Chronic lower limb wounds are especially difficult to heal when further vascular reconstruction is not feasible, yet evidence for noninvasive adjunctive therapies in this population remains limited. Intermittent vacuum therapy (IVT) exposes the limb to alternating negative and positive pressure, but clinical wound-healing evidence is scarce. We evaluated whether adjunctive IVT was associated with faster complete healing in a single-centre retrospective age- and sex-matched cohort. Ninety-four patients treated between December 2019 and June 2022 were included: 47 received IVT plus standard wound care and 47 received standard wound care alone. IVT comprised three 30-40-min sessions weekly. Complete epithelialization was the event; unhealed wounds were censored at the last documented follow-up. Kaplan-Meier analysis and Cox regression stratified by wound aetiology were used. Complete healing occurred in 36 of 47 IVT-treated wounds (76.6%) and 23 of 47 controls (48.9%); the Kaplan-Meier median time to healing was 4.0 versus 17.0 months. After multivariable adjustment, IVT was associated with a higher rate of healing (hazard ratio, 10.73; 95% confidence interval, 4.37-26.38; p < 0.001), and sensitivity analyses supported the direction of the primary association. Because treatment was nonrandomised and clinically important baseline imbalances persisted after matching, residual confounding may substantially affect the magnitude of the estimate. These findings support prospective randomised multicentre evaluation of IVT as an adjunct to standard care.
Previous systematic reviews of stem cell-based therapies for lower limb ulcers have largely focused on arterial, diabetic or mixed-aetiology ulcers, while evidence in strictly defined pure venous ulcers remains scarce. This systematic review evaluated the efficacy and safety of stem cell-based and stem cell-related regenerative therapies for pure venous ulcers. PubMed, Embase, Web of Science and the Cochrane Library were searched up to February 2026 for comparative clinical studies. Studies involving arterial, diabetic, mixed or non-venous ulcers, non-comparative designs or insufficiently extractable data were excluded. Three studies involving 43 patients were included, comprising two randomised controlled trials and one non-randomised comparative study. Interventions included autologous bone marrow-derived mesenchymal stem cells in fibrin spray, hair follicle-containing punch grafts and antlerogenic stem cell extract. In one randomised double-blind pilot trial, mesenchymal stem cells in fibrin spray accelerated linear healing by approximately 10-fold compared with saline spray and fibrin spray alone (p < 0.01). Another randomised trial found greater ulcer area reduction at 18 weeks in hair follicle-treated areas than in control areas (75.15% [SD 23.03] vs. 33.07% [SD 46.17], p = 0.002). The non-randomised study reported significant improvements in wound area, circumference and healing-related indices, although Ki-67 expression did not differ significantly. No major treatment-related safety concerns were reported, although adverse-event data were limited. Current evidence suggests potential benefit, but findings remain preliminary because of small samples, heterogeneous interventions and variable outcome definitions. Larger standardised studies are needed. Trial Registration: CRD420261304878.
Fibroblasts are essential for tissue repair, but persistent activation of matrix-remodelling myofibroblasts can promote fibrosis, tissue stiffening and immune dysfunction. LRRC15 is a leucine-rich repeat-containing cell-surface protein enriched in selected activated mesenchymal compartments, with the strongest functional evidence arising from cancer-associated stroma. State-level evidence also links LRRC15 to a TGF-β-regulated extracellular matrix-remodelling myofibroblast state in idiopathic pulmonary fibrosis and to disease-specific myofibroblast programs in human skin, including inflamed hidradenitis suppurativa associated with scarring risk. However, LRRC15-specific causal evidence in physiological wound repair and pathological scarring remains limited. This review therefore considers LRRC15 positivity a context-dependent stromal state rather than a universal fibroblast lineage or intrinsically pathological identity. Focusing on pulmonary fibrosis and tumour stroma, with skin repair as a comparative framework, we integrate single-cell transcriptomics, spatial mapping, matrix biology and cancer immunology. Current evidence supports LRRC15 as a marker of activated stromal programs and, in selected tumour models, as a contributor to immunoregulatory stromal function, but does not establish universal control of fibroblast contractility, matrix persistence, or scar formation. We propose that temporal persistence and anatomical context may distinguish adaptive from maladaptive LRRC15-associated remodelling. Across tissues, these observations suggest related or convergent programs rather than a demonstrated conserved molecular identity. The proposed repair-to-pathology spectrum is therefore hypothesis-generating and requires validation through temporal lineage tracing, tissue-relevant LRRC15 perturbation, spatial protein analysis, and stage-specific therapeutic studies. LRRC15 is best viewed as a biological readout and potential targeting handle whose significance must be defined in each tissue context.
