Skin Wound Research Articles

Histological and Molecular Biological Changes in Canine Skin Following Acute Radiation Therapy-Induced Skin Injury.

Radiation therapy is a crucial cancer treatment, but it can damage healthy tissues, leading to side effects like skin injuries and molecular alterations. This study aimed to elucidate histological and molecular changes in canine skin post-radiation therapy (post-RT) over nine weeks, focusing on inflammation, stem cell activity, angiogenesis, keratinocyte regeneration, and apoptosis. Four male beagles received a cumulative radiation dose of 48 Gy, followed by clinical observations, histological examinations, and an RT-qPCR analysis of skin biopsies. Histological changes correlated with clinical recovery from inflammation. A post-RT analysis revealed a notable decrease in the mRNA levels of Oct4, Sox2, and Nanog from weeks 1 to 9. VEGF 188 levels initially saw a slight increase at week 1, but they had significantly declined by week 9. Both mRNA and protein levels of COX-2 and Keratin 10 significantly decreased over the 9 weeks following RT, although COX-2 expression surged in the first 2 weeks, and Keratin 10 levels increased at weeks 4 to 5 compared to normal skin. Apoptosis peaked at 2 weeks and diminished, nearing normal by 9 weeks. These findings offer insights into the mechanisms of radiation-induced skin injury and provide guidance for managing side effects in canine radiation therapy.

Multifunctional emulsion for potential wound-healing applications: A development for co-administration of essential vitamins, silver nanoparticles, and potent active ingredients

This research explores the formulation of novel oil-in-water emulsion designed for the co-delivery of compounds with different properties that jointly represent an exceptional system to apply in skin regeneration, such as essential vitamins A and E, silver nanoparticles, silver sulfadiazine, and lidocaine. First, the preparation method of emulsions was optimized, characterizing their stability over storage time. Emulsions, which were prepared with certain stirring speed and time, presented the lower droplet size and the higher stability for 28 days. Second, the active ingredients were incorporated into the optimized emulsion, and their stability and antimicrobial capacity were evaluated. In addition to being a stable colloidal system, the emulsion with active ingredients demonstrated antimicrobial effects against Pseudomonas aeruginosa and Staphylococcus aureus (both usually present in skin wounds). The antimicrobial properties of silver nanoparticles and the healing-promoting characteristics of vitamins make this combination promising for applications in pharmaceutical and cosmetic formulations. Utilizing natural oils and biocompatible components aligns with sustainable and health-conscious product development trends. The findings of this study hold implications for diverse applications in medicine and cosmetics.

Improving Water Solubility and Skin Penetration of Ursolic Acid through a Nanofiber Process to Achieve Better In Vitro Anti-Breast Cancer Activity.

Woman's breast cancer has always been among the top ten causes of cancer death, and nearly 2% to 5% of locally advanced breast cancers develop a fungating breast wound. Fungal breast cancer leads to skin ulcers, wound ruptures, and other bacterial infections in patients. Ursolic acid (UA), a natural pentacyclic triterpene compound, is widely distributed in many fruits. Previous studies demonstrated that UA has anti-breast cancer, antifungal, and improved wound-healing effects. UA, however, had poor water solubility and low bioavailability, restricting its clinical application. Nanofibers have the advantages of rapid dissolution, improved stability, and bioavailability of active ingredients. We had successfully prepared ursolic acid nanofibers (UANFs) and effectively improved their water solubility and skin penetration. UANFs can increase water solubility by improving the physicochemical properties, including increased surface area, intermolecular bonding with excipients, and amorphous transformation. Furthermore, UANFs had better anti-breast cancer activity than raw UA. UANFs inhibited the expression of phospho-signal transducer and activator of transcription 3 (STAT3) and phospho-extracellular regulated protein kinases (ERK)1/2, and induced cleaved caspase-3 protein expression, but had no effect on the raw UA treatment. In summary, UANFs enhanced the skin absorption of UA and improved its anti-breast cancer efficacy. We expect that UANFs can be used as an anti-breast cancer treatment and reduce the discomfort of breast cancer patients during dressing changes, but more detailed efficacy and safety trials still need to be conducted in further studies.

