Skin Defect Model Research Articles

Honokiol@PF127 crosslinked hyaluronate-based hydrogel for promoting wound healing by regulating macrophage polarization

Bacterial infection, oxidative stress and inflammation are the main obstacles in wound healing. Hydrogels with moist and inherent properties are beneficial to wound healing. Here, we fabricated a honokiol-laden micelle-crosslinked hyaluronate-based hydrogel by simply mixing honokiol-laden PF127-CHO micelles, 3,3′-dithiobis(propionohydrazide) grafted hyaluronic acid and silver ions. PF127 could not only effectively load hydrophobic small molecules but also be macromolecular crosslinker for preparing hydrogels. Hyaluronic acid plays an essential role in wound healing processes including regulating macrophage polarization towards M2 phenotype. The chemical dynamic acylhydrazone crosslinking and physical crosslinking among PF127-CHO micelles constructed hydrogel's networks, which endowed hydrogel with excellent self-healing properties. PF-HA-3 hydrogel also exhibited outstanding antioxidant and antibacterial capabilities. In a full-thickness skin defect model, this degradable and biocompatible hydrogel could promote wound healing by remodeling wound tissues, regulating M2 polarization and angiogenesis. In summary, this inherent multifunctional hydrogel will provide a promising strategy for designing bioactive compounds-based wound dressings.

Study of polydopamine-modified β-chitin nanofiber hydrogels for full-thickness wound healing

Developing natural polymer-based hydrogel with excellent injectability, suitable mechanical properties, and the ability to facilitate full-thickness skin wound healing is highly desirable in clinical application. Herein injectable hydrogels made of polydopamine (PDA) modified β-chitin nanofibers (β-ChNFs) were successfully prepared and applied for irregular wound healing. Compared with β-ChNFs hydrogels which were too weak to be used, the surface coating of PDA helped concentrate the β-ChNFs, and hydrogels with much higher strength were obtained and could be conveniently applied to the wound. The incorporation of chitosan oligosaccharide (COS) remarkably increased the hydrogels’ bioactivity. Shown as the biocompatibility measurement, ChNFs-PDA-COS hydrogels significantly promoted the proliferation of L929 cells. Demonstrated by the in vivo study in a rat full-thickness skin defect model, ChNFs-PDA-COS hydrogels with 1 % of COS significantly reduced inflammatory cell infiltration, improved the maturation of granulation tissue and well-organized collagen deposition, and regenerated thick dermis and epidermis with some cutaneous appendages at 9th post-operative day. All these contributed to the acceleration of wound closure and a better healing outcome as compared to the control group, indicating that the COS-incorporated ChNFs-PDA hydrogels are promising wound dressing for full-thickness skin tissue repair.

Concentrated Growth Factor Promotes Wound Healing Potential of HaCaT Cells by Activating the RAS Signaling Pathway.

The aim of this study was to explore the effect of concentrated growth factor (CGF) on the wound healing potential of human epidermal cells (HaCaT) in vitro and in vivo. CGF was extracted from venous blood using the centrifugal separation method. The CGF-conditioned medium was prepared from CGF gel immersed in Dulbecco's Modified Eagle medium. Crystal violet staining and wound healing assay were used to evaluate the proliferation and migration of HaCaT cells, respectively. Lipopolysaccharide (LPS) was used to test the anti-inflammatory function of CGF. An ELISA kit was employed to detect the concentration of growth factors and interleukins in CGF medium. mRNA and protein levels of angiogenic biomarkers (Angiopoietin-1 (ANGPT-1), vascular endothelial growth factor-A (VEGF-A) and Angiopoietin-2 (ANGPT-2) ) were determined by quantitative polymerase chain reaction (qPCR) and Western blot, respectively. A dorsal excisional wound model was recruited to test the wound healing effect of CGF in mice. Three-day treatment of HaCaT cells with CGF significantly promoted cell proliferation, which was followed by an increase in Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF) levels in the medium. Cytokines (IL-6, IL-8 and TNF-α) were increased in LPS-stimulated HaCaT cells after 3 days, and CGF slightly inhibited the mRNA expression of these cytokines. The RAS signaling pathway was activated upon CGF treatment. Both RAS knockdown and an inhibitor of RAS (zoledronic acid) could block the migration of HaCaT cells after CGF treatment. Protein expressions of CD31, ANGPT-1, and VEGF-A were up-regulated in a dose-dependent manner upon CGF exposure. The protein level of ANGPT-2 was down-regulated after CGF treatment. CGF could promote wound healing in vivo, as demonstrated using the full skin defect model in nude mice. CGF was shown to promote wound repair in vitro and in vivo. The RAS cell signaling pathway was responsible for CGF stimulating the wound healing potential of HaCaT cells.