Impairment of cutaneous healing occurs in association with numerous comorbidities including diabetes, vascular insufficiency and immobility. Standard management of chronic wounds includes removal of necrotic tissue and infection management, but no biomarkers are used to guide appropriate debridement distance. We hypothesized that by understanding the spatial distribution of proteins associated with keratinocyte differentiation and activation, oxidative stress biomarkers, as well as accumulation of oxidative damage, debridement protocols could be refined. Human tissue was isolated from (1) routine debridement procedures or (2) endstage at limb amputation. In debridement samples, wound edge epithelium typically exhibited hyperproliferation with or without epibole, with endstage wounds exhibiting a much thinner epidermis. Cytokeratin 14 expression was increased throughout the suprabasal epidermis with cytokeratin 10 and filaggrin expression attenuated; endstage wounds displayed downregulation of both cytokeratin 10 and filaggrin further from the wound edge than observed in debridement tissue. Cytokeratin 6, 16 and 17 were expressed in the wound edge and adjacent uninjured epidermis in both debridement and endstage wounds, while cytokeratin 16 and 17 were expressed in the non-involved interfollicular epidermis in endstage limbs. Both phospho-nuclear factor kappa B and the antioxidant transcription factor phospho-nuclear factor-erythroid 2-related factor 2 show increased nuclear localization in the keratinocytes of endstage compared to debrided wounds concomitant with increased oxidative damage to lipids, protein and DNA in the epidermis. Our observations demonstrate increased tissue damage in endstage wounds compared to debridement tissue, which provides a preliminary starting point for the future investigation of several potential biomarkers associated with wound chronicity in humans.
Cutaneous scarring remains a major clinical challenge, often resulting in impaired function, altered tissue mechanics, and poor aesthetic outcomes. Most current anti-fibrotic therapies target late-stage fibrosis, when extracellular matrix deposition and myofibroblast persistence are already established, limiting regenerative benefit. We propose that scar formation is governed not by gradual accumulation of fibrotic signals but by an early mechanically regulated commitment event, that precedes overt fibrosis. We introduce the concept of a PIEZO-gated mechanotransduction timing window, a finite early interval during which mechanical cues determine whether wound repair remains plastic or becomes irreversibly stabilised. In this framework, tensile load, matrix resistance, and spatial confinement generate force signals sensed by PIEZO mechanosensitive ion channels, triggering calcium-dependent pathways that initiate cytoskeletal remodelling and transcriptional reprogramming. When mechanically induced states are amplified through multicellular feedback linking stromal lineage conversion with immune-mediated matrix reinforcement, repair transitions from reversible intermediates to a self-maintaining fibrotic configuration. Window closure occurs once contractility-stiffness feedback establishes mechanical self-reinforcement, rendering lineage identity persistent even if upstream signals decline. This model predicts that therapeutic efficacy depends primarily on timing: early intervention can redirect repair towards regenerative architecture, whereas delayed intervention mainly reduces fibrotic burden without restoring native tissue organisation. The mechanotransduction timing window therefore represents a measurable and potentially actionable control phase for timing-guided regenerative strategies and predictive mapping of fibrotic risk.
