Cutaneous Wound Healing Research Articles

Innovative hydrogels in cutaneous wound healing: current status and future perspectives

Chronic wounds pose a substantial burden on healthcare systems, necessitating innovative tissue engineering strategies to enhance clinical outcomes. Hydrogels, both of natural and synthetic origin, have emerged as versatile biomaterials for wound management due to their structural adaptability, biocompatibility, and tunable physicochemical properties. Their hydrophilic nature enables efficient nutrient transport, waste removal, and cellular integration, while their malleability facilitates application to deep and irregular wounds, providing an optimal microenvironment for cell adhesion, proliferation, and differentiation. Extracellular matrix (ECM)- based hydrogels retain bioactive molecules that support cellular infiltration, immune modulation, and tissue remodelling, making them highly effective scaffolds for growth factor delivery and regenerative therapies. Additionally, their injectability and potential for in situ polymerization enable minimally invasive applications, allowing on-demand gelation at target sites. By modifying their mechanical properties through crosslinking, hydrogels can achieve enhanced structural stability, prolonged degradation control, and improved surgical handling, optimizing their functionality in dynamic wound environments. This review outlines current approaches to skin tissue engineering, examining the biomaterials employed in hydrogel design, their limitations, and their interactions with host tissues. Furthermore, it highlights the emerging potential of functionalized injectable hydrogels, particularly those engineered for controlled drug release, enhanced bioactivity, and patient-specific therapeutic applications. These hydrogels offer a transformative platform for advanced wound care and regenerative medicine.

REVIEW ON CHROMOTHERAPY AND ITS SIGNIFICANCE IN AYURVEDA

Chromotherapy is a method of treatment that uses wavelengths in the visible region for curing different diseases and medical conditions. It is one of the oldest therapeutic systems and has been used by the ancient civilizations of India, Egypt and China for the treatment of a number of diseases that include psoriasis, rickets and skin cancer. Treatment modalities utilizing wavelengths in the visible region have been proven to produce biological effects in molecules, living cells and tissues. Wavelengths in the visible region have been demonstrated to be an effective therapy in a number of medical conditions including Dengue Fever, Insomnia, Diabetes, Psychiatric Illnesses, Hypertension, Seasonal Affective Disorder (SAD), Immunity, Hyperacidity, Cutaneous wound healing, Chronic joint disorders and Inflammation. Chromotherapy has been purported to provide several benefits ranging from physical to mental, including: Stress relief: Certain colors like blue and green are thought to have soothing effects on people who are stressed or anxious. Boost appetite: Warm and stimulating colors are thought to boost appetite . Seasonal affective disorder: People mainly suffer from seasonal affective disorder during colder weather because of the lack of sunlight. Certain types of bright light therapy have been shown to be of benefit for this mood disorder. Color therapy also suggests that warm colors like yellow and orange could also help with this. To boost energy: Colors such as red and yellow are believed to boost energy and keeps motivated. Keywords: Chromo, Therapy, Color, Ayurveda

In vivo verification of fish keratocyte explant culture for use as innate immunotoxicity screening assay: 2,4-Dicholorphenoxyacetic acid effects in fathead minnow (Pimephales promelas) keratocyte cell sheet migration.

In vivo verification of fish keratocyte explant culture for use as innate immunotoxicity screening assay: 2,4-Dicholorphenoxyacetic acid effects in fathead minnow (Pimephales promelas) keratocyte cell sheet migration.

Association of biocompatible 3D scaffold with pro-resolutive macrophages and adipose-derived mesenchymal stromal cells improves cutaneous chronic wound healing

Association of biocompatible 3D scaffold with pro-resolutive macrophages and adipose-derived mesenchymal stromal cells improves cutaneous chronic wound healing

α-Mangostin encapsulated gellan gum membranes for enhanced antibacterial, anti-inflammatory, antioxidant and wound healing activity.

α-Mangostin encapsulated gellan gum membranes for enhanced antibacterial, anti-inflammatory, antioxidant and wound healing activity.

Dermal fibroblast-derived extracellular matrix (ECM) synergizes with keratinocytes in promoting re-epithelization and scarless healing of skin wounds: Towards optimized skin tissue engineering.

