A carrier-free, injectable, and self-assembling hydrogel based on carvacrol and glycyrrhizin exhibits high antibacterial activity and enhances healing of MRSA-infected wounds.

Inspired by glycyrrhizin's strong pharmacological activities and the directed self-assembly into hydrogels, we created a novel carrier-free, injectable hydrogel (CAR@glycygel) by combining glycyrrhizin with carvacrol (CAR), without any other chemical crosslinkers, to promote wound healing on bacteria-infected skin. CAR appeared to readily dissolve and load into CAR@glycygel. CAR@glycygel had a dense, porous, sponge structure and strong antioxidant characteristics. In vitro, it showed better antibacterial ability than free CAR. For methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, and Escherichia coli, the diameter of inhibition zone values of CAR@glycygel were 3.80 ± 0.04, 3.31 ± 0.20 and 3.12 ± 0.24 times greater, respectively, than those of free CAR. The MICs for CAR@glycygel was 156.25 µg/mL while it was 1250.00 µg/mL for free CAR to these three bacteria. Its antibacterial mechanism appeared to involve destruction of the integrity of the bacterial cell wall and biomembrane, leading to a leakage of AKP and inhibition of biofilm formation. In vivo, CAR@glycygel effectively stopped bleeding. When applied to skin wounds on rats infected with MRSA, CAR@glycygel had strong bactericidal activity and improved wound healing. The wound healing rates for CAR@glycygel were 49.59 ± 15.78 %, 93.02 ± 3.09 % and 99.02 ± 0.55 % on day 3, day 7, and day 11, respectively, which were much better than blank control and positive control groups. Mechanisms of CAR@glycygel accelerating wound healing involved facilitating epidermis remolding, promoting the growth of hair follicles, stimulating collagen deposition, mitigating inflammation, and promoting angiogenesis. Overall, CAR@glycygel showed great potential as wound dressing for infected skin wounds.

Development and characterization of curcumin nanosuspension-embedded genipin-crosslinked chitosan/polyvinylpyrrolidone hydrogel patch for effective wound healing.

This study investigated the development of a genipin-crosslinked chitosan (CS)-based polyvinylpyrrolidone (PVP) hydrogel containing curcumin nanosuspensions (Cur-NSs) to promote wound healing in an excisional wound model. Cur-NSs were prepared, and a simplex centroid mixture design was employed to optimize hydrogel properties for high water absorption, degree of crosslinking, and sufficient toughness. The in vivo wound healing effect was tested in Wistar rats. The optimized hydrogel consisted of a 70:30 ratio of CS:PVP, crosslinked with a 2 % w/w genipin solution. It exhibited high swelling capability (486 %) while maintaining solidity, robustness, and durability. Incorporating 5 % w/w Cur-NSs resulted in a more compact structure, although with a reduction in swelling properties. The release kinetics of Cur from the hydrogel followed the Korsmeyer-Peppas Fickian diffusion model. In vitro biocompatibility studies demonstrated that the hydrogel was non-toxic to skin fibroblast cells. The in vivo experiment revealed a desirable wound healing rate with over 80 % recovery by day 7. Cur-NSs likely aided wound healing by reducing the inflammatory response and stimulating fibroblast proliferation. Additionally, the CS-based hydrogel provided a moist wound environment with hydration and gas transfer, further accelerating wound closure. These findings suggest that the Cur-NS-embedded hydrogel shows promise as a wound dressing material.

Integrating Bioactive Graded Hydrogel with Radially Aligned Nanofibers to Dynamically Manipulate Wound Healing Process.

Skin wound healing is a complex process that requires appropriate treatment and management. Using a single scaffold to dynamically manipulate angiogenesis, cell migration and proliferation, and tissue reconstruction during skin wound healing is a great challenge. We developed a hybrid scaffold platform that integrates the spatiotemporal delivery of bioactive cues with topographical cues to dynamically manipulate the wound-healing process. The scaffold comprised gelatin methacryloyl hydrogels and electrospun poly(ε-caprolactone)/gelatin nanofibers. The hydrogels had graded cross-linking densities and were loaded with two different functional bioactive peptides. The nanofibers comprised a radially aligned nanofiber array layer and a layer of random fibers. During the early stages of wound healing, the KLTWQELYQLKYKGI peptide, which mimics vascular endothelial growth factor, was released from the inner layer of the hydrogel to accelerate angiogenesis. During the later stages of wound healing, the IKVAVS peptide, which promotes cell migration, synergized with the radially aligned nanofiber membrane to promote cell migration, while the nanofiber membrane also supported further cell proliferation. In an in vivo rat skin wound-healing model, the hybrid scaffold significantly accelerated wound healing and collagen deposition, and the ratio of type I to type III collagen at the wound site resembled that of normal skin. The prepared scaffold dynamically regulated the skin tissue regeneration process in stages to achieve rapid wound repair with clinical application potential, providing a strategy for skin wound repair.