Delayed re-epithelialisation is a key feature of chronic and recurrent cutaneous wounds, but the metabolic mechanisms that coordinate keratinocyte migration and epidermal barrier restoration remain incompletely defined. Here, we investigated whether NUCB2/Nesfatin-1 regulates keratinocyte-driven wound repair through cholesterol biosynthesis. Transcriptomic profiling revealed coordinated downregulation of cholesterol biosynthetic genes in NUCB2-deficient keratinocytes. Concurrently, gene signatures associated with cell motility and epithelial plasticity were also suppressed. Functionally, NUCB2 depletion impaired CCK-8-based metabolic/proliferative activity, scratch-wound closure, Transwell migration and epithelial marker expression, whereas exogenous Nesfatin-1 partially restored these defects. Mechanistic analyses showed that NUCB2/Nesfatin-1 enhanced mTORC1 downstream signalling, increased nuclear SREBP2 abundance and HMGCR expression, and promoted intracellular cholesterol accumulation. Cholesterol supplementation or HMGCR overexpression partially restored cholesterol availability and migratory capacity in NUCB2-deficient keratinocytes, whereas rapamycin attenuated Nesfatin-1-associated SREBP2-HMGCR induction, cholesterol accumulation and migration. In a murine full-thickness excisional wound model, local Nesfatin-1 administration accelerated wound closure and enhanced early re-epithelialisation, accompanied by increased SREBP2 and HMGCR expression at the wound-edge epidermis. Complementary local Nucb2 silencing delayed wound closure. These findings define a NUCB2/Nesfatin-1-mTORC1 downstream signalling-SREBP2-HMGCR axis that supports cholesterol-dependent keratinocyte migration and epidermal repair.
This first comprehensive systematic review aimed to summarise evidence on independent prognostic factors for wound healing in people with venous leg ulcers. In June 2025, we searched Ovid MEDLINE, Ovid Embase, CINAHL and additional resources for studies with 100 or more participants that used multivariable analyses and longitudinal data to explore the prognostic value of factors in this area. Two reviewers extracted data and assessed risk of bias using the Quality In Prognosis Studies (QUIPS) tool and certainty of evidence using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach. We synthesised studies narratively and, where applicable, pooled data using meta-analyses. We identified 30 studies with 66,099 participants living with venous leg ulcers. We rated 14 studies at moderate risk of bias, and the remaining 16 studies were at high risk of bias. The included studies explored 116 prognostic factors. The evidence is uncertain or limited for the majority of the 116 prognostic factors. There is moderate-certainty evidence, suggesting no association between complete healing and the factors of age in years (HR 0.99, 95% CI 0.97 to 1.0; OR 1.00, 0.99 to 1.02, for every year increment), and the presence of total deep reflux in the leg veins (HR 0.89, 0.75 to 1.05). Those having the presence of dermatitis likely have lower odds of complete healing (OR 0.51, 0.50 to 0.52). Although a wide range of factors have been investigated as potentially associated with venous leg ulcer healing, the evidence base for most is uncertain or limited.
Topical treatment of burn wounds remains challenging because eschar formation, inflammation and impaired vascularization can limit drug penetration and tissue repair. Here, we introduce a flexible large-area microneedle patch for sustained local delivery of extracellular matrix-derived peptides to deep partial-thickness burn wounds. The microneedles were composed of cellulose acetate phthalate and hydroxypropyl methylcellulose and included a transparent water-soluble backing layer to aid placement and allow dissolution after application. The patch delivered two peptides with previously reported biological activity: TSN6, associated with angiogenic responses and TSN18, associated with cell proliferation and epithelial repair. The microneedles retained sharp conical geometry after peptide loading, showed sufficient compressive strength for skin insertion and produced consistent microchannels in ex vivo porcine skin. In vitro studies showed peptide-dependent release over 48 h: TSN18 reached approximately 50% release within 12 h and exceeded 80% release by 48 h, whereas TSN6 was released more slowly, reaching 45% when loaded alone and 58% when co-loaded with TSN18. In a porcine deep partial-thickness burn model, TSN18-treated wounds showed lower burn depth than SSD-treated wounds at day 4 (1174 ± 35 vs. 1628 ± 178 μm, p < 0.05). Co-delivery of TSN6 and TSN18 preserved more dermis than the scrambled peptide control (1667 ± 134 vs. 938 ± 194 μm, p < 0.05) and increased neoepidermal thickness at day 20 compared with scrambled peptide and SSD controls (417 ± 45 vs. 237 ± 25 and 265 ± 16 μm, respectively). Although consistent improvements in macroscopic wound closure and re-epithelialization were not observed across peptide-treated groups, these results show that microneedle-mediated peptide delivery can improve selected tissue-level measures of burn injury and epidermal repair.
