Chronic diabetic foot ulcers and venous leg ulcers remain difficult to treat due to delayed healing and high complication rates. Biologic skin allografts derived from living or amniotic tissue provide extracellular matrix components, cytokines, growth factors and viable cells that facilitate tissue repair. This investigation systematically reviewed randomised controlled trials comparing Apligraf, Theraskin, Amnioband, Amnioexcel, EpiCord and Epifix for chronic lower extremity wounds. Searches were conducted in PubMed, Embase and Cochrane databases. Primary outcomes included complete wound closure at 12 weeks, time to healing and percent area reduction. Secondary outcomes included infection, amputation and recurrence rates. Nineteen trials with a total of 1303 participants met inclusion criteria. Analysis demonstrated statistical significance in 12-week wound closure (p = 0.0394), with Theraskin achieving the highest mean closure (84.7%) and Amnioexcel the lowest (37.5%). Epifix and Amnioband showed faster healing trends and greater closure advantages compared with standard care. Reported complications were uncommon and inconsistently defined. While no single graft demonstrated statistically superior outcomes, descriptive trends suggest Theraskin, Epifix and Amnioband may offer greater clinical benefit. These findings provide comparative insight to guide clinical selection of skin substitutes and highlight the need for large-scale head-to-head trials to establish relative efficacy.

Immunoglobulin A (IgA)-mediated vasculitis is a small-vessel vasculitis defined by IgA-dominant immune complex deposition. Although common in children, adult-onset cases are rare and may signal underlying malignancies. In this case report, we present a 60-year-old male with chronic lymphocytic leukemia (CLL) under observation for his painful purpura and non-healing leg ulcers, with a biopsy confirming IgA vasculitis. His course was further complicated by steroid-induced diabetes, poor wound healing, recurrent infections, and fatal respiratory failure. He remained steroid-dependent with recurrent ulcer flares on tapering and infections, including pneumonia and varicella-zoster. Flow cytometry revealed persistent clonal B-cell populations with stable lymphocyte counts, suggesting subclinical CLL-driven immune dysregulation. This case highlights adult-onset IgA vasculitis as a potential paraneoplastic clue of indolent CLL even in the absence of leukemia progression. It underscores the importance of early malignancy screening, coordinated multidisciplinary care, and early steroid-sparing therapy in adult vasculitis patients with atypical features.

Smart bioresponsive hydrogels have emerged as a transformative solution for the management of chronic wounds, such as diabetic foot ulcers, venous leg ulcers, and pressure sores, which are often complicated by persistent inflammation, infection, and biochemical dysregulation. Unlike traditional dressings, these advanced materials are engineered to respond to intrinsic wound stimuli such as pH, reactive oxygen species (ROS), glucose, and enzymatic activity, enabling spatially and temporally controlled drug release. This review comprehensively examines the design principles, biochemical triggers, and functionalization strategies behind stimuli responsive hydrogels. We explore diverse hydrogel classes, including single and multi-stimuli systems, and in-depth functional augmentations, such as antibacterial agents, angiogenic growth factors, and self-healing adhesion mechanisms. A major emphasis is placed on emerging integration with digital health platforms such as wearable biosensors, implantable systems, and AI driven wound analytics, which enable real time monitoring and closed loop drug delivery. Comparative analyses between academic prototypes and existing commercial products are discussed alongside translational barriers related to clinical trials, regulatory challenges, and manufacturing scalability. The review concludes by outlining a prospective roadmap for AI personalized, multifunctional all-in-one hydrogel systems that integrate biomaterials with biosensing and telemedicine capabilities. This manuscript provides a detailed and timely resource for researchers, clinicians, and bioengineers seeking to bridge the gap between hydrogel innovation and clinical impact.

Venous leg ulcers (VLUs) are a chronic condition with significant healthcare costs. UK clinical guidelines recommend regular physical activity for VLU management, but evidence on its efficacy in promoting healing and preventing recurrence remains limited. This systematic review aimed to evaluate the effectiveness of exercise interventions, in addition to standard care, on VLU outcomes. A comprehensive search of databases was conducted up to May 22, 2025. The review followed PRISMA guidelines and registered on PROSPERO (CRD420251057818). Eligible studies included adults with VLUs and an ankle-brachial pressure index greater than 0.8. Only randomised controlled trials comparing exercise plus standard care with standard care alone and reporting ulcer-related outcomes were included. Nine trials were included, with 133 patients receiving exercise interventions and 137 receiving standard care. All studies combined exercise with compression therapy. Intervention duration ranged from 4 to 12 weeks. A meta-analysis of eight studies showed a significantly higher healing rate in the exercise group (RR = 1.35). Subgroup analysis revealed statistically non-significant higher effect sizes for hospital-based programmes (RR = 1.69) compared to home-based ones (RR = 1.22). Five studies reported ulcer area reduction, with a non-significant pooled standardised mean difference (SMD) of 0.72. No studies reported ulcer recurrence. Both home- and hospital-based exercise programmes appear to improve VLU healing rates when added to standard care, although current evidence is limited by small sample sizes, methodological variability, and lack of recurrence data. Future trials should standardise protocols and include long-term follow-up to guide clinical practice.

