Skin Regeneration Research Articles

3D bioprinted poly(lactic acid) scaffolds infused with curcumin-loaded nanostructured lipid carriers: a promising approach for skin regeneration.

Nanotechnology and 3D bioprinted scaffolds are revolutionizing the field of wound healing and skin regeneration. By facilitating proper cellular movement and providing a customizable structure that replicates the extracellular matrix, such technologies not only expedite the healing process but also ensure the seamless integration of new skin layers, enhancing tissue repair and promoting overall cell growth. This study centres on the creation and assessment of a nanostructured lipid carrier containing curcumin (CNLC), which is integrated into a 3D bioprinted PLA scaffold system. The goal is to investigate its potential as a vehicle for delivering poorly soluble curcumin for enhanced wound healing. The developed CNLC exhibited an oval morphology and average particle size of 292 nm. The entrapment efficiency (EE) was 81.37 ± 0.85%, and the drug loading capacity was 6.59 ± 1.61%. CNLC was then integrated into PLA-based 3D bioprinted scaffolds, and physicochemical analyses were conducted to evaluate their properties. Cell viability studies carried out using fibroblast cells demonstrated that the PLA/CNLC scaffolds are non-cytotoxic. In vivo experiments showed that the PLA/CNLC scaffolds exhibited complete wound contraction and closure of full-thickness wounds within a period of 21 days. The findings confirmed the scaffold's capacity as a tool for accelerating wound healing. The research emphasises the need for using biomimetic 3D printed scaffold materials and the promise of nanobiotechnology in enhancing treatment efficacy.

The use of three-dimensional bioprinting for skin regeneration and wound healing (literature review)

The use of three-dimensional bioprinting for skin regeneration and wound healing (literature review)

Bioactive Hydrogel Supplemented with Stromal Cell-Derived Extracellular Vesicles Enhance Wound Healing

Background/Objectives: Skin regeneration is a rapidly advancing field with significant implications for regenerative medicine, particularly in treating wounds and burns. This study explores the potential of hydrogels functionalized with fibroblast-derived extracellular vesicles (EVs) to enhance skin regeneration in vivo. Being immunoprivileged, EVs minimize immune rejection, offering an attractive alternative to whole-cell therapies by replicating fibroblasts’ key roles in tissue repair. Methods: To promote EVs’ versatility and effective application across different conditions, a lyophilization method with lyoprotectants was optimized. Then, EVs were used to functionalize a hydrogel to perform experiments on murine cutaneous wound models. Results: Gelatin methacrylate (GelMA) was selected as the polymeric hydrogel due to its biocompatibility, tunable mechanical properties, and ability to support wound healing. Mechanical tests confirmed GelMA’s strength and elasticity for this application. Fibroblast-derived EVs were characterized using Western blot, Transmission Electron Microscopy, and NanoSight analysis, proving their integrity, size distribution, and stability. miRNome profiling identified enriched biological pathways related to cell migration, differentiation, and angiogenesis, emphasizing the critical role of EV cargo in promoting wound repair. In a murine model, hydrogels loaded with fibroblast-derived EVs significantly accelerated wound healing compared to controls (mean wound area 0.62 mm2 and 4.4 mm2, respectively), with faster closure, enhanced epithelialization, increased vascularization, and reduced fibrosis. Notably, the lyoprotectants successfully preserved the EVs’ structure and bioactivity during freeze-drying, reducing EVs loss by 35% compared to the control group and underscoring the feasibility of this approach for long-term storage and clinical application. Conclusions: This study introduces a novel scalable and adaptable strategy for regenerative medicine by combining fibroblast-derived EVs with GelMA, optimizing EVs’ stability and functionality for enhanced wound healing in clinical settings, even in challenging contexts such as combat zones or large-scale natural disasters.

Peptide Nanofibers and Skin Regeneration.

Peptide nanofibers have been attractive targets for regenerative medicine applications due to their tailorability to be easily functionalized for specific bioactivity, biocompatibility, ease of synthesis, adjustability of their physicochemical characteristics, and lack of biological contamination. Research groups have investigated their use for the regeneration of various tissues, such as bone, cartilage, brain, peripheral nerves, cardiac tissue, vascular tissues, endocrine cells, muscles, etc., for the treatment of degenerative diseases or tissue loss due to accidents or aging. Wound healing and skin regeneration are among the most widely investigated research areas for peptide nanofibers as well. In this article, we reviewed the literature on the utilization of peptide nanofibers for various skin regeneration and dermal healing applications, aiming to give the readers a general view of how peptide nanofibers have been used for this purpose so far as well as provide new insight on which avenues more research is necessary to be able to apply these methods in clinics.

