​​The International Journal of Tissue Repair (IJTR) is a global, open-access, peer-reviewed journal focused on cutting-edge research in wound healing and tissue repair, especially in the Cellular, Acellular, Matrix-like Products (CAMPs) space. IJTR publishes a wide range of content, including research articles, reviews, clinical trials, and guidelines. Supported by international experts, IJTR serves healthcare professionals dedicated to advancing wound care and tissue repair.
Global burden to local action: A pilot feasibility study of placental-based solutions for complex pressure ulcers using real-world evidence
Objective: To conduct a pilot feasibility assessment of a human amniotic tissue membrane (ATM) plus standard of care (SOC) compared with SOC alone in the treatment of pressure ulcers (PrUs) using real-world evidence from a national wound care database. Method: A multicenter retrospective matched-cohort study was conducted using de-identified electronic health record data extracted from the U.S. Wound Registry/Intellicure database, using records collected between February 2017 and December 2025. Adults with PrUs treated with ATM plus SOC or SOC alone were identified. Nearest-neighbor Mahalanobis matching balanced cohorts by demographic, comorbidity, mobility and wound-specific variables. Outcomes included percentage area reduction (PAR), wound healing trajectory, and composite clinical outcomes. Results: Following matching, 182 patients were included (91 ATM; 91 SOC). Cohorts were well balanced at baseline for age, sex, comorbidities, wound stage, tissue exposure and wound location. ATM-treated wounds were older and slightly larger at treatment initiation, but ATM was applied earlier following presentation to specialist care. Mean wound size reduction did not significantly differ between groups; however, ATM-treated wounds demonstrated a more favorable overall clinical trajectory. Healing or healed outcomes were observed in 63.7% of ATM-treated wounds compared with 48.4% in the SOC group (p=0.0449). Smoothed PAR trajectories suggested a trend toward greater wound improvement over time in the ATM cohort. Missing outcome data were more common in the SOC group and should be considered when interpreting comparative results. Conclusion: Although ATM was not associated with a statistically significant improvement in PAR, ATM-treated wounds were more frequently classified as healing or healed based on clinician-assessed outcomes.
Copyright (c) 2026 International Journal of Tissue Repair https://creativecommons.org/licenses/by-nc-nd/4.0
Shaping the Future of Wound Care: Highlights from APWCA Tissue Repair Summit Spring and Advanced Wound Care Summit 2026
Recommendations to inform National Coverage Determination development for skin substitutes in hard-to-heal wounds
Rapid growth in Medicare use of skin substitutes (CAMPs) has improved wound outcomes but raised concerns about fraud, waste, and rising costs. Recent reimbursement reforms appear to have caused disruptions in patient access and care delivery. An expert consensus panel recommends a wound‑agnostic national coverage approach focused on clinical need, 30‑day reassessment, and clear discontinuation criteria, while deferring detailed standards of care to local policies.
Calciphylaxis-associated pannicular wounds in end-stage renal disease: Recurrent disease, massive adipose necrosis, and eventual resolution through multidisciplinary management
Introduction: Calciphylaxis, also known as calcific uremic arteriolopathy, is a rare but life-threatening microvascular condition marked by arteriolar calcification, thrombosis, and progressive ischemic tissue necrosis. Mortality rates range from 45–80%, most commonly due to wound-related sepsis. Methods: Retrospective clinical data were extracted from wound center documentation for a 56-year-old woman with end-stage renal disease (ESRD) on dialysis who developed recurrent calciphylaxis-associated pannicular wounds. Care was organized using a structured 7-step wound management approach employed by our clinical team (etiology/perfusion; infection control; debridement; metabolic/nutritional optimization; off-loading/mechanical protection; dressing/host optimization; and advanced modalities such as negative pressure wound therapy (NPWT)). A coordinated multidisciplinary approach included nephrology-guided metabolic optimization, surgical debridement, and NPWT as the principal advanced wound modality. Results: The patient developed extensive coalescent necrosis with liquefactive adipose degeneration requiring aggressive surgical debridement, NPWT, and later transition to selected antimicrobial dressings during epithelialization. Conclusion: Severe recurrent calciphylaxis in adipose-rich regions can achieve full healing through coordinated multidisciplinary management integrating systemic optimization, operative intervention, and structured wound care.