Hidradenitis suppurativa (HS) can be treated surgically to excise recurrent and recalcitrant regions of disease activity. However, surgical outcomes are highly variable depending on closure method, concomitant medical management and area of excision. In this study, we aim to characterise the healing courses from HS excision in a case series. To reduce operator variability, we opted to conduct a case series from a single surgeon. Surgeries conducted from June 2024-December 2025 by surgeon S.T. were included, and the postoperative course was followed until February 2026. Surgical details and postoperative course for 34 sites of HS across 20 patients were analysed. For operations undergoing primary closure (14/34), median wound healing time was 131 days, while sites healing by secondary intention (20/34) had a median wound healing time of 161 days. Four out of seven surgically closed sites on patients undergoing tumour necrosis factor alpha (TNF-α) inhibitor therapy experienced dehiscence, while six out of ten surgically closed sites while the patient was on interleukin-17 (IL-17) inhibition experienced dehiscence. Surgical excision of HS with either primary or secondary closure had a median wound healing time of 138 days. Primary closure of excisions, even with mobilisation of flaps to reduce tension, results in high rates of dehiscence, especially for patients on adjuvant biologic therapy. Our limited case series observed high rates of dehiscence amongst patients receiving either IL-17 inhibitors or TNF-α inhibitors. To our knowledge, this is the first study comparing wound healing between patients on TNF-α inhibitors versus IL-17 inhibitors versus no biologic therapy. HS patients considering surgery should be counselled on these possible risks and expected wound healing times for primary versus secondary intention healing.
The integration of Internet of Things devices in medicine has paved the way for novel diagnostic and therapeutic solutions that offer 'smart' capabilities, especially for at-home wound monitoring. Such capabilities include increasing portability, diminished gaps in care through continuous analysis, and real-time programmable manipulation of device parameters to intervene more rapidly. This scoping review explores the landscape of Internet of Things devices, including smart bandages, wearable and skin-interfaced sensors, and mobile app-connected devices, specifically designed for chronic wound monitoring in a remote, at-home setting. We reviewed literature from PubMed, IEEE Xplore, Scopus, and Web of Science, using keywords related to Internet of Things and chronic wound care. The evaluation criteria focused on biomarkers analysed, Internet of Things connectivity technology, experimental models used for device validation, and unique device strengths or weaknesses. Our review identified 52 unique studies comprising 77 data entries across five biomarker categories: gas and oxygen saturation, pH, metabolic markers, biophysical parameters of the wound microenvironment, and molecular markers of inflammation or infection. These devices span a wide landscape of biomarkers analysed to predict and monitor wound recovery, with the potential to improve patient outcomes through personalised treatment and timely interventions. However, many devices were never validated clinically on humans and faced limitations in power delivery, accuracy, stability, and reliability that challenge their potential usability in humans for wound monitoring. This review provides a comprehensive understanding of the potential and limitations of Internet of Things devices in at-home wound care, highlighting areas for future research and development.
