The 2025 research landscape delivered significant advances across the translational spectrum, from molecular mechanisms to clinical prediction tools. This comprehensive review highlights the year’s most impactful contributions to wound healing science.
The Wound Reporting in Animal and Human Preclinical Studies (WRAHPS) Guidelines
Ojeh N et al., Wound Repair Regen
The Wound Reporting in Animal and Human Preclinical Studies (WRAHPS) Guidelines represent a consensus-driven effort to address the persistent lack of uniform standards in translational wound healing research. The guidelines provide comprehensive checklists and reporting templates for the most frequently employed preclinical models, standardizing methodology reporting across the field.
Clinical significance: Standardized reporting frameworks enable meaningful cross-study comparisons, facilitate meta-analyses, and improve reproducibility of preclinical findings, all critical prerequisites for successful translation to clinical applications.
Read this article at https://pmc.ncbi.nlm.nih.gov/articles/PMC11621255/
High Transepidermal Water Loss at the Site of Wound Closure Is Associated With Increased Recurrence of Diabetic Foot Ulcers: The NIDDK Diabetic Foot Consortium TEWL Study
Sen CK et al., Diabetes Care
The NIDDK Diabetic Foot Consortium conducted a prospective study of 418 patients with diabetes to identify risk factors for diabetic foot ulcer (DFU) recurrence. The investigation revealed that elevated transepidermal water loss (TEWL) at sites of apparent wound closure correlates with increased recurrence risk, indicating incomplete restoration of epidermal barrier function. TEWL measurement provides a non-invasive, objective assessment tool for stratifying recurrence risk.
Clinical application: TEWL-based risk stratification enables targeted allocation of preventive interventions to high-risk patients, potentially reducing the substantial morbidity and healthcare costs associated with recurrent DFUs. This biomarker-driven approach facilitates the transition from empirical follow-up protocols to evidence-based, individualized surveillance strategies.
Read this article at https://pmc.ncbi.nlm.nih.gov/articles/PMC12178626/
Still not sterile: viability-based assessment of the skin microbiome following pre-surgical application of a broad-spectrum antiseptic reveals transient pathogen enrichment and long-term recovery
TOWNSEND et al., Microbiology Spectrum
This study employed viability-based assessment methodologies to characterize the skin microbiome following chlorhexidine gluconate (CHG) application in pre-surgical protocols. While CHG significantly reduced viable microbial load, complete sterilization was not achieved. Notably, CHG exposure induced transient enrichment of potentially pathogenic bacteria, including Acinetobacter, Pseudomonas, Bacillus, and Escherichia-Shigella species, which demonstrate high minimum inhibitory concentrations to CHG. Longitudinal analysis demonstrated that microbial community structure recovers post-operatively in healthy individuals, confirming microbiome resilience.
Clinical implications: These findings challenge the assumed benefits of broad-spectrum antiseptic application and suggest that selective pressure may transiently favor CHG-resistant opportunistic pathogens. The data underscore the need for refined antiseptic protocols that balance microbial reduction against dysbiosis-associated risks.
Read this article at https://pmc.ncbi.nlm.nih.gov/articles/PMC12054058/
Type III Collagen Regulates Matrix Architecture and Mechanosensing during Wound Healing
Stewart D et al., Journal of Investigative Dermatology
Comparative studies utilizing the regenerative African Spiny Mouse (Acomys) model identified sustained type III collagen (COL3) expression as a critical determinant of regenerative versus fibrotic healing outcomes. Conditional knockout of the Col3a1 gene resulted in delayed wound closure, impaired re-epithelialization, increased granulation tissue formation, and elevated myofibroblast activation. Mechanistic investigation revealed that COL3 deficiency promotes integrin switching, specifically upregulating the pro-fibrotic integrin α11, thereby modulating cellular mechanosensing and fibrotic responses.
Mechanistic insight: COL3 functions not merely as a structural component but as an active regulator of extracellular matrix organization and mechanotransduction pathways. The integrin-switching mechanism provides a molecular explanation for the divergence between regenerative and scarring phenotypes, identifying COL3 modulation as a potential therapeutic target for reducing pathological fibrosis.
Read this article at https://pmc.ncbi.nlm.nih.gov/articles/PMC12359077/
GLP-1 Receptor Agonists as Emerging Modulators of Inflammation and Angiogenesis in Chronic Cutaneous Wound Healing
Ghebrehiwet-Kuflom J et al., Journal of Investigative Dermatology
This investigation characterized the effects of glucagon-like peptide-1 (GLP-1) receptor agonists on wound healing parameters, specifically examining their modulatory effects on inflammatory responses and angiogenic processes in chronic cutaneous wounds. The study documents improvements in healing outcomes associated with GLP-1 agonist therapy, expanding the therapeutic profile of this drug class beyond metabolic regulation.