The Role of Mesenchymal Stem Cell-Derived Exosomes in Skin Regeneration, Tissue Repair, and the Regulation of Hair Follicle Growth.

Skin regeneration, repair, and the promotion of hair growth are intricate and dynamic processes essential for preserving the overall health, functionality, and appearance of both skin and hair. These processes involve a coordinated interplay of cellular activities and molecular signaling pathways that ensure the maintenance and restoration of skin integrity and hair vitality. Recent advancements in regenerative medicine have underscored the significant role of mesenchymal stem cell (MSC)-derived exosomes as key mediators in these processes. Exosomes, emerging as a promising cell-free therapy in tissue engineering, hold substantial potential due to their ability to influence various biological functions. This review explores the mechanisms by which MSC-derived exosomes facilitate skin regeneration and repair, and hair growth, their therapeutic applications, and the future research directions in this emerging field.

Biomolecular Microneedle Initiates Fe3O4/MXene Heterojunction-Mediated Nanozyme-Like Reactions and Bacterial Ferroptosis to Repair Diabetic Wounds.

Reactive oxygen species (ROS) play a dual role in wound healing. They act as crucial signaling molecules and antimicrobial agents when present at moderate levels. However, excessive levels of ROS can hinder the healing process for individuals with diabetes. As a result, targeting ROS levels to maintain redox balance has become a promising strategy for improving wound recovery. Currently, no biomaterials have been reported to simultaneously up-regulate and down-regulate ROS to achieve broad-spectrum antibacterial and antioxidant properties. Inspired by the site-dependent effect of nanomaterials, a micron-sized ferroferric oxide (Fe3O4)/MXene (FM) heterojunction is synthesized using a hydrothermal method. The FM heterojunction could scavenge extracellular ROS by activating catalase (CAT)-like and superoxide dismutase (SOD)-like nanozyme activities. Meanwhile, FM heterojunction could release ferric ions and ferrous ions by defect engineering to induce bacterial ferroptosis, up-regulating intercellular ROS, and lipid peroxidation. For applications in vivo, FM heterojunction is incorporated into the tips of gelatin methacryloyl (GelMA)-based microneedle (termed as GFM microneedle) using a two-step casting technique. The results showed that GFM microneedle combined with photothermal therapy could improve S. aureus-infected skin regeneration in diabetic rats. The effectiveness and safety of GFM microneedle are not less favorable than that of a commercial wound dressing. This study provides a proof-of-concept for heterojunction-mediated regenerative medicine via a site-dependent ROS-targeting strategy.

Bioactive Silk Cryogel Dressing with Multiple Physical Cues to Control Cell Migration and Wound Regeneration.

Introducing multiple physical cues to control cell behaviors effectively is considered as a promising strategy in developing bioactive wound dressings. Silk nanofiber-based cryogels are developed to favor angiogenesis and tissue regeneration through tuning hydrated state, microporous structure, and mechanical property, but remained a challenge to endow with more physical cues. Here, β-sheet rich silk nanofibers are used to develop cryogels with nanopore structure. Through optimizing crosslinking time and exposing the reactive group inside the nanofibers, the crosslinking reaction is improved to induce stable cryogel formation. Besides the hydrated state and macroporous structure, the nanopore structure formed on the macroporous walls, providing hierarchical microstructures to improve cell migration. Both in vitro and in vivo results reveal quicker cell migration inside the cryogels, which then accelerates angiogenesis and wound healing. The mechanical properties can further regulate to match with skin regeneration. The wound healing study in vivo reveals lower inflammatory factor secretion in the wounds treated with softer cryogels with nanopores, which then resulted in the best angiogenesis and wound healing with less scar. Therefore, the porous cryogels with multiple physical cues can be fabricated with silk nanofibers to control cell behaviors and tissue regeneration, providing a promising approach for designing bioactive wound dressings.

Transcriptome analysis of regenerated dermis stimulated by mechanical stretch.