Wounds affect millions worldwide and non-healing wounds are characterised by excessive protease activity, impaired extracellular matrix remodelling and persistent inflammation, highlighting the need for innovative extracellular matrix-based therapies. This study evaluated a micronized collagen wound matrix (Collagen Wound Matrix-Micronized; CWM-MZ), a biomaterial derived from porcine small intestinal submucosa and processed into a micronized form. Physical and structural properties of CWM-MZ were characterised using collagen content and structure, sulphated glycosaminoglycan content, deoxyribonucleic acid removal, particle size and its ability to inhibit protease activity. Functional in vitro assays were used to assess biochemical responses using dermal fibroblasts and endothelial cells under conditions simulating wound fluid to evaluate effects on cell viability, migration, sulphated glycosaminoglycan production, collagen type I deposition and tube formation. Physically and structurally, CWM-MZ preserved the native collagen architecture, was robustly decellularized and exhibited dose-dependent inhibition of multiple proteases, achieving over 80% inhibition of matrix metalloproteinases. Using in vitro cell-based assays, CWM-MZ resulted in enhanced fibroblast viability, supported fibroblast migration, increased sulphated glycosaminoglycan and collagen type I production and led to more robust formation of capillary-like structures by endothelial cells. These results highlight how CWM-MZ may support an environment for wound healing and its continued evaluation as a novel extracellular matrix-based biomaterial for wound management.
Whilst total body surface area, burn depth and age are established determinants of hospital stay, the independent influence of the anatomical region's biological microenvironment remains unexamined. This study evaluates the association between regional perforator artery density, hair follicle density and LOS in patients with second-degree burns. A single-centre retrospective cohort study was conducted on 1593 patients with second-degree burns. An isolated single-region subgroup (n = 352) was analysed independently. Regional perforator and hair follicle density data were compiled from published anatomical references. Scald burns were the most common aetiology (78.3%), with a predominantly paediatric population (71.0% under 18 years). In the isolated burn subgroup, LOS differed significantly between anatomical regions. The lower extremity had the longest LOS (4.71 ± 4.35 days), whilst the perineum had the shortest (2.00 ± 1.73 days). Perforator density showed a strong negative correlation with LOS (Spearman rs = -0.900; p = 0.037), and hair follicle density demonstrated a strong trend. The head-neck region, with the highest combined density, had the shortest LOS (2.72 days); the lower extremity, with the lowest combined density, had the longest (4.71 days; post hoc p = 0.004). Regional perforator and hair follicle density are significant biological determinants of LOS in second-degree burns, independent of TBSA.
The detrimental effects of dysfunctional mitochondria on cells and tissues have been shown to improve by healthy mitochondria transplantation. However, the feasibility of intercellular mitochondrial transfer for wound healing remains uncertain. This study examined whether healthy mitochondria transplantation promoted the healing of acute wounds. Isolated mitochondria derived from primary cultured normal human dermal fibroblasts were administered to primary cells of the same lineage, with confirmed cell uptake. Wound closure rate in in vitro scratch wound healing assays increased in a dose-dependent manner and was attenuated by treatment with the mitochondrial function inhibitor antimycin A. Gene expression analysis revealed significant increases in the cell proliferation markers MKI67 and PCNA, although no consistent changes in migration-related genes were observed. Cell proliferation rate increased to a maximum average of 1.4-fold after isolated mitochondrial administration, which was attenuated by antimycin A treatment. To verify the in vivo effects of isolated mitochondrial transplantation, mitochondria were obtained from mouse livers, and wound closure rate was analysed using a mouse wound healing model. The number of days to wound closure was significantly shortened in a dose-dependent manner, and this gain was attenuated by antimycin A. Our findings demonstrate that mitochondrial transplantation accelerates acute wound closure and enhances fibroblast proliferative activity. The observed increase in cell proliferation may contribute, at least in part, to the beneficial effects of mitochondrial transplantation on wound healing. These findings provide insight into the therapeutic potential of mitochondrial transplantation as a novel strategy for wound repair.
