Hydrogel For Wound Healing Research Articles

A functional dual responsive CMC/OHA/SA/TOB hydrogel as wound dressing to enhance wound healing.

Within the clinical realm, the complexities of wound healing have consistently presented formidable challenges. Recent advancements, notably in hydrogel technologies, have broadened the therapeutic spectrum. This study focuses on investigating a novel dual responsive composite hydrogel for wound healing. This hydrogel is ingeniously designed to maintain an optimal moist environment, expedite healing, and combat bacterial infection during wound recovery. This study combining carboxymethyl chitosan (CMC), oxidized hyaluronic acid (OHA), and sodium alginate (SA), in addition, tobramycin (TOB) was incorporated to create a CMC/OHA/SA/TOB hydrogel. Hydrogel cross-linking was verified by infrared spectroscopy, and the microstructure was examined with scanning electron microscopy. We explored its swelling and degradation behaviors in different pH environments. The drug release profile and biocompatibility was evaluated via cytotoxicity and hemolysis assays. The antibacterial efficacy of hydrogel was tested in both solid and liquid media. Additionally, the wound models in Sprague-Dawley (SD) rat was employed to investigate the hydrogel's wound healing capabilities in vivo. Results showed that CMCOHA/SA/TOB hydrogel was effectively cross-linked with a network structure. The hydrogel exhibited pronounced responsiveness in its swelling and degradation characteristics, which was significantly influenced by different levels of pH. In vitro results demonstrated that the CMC/OHA/SA/TOB hydrogel exhibits limited cytotoxicity and hemolysis, coupled with a drug release profile of dual responsive characteristics. Antibacterial activity of the hydrogel against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was confirmed. Furthermore, in vivo experiments underscored the hydrogel's proficiency in promoting wound healing, highlighting its potential for clinical applications. The CMC/OHA/SA/TOB hydrogel not only fosters a moist environment essential for wound healing and enhances structural stability, but it also exhibits functional dual responsive capabilities in swelling and degradation. These distinctive abilities enable the precise release of TOB, thereby optimizing wound healing.

A tissue-adhesive, mechanically enhanced, natural Aloe Vera-based injectable hydrogel for wound healing: Macrophage mediation and collagen proliferation

Macromolecule hydrogels made from natural extracts have received much attention because of their favorable biocompatibility and wound healing properties. However, their clinical applications are limited by their insufficient mechanical strength and low adhesion properties. To overcome these limitations, we developed a novel injectable Aloe vera hydrogel (PDMA-GelMA@AV). By integrating gelatin methacrylate (GelMA) and polydopamine methacrylamide (PDMA), we significantly improved the mechanical and adhesion properties of the hydrogel. The PDMA-GelMA@AV hydrogel degraded in a simulated wound environment, which was synchronized with the sustained release of the bioactive components of A. vera. In vitro and in vivo analyses revealed that this hydrogel has good biocompatibility. In vitro studies also revealed that the sustained release of the active ingredients of A. vera promoted fibroblast proliferation and migration and increased the expression of key proteins and mRNAs required for wound healing. In addition, it modulated LPS-stimulated macrophages and decreased the expression of TNF-α, IL-1β and iNOS while increasing the expression of TGF-β and ARG. In vivo experiments further confirmed the efficacy of hydrogels in wound healing applications. These findings offer a novel perspective on the application of natural macromolecules as hydrogel-based delivery vehicles in wound care.

Sprayable Nanocomposites Hydrogel for Wound Healing and Skin Regeneration.

Wound management remains a critical challenge worldwide and imposes a huge financial burden on every nation. Hydrogels are promising for biomedical applications because of their extracellular matrix (ECM) like structure, good biocompatibility and multifunctional bioactivity. However, the poor mechanical properties and inconvenient operation of traditional hydrogels make it difficult to meet the complex and multifaceted needs of clinical practice. In recent years, the multifunctional nanocomposites hydrogel with especially sprayable feature have shown enhanced mechanical properties and facile operation, which enable their huge clinical applications value. A unique and powerful nanocomposite hydrogels (NCH) platform is developed by combining the many advantages of nanomaterials and hydrogels, which can achieve efficient trauma repair. This work reviews important advances on the preparation, functions and applications of sprayable NCH platforms. The challenges and future trends in the field with the aim of providing researchers with clarity on the past, present, and future of the emerging field of sprayable NCH are also proposed in detail.