Pre-clinical evaluation of thermosensitive decellularized adipose tissue/platelet-rich plasma interpenetrating polymer network hydrogel for wound healing.

Wound healing remains a challenge worldwide, and an ideal wound dressing that promotes healing is urgently needed. In this study, we developed a thermosensitive injectable hydrogel known as the thermosensitive decellularized adipose tissue/platelet-rich plasma interpenetrating polymer network (t-DPI) hydrogel based on decellularized adipose tissue (DAT) and temperature-controlled platelet-rich plasma (t-PRP). Abundant platelets, growth factors (GFs), and bioactive substances from the decellularized extracellular matrix (dECM) in the t-DPI hydrogel had positive effects on wound healing. The morphology, thermosensitivity, and GFs release properties of the t-DPI hydrogel were studied. In vitro, the t-DPI hydrogel showed ideal cytocompatibility and the abilities to promote the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs). Moreover, M2 macrophage polarization was enhanced after treated with t-DPI hydrogel. In vivo, the t-DPI hydrogel notably accelerated the full-thickness wound healing. The positive role of the t-DPI hydrogel on pro-angiogenesis, macrophage polarization and collagen deposition were validated in the nude mouse full-thickness skin defect model. In addition, the clinical application potential was confirmed using a pre-clinical porcine full-thickness wound model. Overall, this study demonstrated that the t-DPI hydrogel achieves fast and ideal wound healing in full-thickness wound defects and provides a potential clinical treatment strategy.

Extraction and characterization of chitosan from Eupolyphaga sinensis Walker and its application in the preparation of electrospinning nanofiber membranes

Due to its capabilities for wound healing, antimicrobial defense, hemostasis, and biodegradation, chitosan has seen increased use in biomedical disciplines in recent years. In the meantime, efforts have been made to develop and use insect chitosan as a source to address the seasonal, irritating, and regional shortcomings of traditional shrimp and crab chitosan. In this study, a new type of insect chitosan (DCS) was first extracted from Eupolyphaga sinensis Walker by a low-temperature intermittent method and was compared with commercially available pharmaceutical chitosan (CS). Firstly, the degree of deacetylation and molecular weight of DCS were determined, and DCS was characterized by FT-IR, 1H NMR, XRD, and TGA-DTG. On this basis, DCS was mixed with PVA and PEO to create a novel electrospun nanofiber membrane. The air permeability, antibacterial properties, and biocompatibility of the nanofiber membrane were evaluated, as well as the membrane's shape, structure, and mechanical characteristics. Finally, the activity of nanofiber membranes in promoting wound healing was verified with a rat full-thickness skin defect model, hoping to provide a reference for the development of new drug delivery carriers and wound dressings.

A novel approach for wound treatment using dried cultured epidermal allograft: A phase I/II, single-center, open-label clinical trial