Antibacterial Mechanism of d-Cysteine/Polyethylene Glycol-Functionalized Gold Nanoparticles and Their Potential for the Treatment of Bacterial Infections.

Bacterial infection has always posed a severe threat to public health. Gold nanoparticles (Au NPs) exhibit exceptional biocompatibility and hold immense potential in biomedical applications. However, their antibacterial effectiveness is currently unsatisfactory. Herein, a chiral antibacterial agent with high stability was prepared by the modification of Au NPs with d-cysteine with the assistance of polyethylene glycol (PEG). The as-synthesized d-cysteine/PEG-Au NPs (D/P-Au NPs) exhibited a stronger (99.5-99.9%) and more stable (at least 14 days) antibacterial performance against Gram-negative (Escherichia coli and Listeria monocytogenes) and Gram-positive (Salmonella enteritidis and Staphylococcus aureus) bacteria, compared with other groups. The analysis of the antibacterial mechanism revealed that the D/P-Au NPs mainly affected the assembly of ribosomes, the biosynthesis of amino acids and proteins, as well as the DNA replication and mismatch repair, ultimately leading to bacterial death, which is significantly different from the mechanism of reactive oxygen species-activated metallic antibacterial NPs. In particular, the D/P-Au NPs were shown to effectively accelerate the healing of S. aureus-infected wounds in mice to a rate comparable to or slightly higher than that of vancomycin. This work provides a novel approach to effectively design chiral antibacterial agents for bacterial infection treatment.

Stimuli-Responsive Release-Active Dressing: A Promising Solution for Eradicating Biofilm-Mediated Wound Infections.

Biofilm-mediated wound infections pose a significant challenge due to the limitations of conventional antibiotics, which often exhibit narrow-spectrum activity, fail to eliminate recurrent bacterial contamination, and are unable to penetrate the biofilm matrix. While the search for alternatives has explored the use of metal nanoparticles and synthetic biocides, these solutions often suffer from unintended toxicity to surrounding tissues and lack controlled administration and release. In this study, we engineered a pH-responsive release-active dressing film based on carboxymethyl cellulose, incorporating a synthetic antibacterial molecule (SAM-17). The dressing film exhibited optimal mechanical stability for easy application and demonstrated excellent fluid absorption properties, allowing for prolonged moisturization at the site of injury. The film exhibited pH-dependent release of cargo, with 78% release within 24 h at acidic pH, enabling targeted antibacterial drug delivery within the wound microenvironment. Furthermore, the release-active film effectively eliminated repeated challenges of bacterial contamination. Remarkably, the film demonstrated a minimal toxicity profile in both in vitro and in vivo models. The film eliminated preformed bacterial biofilms, achieving a reduction of 2.5 log against methicillin-resistant Staphylococcus aureus (MRSA) and 4.1 log against vancomycin-resistant S. aureus (VRSA). In a biofilm-mediated MRSA wound infection model, this release-active film eradicated the biofilm-embedded bacteria by over 99%, resulting in accelerated wound healing. These findings highlight the potential of this film as an effective candidate for tackling biofilm-associated wound infections.

Wound Healing Promotion via Release of Therapeutic Metallic Ions from Phosphate Glass Fibers: An In Vitro and Ex Vivo Study.

