatible. The Res and VEGF gene loaded hydrogel system can be considered as a promising wound dressing for the treatment of various types of wounds.