Mechanical stretch is utilized in the process of tissue expansion to promote skin regeneration, which is crucial for wound healing and organ reconstruction purposes. Enlarged dermal area is one of the significant histological characteristics of the expanded skin. However, the underlying biological processes and molecular pathways associated with dermal regeneration triggered by mechanical stretch are still not well understood. Twelve male Sprague-Dawley (SD) rats were divided into the expansion group and sham group randomly. Upon creating a rat scalp expansion model, the dermis was isolated from the full-thickness skin in both experimental groups for RNA sequencing. This process led to the identification of differentially expressed genes (DEGs). Subsequently, we conducted Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA) to identify the essential biological processes associated with dermal regeneration induced by mechanical stretch, leveraging data from the DEGs. A network of protein-protein interactions (PPI) was built to detect the critical modules and central genes. The expression levels of these hub genes were evaluated using quantitative real-time polymerase chain reaction (qPCR). Increased expanded skin area and dermal thinning which represent the typical changes of expanded skin were observed in the expansion group. A total of 782 DEGs were identified in the expansion group relative to the sham group. The DEGs were associated with several biological processes, including the organization of the extracellular matrix, the enhancement of macrophage activation, and the promotion of angiogenesis, among others. Cell components encompassing Toll-like receptor 2-Toll-like receptor 6 protein complex, interstitial matrix, extracellular matrix (ECM), and collagen trimer were discovered. Molecular function categories including integrin binding, insulin-like growth factor binding, and fatty acid elongase activity were involved. The KEGG pathway analysis demonstrated the significant enrichment of pathways including the PI3K-Akt signaling pathway, fatty acid metabolism, and extracellular matrix-receptor interactions. GSEA results displayed that mechanical stretch correlated with the regulation of cell activation processes, cytokine-mediated signaling pathways, and immune system processes. PPI network resulted in the identification of 598 nodes along with a total of 5,304 interaction pairs between proteins. And ten hub genes containing Ccl2, Cxcl10, Fasn, Itgad, Cd163, Mmp9, Cd36, Tlr2, Igf1, and Wnt2 were identified by bioinformatics analysis and validated by qPCR. This in vivo study for the first time revealed the DEGs related to mechanical stretch stimulated dermal regeneration and identified the involved pathways and hub genes correlated with macrophage recruitment and polarization, fibroblast proliferation and ECM production and angiogenesis, which may benefit further studies aimed at developing therapeutic strategies for facilitating expanded skin regeneration.

A Comparative Analysis of Cell Proliferation and Wound Closure in Cultured Gingival Epithelial Cells Using Plasma Rich in Growth Factors and Platelet-Rich Plasma Containing Leukocytes.

Plasma rich in growth factors (PRGF) is presumed to be able to stimulate the regeneration of skin and periodontal tissue. This effect can be attributed to the fact that PRGF contains fewer leukocyte-derived interleukins in comparison to platelet-rich plasma (PRP). However, a comparison of the effects of PRGF and PRP on gingival epithelial cells has not been conducted yet. Therefore, our objective was to clarify and compare the effects of PRGF and PRP on gingival epithelial cell proliferation, wound healing, and gene expression. PRGF and PRP were obtained from three donors. A complete medium containing bovine pituitary extract (BPE) and growth factors was used as a positive control (PC), while a medium without BPE was used as a negative control (NC). We evaluated the presence of platelets and leukocytes, as well as the number of leukocytes, in PRP and PRGF using the cell block method and a cell counting chamber. We assessed gingival epithelial cell proliferation with WST-1 and wound healing by using cell-free culture inserts. To examine the mRNA expression of tumor necrosis factor-α (TNF-α), which is related to cell growth inhibition, and integrin β4, which contributes to cell adhesion, we used quantitative reverse transcription polymerase chain reactions (RT-PCRs) under PRGF and PRP samples in vitro. The nonparametric data were analyzed using the Kruskal-Wallis test. Large quantities of platelets were observed in both PRGF and PRP. The leukocyte concentration in PRGF was generally lower than that in PRP. Our report indicated that cell proliferation was significantly higher in PRGF than in PRP on day 1 and 2. We found that there was no significant difference in the wound closure rate between PRGF and PRP in comparison to their respective control groups. The quantitative RT-PCR revealed insignificant differences in mRNA expression as TNF-α and integrin β4 between PRGF and PRP in comparison to the each of their respective control groups. Our research indicated that PRGF can promote the proliferation of gingival epithelium more than PRP, contributing to the healing of periodontal tissue. TNF-α and integrin β4 mRNA expression may not be significantly involved in wound closure within the gingival epithelium under the influence of PRGF and PRP.