Clinical relevance: With the widespread and increasing prescription of GLP-1 receptor agonists for diabetes mellitus and obesity management, understanding their pleiotropic effects on tissue repair is of immediate clinical significance. The anti-inflammatory and pro-angiogenic properties may contribute to improved wound healing in the substantial patient population receiving these medications for metabolic indications.
Read this article at https://www.jidonline.org/article/S0022-202X(25)02434-0/abstract
The Role of Endothelial Cell-Derived Extracellular Vesicles in Modulating Fibroblast Function in Skin Wound Healing
Yuan H et al., Journal of Investigative Dermatology
This study demonstrated that endothelial cells secrete extracellular vesicles (EVs) that modify fibroblast function in both in vitro and in vivo wound models. The findings identify a novel paracrine signaling mechanism linking vascular proliferation to fibroblast-mediated matrix deposition during tissue repair.
Mechanistic significance: The endothelial-fibroblast communication pathway mediated by EVs represents an under-utilized dimension of wound healing coordination. This intercellular crosstalk mechanism has implications for understanding the coupling between angiogenesis and matrix remodeling. It presents multiple potential therapeutic intervention points in the EV biogenesis, cargo loading, and recipient cell uptake pathways.
Read this article at https://www.jidonline.org/article/S0022-202X(25)03499-2/fulltext
Implementing a Chronic Wound Care Workshop for Internal Medicine Residents
White-Chu EF et al., Wound Repair and Regeneration
This educational initiative addresses the significant gap in chronic lower extremity wound (CLEW) education within U.S. medical school curricula. The program combines online didactic content with practical workshops targeting clinical-year medical students. Assessment data demonstrate significant improvements in student confidence regarding diagnostic evaluation and treatment planning for chronic wounds.
Educational impact: The demonstrated efficacy of structured CLEW curricula provides a model for addressing systemic deficiencies in wound care education. Future investigation will assess long-term knowledge retention and the curriculum’s effect on clinical practice patterns and potential biases in chronic wound patient care.
Read this article at https://journals.lww.com/aswcjournal/abstract/2019/02000/implementing_a_chronic_wound_care_workshop_for.6.aspx
Using R, Seurat, and CellChat to Analyze a Single-Cell Transcriptomics Dataset of Mouse Skin Wound Healing
Wietecha M et al., JoVE
This protocol provides a comprehensive, step-by-step workflow for analyzing single-cell RNA sequencing time-course datasets from wound healing models using R-based tools (Seurat and CellChat). The methodology requires no prior bioinformatics expertise and includes complete code, quality control procedures, visualization approaches, cell type annotation strategies, and cell-cell interaction analysis frameworks.
Technical advancement: By reducing the technical barriers to single-cell transcriptomic analysis, this resource democratizes access to cutting-edge analytical methodologies. The protocol enables laboratories without dedicated bioinformatics support to leverage single-cell technologies, potentially accelerating discovery across the wound healing research community.
Read this article at https://www.jove.com/t/67266/using-r-seurat-cellchat-to-analyze-single-cell-transcriptomics
Targeting circulating mechanoresponsive monocytes and macrophages to reduce fibrosis
Chen K et al., Nature Biomedical Engineering
This investigation demonstrated that mechanical conditions in fibrotic tissue instruct mechanosensitive macrophage populations to promote fibrosis progression. Using strain devices replicating the mechanical environment of human hypertrophic scars, the study showed that progressive mechanical loading of incisional wounds generates macrophage populations with pro-fibrotic transcriptomic profiles while suppressing anti-inflammatory signatures. Pharmacological inhibition or genetic ablation of focal adhesion kinase (FAK) in macrophages reduced scar formation, eliminated pro-fibrotic macrophage phenotypes, and restored anti-inflammatory immune profiles characteristic of unstressed healing. Mechanosensitive macrophage populations were subsequently identified in human skin and liver fibrosis specimens.
Therapeutic implications: The FAK-dependent mechanotransduction pathway in macrophages represents a targetable mechanism linking biomechanical forces to pathological fibrosis. FAK inhibition may interrupt the positive feedback loop between mechanical stress and pro-fibrotic immune responses, offering a novel therapeutic approach for hypertrophic scarring and fibrotic diseases.
