Dermal Wound Research Articles

Development of Verapamil Hydrochloride-loaded Biopolymer-based Composite Electrospun Nanofibrous Mats: In vivo Evaluation of Enhanced Burn Wound Healing without Scar Formation.

Researchers aim for new heights in wound healing to produce wound dressings with unique features. Natural, synthetic, biodegradable, and biocompatible polymers especially in the nanoscale are being employed to support and provide efficient wound management. Economical and environmentally friendly sustainable wound management alternatives are becoming an urgent issue to meet future needs. Nanofibrous mats possess unique properties for ideal wound healing. They mimic the physical structure of the natural extracellular matrix (ECM), promote hemostasis, and gas permeation. Their interconnected nanoporosity prevents wound dehydration and microbial infiltration. To prepare and evaluate a novel verapamil HCl-loaded environmentally friendly composite, with biopolymer-based electrospun nanofibers suitable for application as wound dressings providing adequate wound healing with no scar formation. Composite nanofibers were prepared by electrospinning of a blend of the natural biocompatible polymers, sodium alginate (SA) or zein (Z) together with polyvinyl alcohol (PVA). Composite nanofibers were characterized in terms of morphology, diameter, drug entrapment efficiency, and release. In vivo study of the therapeutic efficacy of verapamil HCl-loaded nanofibers on a Sprague Dawley rat model with dermal burn wound was investigated in terms of percent wound closure, and presence of scars. Combining PVA with SA or Z improved the electrospinnability and properties of the developed nanofibers. Verapamil HCl-loaded composite nanofibers showed good pharmaceutical attributes favorable for wound healing including, fiber diameter ∼150 nm, high entrapment efficiency (∼80-100%) and biphasic controlled drug release for 24 h. In vivo study demonstrated promising potentials for wound healing without scaring. The developed nanofibrous mats combined the beneficial properties of the biopolymers and verapamil HCl to provide an increased functionality by exploiting the unique advantages of nanofibers in wound healing at a small dose proved to be insufficient in case of the conventional dosage form.

Shengji solution accelerates the wound angiogenesis of full-thickness skin defect in rats via activation of TGF-β1/Smad3-VEGF signaling pathway

ABSTRACT Shengji solution is made according to the classic prescription – Shengji prescription. Shengji solution is a external prescription of traditional Chinese medicine with the functions of nourishing blood, relieving pain, producing muscle and shrinking the wound. In the present study, we investigated the therapeutic effects of Shengji solution on dorsal full-thickness skin defects in rats. We also detected the activation of transforming growth factor beta1 (TGF-β1)/SMAD3/vascular endothelial growth factor (VEGF) signaling pathways in the wound-healing process. The results showed that the wound was cleaned with normal saline followed by bandaging with cotton gauze according to the groups, respectively: (a) control group; (b) Kangfuxin group, the wound was moistened with Kangfuxin solution; (c) Shengji solution group, the wounds were moistened with Shengji solution; (d) Shengji solution+SB431542 inhibitor group, the wound was moistened with Shengji solution, and then SB431542 inhibitor (10 mg/kg) was injected intraperitoneally for 5 days. On the 14th day after operation, the wound-healing rate of Shengji solution group was more than 95% and also greater than that in the control group and Shengji solution+SB431542 inhibitor group. Besides, Shengji solution could inhibit the inflammation and capillary production by enhancing the epithelial regeneration, dermal repair and angiogenesis. Moreover, Shengji solution could also increase CD34 content, the expressions of TGF-β1, VEGF proteins and the phosphorylation of SMAD3 in wound granulation tissue. In conclusion, Shengji solution can accelerate the dermal cutaneous wound healing in rats, stimulate angiogenesis and collagen synthesis by activating TGF-β1/SMAD3/VEGF pathway.