Biomaterials capable of promoting wound healing and preventing infections remain in great demand to address the global unmet need for the treatment of chronic wounds. Phosphate-based glasses (PG) have shown potential as bioresorbable materials capable of inducing tissue regeneration, while being replaced by regenerated tissue and releasing therapeutic species. In this work, phosphate-glass-based fibers (PGF) in the system P2O5-CaO-Na2O added with 1, 2, 4, 6, and 10 mol % of the therapeutic metallic ions (TMI) Ag+, Zn2+, and Fe3+ were manufactured via electrospinning of coacervate gels. Coacervation is a sustainable, cost-effective, water-based method to produce PG. All TMI are effective in promoting wound closure (re-epithelialization) in living human skin ex vivo, where the best-performing system is PGF containing Ag+. In particular, PGF with ≥4 mol % of Ag+ is capable of promoting 84% wound closure over 48 h. These results are confirmed by scratch test migration assays, with the PGF-Ag systems containing ≥6 mol % of Ag+, demonstrating significant wound closure enhancement (up to 72%) after 24 h. The PGF-Ag systems are also the most effective in terms of antibacterial activity against both the Gram-positive Staphylococcus aureus and the Gram-negative Escherichia coli. PGF doped with Zn2+ shows antibacterial activity only against S. aureus in the systems containing Zn2+ ≥ 10 mol %. In addition, PGF doped with Fe3+ rapidly accelerates ex vivo healing in patient chronic wound skin (>30% in 48 h), demonstrating the utility of doped PGF as a potential therapeutic strategy to treat chronic wounds.

Shifts in keratin isoform expression activate motility signals during wound healing.

Keratin intermediate filaments confer structural stability to epithelial tissues, but the reason this simple mechanical function requires a protein family with 54 isoforms is not understood. During skin wound healing, a shift in keratin isoform expression alters the composition of keratin filaments. If and how this change modulates cellular functions that support epidermal remodeling remains unclear. We report an unexpected effect of keratin isoform variation on kinase signal transduction. Increased expression of wound-associated keratin 6A, but not of steady-state keratin 5, potentiated keratinocyte migration and wound closure without compromising mechanical stability by activating myosin motors to increase contractile force generation. These results substantially expand the functional repertoire of intermediate filaments from their canonical role as mechanical scaffolds to include roles as isoform-tuned signaling scaffolds that organize signal transduction cascades in space and time to influence epithelial cell state.

Bioengineered mesenchymal stem cell-derived exosomes: emerging strategies for diabetic wound healing.

Diabetic wounds are among the most common complications of diabetes mellitus and their healing process can be delayed due to persistent inflammatory reactions, bacterial infections, damaged vascularization and impaired cell proliferation, which casts a blight on patients'health and quality of life. Therefore, new strategies to accelerate diabetic wound healing are being positively explored. Exosomes derived from mesenchymal stem cells (MSC-Exos) can inherit the therapeutic and reparative abilities of stem cells and play a crucial role in diabetic wound healing. However, poor targeting, low concentrations of therapeutic molecules, easy removal from wounds and limited yield of MSC-Exos are challenging for clinical applications. Bioengineering techniques have recently gained attention for their ability to enhance the efficacy and yield of MSC-Exos. In this review, we summarise the role of MSC-Exos in diabetic wound healing and focus on three bioengineering strategies, namely, parental MSC-Exos engineering, direct MSC-Exos engineering and MSC-Exos combined with biomaterials. Furthermore, the application of bioengineered MSC-Exos in diabetic wound healing is reviewed. Finally, we discuss the future prospects of bioengineered MSC-Exos, providing new insights into the exploration of therapeutic strategies.

Early wound healing at 1 week postoperatively in periodontal tissue regeneration therapy: enamel matrix derivative versus recombinant human fibroblast growth factor.