Self-healing hydrogel from poly(aspartic acid) and dextran with antibacterial property for burn wound healing

Designing hydrogel dressing with intrinsic antibacterial property to promote skin injury recovery remains a significant challenge. In this research, poly(aspartic hydrazide) with grafted betaine (PAHB) was designed and reacted with oxidized dextran (OD) to fabricate biodegradable PAHB/OD hydrogel and its application as wound dressing was systematically investigated. The PAHB/OD hydrogels exhibited fast gelation, strong tissue adhesion, preferable mechanical properties and biocompatibility. The grafted betaine endowed the hydrogel with antibacterial property and antibacterial rate enhanced through photothermal performance of composited CuS nanoparticles under near infrared (NIR) radiation. The CuS composited PAHB/OD hydrogel (CuS/hydrogel) with microporous morphology was used as burn wound dressing with loaded anti-inflammatory drug diclofenac sodium (DS) in mouse model. The results showed the DS loaded CuS/hydrogel (CuS@DS/hydrogel) promoted the tissue regeneration and suppressed the inflammatory response. The histological analysis and immunohistochemical expression confirmed the CuS@DS/hydrogel promote angiogenesis of the burn wound by regulating the expression of inflammatory cytokines (IL-6 and CD68) and vascular endothelial growth factor (VEGF). Overall, the CuS@DS/hydrogel hydrogel is a promising candidate as wound dressing due to its tissue adhesive, antioxidant, antibacterial and anti-inflammatory activities.

Platelet-Rich Plasma (PRP) Based on Simple and Efficient Integrated Preparation Precises Quantitatively for Skin Wound Repair.

Platelet-rich plasma (PRP) has become an important regenerative therapy. However, the preparation method of PRP has not been standardized, and the optimal platelet concentration for PRP used in skin wound repair is unclear, leading to inconsistent clinical efficacy of PRP. Therefore, the development of standardized preparation methods for PRP and the investigation of the dose-response relationship between PRP with different platelet concentrations and tissue regeneration plays an important role in the development and clinical application of PRP technology. This study has developed an integrated blood collection device from blood drawing to centrifugation. Response surface methodology was employed to optimize the preparation conditions, ultimately achieving a platelet recovery rate as high as 95.74% for PRP (with optimal parameters: centrifugation force 1730× g, centrifugation time 10 min, and serum separation gel dosage 1.4 g). Both in vitro and in vivo experimental results indicate that PRP with a (2×) enrichment ratio is the most effective in promoting fibroblast proliferation and skin wound healing, with a cell proliferation rate of over 150% and a wound healing rate of 78% on day 7.

Effect of 3-hydrazinylquinoxaline-2-thiol hydrogel on skin wound healing process in diabetic rats

Impaired wound healing in diabetic individuals creates huge social and financial burdens for both diabetic patients and the health system. Unfortunately, the current treatment has not resulted in consistently lower amputation rates. Quinoxalines are heterocyclic compounds with multiple important pharmacological properties. Their effect on wound healing have not been closely studied. In the current work, the wound healing effect of 3-hydrazinylquinoxaline-2-thiol hydrogel is tested topically in a full-thickness excision wound in streptozotocin-induced type 1 diabetic rats. We examined the wound closure rate, expression of inflammatory factors, growth factors in addition to the histological analysis. The results revealed a significant acceleration in wound closure in the treated group compared with the control experimental animals. Histological data demonstrated enhanced re-epithelialization and collagen disposition. The healing effect was additionally evaluated by the inhibition of the inflammatory response of interleukin (IL)—1β interleukin (IL)—6, tumor necrosis factor (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) with a marked improvement of the transforming growth factor beta (TGFβ-1), antioxidant markers and collagen-1. In silico study indicated a favorable drug-like properties and toxicity profile. The present work showed that 3-hydrazinylquinoxaline-2-thiol holds great potential for the treatment of diabetic wounds.

Dissolvable microneedle-based wound dressing transdermally and continuously delivers anti-inflammatory and pro-angiogenic exosomes for diabetic wound treatment