BackgroundAutologous cultured epidermis (CE) is successfully used in burn care, but it requires a manufacturing time of three weeks and is very expensive owing to its custom-made nature of treatment. To compensate this disadvantage, dried allogeneic CE promises a novel therapeutic approach; and previous reports have demonstrated its efficacy in promoting wound healing using a murine skin defect model. Herein, a prospective clinical study was conducted to confirm the safety and efficacy of dried allogeneic CE for wound treatment. MethodsDried CE was manufactured using donor keratinocytes obtained from excess surgical skin and applied to skin defects that were at least 3 cm in length and less than 10 % of the body surface area of the patients. The patients were observed for 14 days after CE application. The primary endpoint was the incidence of adverse events and the secondary endpoint was the percentage of wound healed since baseline, on days 7 and 14. Furthermore, as a stratified analysis, the percentage of wound healed, specified as deep dermal burns, was calculated. ResultsSix patients (five burns and one skin ulcer after necrotizing fasciitis) enrolled in the study. As a serious adverse event, a local infection was observed in one patient, which resolved by debridement and conventional skin grafting. Other adverse events that were potentially related to this treatment included two cases of skin erosion, and one case of systemic fever. No unresolved adverse events remained at the end of the study period. The percentage of wound healed was 73.4 ± 19.2 % on Day 7, and 92.2 ± 11.8 % on Day 14. When the targeted disease was restricted to deep dermal burns, the percentage of wound healed was 69.9 ± 28.9 % on Day 7 and 90.5 ± 13.2 % on Day 14. ConclusionTreatment with dried CE was safely performed without any unresolved severe adverse effects. Dried CE is a new and promising modality for skin defect treatment, such as burns and ulcers, and is expected to compensate for the disadvantages of autologous CE. However, large-scale clinical trials are required to confirm their efficacy.

A chitosan derivative-crosslinked hydrogel with controllable release of polydeoxyribonucleotides for wound treatment

Nucleic acid-based agents have advantages in therapeutic efficacy and biological safety. However, due to its facile degradability, it lacks an effective route of administration in wound treatment. Designing smart hydrogels for the spatiotemporally controllable delivery of nucleic acids is of great significance for clinical applications. Here, a near-infrared (NIR)-responsive nanocomposite hydrogel was prepared using methyl methacrylate (GMA)-modified chitosan as the macromolecular cross-linker, N-isopropylacrylamide (NIPAAm) as the backbone, and molybdenum disulfide nanosheets (MoS2 NSs) as the nanocomponents. The polydeoxyribonucleotide (PDRN), a nucleic acid-based agent that promotes tissue regeneration, was loaded and delivered. The photothermal conversion capability of MoS2 NSs enables customized care of PDRNs and antibacterial enhancement. In a full-thickness skin defect model, high-quality wound healing effects were demonstrated under the action of nanocomposite hydrogels. The proposed nanocomposite hydrogel provides a new reference for local delivery of nucleic acid-based agents.

Hybrid membrane of flat silk cocoon and carboxymethyl chitosan formed through hot pressing promotes wound healing and repair in a rat model.

Clinical wound management is always a relatively urgent problem. Moreover, wounds, especially severe wounds with excessive tension or excessive movement are prone to tissue infection, necrosis, and other negative effects during healing. Therefore, research has aimed to develop low-cost complementary treatments to address the urgent need for an innovative low-cost dressing that can adapt to high mechanical requirements and complex wound conditions. At present, tissue engineering to produce artificial skin with a structure similar to that of normal skin is one effective method to solve this challenge in the regeneration and repair of serious wounds. The present study hot pressed flat silk cocoons (FSC) with carboxymethyl chitosan (CMCS) to generate a cross-linked binding without enzymes or cross-linking agents that simulated the 3D structural composites of the skin cuticle. This hybrid membrane showed potential to reduce inflammatory cells and promote neovascularization in skin wound repair. After hot pressing at 130°C and 20 Mpa, the FSC/CMCS composite material was denser than FSC, showed strong light transmission, and could be arbitrarily cut. Simulating the normal skin tissue structure, the hybrid membrane overcame the poor mechanical properties of traditional support materials. Moreover, the combination of protein and polysaccharide simulated the extracellular matrix, thus providing better biocompatibility. The results of this study also demonstrated the excellent mechanical properties of the FSC/CMCS composite support material, which also provided a low-cost and environmentally friendly process for making dressings. In addition, the results of this study preliminarily reveal the mechanism by which the scaffolds promoted the healing of full-thickness skin defects on the back of SD rats. In vivo experiments using a full-thickness skin defect model showed that the FSC/CMCS membranes significantly promoted the rate of wound healing and also showed good effects on blood vessel formation and reduced inflammatory reactions. This bionic support structure, with excellent repair efficacy on deep skin defect wounds, showed potential to further improve the available biomaterial systems, such as skin and other soft tissues.