From Polydeoxyribonucleotides (PDRNs) to Polynucleotides (PNs): Bridging the Gap Between Scientific Definitions, Molecular Insights, and Clinical Applications of Multifunctional Biomolecules.

Polydeoxyribonucleotides (PDRNs) and polynucleotides (PNs) are similar DNA-derived biopolymers that have garnered significant scientific attention since the 1990s for their potential applications in wound healing and skin rejuvenation. These biopolymers exhibit a broad molecular weight (MW) range, typically spanning from 50 to 1500 kDa. However, recent studies have expanded this range to encompass fragments as small as 1 kDa and as large as 10,000 kDa. Clinically, PDRN/PN formulations, commercially available in various galenic forms (gels, creams, serums, masks, and injectables), have demonstrated promising effects in significantly promoting skin regeneration, reducing inflammation, improving skin texture, preventing scar formation, and mitigating wrinkles. Importantly, despite their widespread use in cosmetology and aesthetic dermatology, the interchangeable use of the terms "PDRN" and "PN" in the scientific literature (to describe polymers of varying lengths) has led to considerable confusion within the medical and scientific communities. To specifically address this PDRN/PN ambiguity, this narrative review proposes a standardized structure-based nomenclature for these DNA-derived polymers, the "Marques Polynucleotide Cutoff", set at 1500 kDa. Thus, we propose that the term "PDRN" should be exclusively reserved for small- and medium-chain polymers (MW < 1500 kDa), while the term "PN" should specifically be used to denote longer-chain polymers (MW ≥ 1500 kDa). In a broader perspective, this classification is based on the distinct physicochemical properties and therapeutic effects of these DNA fragments of various MWs, which are comprehensively discussed in the present review.

BCL-2 overexpression exosomes promote the proliferation and migration of mesenchymal stem cells in hypoxic environment for skin injury in rats

ObjectiveThe direction of this study was to detect and analyze the specific mechanism of anti-apoptosis in mesenchymal stem cells (MSCs) cells caused by high expression of BCL2.MethodsBioinformatics was completed in Link omics. GO analysis and KEGG analysis were carried out, and the grope tool of Link omics database was used to evaluate PPI information and other core path analysis information. The cultured cells were divided into MSC + normoxic group (MSCs were cultured in conventional medium, including 10% depleted serum of fetal bovine exosomes, 37 °C, 5% CO2 and 95% air) and Exo-BCL-2 + MSC + normoxic group (a certain concentration of purified BCL-2 exosomes was co-cultured with MSC in conventional medium, 37 °C, 5% CO2 and 95% air), Exo-BCL-2 + MSC + hypoxia group (a certain concentration of purified BCL-2 exosomes and MSC were co-cultured in hypoxia medium at 37 °C, 80% CO2 and 20% air), MSC + hypoxia group (MSCs were cultured in hypoxia medium with 10% depleted serum of fetal bovine exosomes, 37 °C, 80% CO2 and 20% air), exo WT + MSC + normoxic group (co-cultured with MSC in conventional medium at 37 °C, 5% CO2 and 95% air) and exoWT + MSC + hypoxic group (co-cultured with MSC in hypoxic medium at 37 °C, 80% CO2 and 20%). Cell proliferation ability was monitored by cell proliferation test. Cell migration test was used to check the migration capacity of MSCs. The expressions of apoptosis-related proteins BCL-2, caspase3 and caspase9, Runx2, ALP and PPAR‐γ were analyzed by western blot. Tissue damage was scored by H&E and Ma Song trichrome staining. Masson staining was used to evaluate the collagen volume fraction of the wound. The expressions of KRT14, α‐SMA, CD31 and PCNA in rat trauma tissues were analyzed by immunofluorescence staining. The horizontal of apoptosis-related proteins in skin lesions was checked by Western blot. The horizontal of inflammatory factors TNF-α and IL-6 in traumatic tissue of rats were detected by ELISA.ResultsFrom KEGG's results, we can see that BCL2-2 was closely related to base excision and repair, cell cycle, steroid biosynthesis and other pathways. When cultured for 48h and 72h, the proliferation ability and migration number of MSCs in MSC + hypoxia group were lower than MSC + normoxic group, but the expressions of caspase3 and caspase9 were higher. The proliferation ability and migration number of MSCs in Exo-BCL-2 + MSC + hypoxia group and MSC + hypoxia group were lower than those in Exo-BCL-2 + MSC + normoxic group and MSC + normoxic group, and the horizontal of caspase3 and caspase9 were lower. Exo-BCL-2 + MSC + normoxic group increased the proliferation capacity and migration number of MSCs, but decreased the expression of caspase3 and caspase9. Compared with Exo-BCL-2 + MSC + normoxia and Exo-BCL-2 + MSC + normoxia, the proliferation ability and migration quantity of MSCs in exo WT + MSC + normoxia and exo WT + MSC + hypoxia groups were lower, and the horizontal of caspase3 and caspase9 proteins was higher.ConclusionBioinformatics analysis shows that BCL2-2 plays a worthwhile role in the process of cell apoptosis and proliferation. Exosomes with high expression of BCL-2 can encourage the proliferation of MSC in hypoxic environment. The wound treated with MSCs‐BCL-2 promotes the compose of new blood vessels and granulation tissue in the wound, the redifferentiation of epithelial cells and the remodeling of collagen, which has a high therapeutic prospect for chronic wounds and skin regeneration.