Due to overactive inflammation and hindered angiogenesis, self-healing of diabetic wounds (DW) remains challenging in the clinic. Platelet-derived exosomes (PLT-Exos), a novel exosome capable of anti-inflammation and pro-angiogenesis, show great potential in DW treatment. However, previous administration of exosomes into skin wounds is topical daub or intradermal injection, which cannot intradermally deliver PLT-Exos into the dermis layer, thus impeding its long-term efficacy in anti-inflammation and pro-angiogenesis. Herein, a dissolvable microneedle-based wound dressing (PLT-Exos@ADMMA-MN) was developed for transdermal and long-term delivery of PLT-Exos. Firstly, a photo-crosslinking methacrylated acellular dermal matrix-based hydrogel (ADMMA-GEL), showing physiochemical tailorability, fast-gelling performance, excellent biocompatibility, and pro-angiogenic capacities, was synthesized as a base material of our dressing. For endowing the dressing with anti-inflammation and pro-angiogenesis, PLT-Exos were encapsulated into ADMMA-GEL with a minimum effective concentration determined by our in-vitro experiments. Then, in-vitro results show that this dressing exhibits excellent properties in anti-inflammation and pro-angiogenesis. Lastly, in-vivo experiments showed that this dressing could continuously and transdermally deliver PLT-Exos into skin wounds to switch local macrophage into M2 phenotype while stimulating neovascularization, thus proving a low-inflammatory and pro-angiogenic microenvironment for DW healing. Collectively, this study provides a novel wound dressing capable of suppressing inflammation and stimulating vascularization for DW treatment.

A PLGA/Silk Fibroin Nanofibre Membrane Loaded with Natural Flavonoid Compounds Extracted from Green Cocoons for Wound Healing.

The use of biodegradable materials combined with natural metabolites in wound dressings has received much attention. Flavonoids (FLs) from green cocoons, as metabolites, have antibacterial, antioxidant, anti-inflammatory, and other pharmacological effects. In this study, composite membranes of FL-loaded polylactic glycolic acid (PLGA)/silk fibroin (SF) were prepared by an electrospinning method. The prepared membranes, including SF, exhibited a good slow-release effect and cytocompatibility. An in vitro evaluation of the FL-loaded PLGA/SF membranes demonstrated good antioxidant, antibacterial, and anti-inflammatory properties. Animal experiments showed that the wound healing rate of PLGA/SF-2.5FL membranes within 15 days was 97.3%, and that of the control group was 72.5%. The PLGA/SF-2.5FL membranes shortened the inflammatory period of a full-layer wound model and promoted skin regeneration and wound healing by downregulating expression of the pro-inflammatory cytokines IL-1β and TNF-α and promoting expression of the growth factors VEGF, TGF-β, and EGF. In summary, the PLGA/SF-2.5FL composite nanofibre membrane with anti-inflammatory properties is an ideal wound dressing to promote acute wound healing.

Management and outcome of cutaneous diphtheria in adolescent refugees in Germany, June 2022 - October 2023.

From September 2022 an increase in Corynebacterium diphtheriae (C. diphtheriae)infections was reported in Europe. Our study focuses on 31 adolescent and young adult refugees with cutaneous C. diphtheriae infections detected in Germany. We examined treatment regimens and outcomes to provide targeted insights into the management of this infection. We distributed a standardized survey, focused on children and adolescents presenting to paediatric clinics through the German Paediatric Infectious Diseases Society (DGPI) and additional professional contacts in Germany. Data were extracted from routine medical documentation and reported anonymously. A total of 31 individuals with cutaneous C. diphtheriae infection were reported by 9 centres. Two of these showed diphtheria toxin (DT) related systemic symptoms and four exhibited systemic inflammation requiring complex management. The remaining 25 cases, with exclusively cutaneous manifestations, were afebrile. Treatment with topical antiseptics and systemic antibiotics, mainly aminopenicillin/beta-lactamase inhibitors (BLI) (35%) or clindamycin (25%), achieved eradication in all but two cases treated with aminopenicillin/BLI. Treatment duration varied between 5 and 17 days. In refugees presenting with chronic skin wounds, C. diphtheriae should be included into the differential diagnosis. Fever seems to be a valuable marker to differentiate severe cases with potentially DT-mediated sequelae from exclusively cutaneous diphtheria (CD). For afebrile CD, topical antiseptics and oral antibiotic therapy with clindamycin for 7 days, followed by clinical surveillance appears to be a safe treatment regimen. Patients with CD who present with fever or pharyngitis should be thoroughly investigated including blood and pharyngeal swab cultures.