Mechanoactive Nanocomposite Hydrogel to Accelerate Wound Repair in Movable Parts.

Dynamic full-thickness skin wound healing remains an intricate problem due to the humid environment and frequent exercise. Recently, multifunctional hydrogels have a great promise in wound repair. However, traditional hydrogels only keep the wound moist, protect the wound from bacterial infection, and cannot actively drive dynamic wound closure. Inspired by embryo wound active closure, we constructed a double-sided thermoresponsive mechanoactive (DTM) hydrogel that combines good flexibility, self-healing, wet-tissue adhesion, and antibacterial functions. The strong adhesion of the hydrogel to biological tissues is attributed to "multiple hydrogen bonding clusters" without any chemical reaction. The contraction force triggered by temperature is quickly transmitted to dynamic wound edges to resist external mechanical forces and drive wound closure, which can effectively avoid damage to surrounding healthy tissue and reduce the risk of scarring, infection, and inflammation caused by sutures, staples, or clips. Strikingly, in vivo, this hydrogel bandage actively enhanced wound repair in a full-thickness skin defect model by promoting collagen deposition, facilitating angiogenesis, and accelerating wound re-epithelialization. This mechanoactive biological method will provide a facile strategy for joint wound management and demonstrates strong potential in tissue remodeling.

Application of collagen-chondroitin sulfate scaffolds with different pore sizes combined with acidic fibroblast growth factor in repairing full thickness skin defects in nude mice

Wound healing of skin defects is complex. For the treatment of large and deep wounds, it is a good alternative to accept artificial dermis grafting at the first stage surgery, and autologous split-thickness skin grafting 2–3 weeks later at the second stage surgery. In addition, the effectiveness of numerous cytokines such as fibroblast growth factor (FGF) on wounds healing has been widely researched. The traditional view is that direct external application or in vivo injection of exogenous FGFs may not achieve the desired therapeutic effect as the effective concentration cannot be maintained for a long time. Therefore, some researchers have tried to integrate various cytokines into skin substitutes for combined application. However, we believe that considering the current situation, it is still difficult to achieve mass production of these types of artificial dermis. Here, we manufactured a collagen-chondroitin sulfate scaffold material by imitating the marketed artificial dermis materials. Then, we combined it with recombinant human acidic FGF in a single full dose during the first-stage artificial dermis transplantation, which is simple and completely feasible but always controversial in the current clinical work, to explore whether this combinatorial therapy could serve as an efficient way wound healing in the Balb/c-nu mice full-thickness skin defect model.

Evaluation of wound healing effects of micronized acellular dermal matrix in combination with negative pressure wound therapy: In vivo study.

Acellular dermal matrix (ADM) grafts can provide coverage for full-thickness skin defects and substitute for dermal defects. We tested the effectiveness of micronized ADM (mADM) as a dressing material, combined with negative pressure wound therapy (NPWT), for managing superficial wounds. We compared the wound healing effect of mADM in combination with NPWT with those of gelatin and mADM applied with a foam dressing. These therapeutic materials were applied to 36 cm2 excisional wounds in a porcine full-thickness skin defect model. Wound healing kinetics and new tissue formation were assessed 10 days after the initial treatment by measuring the wound area. Collagen deposition and neovascularization were histologically evaluated. Compared with the other two groups, mADM plus NPWT combination group had a significantly larger wound area at the baseline (P=.0040), but the smallest on the 7th day (P=.0093). In addition, collagen formation and neovascularization were more histologically promoted than in the other two groups. mADM showed better results than the gelatin group but less collagen and revascularization than the combination group, and there was no significant difference in wound area. Our results show that the combination of mADM and NPWT has a synergistic wound healing effect.