Copyright (c) 2026 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0
VISTA: A clear view forward – a surgical pathway for limb preservation in diabetic lower extremity wounds
Importance: Lower extremity diabetic ulcers represent a major global healthcare burden, with high recurrence and amputation rates. Standard wound care pathways often emphasize infection control and short-term healing but neglect the structural and biomechanical drivers of re-ulceration and long-term limb loss. Importantly, these pathways often resort to amputation as a first-line treatment rather than prioritizing limb preservation through early, proactive surgical intervention. Objective: To introduce VISTA (Vascular Evaluation, Infection Control, Surgical Correction, Technologies & Therapies, and Amputation Prevention) as a comprehensive, surgical-first strategy for limb preservation in diabetic lower extremity wounds. Evidence review: A narrative synthesis of current diabetic foot ulcer (DFU) literature was performed, emphasizing limitations of conventional care, the role of biomechanical deformity, and the need for proactive, multidisciplinary surgical strategies. The framework was compared against the 2023 IWGDF guidelines and recent innovations in wound care and bone infection management. Findings: VISTA integrates vascular optimization, aggressive and innovative infection control, early surgical correction of deformities, advanced wound technologies, and a long-term commitment to amputation prevention. Minimally invasive and reconstructive procedures, such as tendon balancing, osteotomies, external fixation, and bioactive biomaterials, are emphasized within a staged, multidisciplinary model. VISTA shifts the care paradigm from reactive to proactive. Conclusions: VISTA redefines diabetic lower extremity wound care as a forward-looking, surgically oriented pathway that prioritizes early vascular assessment, structural correction, and innovation to achieve durable healing and long-term limb salvage. Large-scale studies are warranted to evaluate its impact on recurrence, amputation-free survival, and cost-effectiveness.
Use of a biosynthetic cellulose dressing in chronic venous leg ulcer healing: a self-controlled clinical service evaluation study
Aims: To evaluate the clinical effectiveness of Epiprotect, a biosynthetic cellulose (BC) dressing, in promoting healing of chronic venous leg ulcers (VLUs). Methods: A study at two community wound care centres involved 20 patients who received 4 weeks of standard care, followed by 8 weeks of standard care plus the application of Epiprotect. Outcomes measured included percentage wound area reduction (PWAR), pain, exudate, adherence, and the number of Epiprotect sheets used. Healing was evaluated clinically and via photos, with feedback from staff and patients. Results: Epiprotect led to consistent and significant improvements. PWAR increased (p=0.046 and p=0.017). By the end, 11 participants had achieved over 75% healing, out of those 8 had achieved over 90%, and 3 had complete closure. Pain scores fell to zero by weeks 10–12 (p<0.01), and exudate levels decreased (p=0.021). Adherence increased to 100% by week 12 (p=0.035), and strong correlations were observed among adherence, healing, and pain reduction (r>0.7, p<0.05). The average number of sheets used per patient was 2.20±1.05. Visual assessment showed better peri-ulcer skin and granulation tissue. Nursing staff found Epiprotect easy to apply and effective, while patients emphasised rapid pain relief and comfort. Conclusion: This evaluation shows that Epiprotect improves healing, reduces pain and exudate, and enhances adherence in chronic VLUs with minimal dressings. Patients and staff find it suitable for community care. Results support the need for larger trials comparing Epiprotect with standard care and other dressings.