PURPOSE: Recombinant human fibroblast growth factor-2 (rhFGF-2) has demonstrated positive effects on wound healing at 2 weeks after periodontal surgery relative to enamel matrix derivative (EMD). However, the effects at earlier postoperative stages have not been reported. This retrospective study compared the early wound healing outcomes 1 week after surgery using the modified papilla preservation technique (mPPT) with either EMD or rhFGF-2 therapy. METHODS: We compiled a list of all mPPT sites treated with EMD or rhFGF-2 during the survey period (September 2011 to March 2022). Early wound healing was assessed using the early wound healing score (EHS) and the modified early wound healing index (mEHI). Inter-rater reliability for the EHS and mEHI was established using intraclass correlation coefficients. Factors influencing mPPT were identified by analyzing the correlation coefficients between the EHS items, mEHI items, and potential influencing factors. After adjusting for factors impacting EHS, mEHI, and mPPT, we compared the EHS and mEHI between EMD and rhFGF-2 groups. RESULTS: In total, 72 sites were evaluated. The scores for incision line, step, and dehiscence were significantly higher in those receiving rhFGF-2 (n=42) compared to those treated with EMD (n=30). The EHS item scores did not differ significantly between groups. Among patients aged ≥50 years, but not those <50 years, significantly higher step and dehiscence scores were found in the rhFGF-2 group than the EMD group (P<0.01). Additionally, for patients exhibiting a clinical attachment level (CAL) ≥8 mm, the step score was significantly higher in the rhFGF-2 group than in the EMD group (P<0.05), but this trend was not reflected in those with a CAL <8 mm. CONCLUSIONS: In this study, early wound closure at mPPT sites was more effectively achieved with rhFGF-2 than with EMD. Nevertheless, biochemical assessments are required to compare the re-epithelialization effects of these therapies.

Eggshell membrane and green seaweed (Ulva lactuca) micronized powders for in vivo diabetic wound healing in albino rats: a comparative study.

BACKGROUND: Nonhealing diabetic wounds are a serious complication associated with extremely lethargic wound closure and a high risk of infection, leading to amputation or limb loss, as well as substantial health care costs and a poor quality of life for the patient. The effects of either eggshell membrane (ESM) and green seaweed (Ulva lactuca) extracts alone or in combination were evaluated for in vivo skin wound healing in a rat model of induced diabetes. METHODS: Micronized powders of waste hen ESM, Ulva lactuca, and their 1:1 mixture were prepared using regular procedures. The mechanical, electrical, and surface morphology characteristics of powders were examined using direct compression, LCR-impedancemetry, and scanning electron microscopy. The effect of ESM, Ulva lactuca, and their mixture as compared to standard Dermazin treatments were evaluated on wounds inflicted on male Wistar Albino rats with induced diabetes. Quantitative wound healing rates at baseline and at 3, 7, 14, and 21 days of treatments among all rat groups were conducted using ANOVA. Qualitative histological analysis of epidermal re-epithelization, keratinocytes, basement membrane, infiltrating lymphocytes, collagen fibrines, and blood vessels at day 21 were performed using Image J processing program. RESULTS: Compressive strength measurements of tablets showed a Young's modulus of 44.14 and 27.17 MPa for the ESM and ESM + Ulva lactuca mixture, respectively. Moreover, both samples exhibited relatively low relative permittivity values of 6.62 and 6.95 at 1 MHz, respectively, due to the porous surface morphology of ESM shown by scanning electron microscopy. On day 21, rats treated with ESM had a complete diabetic wound closure, hair regrowth, and a healing rate of 99.49%, compared to 96.79% for Dermazin, 87.05% for Ulva lactuca, 90.23% for the mixture, and only 36.44% for the negative controls. A well-formed basement membrane, well-differentiated epithelial cells, and regular thick keratinocytes lining the surface of the epidermal cells accompanied wound healing in rats treated with ESM, which was significantly better than in control rats. CONCLUSION: Ground hen ESM powder, a low-cost effective biomaterial, is better than Ulva lactuca or their mixture for preventing tissue damage and promoting diabetic wound healing, in addition to various biomedical applications.

The Therapeutic Potential of Human Umbilical Cord Mesenchymal Stromal Cells Derived Exosomes for Wound Healing: Harnessing Exosomes as a Cell-free Therapy.

Wound healing is a complicated process that involves many different types of cells and signaling pathways. Mesenchymal stromal cells (MSCs) have shown great potential as a treatment to improve wound healing because they can modulate inflammation, promote the growth of new blood vessels, and stimulate the regeneration of tissue. Recent evidence indicates MSCs-derived extracellular vesicles known as exosomes may mediate many of the therapeutic effects of MSCs on wound healing. Exosomes contain bioactive molecules such as proteins, lipids, and RNAs that can be transferred to recipient cells to modulate cellular responses. This article reviews current evidence on the mechanisms and therapeutic effects of human umbilical cord MSCs (hUCMSCs)-derived exosomes on wound healing. In vitro and animal studies demonstrate that hUCMSC-derived exosomes promote fibroblast proliferation/migration, angiogenesis, and re-epithelialization while reducing inflammation and scar formation. These effects are mediated by exosomal transfer of cytokines, growth factors, and regulatory microRNAs that modulate signaling pathways involved in wound healing. Challenges remain in exosome isolation methods, optimizing targeting/retention, and translation to human studies. Nevertheless, hUCMSCs-derived exosomes show promise as a novel cell-free therapeutic approach to accelerate wound closure and improve healing outcomes. Further research is warranted to fully characterize hUCMSCs-exosomal mechanisms and explore their clinical potential for wound management.