Platelet-rich plasma polyacrylamide (PAM-PRP)-based hydrogel for wound healing via low-intensity ultrasound

Platelet-rich plasma polyacrylamide (PAM-PRP)-based hydrogel for wound healing via low-intensity ultrasound

Computational Designed and Optimized Liposomal Curcumin-Embedded Bifunctional Cross-Linked Hydrogels for Wound Healing.

Curcumin (CUR) bifunctional cross-linked nanocomposite hydrogels are presented as an efficient method for CUR delivery in wound healing. CUR-loaded liposomes (CUR-Ls) were optimized using the Box-Behnken design to augment particle size, size distribution, zeta potential, and CUR concentration. The antioxidant activity and cytotoxicity of CUR-Ls were assessed. Hyaluronic acid (HA)/poly(vinyl alcohol) (PVA) hydrogels were optimized with a central composite design; then, poly(N-vinylpyrrolidone-co-itaconic acid) (PNVP-ITA) was synthesized to enrich the properties of the hydrogels. The drug release kinetics of the CUR-L@HA/PVA/PNVP-ITA hydrogels were studied. Skin recovery was investigated in vivo on rat dorsal skin. The optimized CUR-Ls were constructed from 2.7% Tween® 20, 0.04% oleic acid, and 8.1% CUR, yielding nano-CUR-L with a narrow size distribution, negative surface charge, and CUR content of 19.92 ± 0.54 µg/mg. CUR-Ls improved the antioxidant effects of CUR. The optimized hydrogel contained 5% HA and 10% PVA. PNVP-ITA improved the properties of the hydrogels via enhanced cross-linking. CUR-Ls exhibited a more rapid release than CUR, whereas the hydrogels enhanced CUR release via a diffusion-controlled mechanism. CUR-L@HA/PVA/PNVP-ITA hydrogels improved the skin recovery rate compared to the commercial patch after 5 days. Therefore, the optimized CUR-L@HA/PVA/PNVP-ITA hydrogels facilitated skin recovery and could be a promising nanocomposite for wound dressings.

Preparation of sulfated arabinogalactan-loaded hydrogel for wound healing in mouse burn model

Sulfation of polysaccharides can affect their biological activity by introducing sulfate groups. Skin burns occur regularly and have a great impact on normal survival. In this study, sulfated arabinogalactan (SAG) was prepared by sulfation, and polyvinyl alcohol (PVA) was used to prepare hydrogels for the treatment of scalded skin in mouse. The results show that the main chain of SAG consists of →3-β-D-Galactose (Gal)-(1, →3, 6)-β-D-Gal-(1 and →4)-β-d-Glucose (Glc)-(1. The chain is a neutral polysaccharide composed of T-β-L-Arabinose (Araf)-(1→, with a molecular weight of 17.9 kDa. At the same time, PVA + SAG hydrogel can promote the scald repair of mouse skin by promoting collagen deposition and angiogenesis, and regulating the TLR4/MyD88/NF-κB signaling pathway. Interestingly, the effect of SAG on promoting the repair of scald wounds is enhanced after AG is derivatized by sulfation. Therefore, the preparation of SAG by sulfation can promote scald repair, and has great application potential in the field of food and medicine.

Natural Regenerative Hydrogels for Wound Healing.

