Skin injuries and wounds present significant clinical challenges, necessitating the development of advanced wound dressings for efficient wound healing and tissue regeneration. In this context, the advancement of hydrogels capable of counteracting the adverse effects arising from undesirable reactive oxygen species (ROS) is of significant importance. This study introduces a hybrid hydrogel with rapid photocuring and excellent conformability, tailored to ameliorate the hostile microenvironment of damaged skin tissues. The hybrid hydrogel, composed of photoresponsive Gelatin Methacryloyl (GelMA) and Molybdenum-based nanoclusters (MNC), exhibits physicochemical characteristics conductive to skin regeneration. In vitro studies demonstrated the cytocompatibility and ROS-responsive behavior of the MNC/GelMA hybrid hydrogels, confirming their ability to promote human dermal fibroblasts (HDF) functions. The incorporation of MNC into GelMA not only enhances HDF adhesion, proliferation, and migration but also shields against oxidative damage induced by hydrogen peroxide (H2O2). Notably, in vivo evaluation in murine full-thickness skin defects revealed that the application of hybrid hydrogel dressings led to reduced inflammation, accelerated wound closure, and enhanced collagen deposition in comparison to control groups. Significantly, this study introduced a convenient approach to develop in situ ROS-scavenging hydrogel dressings to accelerate the wound healing process without the need for exogenous cytokines or medications. We consider that the nanoengineering approach proposed herein offers potential possibilities for the development of therapeutic hydrogel dressings addressing various skin-related conditions.

Photoaging, primarily caused by ultraviolet (UV) light, is the major factor in extrinsic skin aging. Existing anti-photoaging strategies mainly focus on early sun protection or repairing damaged skin, lacking a comprehensive treatment strategy. Therefore, this study developed a dressing that actively shields against UV radiation and repairs photoaged skin, offering double protection. This study utilized exosome-like nanovesicles derived from Olea europaea leaves (OLELNVs), enhancing them into a potent core biomaterial with high-dose effects and skin-friendly, non-cytotoxic inhibition of cell aging. These nanovesicles were incorporated into a cross-linked hyaluronic acid (HA) and tannic acid (TA) hydrogel with strong UV-absorbing properties, creating the OLELNVs@HA/TA hydrogel system. In vitro and in vivo experiments demonstrated that OLELNVs@HA/TA hydrogel can effectively reduce UV-induced skin damage and promote skin repair and regeneration. Additionally, RNA-seq and clustering analysis of miR168a-5p predicted targets revealed significant down-regulation of the NF-κB signaling pathway, mediating inflammatory aging responses. Overall, the OLELNVs@HA/TA hydrogel represents a novel dual-strategy approach for clinical application in combating photoaging.

Extensive skin damage requires specialized therapy that stimulates regeneration processes without scarring. The possibility of using combination of a collagen gel application as a wound dressing and fibroblast attractant with verteporfin as an antifibrotic agent was examined in vivo and in vitro. In vitro effects of verteporfin on viability and myofibroblast markers expression were evaluated using fibroblasts isolated from human scar tissue. In vivo the collagen gel and verteporfin (individually and in combination) were applied into the wound to investigate scarring during skin regeneration: deviations in skin layer thickness, collagen synthesis, and extracellular matrix fibers were characterized. The results indicate that verteporfin reduces fibrotic phenotype by suppressing expression of the contractile protein Sm22α without inducing cell death. However, administration of verteporfin in combination with the collagen gel disrupts its ability to direct wound healing in a scarless manner, which may be related to incompatibility of the mechanisms by which collagen and verteporfin control regeneration.

Basic fibroblast growth factor (FGF2 or bFGF) is critical for optimal wound healing. Experimental studies show that local application of FGF2 is a promising therapeutic approach to stimulate tissue regeneration, including for the treatment of chronic wounds that have a low healing potential or are characterised by a pathologically altered healing process. However, the problem of low efficiency of growth factors application due to their rapid loss of biological activity in the aggressive proteolytic environment of the wound remains. Therefore, ways to preserve the efficacy of FGF2 for wound treatment are being actively developed. This review considers the following strategies to improve the effectiveness of FGF2-based therapy: (1) use of vehicles/carriers for delivery and gradual release of FGF2; (2) chemical modification of FGF2 to increase the stability of the molecule; (3) use of genetic constructs encoding FGF2 for de novo synthesis of protein in the wound. In addition, this review discusses FGF2-based therapeutic strategies that are undergoing clinical trials and demonstrating the efficacy of FGF2 for skin wound healing.