Exosomes derived from mouse vibrissa dermal papilla cells promote hair follicle regeneration during wound healing by activating Wnt/ß-catenin signaling pathway.

Hair follicle (HF) regeneration during wound healing continues to present a significant clinical challenge. Dermal papilla cell-derived exosomes (DPC-Exos) hold immense potential for inducing HF neogenesis. However, the accurate role and underlying mechanisms of DPC-Exos in HF regeneration in wound healing remain to be fully explained. This study, represents the first analysis into the effects of DPC-Exos on fibroblasts during wound healing. Our findings demonstrated that DPC-Exos could stimulate the proliferation and migration of fibroblasts, more importantly, enhance the hair-inducing capacity of fibroblasts. Fibroblasts treated with DPC-Exos were capable of inducing HF neogenesis in nude mice when combined with neonatal mice epidermal cells. In addition, DPC-Exos accelerated wound re-epithelialization and promoted HF regeneration during the healing process. Treatment with DPC-Exos led to increased expression levels of the Wnt pathway transcription factors ß-catenin and Lef1 in both fibroblasts and the dermis of skin wounds. Specifically, the application of a Wnt pathway inhibitor reduced the effects of DPC-Exos on fibroblasts and wound healing. Accordingly, these results offer evidence that DPC-Exos promote HF regeneration during wound healing by enhancing the hair-inducing capacity of fibroblasts and activating the Wnt/ß-catenin signaling pathway. This suggests that DPC-Exos may represent a promising therapeutic strategy for achieving regenerative wound healing.

Black Phosphorus Nanosheets-Based Hydrogel for Efficient Bacterial Inhibition and Accelerating Wound Healing.

With the swift evolution of multidrug-resistant bacteria resulting from the intense and inappropriate use of antibiotics, there is a pressing need for innovative solutions. In this study, a thermosensitive hydrogel was developed for efficient bacterial inhibition and promotion of wound healing. The antibacterial chitosan (CS) thermosensitive hydrogel, cross-linked with two-dimensional photothermal nanomaterial black phosphorus (BP) nanosheets through electrostatic interactions, effectively encapsulates and sustains the release of angiogenic drug deferoxamine mesylate (DFO). This facilitates the acceleration of re-epithelialization and neovascularization by enhancing cell migration and proliferation. Following near-infrared (NIR) treatment, this hydrogel demonstrates rapid eradication of the most common multidrug-resistant bacteria encountered in clinical settings, achieved through physical disruption of bacterial membranes and photothermal therapies. Noteworthy is the significant upregulation of IL-19 expression via STAT3 signaling pathways by the BP/CS-DFO hydrogel in a full-thickness wound model. This results in the polarization of the anti-inflammatory M2 macrophage phenotype, altering the microenvironment to a pro-healing state and enhancing extracellular matrix deposition and blood vessel formation. In conclusion, the BP/CS-DFO hydrogel shows immense promise as a potential clinical candidate for wound healing and antimicrobial therapy. Its innovative design and multifunctional capabilities position it as a valuable asset in combating antibiotic resistance and enhancing efficiency in wound healing.

Extracellular matrix-inspired biomaterials for wound healing.

Diabetic foot ulcers (DFU) are a debilitating and life-threatening complication of Diabetes Mellitus. Ulceration develops from a combination of associated diabetic complications, including neuropathy, circulatory dysfunction, and repetitive trauma, and they affect approximately 19-34% of patients as a result. The severity and chronic nature of diabetic foot ulcers stems from the disruption to normal wound healing, as a result of the molecular mechanisms which underly diabetic pathophysiology. The current standard-of-care is clinically insufficient to promote healing for many DFU patients, resulting in a high frequency of recurrence and limb amputations. Biomaterial dressings, and in particular those derived from the extracellular matrix (ECM), have emerged as a promising approach for the treatment of DFU. By providing a template for cell infiltration and skin regeneration, ECM-derived biomaterials offer great hope as a treatment for DFU. A range of approaches exist for the development of ECM-derived biomaterials, including the use of purified ECM components, decellularisation and processing of donor/ animal tissues, or the use of in vitro-deposited ECM. This review discusses the development and assessment of ECM-derived biomaterials for the treatment of chronic wounds, as well as the mechanisms of action through which ECM-derived biomaterials stimulate wound healing.