Critical role of keratinocytes in cutaneous immune responses

Keratinocytes play an integral role in the human epidermis, serving as a barrier between the internal and external environment. They are immune-competent cells involved in both innate and adaptive cutaneous immune responses, crucial for maintaining skin integrity. Keratinocytes are essential for epidermal repair, facilitating proliferation and re-epithelialization following injury. They secrete pro-inflammatory markers such as cytokines and chemokines, which promote the recruitment of inflammatory cells like polymorphs and macrophages to the site of skin injury. The immune response mediated by keratinocytes involves signaling molecules like tumor necrosis factor (TNF), interleukin (IL)-1β, and IL-6. Langerhans cells respond to factors secreted by keratinocytes, migrating towards draining lymph nodes to activate T cells and initiate an adaptive immune response. Additionally, keratinocytes express Toll-like receptors (TLRs), enabling them to detect molecular patterns of pathogens. Recent studies have focused on understanding these interactions of keratinocytes to develop therapeutic strategies for managing various skin diseases. Genetic defects in keratinocytes underlie conditions like psoriasis. We also discuss the role of keratinocytes and the effect of neuro-endocrinal signaling and interventions, associated corticosteroidogenic pathways, and response to UV radiations to maintain a state of homeostasis. This article underlines and improves our understanding of the immune function of keratinocytes, which is crucial for developing more effective therapies against skin diseases.

Copper doped carbon dots modified bacterial cellulose with enhanced antibacterial and immune regulatory functions for accelerating wound healing

The microenvironment of wound healing is susceptible to bacterial infection, chronic inflammation, oxidative stress, and inadequate angiogenesis, requiring the development of innovative wound dressings with antibacterial, anti-inflammatory, antioxidant, and angiogenic capabilities. This research crafted a new multifunctional bacterial cellulose composite membrane infused with copper-doped carbon dots (BC/Cu(II)-RCDs). Findings validated the successful loading of copper-doped carbon dots onto the BC membrane via hydrogen bonding interactions. Compared to the pure BC membrane, the BC/Cu(II)-RCDs composite membrane exhibited significantly enhanced hydrophilicity, tensile properties, and thermal stability. Diverse in vitro assays demonstrated excellent biocompatibility and antibacterial activity of BC/Cu(II)-RCDs composite membranes, alongside their ability to expedite the inflammatory phase and stimulate angiogenesis. In vivo trials corroborated the membrane's ability to foster epithelial regeneration, collagen deposition, and tissue regrowth in full-thickness skin wounds in rats while also curbing inflammation in infected full-thickness skin wounds. More importantly, the treatment of the BC/Cu(II)-RCDs composite membrane may result in the activation of VEGF and MAPK signaling proteins, which are key players in cell migration, angiogenesis, and skin tissue development. In essence, the developed BC/Cu(II)-RCDs composite membrane shows promise for treating infected wounds and serves as a viable alternative material for medicinal bandages.

Metformin as a Modulator of Autophagy and Hypoxia Responses in the Enhancement of Wound Healing in Diabetic Rats.

The molecular mechanisms underlying delayed wound repair in diabetes involve dysregulation of key cellular processes, including autophagy and hypoxia response pathways. Herein, we investigated the role of topical metformin, an established anti-diabetic drug with potential autophagy-inducing properties, in improving wound healing outcomes under hypoxic conditions. Full-thickness skin wounds were created in streptozotocin-induced diabetic rats, and tissue samples were collected at regular intervals for molecular and histological analysis. The expression levels of autophagy markers LC3B and Beclin-1 were evaluated via immunohistochemistry and qRT-PCR, while the amount of AMP-activated protein kinase (AMPK) and hypoxia-inducible factor-1α (HIF-1α) were determined via ELISA. Our results demonstrated that metformin administration resulted in the upregulation of LC3B and Beclin-1 in the wound bed, suggesting induction of autophagy in response to the treatment. Mechanistically, metformin treatment also led to the increased amount of AMPK, a critical regulator of cellular energy homeostasis, and a subsequent reduction in HIF-1α amount under hypoxic conditions. In conclusion, our findings demonstrate that metformin promotes wound healing in diabetes mellitus by enhancing autophagy through AMPK activation and modulating HIF-1α amount in a hypoxic microenvironment. This study offers a new therapeutic approach by shedding light on the potential benefits of metformin as adjunctive therapy in diabetic wound management.

Global hotspots and research trends of radiation-induced skin injury: a bibliometric analysis from 2004 to 2023.