FGF signaling induces the regeneration of collagen fiber structure during skin wound healing in axolotls

Axolotls have been considered to be able to regenerate their skin completely. Our recent study updated this theory with the finding that the lattice structure of dermal collagen fibers was not fully regenerated after skin injury. We also discovered that nerves induce the regeneration of collagen fibers. The mechanism of collagen fiber regeneration remains unknown, however. In this study, we focused on the structure of collagen fibers with collagen braiding cells, and cell origin in axolotl skin regeneration. In the wounded dermis, cells involved in skin repair/regeneration were derived from both the surrounding dermis and the subcutaneous tissue. Regardless of cell origin, cells acquired the proper cell morphology to braid collagen fiber with nerve presence. We also found that FGF signaling could substitute for the nerve roles in the conversion of subcutaneous fibroblasts to lattice-shaped dermal fibroblasts. Our findings contribute to the elucidation of the fundamental mechanisms of true skin regeneration and provide useful insights for pioneering new skin treatments.

Gallic acid-modified bioglass with combined photothermal and antibacterial effects for the regeneration of infected diabetic wound

Diabetes-associated chronic wound management has been a serious worldwide issue, which is obstructed by multiple factors such as sustained inflammation, attenuated angiogenesis, and fragile defense against bacterial infection in the wound niche. Thus, there stands an urgent demand for biomaterial dressings that are able to treat such complex conditions. Herein, we developed a composite biomaterial of gallic acid-modified bioglass (GA@BG) in an anhydrous system, by using two agents which have already been used in clinical practice. The prepared GA@BG not merely promoted the migration and angiogenesis of vascular endothelial cells but also provided superior antibacterial performance in the local environment. Significantly, the gallic acid-assisted modification made the color of bioglass (BG) change from white to black, endowing it with high light absorption to successfully achieve a significant photothermal property. Then, the strengthened antibacterial effects were further realized by irradiation with near-infrared light (NIR) based on this photothermal property. Particularly, the combined therapy (GA@BG + NIR) was demonstrated as an effective strategy in treating the infected full-thickness dermal wounds of diabetic rats. This research provides a convenient non-antibiotic medicine formula for diabetic wounds with infection, and demonstrates a valid modification for inorganic bioglass-based material with organic polyphenol, which inspires more expansive composites for wound biomaterials.

Evaluation of collagen type I and III, TGF-β1, and VEGF gene expression in rat skin wound healing treated by alginate/chitosan hydrogel containing crocetin

Skin tissue engineering is one of the popular strategies are used to improve the wound healing process. In this study, different concentration of Crocetin (Crot) were loaded into a three-dimensional (3D) alginate (Alg) and chitosan (CS) hydrogel to improve wound healing process. After hydrogel preparation, it is characterized with different experiments such as morphology evolution, water absorption, cumulative release, weight loss, hemo- and cytocompatibility, cell viability, and antibacterial properties. Then, the therapeutic role of the prepared hydrogel was investigated in a full-thickness dermal wound in a rat model with analyzing RNA expression and histology. The results showed that fabricated hydrogels had sufficient porosity and the weight loss test verified the appropriate biodegradability of the prepared hydrogel (about 90% after 14 days) that can release enough of the Crot without any toxicity effect. In addition, the in vivo findings showed that the alginate/chitosan/crocetin 150 µM group had the highest wound closure percentage, re-epithelialization, and gene expression. Furthermore, rt-PCR revealed that 150 µM crocetin increased the expression of Collagen type I, III, VEGF, and TGF-β mRNA. Overall, this research indicates that 3D Alg/CS hydrogels containing 150 µM crocetin may be used in the clinic to treat skin injuries.

Introducing aesthetic regenerative scaffolds: An immunological perspective.