Single-atom nanozymes with intelligent response to pathological microenvironments for bacterially infected wound healing.

Wound healing is a complex and dynamic process often accompanied by bacterial infection, inflammation, and excessive oxidative stress. Single-atom nanozymes with multi-enzymatic activities show significant potential for promoting the healing of infected wounds by modulating their antibacterial and anti-inflammatory properties in response to the wound's physiological environment. In this study, we synthesized MN4 single-atom nanozymes with multi-enzymatic activities that intelligently respond to pH value changes in the wound healing process. In vitro experiments confirm their effectiveness against Gram-negative bacteria, attributed to elevated reactive oxygen species (ROS) accumulation within the bacterial cells. Moreover, a full-thickness skin wound-infected model demonstrates that MN4 single-atom nanozymes accelerate wound repair and skin regeneration by suppressing the expression of tumor necrosis factor-alpha (TNF-α), promoting angiogenesis, and enhancing collagen deposition. In vivo biocompatibility experiments further demonstrate the favorable biocompatibility of these nanozymes, highlighting their potential for clinical applications in infected wound healing. These nanozymes respond intelligently to different microenvironments and may be suitable for addressing further complex and variable diseases.

The role of multiomics in revealing the mechanism of skin repair and regeneration

The role of multiomics in revealing the mechanism of skin repair and regeneration

Regenerative failure of sympathetic axons contributes to deficits in functional recovery after nerve injury.

Renewed scientific interest in sympathetic modulation of muscle and neuromuscular junctions has spurred a flurry of new discoveries with major implications for motor diseases. However, the role sympathetic axons play in the persistent dysfunction that occurs after nerve injuries remains to be explored. Peripheral nerve injuries are common and lead to motor, sensory, and autonomic deficits that result in lifelong disabilities. Given the importance of sympathetic signaling in muscle metabolic health and maintaining bodily homeostasis, it is imperative to understand the regenerative capacity of sympathetic axons after injury. Therefore, we tested sympathetic axon regeneration and functional reinnervation of skin and muscle, both acute and long-term, using a battery of anatomical, pharmacological, chemogenetic, cell culture, analytical chemistry, and electrophysiological techniques. We employed several established growth-enhancing interventions, including electrical stimulation and conditioning lesion, as well as an innovative tool called bioluminescent optogenetics. Our results indicate that sympathetic regeneration is not enhanced by any of these treatments and may even be detrimental to sympathetic regeneration. Despite the complete return of motor reinnervation after sciatic nerve injury, gastrocnemius muscle atrophy and deficits in muscle cellular energy charge, as measured by relative ATP, ADP, and AMP concentrations, persisted long after injury, even with electrical stimulation. We suggest that these long-term deficits in muscle energy charge and atrophy are related to the deficiency in sympathetic axon regeneration. New studies are needed to better understand the mechanisms underlying sympathetic regeneration to develop therapeutics that can enhance the regeneration of all axon types.