The Stimulation of Macrophages by Systematical Administration of GM-CSF Can Accelerate Adult Wound Healing Process.

Skin wound repair remains a major challenge in clinical care, and various strategies have been employed to improve the repair process. Recently, it has been reported that macrophages are important for the regeneration of various tissues and organs. However, their influence on wound repair is unclear. Here, we aimed to explore whether macrophages would participate in the wound healing process and to explore new possibilities of treatment for skin defects. We firstly created a mouse full-thickness skin defect model to observe the distribution of macrophages in the regenerating tissue and then detected the influence of macrophages on skin defect repair in both macrophage-depletion and macrophage-mobilization models. We found that the number of macrophages increased significantly after skin defect and persisted during the process of wound repair. The regeneration process was significantly prolonged in macrophage-depleted animals. RT-qPCR and ELISA assays further demonstrated that the expression of growth factors was perturbed in the regenerating tissue. The activation of macrophages by granulocyte-macrophage colony-stimulating factor (GM-CSF) injection could significantly improve wound healing, accompanied with an upregulation of the expression of various growth factors. In conclusion, the current study demonstrated that macrophages are critical for skin regeneration and that GM-CSF exhibited therapeutic potential for wound healing.

Preparation of biodegradable carboxymethyl cellulose/dopamine/Ag NPs cryogel for rapid hemostasis and bacteria-infected wound repair

Massive hemorrhage caused by accident or surgery is a major factor in accidental death. In addition, bacterial infection is also an important threat after bleeding. Cryogels with interpenetrating macroporous structures pose great application prospects in rapid hemostasis and infected wound repair. In this study, cryogels with different pore size are prepared by carboxymethyl cellulose (CMC) and dopamine (DA). The CMC grafted with different DA amounts is crosslinked by free DA through oxidative polymerization at low temperatures to form cryogels with different pore sizes. And the CMC/DA-3 cryogel is chosen as the optimal group for its high porosity, suitable mechanical, and good hemostatic ability. CMC/DA-3 cryogel is loaded with silver nanoparticles (Ag NPs) to prepare hemostatic cryogel with antibacterial properties. Antibacterial tests and animal hemostasis experiments confirm that the CMC/DA-3/Ag cryogel has good antibacterial properties and can finish rapid hemostasis. In the S. aureus infection skin defect model, the wound healing is significantly improved compared with commercial gelatin sponge. In summary, the novel cryogel has great potential in rapid hemostasis and infected wound healing.

Injectable chitosan hydrogels tailored with antibacterial and antioxidant dual functions for regenerative wound healing

Herein, an injectable self-healing hydrogel with inherent antibacterial activity was fabricated based on the dynamic covalent bond formation between boronic acid and catechol groups in quaternized chitosan as building blocks in conjunct with the in-situ encapsulation of epigallocatechin-3-gallate (EGCG, a green tea derivative). Benefiting from the catechol groups and therapeutic effect of EGCG, the resulting natural-based injectable hydrogels showed excellent antibacterial and antioxidant dual functions in preventing bacterial infection and scavenging radicals. The hydrogels loaded with EGCG also exhibited good biocompatibility along with contact-active antibacterial activity via a “capture and kill” strategy. The dynamic covalent bonding enables shear-thinning delivery of the gels via syringe, followed by rapid self-healing. Additionally, the in vivo wound healing evaluation in a full-thickness skin defect model revealed the appreciable and regenerative wound healing performance of the hydrogels, demonstrating their great potential as novel wound dressings for wound management.