We designed and performed this meta-analysis to investigate the impact of the application of extracellular small vesicle therapies on regeneration of skin and wound healing. The findings of this study were computed using fixed or random effect models. The mean differences (MDs), and odds ratio (ORs) with their 95% confidence intervals (CIs) were calculated. In this study, 43 publications were included, encompassing 530 animals with artificial wounds. Small extracellular vesicle therapy had a significant greater rate of wound closure (MD, 24.0; 95% CI, 19.98-28.02, P < 0.001), lower scar width (MD, -191.33; 95%CI, -292.26--90.4, P < 0.001), and higher blood vessel density (MD,36.11; 95%CI, 19.02-53.20, P < 0.001) compared to placebo. Our data revealed that small extracellular vesicle therapy had a significantly higher regeneration of skin and healing of wounds based on the results of wound closure rate, lower scar width, and higher blood vessel density compared to placebo. Future studies with larger sample size are needed.

Recent data indicate that extracellular ATP affects wound healing efficacy via P2Y2-dependent signaling pathway. In the current work, we propose double-modified ATP analogue-alpha-thio-beta,gamma-methylene-ATP as a potential therapeutic agent for a skin regeneration. For the better understanding of structure-activity relationship, beside tested ATP analogues, the appropriate single-modified derivatives of target compound, such as alpha-thio-ATP and beta,gamma-methylene-ATP, were also tested in the context of their involvement in the activation of ATP-dependent purinergic signaling pathway via the P2Y2 receptor. The diastereomerically pure alpha-thio-modified-ATP derivatives were obtained using the oxathiaphospholane method as separate SP and RP diastereomers. Both the single- and double- modified ATP analogues were then tested for their impact on the viability and migration of human keratinocytes. The involvement of P2Y2-dependent purinergic signaling was analyzed in silico by molecular docking of the tested compounds to the P2Y2 receptor and experimentally by studying intracellular calcium mobilization in the human keratinocytes HaCaT. The effects obtained for ATP analogues were compared with the results for ATP as a natural P2Y2 agonist. To confirm the contribution of the P2Y2 receptor to the observed effects, the tests were also performed in the presence of the selective P2Y2 antagonist-AR-C118925XX. The ability of the alpha-thio-beta,gamma-methylene-ATP to influence cell migration was analyzed in vitro on the model HaCaT and MDA-MB-231 cells by wound healing assay and transwell migration test as well as in vivo using zebrafish system. The impact on tissue regeneration was estimated based on the regrowth rate of cut zebrafish tails. The in vitro and in vivo studies have shown that the SP-alpha-thio-beta,gamma-methylene-ATP analogue promotes regeneration-related processes, making it a suitable agent for enhance wound healing. Performed studies indicated its impact on the cell migration, induction of epithelial-mesenchymal transition and intracellular calcium mobilization. The enhanced regeneration of cut zebrafish tails confirmed the pro-regenerative activity of this ATP analogue. Based on the performed studies, the SP-alpha-thio-beta,gamma-methylene-ATP is proposed as a potential therapeutic agent for wound healing and skin regeneration treatment.

Gelatin-methacryloyl (GelMA) is a highly adaptable biomaterial extensively utilized in skin regeneration applications. However, it is frequently imperative to enhance its physical and biological qualities by including supplementary substances in its composition. The purpose of this study was to fabricate and characterize a bi-layered GelMA-gelatin scaffold using 3D bioprinting. The upper section of the scaffold was encompassed with keratinocytes to simulate the epidermis, while the lower section included fibroblasts and HUVEC cells to mimic the dermis. A further step involved the addition of amniotic membrane extract (AME) to the scaffold in order to promote angiogenesis. The incorporation of gelatin into GelMA was found to enhance its stability and mechanical qualities. While the Alamar blue test demonstrated that a high concentration of GelMA (20%) resulted in a decrease in cell viability, the live/dead cell staining revealed that incorporation of AME increased the quantity of viable HUVECs. Further, gelatin upregulated the expression of KRT10 in keratinocytes and VIM in fibroblasts. Additionally, the histological staining results demonstrated the formation of well-defined skin layers and the creation of extracellular matrix (ECM) in GelMA/gelatin hydrogels during a 14-day culture period. Our study showed that a 3D-bioprinted composite scaffold comprising GelMA, gelatin, and AME can be used to regenerate skin tissues.