Regenerative hydrogels from natural polymers have come forth as auspicious materials for use in regenerative medicine, with interest attributed to their intrinsic biodegradability, biocompatibility, and ability to reassemble the extracellular matrix. This review covers the latest advances in regenerative hydrogels used for wound healing, focusing on their chemical composition, cross-linking mechanisms, and functional properties. Key carbohydrate polymers, including alginate, chitosan, hyaluronic acid, and polysaccharide gums, including agarose, carrageenan, and xanthan gum, are discussed in terms of their sources, chemical structures and specific properties suitable for regenerative applications. The review further explores the categorization of hydrogels based on ionic charge, response to physiological stimuli (i.e., pH, temperature) and particularized roles in wound tissue self-healing. Various methods of cross-linking used to enhance the mechanical and biological performance of these hydrogels are also examined. By highlighting recent innovations and ongoing challenges, this article intends to give a detailed understanding of natural hydrogels and their potential to revolutionize regenerative medicine and improve patient healing outcomes.

Screening of Short-Chain Peptide RKIIIRW and Its Use as a Hydrogel for Wound Healing and Bacterial Infection Treatment

Screening of Short-Chain Peptide RKIIIRW and Its Use as a Hydrogel for Wound Healing and Bacterial Infection Treatment

A tea polyphenol-loaded cellulose/silk fibroin/polyacrylic acid hydrogel for wound healing

A tea polyphenol-loaded cellulose/silk fibroin/polyacrylic acid hydrogel for wound healing

A bioactive xyloglucan polysaccharide hydrogel mechanically enhanced by Pluronic F127 micelles for promoting chronic wound healing

Chronic wounds represent a formidable global healthcare challenge due to the bacteria infections and uncontrollable inflammation responses, while developing wound healing materials capable of resolving these issues remains a challenge. In this study, we integrated xyloglucan (XG) with Pluronic F127 diacrylate (F127DA)to develop a composite hydrogel for wound healing, where the XG introduced anti-inflammation and anti-bacterial properties to the construct, and F127DA provides the photocurable properties essential for hydrogel formation and robust mechanical characteristics to achieve physical strength that matches tissue regeneration. The material characterizations suggested that XG/F127DA hydrogels had great biostability, blood compatibility and antibacterial effects, which was suitable to be used as a wound healing material. The in vitro analysis by culturing L929 fibroblasts on the hydrogel surface demonstrated that the inclusion of XG could promote the cellular proliferation rate, migration rate, and re-epithelialization-related marker expression, while downregulate the inflammation process. The XG/F127DA hydrogel was further used for the full-thickness skin wound healing test on mice, where the inclusion of XG significantly increased the wound closure rate through reducing the inflammation responses, and promote re-epithelialization and angiogenesis. These results indicated that XG/F127DA hydrogel has great potential to be used for wound healing in future clinical translation.

Injectable Biomimetic Gels for Biomedical Applications.

Biomimetic gels are synthetic materials designed to mimic the properties and functions of natural biological systems, such as tissues and cellular environments. This manuscript explores the advancements and future directions of injectable biomimetic gels in biomedical applications and highlights the significant potential of hydrogels in wound healing, tissue regeneration, and controlled drug delivery due to their enhanced biocompatibility, multifunctionality, and mechanical properties. Despite these advancements, challenges such as mechanical resilience, controlled degradation rates, and scalable manufacturing remain. This manuscript discusses ongoing research to optimize these properties, develop cost-effective production techniques, and integrate emerging technologies like 3D bioprinting and nanotechnology. Addressing these challenges through collaborative efforts is essential for unlocking the full potential of injectable biomimetic gels in tissue engineering and regenerative medicine.

Incorporation of natural and synthetic polymers into honey hydrogel for wound healing: A review.