Dermal fibroblast-derived extracellular matrix (ECM) synergizes with keratinocytes in promoting re-epithelization and scarless healing of skin wounds: Towards optimized skin tissue engineering.

LA-peptide Hydrogel-Regulation of macrophage and fibroblast fates and their crosstalk via attenuating TGF-β to promote scarless wound healing.

LA-peptide Hydrogel-Regulation of macrophage and fibroblast fates and their crosstalk via attenuating TGF-β to promote scarless wound healing.

Hypoxic HucMSC-derived Exosomal miR-542-3p Promote Cutaneous Wound Healing by Activation of LATS1/Yap Pathway

Hypoxic HucMSC-derived Exosomal miR-542-3p Promote Cutaneous Wound Healing by Activation of LATS1/Yap Pathway

Skin-inspired elastomer-hydrogel Janus fibrous membrane creates a superior pro-regenerative microenvironment toward complete skin regeneration.

Skin-inspired elastomer-hydrogel Janus fibrous membrane creates a superior pro-regenerative microenvironment toward complete skin regeneration.

Olfactory receptors and human diseases.

Olfaction plays a crucial role in distinguishing odors, enabling organisms to seek benefits and evade hazards. Olfactory receptors (ORs), characterized by highly variable binding pockets, facilitate the detection of diverse odorants from both external and internal environments. Nasal ORs, expressed in olfactory sensory neurons (OSNs), are critical for olfactory cognition and associated neuronal plasticity. In contrast, extra-nasal ORs, expressed in extra-olfactory tissues, detect specific chemicals and modulate cellular processes such as proliferation, migration, inflammation, and apoptosis. Aberrant OR expression or dysfunction has been implicated in numerous human diseases, including anosmia, dementia, dermatopathies, obesity, infertility, cancers, respiratory disorders, atherosclerosis and viral infections. Olfactory training, such as aromatherapy, demonstrates significant therapeutic potential for anosmia, dementia and psychological distress. Natural or synthetic odorants have been applied for promoting hair regeneration and cutaneous wound healing. Conversely, overexpression of specific ORs in cancer cells may drive tumor progression. Additionally, ORs may mediate virus-host interactions during infection, owing to their structural variability. Collectively, OR-targeted agonists and antagonists (odorants) represent promising candidates for treating OR-associated pathologies.

Inhibition of miRNA-365-2-5p Targeting SIRT1 Regulates Functions of Keratinocytes to Enhance Wound Healing.

The development of drugs to accelerate wound healing is an important area of clinical research. Recent advancements have highlighted the prospects of microRNAs as therapeutic targets for various disorders, although their involvement in mice wound healing remains unclear. Peptides have been proved to be unique and irreplaceable molecules in the elucidation of competing endogenous RNAs mechanisms (ceRNA) involved with skin wound healing. In the present work, CyRL-QN15, a peptide characterized by its minimal length and maximal wound healing efficacy, was applied as a probe to explore the ceRNA mechanism in regard to accelerated wound healing. Results showed that the use of CyRL-QN15 significantly reduced the expression of miRNA-365-2-5p at the wound in mice. In mouse keratinocytes, miRNA-365-2-5p inhibition increased SIRT1 and FOXO1 protein expression and decreased STAT2 protein expression, promoting cell proliferation, migration, and reducing inflammatory factors. Similarly, inhibiting miRNA-365-2-5p at mouse wounds promoted Full-thickness injured skin wounds healing, increased SIRT1 and FOXO1 protein expression, decreased STAT2 protein expression, and reduced inflammatory factors. Overall, these findings demonstrate that miRNA-365-2-5p serves a crucial function in the biological processes underlying cutaneous wound healing in mice, offering a novel target for future therapeutic interventions in wound healing.