The rising prevalence of diabetes has underscored concerns surrounding diabetic wounds and their potential to induce disability. The intricate healing mechanisms of diabetic wounds are multifaceted, influenced by ambient microenvironment, including prolonged hyperglycemia, severe infection, inflammation, elevated levels of reactive oxygen species (ROS), ischemia, impaired vascularization, and altered wound physicochemical properties. In recent years, hydrogels have emerged as promising candidates for diabetic wound treatment owing to their exceptional biocompatibility and resemblance to the extracellular matrix (ECM) through a three-dimensional (3D) porous network. This review will first summarize the microenvironment alterations occurring in the diabetic wounds, aiming to provide a comprehensive understanding of its pathogenesis, then a comprehensive classification of recently developed hydrogels will be presented, encompassing properties such as hypoglycemic effects, anti-inflammatory capabilities, antibacterial attributes, ROS scavenging abilities, promotion of angiogenesis, pH responsiveness, and more. The primary objective is to offer a valuable reference for repairing diabetic wounds based on their unique microenvironment. Moreover, this paper outlines potential avenues for future advancements in hydrogel dressings to facilitate and expedite the healing process of diabetic wounds.

Contemporary trends reveal an escalating interest in regenerative medicine-based interventions for addressing refractory skin defects. Conventional wound healing treatments, characterized by high costs and limited efficacy, necessitate a more efficient therapeutic paradigm to alleviate the economic and psychological burdens associated with chronic wounds. Mesenchymal stem/stromal cells (MSCs) constitute cell-based therapies, whereas cell-free approaches predominantly involve the utilization of MSC-derived extracellular vesicles or exosomes, both purportedly safe and effective. Exploiting the impact of MSCs by paracrine signaling, exosomes have emerged as a novel avenue capable of positively impacting wound healing and skin regeneration. MSC-exosomes confer several advantages, including the facilitation of angiogenesis, augmentation of cell proliferation, elevation of collagen production, and enhancement of tissue regenerative capacity. Despite these merits, challenges persist in clinical applications due to issues such as poor targeting and facile removal of MSC-derived exosomes from skin wounds. Addressing these concerns, a three-dimensional (3D) platform has been implemented to emend exosomes, allowing for elevated levels, and constructing more stable granules possessing distinct therapeutic capabilities. Incorporating biomaterials to encapsulate MSC-exosomes emerges as a favorable approach, concentrating doses, achieving intended therapeutic effectiveness, and ensuring continual release. While the therapeutic potential of MSC-exosomes in skin repair is broadly recognized, their application with 3D biomaterial scenarios remains underexplored. This review synthesizes the therapeutic purposes of MSCs and exosomes in 3D for the skin restoration, underscoring their promising role in diverse dermatological conditions. Further research may establish MSCs and their exosomes in 3D as a viable therapeutic option for various skin conditions.

BACKGROUND: Striae distensae (SD), or stretch marks, result from rapid stretching of the skin due to various factors. Conventional treatments often yield unsatisfactory results, leading to the exploration of alternative methods. Laser-induced microjet technology offers a promising approach for drug delivery to target areas. This study investigates the efficacy of using a microjet injector with poly-d,l-lactic acid for treating SD.
METHODS: Four female participants with SD were treated with poly-d,l-lactic acid solution using a microjet injector over five sessions. Patients were assessed based on severity scales before and after treatment. Topical anesthetics were applied to minimize discomfort. Injection techniques were optimized to reduce side effects such as bleeding and pain.
RESULTS: All patients showed significant improvement in SD appearance after 5-7 treatments. Assessment scales indicated positive outcomes both immediately after treatment and at the 32-week follow-up. Minimal side effects, primarily petechiae, were observed.
CONCLUSIONS: Laser-induced microjet technology offers several advantages, including rapid drug delivery and mechanotransduction effects, promoting skin regeneration. Poly-d,l-lactic acid injections demonstrated effectiveness in treating SD, particularly when delivered via microjet injectors. Patients expressed high satisfaction due to the procedure\'s minimal invasiveness and quick recovery.
CONCLUSIONS: Utilizing a needleless microjet injector with poly-d,l-lactic acid shows promise as a treatment for SD, typically requiring 5-7 sessions for optimal results. Mild petechiae may occur as a common side effect. This approach offers an effective and minimally invasive alternative for addressing this common cosmetic concern.