Diabetic foot ulcers (DFUs) are the leading cause of amputations in people with diabetes, mainly due to poor wound healing. This study evaluated DFU trial designs and analysed observational data from the two prospective Diabetic Foot Consortium (DFC) studies to estimate longitudinal healing and amputation rates, assess the effects of wound surface area and duration on healing, and inform sample size considerations for future trials. We analysed data from Open Wound Master Protocol (MP, n = 419) and c-Myc Biomarker (n = 140). The primary outcome was complete wound healing. Time-to-event analysis estimated healing and amputation rates, with amputations classified as non-healed. Logistic regression assessed the prediction of healing based on baseline wound characteristics, with model performance evaluated using AUC (area under the curve). Sample size calculations were performed to achieve 80% power. In the MP study, healing rates were 26% by week 12% and 49% by week 32; amputation rates were 4% and 10%, respectively. The c-Myc study showed 38% healing and 2.5% amputation by week 12. Wound area and duration significantly predicted healing (AUC ≥ 0.70 by 24 weeks). For smaller treatment effects, predicted healing rates varied by up to 40% between small and large wounds, impacting sample size. Contemporary DFU trial designs and healing times remained largely unchanged over two decades. While shorter trials (e.g., 12 weeks) theoretically require smaller sample sizes due to reduced outcome variance, they risk failing to capture the full treatment effect. Trial design must account for baseline wound characteristics, which should inform eligibility criteria and follow-up.
Elevated lactate dehydrogenase (LDH) levels are associated with tissue hypoxia, ischemia and inflammation, and have been linked to increased risks of multiple diseases. However, evidence regarding the association between LDH and diabetic lower extremity ulcers (DLEU) remains limited. This cross-sectional study aimed to evaluate this relationship using data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). Among 1620 enrolled diabetic participants, DLEU prevalence was 8.1% (131/1489). Serum LDH levels were categorised into sextiles: < 113, 113-125, 126-137, 138-152, 153-172 and > 172 U/L. Multivariable logistic regression, subgroup analysis, restricted cubic spline (RCS) modelling and sensitivity analysis revealed a U-shaped association between LDH and DLEU. The inflection point occurred at approximately 125 U/L: Below 125 U/L, each 10-U/L increase in LDH was associated with a 26% reduction in DLEU risk (odds ratio [OR] 0.740, 95% confidence interval [CI]: 0.560-0.978, p = 0.034); above 125 U/L, each 10-U/L increment corresponded to a 6.5% increase in DLEU risk (OR 1.065, 95% CI: 1.003-1.131, p = 0.039). Thus, analysis of this nationally representative cohort demonstrates a nonlinear relationship between LDH and DLEU incidence, characterised by distinct risk thresholds.
Chronic and complex wounds represent a major clinical and economic burden, requiring frequent assessment, early detection of complications, and accurate prediction of healing outcomes. Conventional wound evaluation is often subjective and time-intensive, motivating the development of automated approaches. Machine learning (ML) has emerged as a powerful tool for wound management by enabling wound detection, segmentation, tissue characterisation, infection assessment, and healing prediction using wound images, clinical records, and sensor-derived data. This structured narrative review summarises key ML and deep learning (DL) methods applied in wound care, including commonly used architectures, data modalities, and evaluation strategies. We critically discuss persistent barriers limiting clinical adoption, such as limited dataset size and diversity, annotation inconsistency, poor generalizability, bias, lack of external and prospective validation, and challenges related to privacy, regulation, and clinical workflow integration. Finally, we highlight emerging opportunities including multimodal learning, self-supervised learning, federated learning, explainable AI (XAI), and mobile or wearable technologies for continuous wound monitoring. Overall, ML has strong potential to improve the objectivity, efficiency, and personalization of wound care; however, clinically deployable solutions will require standardised datasets, transparent reporting, rigorous validation, and interdisciplinary collaboration.