S-nitrosoglutathione releasing nano-micron combination hydrogel enhances cutaneous wound healing via promoting angiogenesis and collagen deposition

Nitric oxide (NO) is essential for wound healing, promoting angiogenesis and collagen deposition. This study investigates a novel dual-matrix nanocomposite hydrogel incorporating S-nitrosoglutathione (GSNO), a physiological NO donor, to enhance cutaneous wound healing. GSNO was encapsulated in ammonio methacrylate copolymer nanoparticles and embedded in an alginate-based matrix, achieving controlled NO release. GSNO-loaded nanoparticles were prepared using solvent displacement and solvent evaporation methods, resulting in spherical, well-distributed and positively charged particles. These nanoparticles were cross-linked with negatively charged alginic acid to form a nanocomposite hydrogel. The hydrophobic nanoparticles protected GSNO from degradation, while the hydrophilic alginate matrix sustained the release of active GSNO for up to 10 h, promoting haemostasis and maintaining a moist wound environment. The hydrogel exhibited good biocompatibility in human fibroblasts and significantly enhanced wound repair by promoting fibroblast formation, neovascularisation and collagen deposition, as demonstrated by haematoxylin and eosin staining and Masson’s trichrome staining. In conclusion, the GSNO-loaded nanocomposite hydrogel significantly accelerated the healing process by enhancing angiogenesis and collagen deposition, offering a promising strategy for improving wound healing.

RETRACTION: Impact of Preoperative Chemotherapy on Cutaneous Wound Healing in Lung Cancer Patients: A Meta-Analysis.

J. Zhao, H. Cui, M. Qu, Z. Xu, Y. Zhang, and C. Ma, "Impact of Preoperative Chemotherapy on Cutaneous Wound Healing in Lung Cancer Patients: A Meta-Analysis," International Wound Journal 21, no. 4 (2024): e14518, https://doi.org/10.1111/iwj.14518. The above article, published online on 20 December 2023, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor in Chief, Professor Keith Harding; and John Wiley & Sons, Ltd. Following an investigation by the publisher, all parties have concluded that this article was accepted solely on the basis of a compromised peer review process. The editors have therefore decided to retract the article. The authors did not respond to our notice regarding the retraction.

RETRACTION: Meta-Analysis on the Impact of Immune Senescence: Unravelling the Interplay in Cutaneous Wound Healing and Lung Cancer Progression.

M. Dong, Y. Jin, X. Lin, S. Wang, and P. Shen, "Meta-Analysis on the Impact of Immune Senescence: Unravelling the Interplay in Cutaneous Wound Healing and Lung Cancer Progression," International Wound Journal 21, no. 2 (2024): e14756, https://doi.org/10.1111/iwj.14756. The above article, published online on 09 February 2024, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor in Chief, Professor Keith Harding; and John Wiley & Sons Ltd. Following an investigation by the publisher, all parties have concluded that this article was accepted solely on the basis of a compromised peer review process. The editors have therefore decided to retract the article. The authors did not respond to our notice regarding the retraction.

Randomized-Controlled Trial Comparing Safety and Efficacy of Repairing Balm vs Topical Antimicrobial for Post-Procedural Wounds.

Actinic keratoses (AK) are pre-cancerous, intraepidermal lesions that exist on a continuum with squamous cell carcinoma. Cryotherapy using liquid nitrogen freezing is the most common method for treating AKs. Following cryotherapy, wound care often involves antimicrobial ointments as prophylactics against infection. However, given the rise in antibacterial resistance and possible contact dermatitis, equivalent alternatives should be identified. Cutaneous wound healing is important in dermatologic conditions. Evaluate the safety (adverse events) and efficacy (erythema and oozing/crusting, speed of recovery) of post-procedural wound healing of AK lesions, when using either a topical antibiotic (PSO), or a nonprescription repairing balm containing panthenol, madecassoside, and metal salts (CB5). A multicenter, intra-individual, randomized control trial was conducted. Sixty participants with at least 3 AK lesions on each arm were enrolled. Following cryotherapy, 3 lesions were selected on each arm for study and control treatment. The treatment of the right or left arm was randomly assigned to either the control group (PSO) or the investigational group (CB5), so that each subject participated in both the investigational and control arms. At each visit, the physician assessed the skin condition (erythema, oozing/crusting) and adverse events, and subject satisfaction was recorded. Results: There were no clinically significant differences in time to lesion healing, erythema, or oozing/crusting between groups. On day 21, 100% of patients agreed that their lesions had improved. No adverse events related to the study products were reported throughout the trial. Conclusion: Post-procedural treatment with CB5 and PSO demonstrated equivalent wound healing in participants undergoing liquid nitrogen cryotherapy for AKs without the potential for further adverse effects. Lynde CW, Andriessen A, Guenther L, et al. Randomized-controlled trial comparing safety and efficacy of repairing balm versus topical antimicrobial for post-procedural wounds. J Drugs Dermatol. 2025;24(5):507-515. doi:10.36849/JDD.8746R1.