Radiation therapy has become an important treatment for many malignant tumours after surgery and for palliative tumour care. Although modern radiotherapy technology is constantly improving, radiation damage to normal tissues is often difficult to avoid, and radiation-induced skin injury (RSI) is a common complication, manifested as skin erythema, peeling, ulceration, and even bone and deep organ damage, seriously affect the quality of life for patients. Basic research and clinical trials related to RSI have achieved certain results, while no researchers have conducted comprehensive bibliometric studies. A comprehensive bibliometric analysis of publications on RSI published between 2004 and 2023 was conducted to identify current hotspots and future directions in this area of study. RSI-related publications published between January 1, 2004, and December 31, 2023, were retrieved from the Web of Science Core Collection (WoSCC) database for analysis using VOSviewer and CiteSpace analytics. A total of 1009 publications on RSI from 2004 to 2023 were included in the WoSCC database. The United States had the highest productivity with 299 papers, accounting for 29.63% of the total production, followed by China with 193 papers (19.13%) and Japan with 111 papers (11.00%). In terms of research institutions and journals, the University of Toronto and Journal of Supportive Care in Cancer published the highest number of papers. Professor Edward Chow published the most articles, while Professor Shuyu Zhang was the most cited. The top ten most-cited papers focused on the pathogenesis, prevention, and management of RSI. Keyword co-occurrence analysis and the top 25 keywords with the strongest citation bursts suggest that current research focuses on the pathogenesis, prevention, and treatment management of RSI. This study conducted a systematic bibliometric analysis of RSI publications from 2004 to 2023; identified the trends in RSI publications, major research countries, major research institutions, major research journals, major research authors, and major research keywords; and revealed the future development direction and research hotspots of this field. This study provides a valuable reference for future RSI research.

DISTANT SOFT TISSUE FLAPS IN A DEGLOVING SKIN INJURY

Avulsion skin injuries of the glove removal type are one of the most challenging and difficult problems in reconstructive hand surgery. Immediate or early coverage of the hand is of utmost importance. Several options are proposed for early covering the preserved structures (tendons, bones and nerves) early, mainly skin grafting on the preserved viable structures. Case description: We present a case of a patient with 4th and 5th finger crushing and avulsion skin injury of thumb and index finger and lost distal phalanges. The 4th and 5th fingers had been amputated due to gangrene. Two anterior abdominal wall flaps were applied: a thoraco-umbilical flap and a horizontal Filatov stem" flap. On the 25th day, the flaps were separated from the fingers and following commissuroplasty 10 months later. Result: Fusion between the donor flap and the recipient structures was obtained without clinical evidence of infection, ulceration and flap necrosis. Conclusions: The usage of remote skin flaps is a safe and simple method to restore hand function when microsurgery cannot be applied.

Fabrication of Mupirocin-Loaded PEGylated Chitosan Nanoparticulate Films for Enhanced Wound Healing.

Chitosan-based biomaterials are being investigated for their unique properties that support skin regeneration and wound healing. This study focused on the preparation and characterization of a mupirocin (Mup)-loaded PEGylated chitosan (CS-PEG) nanoparticulate film (NF) [CBNF]. The CBNF was characterized using FTIR spectroscopy and SEM analysis. The results demonstrated that CBNF was successfully incorporated into the composites, as shown by functional group modification through FTIR analysis. Additionally, the SEM micrograph revealed the deposition of nanoparticles (<200 nm) on the surface of transparent CBNF. The film has higher water absorption (≥1700%) and moderate water retention ability within 6 h. Furthermore, histological findings showed significant development, with re-epithelialization and granulation of tissues after 19 days, indicating the healing efficiency of CNBF. These results suggest that drug-loaded films could be an effective carrier and delivery agent for Mup-like anti-inflammatory drugs.

Bacterial cellulose with CHAPK-mediated specific antimicrobial activity against Staphylococcus aureus

Wound healing represents a complex biological process often hampered by bacterial infections, in particular those caused by Staphylococcus aureus, which is already multiresistant to many antibiotics. In this sense, enzybiotics have additional advantages over conventional antibiotics, since they provide pathogen specificity and do not contribute to antibiotic resistance. However, their soluble administration at the wound site would result in enzyme leakage. On the other hand, bacterial cellulose (BC) pellicles present a very promising dressing and scaffold, given its high purity, water retention capacity, and barrier effect in the wound against possible contaminants. In this study, we present a novel approach that incorporates the enzybiotic CHAPK into BC to develop functionalized membranes that exhibit targeted and controlled antimicrobial activity against S. aureus. The kinetic tests revealed a continuous loading of the enzybiotic into BC until it reaches a maximum and a two-stage release process, characterized by an initial fast release followed by a sustained release. Attenuated total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR), Scanning Electron Microscopy (SEM), and Confocal Laser Scanning Microscopy (CLSM) confirmed the incorporation and the preferential surface localization of CHAPK within the BC membranes. Finally, the BC/CHAPK materials demonstrated the sustained reduction of up to 4 logarithmic units in the viability of S. aureus. Overall, the biomaterials developed here exhibit promising antimicrobial efficacy against S. aureus, offering a potential strategy for wound management and skin infection control while maintaining unharmed the commensal skin microbiota, which impairment could compromise the integrity of the skin barrier function.