IGF-1 inhibits inflammation and accelerates angiogenesis via Ras/PI3K/IKK/NF-κB signaling pathways to promote wound healing.

Exogenous insulin-like growth factor-1 (IGF-1) has been reported to promote wound healing through regulation of vascular endothelial cells (VECs). Despite the existing studies of IGF-1 on VEC and its role in angiogenesis, the mechanisms regarding anti-inflammatory and angiogenetic effects of IGF-1 remain unclear. In this study, we investigated the wound-healing process and the related signaling pathway of IGF-1 using an inflammation model induced by IFN-γ. The results demonstrated that IGF-1 can increase cell proliferation, suppress inflammation in VECs, and promote angiogenesis. In vivo studies further confirmed that IGF-1 can reduce inflammation, enhance vascular regeneration, and improve re-epithelialization and collagen deposition in acute wounds. Importantly, the Ras/PI3K/IKK/NF-κB signaling pathways was identified as the mechanisms through which IGF-1 exerts its anti-inflammatory and pro-angiogenic effects. These findings contribute to the understanding of IGF-1's role in wound healing and may have implications for the development of new wound treatment approaches.

Transplantation of bioengineered dermal derived matrix-scaffold in combination with hyperbaric oxygen therapy improves wound healing in diabetic rats.

Successful treatment of diabetic wounds requires multifactorial approaches. Herein we investigated the effects of a bioengineered three-dimensional dermal derived matrix-scaffold (DMS) in combination with hyperbaric oxygen (HBO) in repairing of wound model in diabetic rats. Thirty days after induction of diabetes, a circular wound was created and treatments were performed for 21 days. Animals were randomly allocated into the untreated group, DMS group, HBO group, and DMS+HBO group. On days 7, 14, and 21, tissue samples were obtained for stereological, molecular, and tensiometrical assessments. Our results showed that the wound closure rate, volume of new dermis and epidermis, numerical density fibroblasts and blood vessels, collagen density, and biomechanical characterize were significantly higher in the treatment groups than in the untreated group, and these changes were more obvious in the DMS+HBO ones. Moreover, the expression of TGF-ß, bFGF, miRNA-21, miRNA-146a, and VEGF genes were meaningfully upregulated in treatment groups compared to the untreated group and were greater in the DMS+HBO group. This is while expression of TNF-α and IL-1ß, as well as the numerical density of neutrophil and macrophage decreased more considerably in the DMS+HBO group than in the other groups. Overall, using both DMS engraftment and HBO treatment has more effects on diabetic wound healing.

[Tongyangxiao Lotion promotes postoperative wound healing in a rat model of anal fistula by downregulating inflammatory factors and suppressing inflammation].

OBJECTIVE: To explore the mechanism of Tongyangxiao Lotion (TYX) for promoting wound healing following surgery for anal fistula. METHODS: The active ingredients and drug targets of TYX were explored using TCMSP and BATMAN databases, and the targets associated with wound healing were screened using GeneCards and OMIM databases; the intersecting drug and wound-related targets were analyzed with protein-protein interaction (PPI) analysis and GO and KEGG enrichment analyses. In 25 SD rat models with simulated anal fistula surgery, the effect of wound dressing with TYX at low, medium and high doses (once daily for 14 days) on wound healing were assessed in comparison with potassium permanganate (PP) solution. The granulation tissues collected from the wounds were examined for pathological changes with HE staining and for TNF-α expression using immunohistochemistry. The expressions of 1ß, TNF-α, IL-6 mRNA and proteins in the granulation tissue were detected using RT-qPCR, Western blotting or ELISA. RESULTS: Network pharmacology analysis yielded 156 common targets between TYX and wound healing, and among them IL-1ß, TNF- α, and IL-6 were identified as potential targets of TYX for promoting wound healing. Six core components of TYX were capable of binding to IL-1ß, TNF-α, and IL-6 with binding energies all below -6.0 Kcal/mol. In the rat models, the wounds with TYX and PP solution dressing showed significantly reduced inflammatory cell infiltration and increased fibroblasts and collagen deposition. TYX at the 3 doses and PP solution all significantly reduced the expressions of IL-6, IL-1ß, TNF-α mRNA and IL-6 protein in the granulation tissues, but TYX at the medium and high doses produced significantly stronger effects than PP solution for lowering TNF-α protein expression and mRNA expressions of TNF- α and IL-6. CONCLUSION: TYX accelerates wound healing by down-regulating the inflammatory factors and reducing inflammation in the wounds.