The antiprotease Spink7 promotes inflammation resolution by modulating multiple proteases activities during wound healing.

Effective control of inflammation is crucial for the healing of cutaneous wounds, but the molecular mechanisms governing inflammation resolution during wound closure are still not yet clear. Here, we describe a homeostatic mechanism that facilitates the inflammation resolution by timely regulating the targeted proteases activities through antiprotease Spink7 (serine peptidase inhibitor, kazal type 7). The expression pattern of Spink7 was investigated by quantitative RT-PCR, immunohistochemistry (IHC) and in situ hybridization. In both Spink7 knockdown and knockout models, quantitative comparisons were made between the healing rate of wounds and histopathological morphometric analysis. Microarrays, multiple chemokine assays, IHC, immunofluorescence, protease activity measurement were performed to explore the underlying mechanisms of Spink7 knockout in impaired wound healing. Radiation-wound combined injury (R-W-CI) model was employed to evaluate the therapeutic effects of Spink7 manipulation. Our study demonstrates that Spink7 is significantly upregulated in the differentiated epidermal granular keratinocytes of proliferative phase during murine wound closure. Both local knockdown of Spink7 levels in wounds using siRNA gel and systemic knockout of Spink7 using KO mice resulted in delayed wound closure with sustained neutrophil infiltration. Loss of Spink7 leads to augmented inflammatory responses, increased production of multiple chemokines/cytokines, and impaired M2 polarization of macrophages in wound healing. Furthermore, loss of Spink7 results in elevated proteolytic activities of uPA, MMP2/9 and KLK5/7 in proliferative phase. However, inhibiting KLK5/7 downstream PAR2 activation exacerbates the phenotype of KO mice. In R-W-CI model, further significant induction of Spink7 is observed in wounds with insufficient inflammatory response. Local suppression of Spink7 promotes wound healing in the R-W-CI model by augmenting inflammation. Maintaining an endogenous balance between Spink7 and its target proteases is a crucial checkpoint for regulating inflammation resolution during healing. Therefore, manipulating levels of Spink7 might be an effective treatment for impaired wounds caused by inflammatory dysregulation.

Interleukin-8/Matrix Metalloproteinase-9 Axis Impairs Wound Healing in Type 2 Diabetes through Neutrophil Extracellular Traps-Fibroblast Crosstalk.

Neutrophils interact with and activate fibroblasts through the release of neutrophil extracellular traps (NETs). We investigated the role of NETs-fibroblast crosstalk in the cutaneous wound healing of type 2 diabetes (T2D). Neutrophils/NETs, serum, and primary human skin fibroblasts (HSFs) were obtained from individuals with T2D and age/sex-matched controls. NET-stimulation studies were performed on neutrophils/HSFs, with and without specific inhibitors, while HSF healing capacity was assessed using a scratch wound healing assay. T2D HSFs display a profibrotic phenotype, showing increased CCN2/CTGF, α-smooth muscle actin, and collagen release, albeit with impaired healing capacity, elevated type I collagen C-terminal telopeptide, and collagen degradation associated with increased (∼3.5-fold) matrix metalloproteinase-9 (MMP-9) in T2D neutrophils/NETs. IL-8 induced the expression of MMP-9 in neutrophils/NETs. Moreover, T2D neutrophils/NETs exhibited increased IL-8 content, which acted in an autocrine/paracrine fashion to further augment its production by neutrophils/HSFs. The findings were validated in normoglycemic individuals during a hyperglycemic clamp with concomitant lipid infusion and further corroborated immunohistochemically in diabetic plantar ulcer biopsies. This novel, vicious circle of NETs/interleukin-8/MMP-9/HSFs was hindered by IL-8 or MMP-9 blockade via specific inhibitors or by dismantling the NET-scaffold with DNase I, suggesting candidate therapeutic targets in wound healing impairment of T2D.