Phototherapy may improve chronic wound healing through different mechanisms. We have investigated whether escalating doses of blue LED light treatment (λ = 405 nm) impact the chronic wound microbiota. Twenty-two patients with chronic wounds were sequentially assigned to a low dose (20 J/cm2, n = 7), medium dose (60 J/cm2, n = 8), or high dose (100 J/cm2, n = 7) of blue LED light. Bacterial counts, cytokine levels in wound fluid obtained by surface swab and wound size were determined at baseline. Four days after the baseline visit, wounds were irradiated six times with blue LED light at 2-3-day intervals over 2 weeks. Bacteria were semi-quantified just before and directly after each irradiation. Blue LED light reduced bacterial counts dose-dependently (p < 0.0001) and the mean ± SD log10 reduction of colony-forming units/swab from the six treatments was significantly larger for 60 J/cm2 (1.55 ± 0.33) and 100 J/cm2 (1.82 ± 0.22) compared with the 20 J/cm2 fluence (0.65 ± 0.095). The reductions of the 60 J/cm2 and 100 J/cm2 fluences did not differ (p = 0.180). Bacterial counts at follow-up (p = 0.668), 4 days after the last irradiation and the levels of selected cytokines (IL-1α, IL-1β, IL-6, GM-CSF, TNF-α and VEGF) did not change significantly from baseline. The linear healing rates from baseline to follow-up did not differ (p = 0.815) among the three groups. In conclusion, blue LED light treatment resulted in an immediate but transient reduction of bacterial quantities in chronic wounds, with no apparent advantage to increasing the dose from 60 J/cm2. There was no significant effect on wound healing of blue light treatment.
Ischial pressure ulcers (IPUs), severe complications in patients with prolonged immobility, are challenging due to high recurrence. Moving beyond anatomical closure, the field now prioritises functional-integrated reconstruction. This paradigm emphasises radical debridement and the transfer of well-vascularized perforator flaps to obliterate dead space, cover wounds, and restore protective sensation, aiming to break the recurrence cycle and restore patient autonomy. This review critically synthesises contemporary advances driving this shift. It details the development of precision and minimally invasive perforator flap techniques, including sensory nerve coaptation and chimeric designs. The integration of multimodal perioperative strategies, such as antibiotic-loaded bone cement and fluorescence angiography, is discussed. The adjunctive role of traditional Chinese medicine and the exploratory potential of regenerative approaches (stem cells, 3D-bioprinting) are considered. Finally, practical recommendations for implementing this holistic approach are provided, along with a clinical flowchart to guide staged management. By consolidating these advances, this review provides a framework to transition IPU management from simple wound healing towards comprehensive functional and social rehabilitation.
The purpose of this systematic review was to determine whether the addition of antimicrobial peptides (AMPs) to dressing materials enhances their wound healing capabilities when applied to S. aureus-infected wounds in rodent models. The primary objective was not to derive definitive efficacy conclusions, but to systematically assess the quality, consistency, and translational readiness of existing in vivo evidence for AMP-based dressings in excisional wound models to inform future in vivo experimental design. The systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two authors independently completed the literature search using three electronic databases and two databases for grey literature. Studies were included if they met pre-established inclusion criteria. Rate of wound healing was considered as the primary outcome; the secondary outcome involved histological analyses of tissue samples of the wounds. Risk of bias was assessed using the SYRCLE risk of bias tool for animal studies and meta-analysis was performed with pooled data from three or more studies reporting the same outcome, employing a random effects model. By the final timepoint, the meta-analyses identified a significant increase in wound healing rate in both rats (mean difference = 2.79%, 95% CI [1.52%, 4.06%], p < 0.0001) and mice (mean difference = 32.30%, 95% CI [18.06%, 46.54%], p < 0.00001) exposed to AMP-based dressing materials compared to AMP-free carrier materials. The significantly improved wound healing rates provide promising evidence that these materials are suitable for promoting the wound healing of S. aureus-infected wounds that may be investigated further in clinical studies.