Leg ulceration is a complex clinical presentation; accurate assessment and diagnosis are essential to ensure safe and effective treatment. Misdiagnosis can result in delayed healing, unmanaged pain, inappropriate use of compression therapy and avoidable complications. The Lindsay Leg Club Foundation supports both nurses and patients by promoting evidence-based education and social engagement. Ongoing professional development is essential to improve diagnostic competence and reduce variation in care.

Venous leg ulcers are the most common type of chronic wound, representing the most advanced stage of chronic venous insufficiency. Their long healing time and high recurrence rates significantly impair patients' quality of life. Management largely relies on self-management strategies, including wearing compression therapy, engaging in physical activity, and following an adapted diet. Structured and individualized educational interventions improve knowledge, foster engagement in treatment, and contribute to earlier wound healing. This article summarizes the available evidence on the role of therapeutic patient education in managing venous leg ulcers.

Objective: To explore the clinical efficacy of using the anterolateral thigh flap (ALTF) combined with "Y"-shaped great saphenous vein graft in repairing large soft tissue defects in the proximal-middle segment of the lower leg. Methods: This study was a retrospective case series study. From January 2019 to December 2023, 8 patients with large soft tissue defects in the proximal-middle segment of the lower leg meeting the inclusion criteria were admitted to the Department of Hand & Foot and Reconstructive Microsurgery of Shandong Provincial Hospital Affiliated to Shandong First Medical University, including 7 males and 1 female, aged 15 to 63 years. After the wounds were cleaned and the infection was controlled, the areas of soft tissue defects in the lower leg ranged from 18 cm×7 cm to 30 cm×14 cm. The ALTF combined with "Y"-shaped great saphenous vein graft was conducted to repair the soft tissue defects in the lower leg. The flap harvest areas were 19 cm×8 cm to 31 cm×15 cm. Intraoperatively, the bifurcated ends of the "Y"-shaped great saphenous vein were end-to-end anastomosed with the descending genicular artery and the medial femoral muscle branch (MFMB), respectively, and the main trunk end was end-to-end anastomosed with the descending branch of lateral femoral circumflex artery (LFCA-DB), constructing a "dual-in, single-out" venous bridging mode. The dominant concomitant vein of LFCA-DB was end-to-end anastomosed with the recipient great saphenous vein. If there was no suitable vein in the recipient area of the lower leg for anastomosis with the dominant concomitant vein of LFCA-DB, a segment of the great saphenous vein from the contralateral lower leg was harvested and bridged to the dominant concomitant vein of LFCA-DB, and then end-to-end anastomosed with the above-knee great saphenous vein. The flap donor site wounds were directly sutured in 3 cases, and repaired with full-thickness skin grafts from the ipsilateral inguinal region in 5 cases. The length of the flap pedicle vessels and the length of the defect between the flap pedicle vessels and the planned anastomotic descending genicular artery and MFMB were recorded. Postoperatively, the flap survival and the wound healing in the donor sites were observed. During follow-up, the appearance, texture, and sensory recovery of the flaps, the recovery of flap donor sites, and the limb swelling in the vein donor sites were observed. At the last follow-up, the 5-point Likert scale was used to investigate the satisfaction of patients with the treatment effects in the flap recipient and donor sites. Results: The lengths of the flap pedicle vessels of patients were 12 to 17 cm, with an average of 14.1 cm. The lengths of the defects between the flap pedicle vessels and the planned anastomotic descending genicular artery and MFMB were 9 to 16 cm, with an average of 12.3 cm. Postoperatively, all flaps survived completely, without vascular crisis; all flap donor site wounds healed well. During follow-up of 12 to 40 months, the flaps of 6 patients showed no bulkiness; two flaps developed local bulkiness due to compression during the subsequent tibial bone transport treatment, of which one case improved after surgical debulking, and one case received no modification treatment. The flaps were soft in texture, with moderate tension and no ulcer, and all regained protective sensation. The flap donor sites all recovered well. The direct suture areas left slight linear scars, the skin grafted areas left slight scars, and the limbs in the vein donor sites showed no swelling. At the last follow-up, the satisfaction scores of patients with the treatment effects in the recipient and donor sites were all 4 and 5. Conclusions: The application of ALTF combined with "Y"-shaped great saphenous vein graft anastomosed to the descending genicular artery and MFMB to repair large soft tissue defects in the proximal-middle segment of the lower leg can effectively achieve the caliber physiological matching of the donor and recipient vessels, ensure the blood supply of the large-area flaps through dual blood supply, and avoid the periwound inflammation to reduce the risk of vascular crisis. The patients are satisfied with the treatment effect of the donor and recipient sites.