Skin aging arises from immunological responses to tissue deterioration and damage. Tissue repair processes encompass the regeneration of original tissue and 'scarless' wound healing seen in foetuses, and the extreme fibrotic responses and scarring seen in adults. Anti-aging aesthetic medicine uses interventions like biomaterial-based fillers to influence these immunological responses and renew aged tissue structure and function. At filler injection sites, an inflammatory response occurs that causes a spectrum of outcomes, ranging from tissue regeneration to fibrosis and filler encapsulation. Importantly, the resulting inflammatory pathway can be predetermined by the biomaterial injected. By understanding this immunological process, we can develop Aesthetic Regenerative Scaffolds (ARS) - aesthetic injectable biomaterials - to direct inflammatory wound healing away from chronic, fibrotic responses, and towards physiological tissue regeneration. We identified and reviewed literature on the immunological and cellular responses to injected dermal fillers, whereby the wound healing response to the injection was moderated under the influence of an injected biomaterial. We described the mechanisms of dermal wound healing and the use of ARS to direct healing towards tissue regeneration instead of scarring. We also summarised studies on extracellular matrix remodeling by calcium hydroxylapatite. We found that Calcium hydroxylapatite fillers produce collagen as they gradually degrade and their spherical structures serve as a scaffold for tissue regeneration. Furthermore, CaHA improved fibroblast contractility, collagen type III and elastin production, proliferation and angiogenesis with less inflammation than hyaluronic acid fillers. Regneration pathways can be influenced at specific points between a facial filler biomaterial and the wound healingmechanisms at its site of implantaion. Physicians can select scaffolds that direct the immune response away from a fibrotic chronic inflammatory pathway and towards regeneration to enable true repair of the aging skin.

Regeneration of the dermal skeleton and wound epidermis formation depend on BMP signaling in the caudal fin of platyfish.

Fin regeneration has been extensively studied in zebrafish, a genetic model organism. Little is known about regulators of this process in distant fish taxa, such as the Poeciliidae family, represented by the platyfish. Here, we used this species to investigate the plasticity of ray branching morphogenesis following either straight amputation or excision of ray triplets. This approach revealed that ray branching can be conditionally shifted to a more distal position, suggesting non-autonomous regulation of bone patterning. To gain molecular insights into regeneration of fin-specific dermal skeleton elements, actinotrichia and lepidotrichia, we localized expression of the actinodin genes and bmp2 in the regenerative outgrowth. Blocking of the BMP type-I receptor suppressed phospho-Smad1/5 immunoreactivity, and impaired fin regeneration after blastema formation. The resulting phenotype was characterized by the absence of bone and actinotrichia restoration. In addition, the wound epidermis displayed extensive thickening. This malformation was associated with expanded Tp63 expression from the basal epithelium towards more superficial layers, suggesting abnormal tissue differentiation. Our data add to the increasing evidence for the integrative role of BMP signaling in epidermal and skeletal tissue formation during fin regeneration. This expands our understanding of common mechanisms guiding appendage restoration in diverse clades of teleosts.

Beneficial Effects of a Blended Fibroin/Aloe Gel Extract Film on the Biomolecular Mechanism(s) via the MAPK/ERK Pathway Relating to Diabetic Wound Healing.

In diabetic patients, the process of wound healing is usually delayed or impaired. A diabetic environment could be associated with dermal fibroblast dysfunction, reduced angiogenesis, the release of excessive proinflammatory cytokines, and senescence features. Alternative therapeutic treatments using natural products are highly demanded for their high potential of bioactive activity in skin repair. Two natural extracts were combined to develop fibroin/aloe gel wound dressing. Our previous studies revealed that the prepared film enhances the healing rate of diabetic foot ulcers (DFUs). Moreover, we aimed to explore its biological effects and underlying biomolecular mechanisms on normal dermal, diabetic dermal, and diabetic wound fibroblasts. Cell culture experiments showed that the γ-irradiated blended fibroin/aloe gel extract film promotes skin wound healing by enhancing cell proliferation and migration, vascular epidermal growth factor (VEGF) secretion, and cell senescence prevention. Its action was mainly linked to the activation of the mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway known to regulate various cellular activities, including proliferation. Therefore, the findings of this study confirm and support our previous data. The blended fibroin/aloe gel extract film displays a biological behavior with favorable properties for delayed wound healing and can be considered as a promising therapeutic approach in the treatment of diabetic nonhealing ulcers.