Mast cell-derived BH4 and serotonin are critical mediators of postoperative pain.

Postoperative pain affects most patients after major surgery and can transition to chronic pain. The considerable side effects and limited efficacy of current treatments underline the need for new therapeutic options. We observed increased amounts of the metabolites BH4 and serotonin after skin injury. Mast cells were primary postoperative sources of Gch1, the rate-limiting enzyme in BH4 synthesis, itself an obligate cofactor in serotonin production by tryptophan hydroxylase (Tph1). Mice deficient in mast cells or in mast cell-specific Gch1 or Tph1 showed drastically decreased postoperative pain. We found that injury induced the nociceptive neuropeptide substance P, mast cell degranulation, and granule nerve colocalization. Substance P triggered serotonin release in mouse and human mast cells, and substance P receptor blockade substantially ameliorated pain hypersensitivity. Our findings highlight the importance of mast cells at the neuroimmune interface and substance P-driven mast cell BH4 and serotonin production as a therapeutic target for postoperative pain treatment.

Topical Probiotic Hydrogels for Burn Wound Healing.

Hydrogels have increasingly been used to enhance the effective healing of various wounds, including burn wounds. Similarly, the application of probiotics has recently been explored in wound healing and skin repairs. While probiotics have been consumed to provide therapeutic effects that aid with improving gut health, topical applications have been found to accelerate wound healing both in vitro and in vivo. For wounds that have complex healing mechanisms, such as burn wounds which depend on factors such as the depth of the burn, size of the afflicted area, and cause of the injury, probiotics with or without conventional therapeutic agents topically delivered via hydrogel technology are proven to be effective in the recovery of the damaged skin. This article aims to investigate the microorganisms present in the human skin microbiome and observe the effects of probiotics delivered by hydrogels on burn wound healing.

Hydrogel for slow-release drug delivery in wound treatment

Abstract When skin comes into direct contact with the outside environment, it becomes extremely prone to injury and external factors can make wounds difficult to heal. Traditional medical dressings often cause secondary injury and are poorly resistant to infection. Hydrogels offer a promising alternative to overcome these difficulties. In this study, chitosan (CS)/gelatin (GEL)/polyvinyl alcohol (PVA) hydrogels were developed by chemical cross-linking and loaded with the drug kitasamycin (KM) for testing. The hydrogels’ in vitro drug release and wound-healing properties were assessed. For 48 h, the drug release from the hydrogel in vitro persisted, which was significantly longer than the release time of the KM solution. Antimicrobial activity tests showed that the loaded KM hydrogel maintained its bacteriostatic ability at the same concentration as the KM solution, and during in vitro bacteriostatic inhibition, the duration of bacteriostatic inhibition of the KM hydrogel was significantly prolonged compared to that of the KM solution. This confirms the controlled release capability of the hydrogel. In addition, the hydrogel reduced the wound size in mice by 96 % and histopathological tests showed complete re-epithelialization of the wound. The prepared hydrogels successfully demonstrated their potential ability to control drug release and promote skin wound healing.

Adipose-Derived Stem-Cell-Membrane-Coated PLGA-PEI Nanoparticles Promote Wound Healing via Efficient Delivery of miR-21.

miRNAs have been shown to be involved in the regulation of a variety of physiological and pathological processes, but their use in the treatment of diseases is still limited due to their instability. Biomimetic nanomaterials combine nanomaterials with cellular components that are readily modifiable and biocompatible, making them an emerging miRNA delivery vehicle. In this study, adipose-derived MSC membranes were wrapped around PLGA-PEI loaded with miR-21 through co-extrusion and later transplanted into C57BL/6 mice wounds. The wound-healing rate, epithelialization, angiogenesis, and collagen deposition were assessed after treatment and corroborated in vitro. Our study demonstrated that m/NP/miR-21 can promote wound healing in terms of epithelialization, dermal reconstruction, and neovascularization, and it can regulate the corresponding functions of keratinocytes, fibroblasts, and vascular endothelial cells. m/NP/miR-21 can inhibit the expression of PTEN, a gene downstream of miR-21, and increase the phosphorylation activation of AKT, which can then regulate the functions of fibroblasts. In conclusion, this provides a new approach to therapy for skin wounds using microRNA transporters and biomimetic nanoparticles.