Chronic wounds, diabetic foot ulcers, venous leg ulcers, and pressure injuries affect millions of patients worldwide and cost healthcare systems in the order of $150 billion annually, yet treatment options have changed less than the scale of the problem would suggest. Biofilm formation, documented in up to 78% of chronic wounds, is a central cause: bacteria embedded in extracellular polymeric matrices tolerate antimicrobial concentrations up to 1000-fold higher than planktonic cells and sustain a chronic inflammatory state that actively prevents tissue repair. Hydrogels, crosslinked polymer networks with high water content and tunable physicochemical properties, have been widely studied as platforms for addressing these challenges, though the distance between laboratory results and clinical practice remains considerable. While recent reviews have summarized hydrogel materials or antimicrobial strategies in isolation, this review takes a different approach: we treat infection, biofilm persistence, and impaired regeneration as interconnected processes that must be addressed simultaneously, and we examine biofilm management as a distinct therapeutic target rather than merely a subset of antimicrobial delivery. We analyze hydrogel-based wound care across three integrated domains: design principles (natural, synthetic, and hybrid polymer systems; crosslinking strategies; and stimuli-responsive architectures), antimicrobial delivery (silver, antibiotics, antimicrobial peptides, natural agents, and controlled-release systems), and biofilm management (nanoparticle-mediated disruption, enzymatic EPS degradation, photodynamic approaches, quorum-sensing inhibition, and anti-adhesive surface engineering). For each area, we critically evaluate what the preclinical evidence supports, where it falls short, and what would be needed to bridge the gap to clinical application. Translation remains uneven. Among the many FDA- and EMA-cleared hydrogel dressings currently in clinical use, most are simple moisture-retaining or silver-containing formulations, while the multifunctional systems that dominate the research literature are at earlier stages of development. We discuss the main translational priorities, including more predictive preclinical models, long-term nanomaterial safety, harmonized outcome reporting, manufacturing scalability, and health economic evidence, as areas where further work can meaningfully accelerate clinical adoption.

Leg ulcer (LU) is a chronic complication of sickle cell disease (SCD), characterised by intense pain, treatment resistance and a high impact on the patient's quality of life (QoL), representing a significant public health challenge. Clinical management involves multifaceted approaches; however, the variability in response to conventional treatments highlights the need for more effective and evidence-based alternatives. Photobiomodulation (PBM) emerges as a promising intervention, with the potential to accelerate tissue healing and reduce pain in patients with SCD-associated LUs. This study conducted a systematic literature review following PRISMA 2020 guidelines, covering relevant databases. Four studies meeting the inclusion criteria were selected, and methodological quality was assessed using the Joanna Briggs Institute tool. Findings indicated that PBM promoted cell growth, accelerated healing and relieved pain, with three studies reporting pain reduction and one study describing a decrease in edema and inflammation. Granulation tissue formation was observed in three of the four studies analysed, and ulcer area reduction was noted in three studies, with one reporting complete healing. Despite the encouraging results, the scarcity of specific studies and the absence of robust randomised clinical trials underscore the need for further research to validate its effectiveness and establish consistent clinical protocols. Expanding these investigations may consolidate PBM as a safe, effective and cost-efficient therapeutic option for patients with SCD-related LUs, contributing to the optimisation of healthcare practices.

Cellular, acellular or matrix-like products (CAMPs), also referred to as 'skin substitutes', are applied to chronic wounds to help expedite healing when standard therapies fail. However, their efficacy is compromised by infection, and possibly high bacterial loads, as suggested in prior literature. This prospective observational pilot study explored the association between bacterial burden and early healing outcomes in chronic diabetic foot ulcers and venous leg ulcers following skin substitute application. Bacterial fluorescence imaging was performed immediately prior to skin substitute placement to identify areas of high bacterial load (positive fluorescence), with wound area reduction tracked at 4 ± 1 weeks postapplication. Of the 10 patients analysed, the primary endpoint of achieving 40% wound area reduction was met by 4/5 of baseline fluorescence negative wounds, compared to 0/5 baseline fluorescence positive wounds (p < 0.05). The baseline fluorescence negative group showed a 68.0% wound area reduction, in contrast to the baseline fluorescence positive group, which showed a 33.7% increase in wound area (p < 0.05). Taken together with existing evidence, these findings suggest that elevated bacterial load during CAMP application significantly impedes early wound healing. Bacterial fluorescence imaging is an effective tool to optimise wound bed preparation and identify the best candidate for skin substitute application.

Wound healing is a major medical challenge as acute injuries affect millions annually, while chronic wounds such as diabetic foot and venous leg ulcers persist in 1-2% of patients, driving substantial morbidity and ~4% of global health-care expenditure. In response to an injury, restoration of skin barrier is critical process and regulated at multiple levels involving coordinated communications and interaction among keratinocytes, immune cells, and fibroblasts. In vivo mouse models are essential for dissecting the cellular and molecular regulators of normal and pathological repair, especially given the availability of transgenic tools and cell-sorting methods. However, the most common back-punch excisional model heals predominantly by panniculus carnosus-mediated contraction (up to 90%), which limits granulation tissue formation and affects reepithelialization. The mouse tail excisional model provides an alternative to back-punch model as wound closure yielding robust granulation and epithelial coverage due to the "splinting" effect of the tail structure. Here, we describe a detailed, reproducible protocol for tail excisional wounds optimized for histology, cryosectioning, and downstream cell isolation for single-cell multi-omic analyses.