Nile Tilapia Skin as Dermal Wound Healing Promoter in Cats

Background: In cats major skin injuries need aggressive veterinary assistance for safe and speedy healing. These days Nile tilapia fish skin is gaining hype as wound healing promoter biological dressing in medical field. Keeping in view the successful findings on tilapia skin in human medical practice the present study was designed to evaluate the efficacy of Nile Tilapia fish skin as dermal wound healing promoterin cats. Methods: The study was conducted on 10 clinical cases of cats received with different types of fresh dermal woundsat Department of Small Animal Clinical Sciences, University of Veterinary and Animal Sciences (UVAS), Lahore, Pakistan. Cats were divided into 2 groups i.e. A and B, 5 cats each group. Wounds in group A and B were treated with tilapia fish skin as a biological dressing and as open wounds, respectively. The parameter of study included wound size, physical characteristics of wounds and quality of wound healing and histo-pathological findings. Result: On the basis of findings of this study it was concluded that Nile Tilapia fish skin derived biological dressing promotes the fast, safe and infection free healing of the dermal wounds in cats as compared to open wound healing.

Wound healing properties of a new formulated flavonoid-rich fraction from Dodonaea viscosa Jacq. leaves extract.

Background: Dodonaea viscosa Jacq. (D. viscosa) belongs to the family of Sapindaceae, commonly known as "Sinatha," and is used as a traditional medicine for treating wounds due to its high flavonoids content. However, to date there is no experimental evidence on its flavonoid-rich fraction of D. viscosa formulation as an agent for healing wounds. Objective: The present study aimed to evaluate the wound healing effect of ethyl acetate fraction of D. viscosa leaves on dermal wounds. Methods: The ethyl acetate fraction was produced from a water-ethanol extract of D. viscosa leaves and was quantitatively evaluated using the HPLC technique. The in-vivo wound healing ability of the ethyl acetate fraction of D. viscosa ointment (DVFO, 2.5%w/w and 5%w/w) was investigated in Sprague-Dawley rats utilizing an incision and excision paradigm with povidone-iodine ointment (5% w/w) as a control. The percentage of wound closure, hydroxyproline and hexosamine concentrations, tensile strength and epithelialization duration were measured. Subsequently, histopathology analysis of skin samples as well as western blots were performed for collagen type 3 (COL3A1), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Results: The ethyl acetate fraction of D. viscosa revealed flavonoids with high concentrations of quercetin (6.46% w/w) and kaempferol (0.132% w/w). Compared to the control group, the DVFO (2.5% and 5.0% w/w) significantly accelerated wound healing in both models, as demonstrated by quicker wound contraction, epithelialization, elevated hydroxyproline levels and increased tensile strength. Histopathological investigations also revealed that DVFO treatment improved wound healing by re-epithelialization, collagen formation and vascularization of damaged skin samples. Western blot analysis further demonstrated an up-regulation of COL3A, vascular endothelial growth factor and bFGF protein in wound granulation tissue of the DVFO-treated group (p < 0.01). Conclusion: It is concluded that flavonoid-rich D. viscosa ethyl acetate fraction promotes wound healing by up-regulating the expressions of COL3A, VEGF and bFGF protein in wound granulation tissue. However, extensive clinical and pre-clinical research on the flavonoid-rich fraction of D. viscosa is needed to determine its significant impact in the healing of human wounds.

In vitro assessment of Neuronal PAS domain 2 mitigating compounds for scarless wound healing.

The core circadian gene Neuronal PAS domain 2 (NPAS2) is expressed in dermal fibroblasts and has been shown to play a critical role in regulating collagen synthesis during wound healing. We have performed high throughput drug screening to identify genes responsible for downregulation of Npas2 while maintaining cell viability. From this, five FDA-approved hit compounds were shown to suppress Npas2 expression in fibroblasts. In this study, we hypothesize that the therapeutic suppression of Npas2 by hit compounds will have two effects: (1) attenuated excessive collagen deposition and (2) accelerated dermal wound healing without hypertrophic scarring. To test the effects of each hit compound (named Dwn1, 2, 3, 4, and 5), primary adult human dermal fibroblasts (HDFa) were treated with either 0, 0.1, 1, or 10 μM of a single hit compound. HDFa behaviors were assessed by picrosirius red staining and quantitative RT-PCR for in vitro collagen synthesis, cell viability assay, in vitro fibroblast-to-myofibroblast differentiation test, and cell migration assays. Dwn1 and Dwn2 were found to significantly affect collagen synthesis and cell migration without any cytotoxicity. Dwn3, Dwn4, and Dwn5 did not affect collagen synthesis and were thereby eliminated from further consideration for their role in mitigation of gene expression or myofibroblast differentiation. Dwn1 also attenuated myofibroblast differentiation on HDFa. Dwn1 and Dwn2 may serve as possible therapeutic agents for future studies related to skin wound healing.