The difficulty in treating chronic wounds due to the prolonged inflammation stage has affected a staggering 6.5 million people, accompanied by 25 billion USD annually in the United States alone. A 1.9% rise in chronic wound prevalence among Medicare beneficiaries was reported from 2014 to 2019. Besides, the global wound care market values were anticipated to increase from USD 20.18 billion in 2022 to USD 30.52 billion in 2030, suggesting an expected rise in chronic wounds financial burdens. The lack of feasibility in using traditional dry wound dressings sparks hydrogel development as an alternative approach to tackling chronic wounds. Since ancient times, honey has been used to treat wounds, including burns, and ongoing studies have also demonstrated its wound-healing capabilities on cellular and animal models. However, the fluidity and low mechanical strength in honey hydrogel necessitate the incorporation of other polymers. Therefore, this review aims to unravel the characteristics and feasibility of natural (chitosan and gelatin) and synthetic (polyvinyl alcohol and polyethylene glycol) polymers to be incorporated in the honey hydrogel. Relevant articles were identified from databases (PubMed, Google Scholar, and Science Direct) using keywords related to honey, hydrogel, and polymers. Relevant data from selected studies were synthesized narratively and reported following a structured narrative format. The importance of honey's roles and mechanisms of action in wound dressings were discussed. Notable studies concerning honey hydrogels with diverse polymers were also included in this article to provide a better perspective on fabricating customized hydrogel wound dressings for various types of wounds in the future. Honey's incapability to stand alone in hydrogel requires the incorporation of natural and synthetic polymers into the hydrogel. With this review, it is hoped that the fabrication and commercialization of the desired honey composite hydrogel for wound treatment could be brought forth.

Multifunctional sprayable carboxymethyl chitosan/polyphenol hydrogel for wound healing

The use of facile methods to synthesize environmentally friendly and multifunctional hydrogel dressings is still a major challenge in development. Herein, Turkish gall extract (TGE) and carboxymethyl chitosan (CMCS) were combined and sprayed using a dual syringe to form a multifunctional TGE-CMCS hydrogel (TC gel) in one step through abundant hydrogen bonding between functional groups as a green approach. TC gel showed rapid gelation at 19.0 ± 2.9 s. Apart from the advantage of being able to adapt to different wound shapes, TC gel retained the antioxidant, antibacterial, hemostatic and anti-inflammatory properties of TGE. In vitro antibacterial experiments showed that TC-gel eliminated 98.27 ± 0.79 % of Staphylococcus aureus and 98.87 ± 1.08 % of Escherichia coli. Compared with TGE or CMCS alone, TC gel accelerates skin wound healing due to its three-dimensional network structure and continuous release of active components at the wound site, enhancing re-epithelialization, improving collagen deposition, and increasing angiogenesis. The wound healing rate of full-thickness skin defect rats treated with TC gel was 93.98 ± 0.63 % on the 10th day. These results suggest that TC gel combined with a facile and scalable manufacturing method is a promising multifunctional wound dressing for clinical wound management.

Application of Bletilla striata polysaccharide hydrogel for wound healing among in diabetes

Diabetes has become an increasingly serious global health crisis. Long-term hyperglycemia can lead to vascular and neurological disorders, thus deterring wound healing. Therefore, exploring treatment modalities for wounds in individuals with diabetes is clinically significant. Bletilla striata polysaccharide and bioactive natural polymers carbomer 940 and carboxymethyl chitosan (CMC) are cross-linked to form the Bletilla striata polysaccharide hydrogel (named CCHG/BSP). Upon characterization, we found that the hydrogel has a porous structure and good mechanical and moisture retention properties. A hemolysis test revealed that the hydrogel had high safety. Furthermore, the hydrogel effectively promoted proliferation and migration in mouse L929 fibroblasts. In back wounds inflicted in a streptozotocin-induced mouse model of diabetes, the CCHG/BSP hydrogel significantly promoted wound healing. Hematoxylin-eosin, Masson’s trichrome, and immunohistochemical staining of tissues around the wound suggest that the mechanism underlying wound healing in diabetes may involve the promotion of angiogenesis, regulation of inflammation, and promotion of collagen regeneration. This provides a foundation for studies on and the development of new BSP pharmacotherapeutic products and the clinical application of its hydrogel dressing, and provide novel avenues for treating wounds in individuals with diabetes.