Tongue Prick Bionic Angularly Adjustable Microneedles for Enhanced Scarless Wound Healing

AbstractHigh‐tension site wounds are frequently accompanied by challenges associated with hypertrophic scarring. The key to achieving scar‐free healing is the creation of a mechanical environment conducive to scar‐free skin regeneration. Herein, simple rolling punctures are utilized on angle transform molds to develop cat tongue prick bionic angle‐adjustable microneedles (TPMNs) to maintain a firm grip on the periwound skin, thereby reducing tissue tension. The integration of TPMNs with triboelectric nanogenerators (TENGs) enables excellent conductive and triboelectric properties. The system can provide a stable spatial electric field around the wound to promote cell migration. As the microfluid reaches the TPMNs, the self‐driving force is enhanced by a unique angle design to control the microfluid flow rate. Sufficient evidence has shown that TPMNs expedite wound contraction and skin tissue regeneration while concurrently reducing scar formation in mouse trauma model experiments. The innovative TPMNs‐TENGs synergistically provides a highly functional platform for wound tension relief, which is suitable for scar treatment in this study and potentially extends to the construction and regulation of smart wearable devices.

Elevating Dermatology Beyond Aesthetics: Perinatal-Derived Advancements for Rejuvenation, Alopecia Strategies, Scar Therapies, and Progressive Wound Healing.

Dermatologists have been interested in recent advancements in regenerative therapy. Current research is actively investigating the possibility of placental tissue derivatives to decelerate the skin aging process, enhance skin regeneration, reduce scarring, and prevent hair loss. Amniotic membranes (AM) play a crucial role in regenerative medicine as they serve as a suitable means of transporting stem cells, growth hormones, cytokines, and other essential compounds. Regulating an intricate network of biological processes improves the development and repair of tissues. Studies done by dermatologists indicate that several compounds found in the decidua, umbilical cord, and amniotic membrane have the potential to be used for regeneration. Examples include mesenchymal stem cells, growth factors, and immunomodulatory pharmaceuticals. Due to research and technological developments, scientists may use placental sections to facilitate skin regeneration, minimize scarring, and expedite wound healing. This study examines the current state of dermatological therapy, with a focus on using derivatives obtained from fetal tissue as the basis. The critical areas of study focus on this strategy are the potential benefits, growth opportunities, and recovery rates. Based on a thorough examination of the available literature and clinical data, we want to make definitive conclusions on the possible influence of fetal tissue derivatives in dermatological therapy.

Mealworm-Derived Protein Hydrolysates Enhance Adipogenic Differentiation via Mitotic Clonal Expansion in 3T3-L1 Cells.

Adipocytes secrete adipokines, bioactive molecules crucial for various physiological processes, such as enhancing insulin sensitivity, promoting wound healing, supporting hair growth, and exhibiting anti-aging effects on the skin. With the growing global demand for sustainable and alternative protein sources, insect-derived proteins, particularly from Tenebrio molitor (mealworms), have gained attention due to their high nutritional value and functional bioactivities. This study aims to explore the potential of mealworm-derived protein hydrolysates as novel bioactive materials for promoting adipogenesis and improving adipokine expression, with applications in metabolic health and skin regeneration. Protein hydrolysates (<1 kDa) were prepared using enzymatic hydrolysis with three proteases (alcalase, flavourzyme, and neutrase) and evaluated for their adipogenic activity in 3T3-L1 preadipocytes. Among them, the flavourzyme-derived hydrolysate (Fh-T) exhibited the most significant effects, enhancing adipogenic differentiation and lipid accumulation. Fh-T facilitated adipogenesis by promoting mitotic clonal expansion (MCE) during the early stage of differentiation, which was associated with the upregulation of C/EBPδ and the downregulation of p27. These findings underscore the potential of mealworm-derived protein hydrolysates, particularly Fh-T, as sustainable and functional ingredients for use in glycemic control, skin health, and tissue regeneration. This study provides valuable insights into the innovative use of alternative protein sources in functional foods and cosmeceuticals.

Recombinant collagen microneedles for transdermal delivery of antibacterial copper-DNA nanoparticles to treat skin and soft tissue infections.