Collagen as the extracellular matrix biomaterials in the arena of medical sciences.

Collagen is a multipurpose material that has several applications in the health care, dental care, and pharmaceutical industries. Crosslinked compacted solids or lattice-like gels can be made from collagen. Biocompatibility, biodegradability, and wound-healing properties make collagen a popular scaffold material for cardiovascular, dentistry, and bone tissue engineering. Due to its essential role in the control of several of these processes, collagen has been employed as a wound-healing adjunct. It forms a major component of the extracellular matrix and regulates wound healing in its fibrillar or soluble forms. Collagen supports cardiovascular and other soft tissues. Oral wounds have been dressed with resorbable forms of collagen for closure of graft and extraction sites, and to aid healing. This present review is concentrated on the use of collagen in bone regeneration, wound healing, cardiovascular tissue engineering, and dentistry.

Development and characterization of contraction-suppressed full-thickness skin wound model in rabbits.

The wound healing process in rodents (rats and mice) and lagomorphs (rabbits) predominantly relies on wound contraction rather than re-epithelialization and granulation tissue formation. As a result, existing laboratory animal models for wound healing often fail to mimic human wound healing mechanisms accurately. This study introduces a standardized rabbit model with superior translational potential for skin wound healing research. Two full-thickness dermal wounds were created on the posterior dorsal surface of each rabbit using a standard 2 ×2 cm² template. One of these wounds was randomly selected to be treated as a contraction-suppressed wound by applying a transparent adhesive elastic bandage. At the same time, the other was retained as a standard full-thickness wound. Wound contraction was measured on 7, 14, 21, 28, and 35 days. Histomorphological evaluation was done on day 35 to evaluate the quality of wound healing. The findings indicate that transparent adhesive elastic bandage prolonged the wound healing time and suppressed wound contraction in rabbits. In addition, the healed contraction-suppressed full-thickness wounds had denser and thicker collagen fibers than the healed standard full-thickness wounds, indicating better collagen fiber deposition. Our model achieved a 100 % success rate in maintaining the transparent adhesive elastic bandage in the rabbits. Therefore, we have developed a simple, non-invasive, cost-effective method for preventing wound contraction. Further studies are required to establish the utility of this model for studying wound healing mechanisms and evaluating therapeutic interventions.

Berberine-doped montmorillonite nanosheet for photoenhanced antibacterial therapy and wound healing.

Bacterial infections pose a substantial threat to human health, particularly with the emergence of antibiotic-resistant strains. Therefore, it is essential to develop novel approaches for the efficient treatment of bacterial diseases. This study presents a therapeutic approach involving BBR@MMT nanosheets (NSs), wherein montmorillonite (MMT) was loaded with berberine (BBR) through an ion intercalation reaction to sterilize and promote wound healing. BBR@MMT exhibits nano-enzymatic-like catalytic activity, is easy to synthesize, and requires low reaction conditions. This nanocomplex showed photodynamic properties and superoxide dismutase (SOD) activity. The in vitro experiments indicated that BBR@MMT was able to effectively inhibit the growth of Gram-positive bacteria (S. aureus) and Gram-negative bacteria (E. coli) through the production of ROS when exposed to white light. Meanwhile, BBR@MMT inhibited the secretion of pro-inflammatory factors and scavenged free radicals via its SOD-like activity. In vivo results showed that BBR@MMT NSs were capable of effectively promoting the wound-healing process in infected mice under white light irradiation. Hence, it can be concluded that photodynamic therapy based on BBR@MMT NSs with nano-enzymatic activity has the potential to be used in treating infections and tissue repair associated with drug-resistant microorganisms.