Carboxymethyl chitosan-methacrylic acid gelatin hydrogel for wound healing and vascular regeneration

At present, wound dressings in clinical applications are primarily used for superficial skin wounds. However, these dressings have significant limitations, including poor biocompatibility and limited ability to promote wound healing. To address the issue, this study used aldehyde polyethylene glycol as the cross-linking agent to design a carboxymethyl chitosan-methacrylic acid gelatin hydrogel with enhanced biocompatibility, which can promote wound healing and angiogenesis. The CSDG hydrogel exhibits acid sensitivity, with a swelling ratio of up to 300%. Additionally, it exhibited excellent resistance to external stress, withstanding pressures of up to 160 kPa and self-deformation of 80%. Compared to commercially available chitosan wound gels, the CSDG hydrogel demonstrates excellent biocompatibility, antibacterial properties, and hemostatic ability. Both in vitro and in vivo results showed that the CSDG hydrogel accelerated blood vessel regeneration by upregulating the expression of CD31, IL-6, FGF, and VEGF, thereby promoting rapid healing of wounds. In conclusion, this study successfully prepared the CSDG hydrogel wound dressings, providing a new approach and method for the development of hydrogel dressings based on natural macromolecules.

Puerarin-containing rhein-crosslinked tyramine-modified hyaluronic acid hydrogel for antibacterial and anti-inflammatory wound dressings

Wound infections, posing a grave risk of severe physical consequences and even mortality, exact a substantial financial toll on society, rendering them among the most formidable challenges confronting our world today. A critical imperative is the development of hydrogel dressings endowed with immune-regulating and antibacterial properties. This study is founded upon the symbiotic physical and efficacious attributes of two small natural molecules. An injectable hydrogel is meticulously crafted by encapsulating puerarin (PUE) into tyramine-modified hyaluronic acid, subsequently introducing rhein (RHE), and catalyzing the formation of inter-phenol crosslinks with H2O2/horseradish peroxidase (HA-Tyr-R@P). Exhibiting a favorable microenvironmental impact the developed hydrogel attains an antibacterial efficacy exceeding 95 %, coupled with a wound closure rate twice that of the control group. HA-Tyr-R@P hydrogels not only inhibit bacterial growth but also mitigate inflammation, fostering wound healing, owing to their harmonized physicochemical characteristics and synergistic therapeutic effects. This work underscores the creation of a singular, versatile hydrogel platform, negating the complexities and side effects associated with pharmaceutical preparations. Furthermore, it offers new ideas for the formulation of RHE-based hydrogels for wound healing, emphasizing the pivotal role of natural small molecules in advancing biological materials.

IPN based hydrogels for in-vivo wound dressings; catalytic wound healing dynamics and isothermal adsorption models

Interpenetrating network (IPN) methacrylated chitosan or methacrylated flaxseed gum based hydrogels have been utilized to make outstanding in-vivo wound dressings. The photopolymerization process was accomplished in presence of Eosin-Y photoinitiator with average exposure time of 13–14 s for gelation. Spectroscopic structural investigations of 1H NMR. ATR-FTIR, TGA, and AFM techniques were used. In-vitro hemolysis test provided evidence of no cytotoxicity in both hydrogels observed. The in-vivo wound dressings were monitored for five mice coated with each hydrogel and another uncoated five mice for control (self-healing). All measurements were performed in quintuplicate (n = 5) and expressed as mean ± SD values. In wound healing dynamics, our data confirmed that wound healing pass through two stages; hemostasis and inflammation for stage 1, and proliferation and remodeling for stage 2. It also provided evidence of 1st order kinetics with descending rate of healing. Consequently, catalytic role of hydrogels in wound healing was checked via half-life (δ) and negative change of activation energy values (ΔEa). Various isothermal adsorption models demonstrated spontaneous and high binding affinities of hydrogels. It also confirmed the two-stage healing process in presence of hydrogels. Conclusively, the outstanding properties of the two hydrogels suggest their potential applications in treating venous ulcers and diabetic wound healing dressings.

Dual Self-Assembly of Puerarin and Silk Fibroin into Supramolecular Nanofibrillar Hydrogel for Infected Wound Treatment.