Read this article at https://www.nature.com/articles/s41551-025-01479-5
Chronic Wound Initiation: Single-Cell RNAseq of Cutaneous Wound Tissue and Contributions of Oxidative Stress to Initiation of Chronicity
Jabbari P et al., PMC
Single-cell transcriptomic analysis of cutaneous wound tissue during the transition from acute to chronic healing revealed that chronicity initiation is multifactorial, involving diverse cell types and cellular functions. The investigation identifies elevated oxidative stress (OS) and its association with wound infection and biofilm formation as fundamental processes underlying chronic wound development.
Conceptual framework: The multifactorial nature of chronic wound pathophysiology explains the limited efficacy of single-target therapeutic approaches. The identification of oxidative stress as a common upstream mediator provides a unifying mechanism that, if addressed, may simultaneously impact multiple downstream pathological processes, including persistent inflammation, impaired angiogenesis, and defective matrix remodeling.
Read this article at https://pmc.ncbi.nlm.nih.gov/articles/PMC11852160/
Increased ROS and Persistent Pro-Inflammatory Responses in a Diabetic Wound Healing Model (db/db): Implications for Delayed Wound Healing
Elajaili H et al., International Journal of Molecular Sciences
This study characterized the diabetic wound microenvironment in db/db mice, revealing dramatically elevated reactive oxygen species (ROS) levels and persistent pro-inflammatory conditions dominated by Ly6C^hi macrophage populations. These alterations impair fibroblast function and arrest tissue repair progression, providing a molecular-level definition of the cellular and oxidative mechanisms underlying delayed diabetic wound healing.
Mechanistic specificity: The identification of Ly6C^hi macrophages as key mediators of ROS production and sustained inflammation provides specific cellular and molecular targets for therapeutic intervention. This mechanistic precision enables the development of targeted therapies addressing the root causes of diabetic healing impairment rather than symptomatic management of downstream consequences.
Read this article at https://www.mdpi.com/1422-0067/26/10/4884
CYP24A1 is overexpressed in keloid keratinocytes and its inhibition alters profibrotic gene expression
Hahn JM et al., Burns & Trauma
This investigation identified overexpression of CYP24A1, a vitamin D-metabolizing enzyme, in keloid lesions and keloid-derived cells. Elevated CYP24A1 activity reduces local active vitamin D concentrations, potentially creating a pro-fibrotic microenvironment. Pharmacological inhibition of CYP24A1 using ketoconazole or VID400 increased active vitamin D levels and reduced pro-fibrotic gene expression in keloid cells.
Translational potential: The connection between dysregulated vitamin D metabolism and keloid pathogenesis identifies a novel mechanistic pathway and potential therapeutic targets. The availability of FDA-approved CYP24A1 inhibitors (ketoconazole) facilitates rapid clinical translation through drug repurposing approaches, potentially bypassing lengthy development timelines associated with novel therapeutics.
Read this article at https://pmc.ncbi.nlm.nih.gov/articles/PMC11736898/
CDK1-loaded extracellular vesicles promote cell cycle to reverse impaired wound healing in diabetic obese mice
Choi W et al., Molecular Therapy
This study demonstrated that engineered extracellular vesicles loaded with cyclin-dependent kinase 1 (CDK1) protein cargo promote cell cycle entry and reverse impaired wound healing in diabetic obese mice. The approach utilizes naturally-derived vesicles as delivery vehicles for specific protein payloads, enabling targeted local delivery with minimal systemic effects.
Platform technology implications: Engineered EV-based protein delivery represents a novel therapeutic modality combining the targeting capabilities of biologics with the cellular uptake efficiency of endogenous communication systems. The platform’s modularity enables adaptation for the delivery of diverse protein cargos, establishing a new class of cell-free biologics for wound therapy applications.
Read this article at https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(25)00044-9
Synthesis and Future Directions
The 2025 research landscape demonstrates the strength and breadth of the WHS community, with members driving increasing sophistication in mechanistic understanding across multiple scales, from molecular pathways to cellular interactions to systems-level integration. WHS researchers are simultaneously advancing discovery science while establishing critical infrastructure through standardized reporting frameworks, educational curricula, and accessible analytical tools that benefit the entire field.
The trajectory indicates a maturing discipline led by WHS members who are capable of dissecting complex, multifactorial pathophysiology while maintaining focus on clinically actionable insights. The challenge ahead lies in translating these mechanistic advances into therapeutic interventions that demonstrate efficacy in the heterogeneous patient populations encountered in clinical practice, a challenge that the WHS community will continue to address with the same level of rigor, collaboration, and innovation that characterized 2025.
Translation happens faster with a community. Join WHS now to connect with researchers accelerating discovery into clinical impact through our annual meeting and member network. Your next breakthrough collaboration starts here.