Multifunctional hydrogel based on dopamine-modified hyaluronic acid, gelatin and silver nanoparticles for promoting abdominal wall defect repair

Abdominal wall defects are often accompanied by severe infections and complications, creating a significant challenge for clinicians. There is an urgent need to develop a novel wound dressing that can effectively prevent intra-abdominal infection and promote the healing of defective abdominal walls. Based on a hydrogel dressing containing hyaluronic acid (HA) and gelatin (GT), herein we integrated dopamine with a catechol structure to enhance its antioxidant and adherent properties. HA is oxidized to form an aldehyde group, and subsequently grafted with dopamine. The dopamine-modified HA undergoes amidation reaction with GT at different concentrations. In addition, silver nanoparticles (AgNPs) were introduced to the hydrogel to enhance the antibacterial properties. The in vitro studies on GT/DA-HA demonstrated excellent physical and chemical properties, biodegradability, and biocompatibility. In a rat full-thickness skin defect model and a full-thickness abdominal wall defect model, the GT/DA-HA hydrogel could accelerate the healing process by improving wet adhesion, reducing wound inflammation, and promoting angiogenesis and formation of granulation tissues. The multifunctional hydrogel developed in this study shows great potential for treating full-thickness abdominal wall defects.

Combination of natural polyanions and polycations based on interfacial complexation for multi-functionalization of wound dressings.

Multi-functionalization of wound dressings with natural polymers is meaningful and remains a challenge. The combination of natural polyanions and polycations appears to be a promising strategy. Still, its performances based on current layer-by-layer self-assembly or homogeneous complexation are mutable and limited. Herein, Ca2+-incorporated carboxymethyl cellulose (Ca/Na-CMC) and hydroxypropyltrimethyl ammonium chloride chitosan (HACC) are adopted as the model polyanion and polycation, respectively, to develop multi-functionalized dressings based on interfacial complexation. The dressings exhibit a multilayer structure composed of a polyanion layer (Ca/Na-CMC) for hemostasis and promotion of cell proliferation, a formed polyelectrolyte complex (PEC) layer for structural stability, and a polycation layer (HACC) for antibiosis. Compared to the dressing based on homogeneous complexation, the multilayer dressings show stronger moisture penetrability (around 1,150 g/m2/24 h), higher hemostatic activity, and higher antibacterial rate (up to 100%) and promoted effect on cell proliferation. An in vivo evaluation using a rat full-thickness skin defect model reveals that the multilayer dressings can accelerate wound healing in 2 weeks. Overall, owing to interfacial complexation resulting in separate layers, the performances of polyanions and polycations after combination are more predictable, and their biological functions can be effectively preserved. These findings not only support the extensive application of multilayer dressings but also offer an alternative strategy for multi-functionalizing wound dressings with natural polyanions and polycations.

Generation of cost-effective MXene@polydopamine-decorated chitosan nanofibrous wound dressing for promoting wound healing.

Herein, we designed and fabricated a MXene@polydopamine (MXene@PDA)-decorated chitosan non-woven fabric (M-CNF) hemostatic dressing with super hydrophilic properties for wound repair and regeneration. The M-CNF exhibit excellently wettability characteristics which can rapidly absorb water from blood. Moreover, M-CNF with 15mg/mL MXene@PDA (M-CNF-15) show better antibacterial performance, excellent blood-clotting performance, better blood cell and platelet adhesion ability than CNF, displaying both active and passive hemostatic mechanisms to accelerate blood clotting in mouse-liver injury model. In addition, the M-CNF-15 also shows better wound healed performance than Tegaderm™ film in a full-thickness skin defect model, and further demonstrating that the MXene@PDA can promote fibrinogen reformation the at the initial phases of the wound healing process. Therefore, this strategy for designing and manufacturing of multi-functional M-CNF wound dressing will have great potential for active local hemostasis and wound repair and regeneration.

Porous photothermal antibacterial antioxidant dual–crosslinked cryogel based on hyaluronic acid/ polydopamine for non-compressible hemostasis and infectious wound repair