Depilatory double-disc mouse model for evaluation of vesicant dermal injury pharmacotherapy countermeasures.

Sulfur mustard (SM) is a chemical warfare vesicant that severely injures exposed eyes, lungs, and skin. Mechlorethamine hydrochloride (NM) is widely used as an SM surrogate. This study aimed to develop a depilatory double-disc (DDD) NM skin burn model for investigating vesicant pharmacotherapy countermeasures. Hair removal method (clipping only versus clipping followed by a depilatory), the effect of acetone in the vesicant administration vehicle, NM dose (0.5-20 μmol), vehicle volume (5-20 μl), and time course (0.5-21 days) were investigated using male and female CD-1 mice. Edema, an indicator of burn response, was assessed by biopsy skin weight. The ideal NM dose to induce partial-thickness burns was assessed by edema and histopathologic evaluation. The optimized DDD model was validated using an established reagent, NDH-4338, a cyclooxygenase, inducible nitric oxide synthase, and acetylcholinesterase inhibitor prodrug. Clipping/depilatory resulted in a 5-fold higher skin edematous response and was highly reproducible (18-fold lower %CV) compared to clipping alone. Acetone did not affect edema formation. Peak edema occurred 24-48 h after NM administration using optimized dosing methods and volume. Ideal partial-thickness burns were achieved with 5μmol of NM and responded to treatment with NDH-4338. No differences in burn edematous responses were observed between males and females. A highly reproducible and sensitive partial-thickness skin burn model was developed for assessing vesicant pharmacotherapy countermeasures. This model provides clinically relevant wound severity and eliminates the need for organic solvents that induce changes to the skin barrier function.

A novel injectable and self-biodegradable poly(aspartic acid) hydrogel

Severely chronic dermal wounds with irregular rupture shapes or even cavities are calling for injectable and self-biodegradable wound dressings for skin lesion with complex contours remain a great challenge. Here, we report an injectable, self-biodegradable poly(aspartic acid)-l-poly(aspartyl hydrazide) (PASP-l-PAHy) hydrogel to address these issues. The starting materials were cheap, and the new strategy for fabrication of self-biodegradable poly(aspartic acid) based hydrogel was facile, efficient, mild and environmentally friendly, which is consistent with the concept of green chemistry. The hydrogel possesses the comprehensive merits of injectability, self-biodegradability, shape-adaptability, transparence, biocompatibility, and adhesion, and shows specific autolytic biodegradation. The hydrogel was generated by in-situ gelation of poly(aspartic acid) (PASP) and poly(aspartyl hydrazide) (PAHy) polymers based on dual chemical (amide bond) and physical (hydrogen bond and ionic bond) crosslinks. The acceleration of wound healing could be observed in a rat skin full-thickness wound model for repairing skin tissue defects via hydrogel injection and autolytic biodegradation, highlighting great potential applications in wound dressing for the irregular dermal lesions without secondary skin damage. The injectable and self-biodegradable hydrogel augments formation of blood vessels and mature granulation tissue, thus enabling faster skin tissue restoration outcomes.