The treatment of infected wounds remains a challenging biomedical problem. Some bioactive small-molecule hydrogelators with unique rigid structures can self-assemble into supramolecular hydrogels for wound healing. However, they are still suffered from low structural stability and bio-functionality. Herein, a supramolecular hydrogel antibacterial dressing with a dual nanofibrillar network structure is proposed. A nanofibrillar network created by a small-molecule hydrogelator, puerarin extracted from the traditional Chinese medicine Pueraria, is interconnected with a secondary macromolecular silk fibroin nanofibrillar network induced by Ga ions via charge-induced supramolecular self-assembly. The resulting hydrogel features adequate mechanical strength for sustainable retention at wounds. Good biocompatibility and efficient bacterial inhibition are obtained when the Ga ion concentration is 0.05%. Otherwise, the substantial release of Ga ions and puerarin endows the hydrogel with excellent hemostatic and antioxidative properties. In vivo, evaluation of a mouse-infected wound model demonstrates that its healing effect outperformed that of a commercially available silver-containing wound dressing. The experimental group successfully achieves a 100% wound closure rate on day 10. This study sheds new light on the design of nanofibrillar hydrogels based on supramolecular self-assembly of naturally derived bioactive molecules as well as their clinical use for treating chronic infected wounds.

The effect of Bletilla striata polysaccharide on the physical and healing properties of curdlan-based hydrogel for wound healing.

Bletilla striata polysaccharide (BSP) was added to curdlan to form a blend hydrogel through a simple heating-cooling procedure to improve the hydrophilicity and healing efficacy of curdlan-based hydrogel used in wound healing. We explored the interplay between BSP and curdlan, studied how BSP concentration affects the physical properties and microstructures of hydrogels, and examined the biocompatibility and healing properties of the blend hydrogel. It was proved that the hydrogel framework was primarily formed by ordered arranged curdlan molecules, with BSP uniformly dispersed and intertwined with curdlan through hydrogen bonding. This effectively improved its hydrophilicity and strengthened the microstructure. Curdlan was found to be compatible with BSP. The blend hydrogel B3Cd3 (containing 1.5% BSP and 1.5% curdlan, w/v) was identified as the optimal formulation based on its higher water adsorption, water retention, thermal stability and interconnected microstructure, and was thus selected for further research. In vitro experiments revealed the highest cell viability of L929 in B3Cd3 extracts compared to those extracts of single-component curdlan hydrogel (Cd). In vivo, animal studies indicated that the B3Cd3 accelerated wound healing compared to the control group by improving re-epithelialization and blood vessel regeneration. On Days 3 and 11, the therapeutic benefits of B3Cd3 exceeded those of the Cd group, and no significant differences were observed in wound healing rates between the B and B3Cd3 groups from Day 7. The study proves that BSP enhances the physical and healing properties, as well as cell proliferation, of the curdlan-based hydrogel. The blend hydrogel B3Cd3, with its exceptional properties, holds potential for future application as a material for non-infected wound healing.

A Novel Food Bore Protein Hydrogel with Silver Ions for Promoting Burn Wound Healing.

Hydrogels have emerged as a promising option for treating local scald wounds due to their unique physical and chemical properties. This study aims to evaluate the efficacy of ovalbumin/gelatin composite hydrogels in repairing deep II-degree scald wounds using a mouse dorsal skin model. Trauma tissues collected at various time points are analyzed for total protein content, hydroxyproline content, histological features, and expression of relevant markers. The results reveal that the hydrogel accelerates the healing process of scalded wounds, which is 17.27% higher than the control group. The hydrogel treatment also effectively prevents wound enlargement and redness of the edges caused by infection during the initial stage of scalding. The total protein and hydroxyproline content of the treated wounds are significantly elevated. Additionally, the hydrogel up-regulates the expression of VEGF (a crucial angiogenic factor) and down-regulates CD68 (a macrophage marker). In summary, this study provides valuable insights into the potential of multifunctional protein-based hydrogels in wound healing.