• A series of antioxidant and photothermal antibacterial dual–crosslinked cryogels was designed. • The cryogels showed stable mechanical property and biocompatibility. • These cryogels rapidly stopped irregularly shaped and non-compressible bleeding. • The cryogels significantly improved the MRSA-infected full-thickness skin defect wound healing. Cryogel dressings with good absorption ability and photothermal antibacterial properties for preventing wound infections and treating infected wounds have attracted widespread attention. In this work, a series of cryogels with macroporous structure, antioxidant and photothermal properties were prepared based on adipic dihydrazide modified hyaluronic acid (HA-ADH), and dopamine (DA). The antioxidant properties, hemostatic properties, near infrared (NIR) assisted photothermal antibacterial ability provided by polydopamine, recyclable compression mechanical properties, and cytocompatibility were tested. The results demonstrated that the HA-ADH/DA cryogels have stable mechanical properties, great antibacterial properties against E. coli (EC) and methicillin-resistant S. aureus (MRSA). The high swelling ratio due to the high water retention of HA equipped the cryogels with the capability of absorbing exuded blood and excessive tissue fluid in the infected full-thickness skin defect model of mouse. The cryogels demonstrated good cytocompatibility and antioxidant performance through cell tests and 1, 1-diphenyl-2-methylbenzohydrazino (DPPH) scavenging efficiency test. The cryogels showed enhanced blood-clotting index (BCI) and better hemostatic ability in the mouse liver trauma model and the rat deep non-compressible liver defect model compared with gauze and gelatin sponge. Furthermore, compared with commercial Tegaderm TM dressing in vivo , the HA-ADH/DA cryogels could greatly promote infected skin wound healing in a full-thickness infected skin defect wound model. In summary, the macroporous HA-ADH/DA cryogels with good antioxidant, high swelling ratio, photothermal antibacterial property, and biocompatibility are a promising hemostatic material and wound healing dressing.

Fabrication of Curcumin-Loaded Silk Fibroin and Polyvinyl Alcohol Composite Hydrogel Films for Skin Wound Healing.

Skin regeneration of full-thickness wounds remains a challenge, requiring a well-regulated interplay of cell-cell and cell-matrix signaling. Herein, the composite hydrogel films composed of silk fibroin (SF) and polyvinyl alcohol (PVA) as scaffolds loaded with curcumin nanoparticles (Cur NPs) were developed for skin wound healing. The structure and physicochemical properties of hydrogel films were first evaluated by scanning electron microscopy (SEM), water contact angle, and chemical and mechanical measurements. In addition, the as-fabricated composite hydrogel films have a unique 3D structure and excellent biocompatibility that facilitates the adhesion and growth of cells. Antimicrobial tests in vitro showed that they could inhibit the growth of bacteria due to the incorporation of Cur NPs into composite hydrogel films. The efficacy of the curcumin-loaded SF/PVA composite hydrogel films for skin wound healing was investigated on the skin defect model in vivo. Immunological analysis showed that the as-fabricated Cur NP-loaded SF/PVA composite hydrogel films inhibited inflammation at the wound sites, while promoting angiogenesis during the wound healing process.

ε-Poly-l-lysine-modified natural silk fiber membrane wound dressings with improved antimicrobial properties

Many complex diseases, such as bacterial infections, frequently accompany cutaneous wound healing, adding to the difficulty of clinical wound management. Consequently, in addition to displaying strong biocompatibility and actively promoting wound healing, an optimal wound dressing should also possess antimicrobial qualities to address issues with bacterial infection. This paper developed natural silk fiber (SF) membranes (also known as a flat silk cocoon (FSC)) with antimicrobial properties as a dressing for skin wounds. By changing the spinning tools and environment of silkworm larvae, a novel natural SF membrane with a cocoon structure and controllable size was prepared. The functional SF membranes were obtained via a hot press process and grafted with ε-Poly-l-lysine (EPL). The results showed that the SF membrane dressing was adjustable in size with a similar structure to the extracellular matrix (ECM), displaying inherent mechanical properties, excellent antimicrobial qualities, and biocompatibility. In vivo experiments using a full-thickness skin defect model indicated that EPL-modified SF membranes significantly promoted the rate of wound healing, exhibiting thicker granulation tissue and higher collagen disposition than commercial dressings (Tegaderm™ film). Therefore, the excellent mechanical qualities and cytocompatibility of the antimicrobial EPL-modified SF membranes substantially promote their potential application as a chronic wound dressing.