Skin and soft tissue infections (SSTI) include bacterial infections of the skin, muscles, and connective tissue such as ligaments and tendons. SSTI in patients with immunocompromising diseases may lead to chronic, hard-to-heal infected wounds, resulting in disability, amputation, or even death. To treat SSTI and rebuild the defensive barrier of the skin, here we utilize recombinant type XVII collagen protein (rCol XVII) to construct biodegradable, regenerative collagen microneedles (rCol-MNs) for transdermal delivery of antibacterial agents. Spheroidal copper-DNA antibacterial nanoparticles (Cu-CpG NPs; CpG represents short single-stranded synthetic DNA molecules of cytosine and guanine) are synthesized with copper ions and CpG oligodeoxynucleotides (ODNs), followed by polydopamine (PDA) coating to obtain Cu-CpG@PDA. Doping Cu-CpG@PDA into rCol-MNs yields Cu-CpG@PDA-loaded rCol-MNs. These microneedles combine the photothermal conversion property of PDA, antibacterial properties of copper ions, innate immune activation of CpG ODNs, and skin regenerating ability of rCol XVII, allowing the treatment of SSTI and also regenerating the damaged skin. In a mouse model, we show that the Cu-CpG@PDA-loaded rCol-MNs rescue skin wound infections, facilitate the orderly deposition of collagen at the wound site, and promote the healing of infected full-thickness wounds without noticeable scar formation. rCol-MNs serve as a transdermal delivery vehicle and, simultaneously, a reservoir of skin-regenerating recombinant collagen, bringing combined benefits of infection control and skin regeneration. SIGNIFICANCE STATEMENT: Treatment of soft tissue infection requires the delivery of antibacterial agents into the soft tissue or dermis while providing a regenerating environment for open wounds. Here, we devise recombinant collagen microneedles (rCol-MNs) to meet both requirements.

Autocatalytic Ceria Nanoparticle-Embedded Tilapia Collagen Hydrogels as Enhanced Antioxidative and Long-Lasting Dermal Fillers for Photoaged Skin.

Excessive reactive oxygen species (ROS) generated by ultraviolet (UV) irradiation significantly contribute to photoaging by increasing the level of matrix metalloproteinases (MMPs), accelerating collagen degradation. Commercial dermal fillers offer temporary wrinkle reduction via volume enhancement. In this study, we propose tilapia-derived collagen hydrogels embedded with ceria nanoparticles (Ce@Col gels) as long-lasting dermal fillers for UVB-induced photoaging. Ceria nanoparticles (CeNPs) significantly enhance the stability of the collagen matrix against enzymatic degradation. These gels exhibit mechanical stability and injectability comparable to those of commercial alternatives. Additionally, CeNPs effectively eliminate ROS to suppress MMP production, curbing both collagen degradation and inflammatory responses. In a UVB-induced photoaging mouse model, the Ce@Col gels significantly reduced the level of oxidative stress in the skin, decreased the number of wrinkles, reduced epidermal thickness, and decreased levels of aging-related biomarkers while increasing the level of collagen deposition. These antiaging effects persisted for seven months post-injection, highlighting Ce@Col gels as a promising approach for prolonged collagen regeneration and sustained anti-inflammatory benefits in photoaged skin.

Recent advances in the role of neuroregulation in skin wound healing.

Neuroregulation during skin wound healing involves complex interactions between the nervous system and intricate tissue repair processes. The skin, the largest organ, depends on a complex system of nerves to manage responses to injury. Recent research has emphasized the crucial role of neuroregulation in maximizing wound healing outcomes. Recently, researchers have also explained the interactive contact between the peripheral nervous system and skin cells during the different phases of wound healing. Neurotransmitters and neuropeptides, once observed as simple signalling molecules, have since been recognized as effective regulators of inflammation, angiogenesis, and cell proliferation. The significance of skin innervation and neuromodulators is underscored by the delayed wound healing observed in patients with diabetes and the regenerative capabilities of foetal skin. Foetal skin regeneration is influenced by the neuroregulatory environment, immature immune system, abundant growth factors, and increased pluripotency of cells. Foetal skin cells exhibit greater flexibility and specialized cell types, and the extracellular matrix composition promotes regeneration. The extracellular matrix composition of foetal skin promotes regeneration, making it more capable than adult skin because neuroregulatory signals affect skin regeneration. The understanding of these systems can facilitate the development of therapeutic strategies to alter the nerve supply to the skin to enhance the process of wound healing. Neuroregulation is being explored as a potential therapeutic strategy for enhancing skin wound repair. Bioelectronic strategies and neuromodulation techniques can manipulate neural signalling, optimize the neuroimmune axis, and modulate inflammation. This review describes the function of skin innervation in wound healing, emphasizing the importance of neuropeptides released by sensory and autonomic nerve fibres. This article discusses significant discoveries related to neuroregulation and its impact on skin wound healing.