The highly absorbent polyurethane/polylactic acid blend electrospun tissue scaffold for dermal wound dressing

The highly absorbent polyurethane/polylactic acid blend electrospun tissue scaffold for dermal wound dressing

Endogenous Interleukin-10 Contributes to Wound Healing and Regulates Tissue Repair

IntroductionInterleukin-10 (IL-10) is essential in fetal regenerative wound healing and likewise promotes a regenerative phenotype in adult dermal wounds. However, the role of endogenous IL-10 in postnatal dermal wound healing is not well-established. We sought to determine the function of endogenous IL-10 in murine full thickness excisional wounds that are splinted to prevent contracture and mimic human patterns of wound closure. MethodsFull-thickness excisional wounds were made in wildtype (WT) and IL-10−/− mice on a C57BL/6J background (F/M, 8 wk old). In a subset of wounds, contraction was prevented by splinting with silicone stents (stenting) and maintaining a moist wound microenvironment using a semiocclusive dressing. Wounds were examined for re-epithelialization, granulation tissue deposition, and inflammatory cell infiltrate at day 7 and fibrosis and scarring at day 30 postwounding. ResultsWe observed no difference in wound healing rate between WT and IL-10−/− mice in either the stented or unstented group. At day 7, unstented IL-10−/− wounds had a larger granulation tissue area and more inflammatory infiltrate than their WT counterparts. However, we did observe more F4/80+ cell infiltrate in stented IL-10−/− wounds at day 7. At day 30, stented wounds had increased scar area and epithelial thickness compared to unstented wounds. ConclusionsThese data suggest that endogenous IL-10 expression does not alter closure of full thickness excisional wounds when wound hydration and excessive contraction of murine skin are controlled. However, the loss of IL-10 leads to increased inflammatory cell infiltration and scarring. These new findings suggest that IL-10 contributes to the regulation of inflammation without compromising the healing response. These data combined with previous reports of increased rates of healing in IL-10−/− mice wounds not controlled for hydration and contraction suggest an important role for murine wound healing models used in research studies of molecular mechanisms that regulate healing.

Antimicrobial Peptide Pt5‐1c Promotes Keratinocyte Migration and Proliferation via EGFR‐mediated Akt/MAPK/STAT3 pathways

AbstractKeratinocytes, as the most dominant cell type in the epidermis, play multiple roles in skin wound healing. Recently, we have shown that a short antimicrobial peptide Pt5‐1c can promote skin wound healing via enhancing fibroblast proliferation and migration in vitro, and accelerating re‐epithelialization of murine dermal wounds in vivo.[1] However, its effects on keratinocytes is unknown. Here we clearly showed that Pt5‐1c markedly enhanced keratinocyte migration and proliferation. Moreover, Pt5‐1c stimulated keratinocyte activation by inducing the phosphorylation of epidermal growth factor receptor (EGFR), Akt, extracellular signal‐regulated kinase (ERK), p38, and signal transducer and activator of transcription 3 (STAT3) in keratinocytes. Importantly, Pt5‐1c also increased collagen production, stimulated cell proliferation, and enhanced the phosphorylation of Akt, p38 and STAT3 in the wound skin tissues. These together indicate that Pt5‐1c can promote keratinocyte migration and proliferation via activation of EGFR‐mediated Akt, MAPK, and STAT3 pathways, thereby contributing to skin wound healing.

Radiofrequency Microneedling: Technology, Devices, and Indications in the Modern Plastic Surgery Practice.

Since the initial invention of microneedling, advancements have been made to improve the desired effects. The addition of radiofrequency to microneedling devices was developed within the past decade as a way to induce thermal injury and increase dermal heating to enhance the dermal wound healing cascade. With an overabundance of literature and mainstream media focused on microneedling and radiofrequency microneedling, this review aims to focus on the available high-quality evidence. A comprehensive review of the literature was performed across PubMed (National Institutes of Health, Bethesda, MD) and Embase (Elsevier, Amsterdam, the Netherlands) databases. Attention was focused on manuscripts that provided objective data with respect to clinical application, innovation, anatomy, and physiology. Optimal outcomes are achieved when needle depth is targeted to the reticular dermis. Needle depth should reflect the relative differences in epidermal and dermal thickness throughout the face. A depth of at least 1.5 mm should be used for the forehead and temporal skin, 1.0 mm for the malar region, 2.0 mm (maximum depth for radiofrequency microneedling) for the nasal side walls, 0.5 mm for the perioral skin, and 1.5 mm for the neck. Deeper settings can be used with care to provide some fat reduction in the submentum. The authors find herein that radiofrequency microneedling is a safe adjunctive tool to surgical aesthetic procedures. The addition of radiofrequency poses an advance over traditional microneedling devices for skin tightening, with improvements in both safety and efficacy over time.