Comparative evaluation of cutaneous wound healing in castrated and uncastrated black bengal goats

Castration leads to testosterone depletion, which may impact the efficacy of cutaneous wound healing. The present study aims to compare cutaneous wound healing in castrated and uncastrated goats, assessing morphological, hemato-biochemical, and histopathological parameters. Ten apparently healthy goats, who have body weights of 15 to 20 kg and ages ranging from 2 to 3 years, were used in this experiment. A total of 40 full-thickness incised wounds were made by giving a 1-inch-long linear incision on either side of the vertebral column, and studies were conducted in two groups: uncastrated (group A) and castrated (group B). Morphological characters with morphometric data were recorded at different day intervals. On days 3rd, 7th, and 15th post-wound creation, blood and biopsies were taken for hemato-biochemical and histopathological assessment. The wound healing days were monitored for 18 days, and morphological and morphometric data indicated that wound healing occurred faster in the animals of Group B (15 days) compared to those in Group A (18 days), as confirmed by histopathological findings of biopsy samples. The average wound contraction rate in Group B was significantly higher (P<0.05) than that in Group A. During this study, the values of hemoglobin, packed cell volume, total erythrocyte count, total leukocyte count, total protein, and albumin were altered at different time intervals, but these changes were not statistically significant in both groups. These findings suggest that castration positively influences wound healing efficiency by optimizing the inflammatory phase and promoting faster tissue regeneration.

Maresin-1 impairs cutaneous wound healing response.

Maresin-1 is a derivative of docosahexaenoic acid with strong anti-inflammatory action in various disease models. However, these effects may not always be beneficial. In instances like cutaneous diseases in which wound healing is important, inflammation is required. In this study, we investigated the effects of maresin-1 on cutaneous wound healing and found that wound healing was significantly delayed in maresin-1-treated mouse skin in the early phase of wound healing on days 1 to 3. Histological analyses revealed that maresin-1 suppressed re-epithelization in the wounded skin. Despite the direct influence of maresin-1 on keratinocyte migration, a comprehensive quantitative polymerase chain reaction analysis revealed that maresin-1-treated wound skin showed a decrease in tumor necrosis factor α, indicating that maresin-1 indirectly suppresses keratinocyte migration mediated by reduced tumor necrosis factor α derived from wounded skin, leading to delayed wound healing.

Cutaneous wound healing functions of novel milk-derived antimicrobial peptides, hLFT-68 and hLFT-309 from human lactotransferrin, and bLGB-111 from bovine β-lactoglobulin

The absence of multi-functional antimicrobial agents in clinical settings hinders cutaneous wound healing. Milk-derived antimicrobial peptides (MAPs) may be the imperative solution to wound repair, combining the dermatic curative properties of antimicrobial peptides with the biological activity of milk. Three novel MAPs, which were hLFT-68 (IAENRADAV) and hLFT-309 (GSPSGQKDLLF) identified in human milk and bLGB-111 (LDTDYKKY) identified in bovine milk in our previous work, were initially investigated for their function in wound healing. In vitro, the antibacterial activity and cellular mechanism of the MAPs were examined. It was found that they presented inhibition for Staphylococcus aureus and Escherichia coli, decreased the secretion of inflammatory factors (IL-1β, IL-6, and TNF-α), and promoted fibroblast and keratinocyte proliferation. An infected wound model was established to evaluate the in vivo anti-inflammatory and regeneration properties of the MAPs. The wound area shrank more rapidly, and the wound inflammation was reduced by MAP treatment. Especially on days 3–5 after mouse modeling, the wound repair rate increased by up to 35%. Furthermore, it was suggested that they encouraged collagen synthesis and deposition, and tissue regeneration. The presented results indicated that MAPs accelerated the recovery of infected wounds, possessing the potential for developing wound-healing therapy.