Comparison of Leukocyte-Rich and Leukocyte-Poor Platelet-Rich Plasma on Pressure Ulcer in a Rat Model.

Pressure ulcer (PU) is a common type of chronic wound that is difficult to treat. Platelet-rich plasma (PRP) is rich in cytokines and growth factors, and it can be divided into two categories according to its leukocyte content: leukocyte-poor PRP (P-PRP) and leukocyte-rich PRP (L-PRP). PRP has been applied in a variety of wound treatments, due to its strong ability to promote repair. This study aims to investigate the therapeutic effects of PRP on PU and elucidate the role of leukocytes in the treatment process. Sprague-Dawley rats were used to establish PU models of ischemia-reperfusion injury by applying magnets externally. L-PRP, P-PRP, and saline were injected into the dermal wounds. Wound healing analysis and sampling were performed on days 3, 7, 11, and 15 after treatment. Histological examinations, real-time PCR, immunohistochemical examinations, and biomechanical assay were carried out on the wound samples. The PRP groups exhibited greater wound inflammatory response than the control group in the early stage but the response reduced rapidly as the wound healed. On days 7, 11, and 15, the PRP groups also yielded better wound healing rates and histological outcomes than the control group, with superior biomechanical properties observed on day 15. Among both PRP groups, the L-PRP group attained a higher wound healing rate than the P-PRP group on day 7, with greater significant early inflammatory responses, and more prominent angiogenesis. Therefore, PRP is proven to accelerate the healing of PU, with L-PRP being more effective in regulating inflammation and promoting angiogenesis than P-PRP.

Expression of concern: Ameliorative effect of biofabricated ZnO nanoparticles of Trianthema portulacastrum Linn. on dermal wounds via removal of oxidative stress and inflammation.

Expression of concern for 'Ameliorative effect of biofabricated ZnO nanoparticles of Trianthema portulacastrum Linn. on dermal wounds via removal of oxidative stress and inflammation' by Ekta Yadav et al., RSC Adv., 2018, 8, 21621-21635, https://doi.org/10.1039/C8RA03500H.

An antibacterial and healing-promoting collagen fibril constructed by the simultaneous strategy of fibril reconstitution and ε-polylysine anchoring for infected wound repair.

The development of antibacterial dressings has attracted much attention to address the disordered wound healing caused by bacterial infection. Constructing dressings that have desirable antibacterial activity and could promote wound healing is important for infected wound repair. Inspired by the role of the key regulator collagen fibrils with D-periodic functional domains in the physiological wound healing process, we developed an antibacterial and wound healing-promoting collagen fibril with a structure highly similar to natural collagen in ECM and inherent antibacterial activity by the simultaneous strategy of fibril reconstitution and the antibacterial agent ε-polylysine (ε-PL) anchoring. Accompanied by the fibrillogenesis of collagen molecules, the anchorage of ε-PL into collagen fibrils was actualized through the formation of the covalent bond catalyzed by transglutaminase (TGase) between ε-PL and collagen. The collagen fibril possessed natural D-periodicity and achieved 20% ε-PL graft yield by co-assembling collagen/ε-PL mediated by 25 U g-1 TGase, which showed a satisfactory proliferation of L929 fibroblasts and sustained inhibition rates above 90% against E. coli and S. aureus. The rat S. aureus-infected dermal wound model further demonstrated that the reconstituted antibacterial collagen fibril visibly promoted re-epithelialization, new collagen deposition, and angiogenesis by down-regulating the inflammatory-relative gene IL-6 and up-regulating the relative activity factor expression of CD31, achieving accelerated infected wound healing with 61.89% ± 3.96% wound closure on postoperative day 7 and full closure on day 14.