Real-world outcomes of cellular, acellular, and matrix-like products (CAMPs) in Stage 3 pressure injury ulcers: A matched Medicare claims analysis (2016–2024)
Background: Stage 3 pressure injuries (PIs) are full-thickness wounds associated with high morbidity, frequent infection-related complications, and substantial healthcare utilization in adults with compromised mobility. Real-world outcomes of cellular, acellular, and matrix-like products (CAMPs) for Stage 3 PIs in Medicare populations have not been well characterized. Methods: We conducted a retrospective, matched-cohort study using Medicare claims data (2016–2024). Stage 3 PI ulcer treatment episodes were constructed using a 90-day clean period (defined as ≥90 days without wound-related services) and a 90-day episode definition and evaluated in a hospital outpatient department (HOPD)/inpatient-only sample. Episodes receiving CAMPs (identified by Q- and A- Healthcare Common Procedure Coding System (HCPCS) codes) were matched 1:1 to standard-of-care (SOC) episodes (which included sharp debridement without CAMPs) using a prespecified set of exact and range-based covariates including demographics, comorbidity burden, PI location markers, and timing measures. Outcomes included episode characteristics, complications (including sepsis), healthcare utilization, costs, and mortality (death within 90 days of episode end). Two minimum-duration cohorts were analyzed (90 and 120 days). Results: For the 90-day minimum cohort (n=7223 matched episodes per group), CAMP episodes had lower mean PI-associated spending ($36,397 vs $39,886; p=0.0003) and lower mean total all-cause spending ($46,905 vs $50,686; p=0.0006). Compared with SOC, CAMP episodes were associated with lower complications and healthcare resources utilization, including lower sepsis (26.1% vs 36.1%; p<0.0001), lower major amputation (2.2% vs 3.1%; p=0.0004), fewer emergency department (ED) visits (1.34 vs 2.04; p<0.0001) and inpatient visits (1.52 vs 2.24; p<0.0001), and lower mortality (17.8% vs 22.3%; p<0.0001). Episode length was longer with CAMPs (323.8 vs 302.1 days; p<0.0001). Findings were consistent in the 120-day minimum cohort (n=6139 per group), including lower mean total all-cause spending ($51,585 vs $56,865; p<0.0001), lower sepsis (28.8% vs 39.9%; p<0.0001), lower major amputation (2.4% vs 3.3%; p=0.0041), fewer ED visits (1.50 vs 2.29; p<0.0001) and inpatient visits (1.70 vs 2.49; p<0.0001), and lower mortality (18.4% vs 22.8%; p<0.0001). Episode length remained longer with CAMPs (359.6 vs 339.1 days; p<0.0001). Conclusions: In matched Medicare Stage 3 PI episodes managed in the HOPD setting, CAMP use was associated with lower rates of sepsis, acute-care utilization, major amputations, mortality, total and PI ulcer–associated spending despite longer episode duration. These results further support confirmatory work incorporating greater clinical granularity and direct healing endpoints.
Human keratin matrix use and wound healing outcomes in post-acute care of pressure ulcers: Evidence from a Bayesian real-world study
Aims: To evaluate the real-world effectiveness of a human keratin matrix (HKM) compared with standard of care (SOC) in promoting pressure ulcer (PU) healing among patients treated in post-acute care settings. Methods: This observational comparative effectiveness study analyzed deidentified PU-level data from the LiftOff Registry, a national real-world database capturing post-acute wound care delivered in long-term acute care hospitals and skilled nursing facilities. PUs treated with HKM plus SOC were compared with those managed with SOC alone. Bayesian propensity score methods were used to reduce confounding and balance baseline demographic and clinical characteristics measured at PU identification. Healing—defined as complete epithelialization or closure—was modeled using Bayesian logistic regression with study arm and baseline PU stage as predictors. Treatment effects were summarized as posterior risk ratios (RR) with 95% highest density intervals (HDI) and posterior probabilities of benefit. Results: Before matching, the SOC cohort included 9356 patients with 14,740 PUs (33.2% healed), while the HKM cohort included 58 patients with 81 PUs (54.3% healed). After matching, 161 PUs were analyzed (81 HKM; 80 SOC); most were Stage 3 or Stage 4. HKM treatment was associated with higher modeled probabilities of healing compared with SOC alone. The posterior mean RR for healing was approximately 1.6 (95% HDI ≈ 1.0–2.1), with a posterior probability of benefit (RR > 1) of approximately 99.4%. Conclusion: In this real-world post-acute care cohort of patients with PUs, HKM use was associated with a high posterior probability of improved healing compared with SOC alone. These findings support HKM as an adjunctive therapy for complex or non-healing pressure ulcers in post-acute care settings.
Expert guidance for a pragmatic, evidence-based framework for skin substitutes (CTPs/CAMPs) across all chronic wound types
Efficacy of a dehydrated porcine placental extracellular matrix for the treatment of multiple chronic wound types in a private practice model: a retrospective feasibility study
Objective: To assess real-world effectiveness of Innovamatrix™, a dehydrated porcine placental extracellular matrix (PPECM), in chronic wounds refractory to 30 days of optimized standard-of-care (SOC) therapy. Methods: Multicenter retrospective analysis of 72 chronic wounds (18 diabetic foot ulcers (DFUs), 4 venous leg ulcers (VLUs), 12 pressure injuries, 38 open wounds) in 66 patients treated with sequential PPECM applications (between October 2023 and June 2025). All wounds showed <50% area reduction during SOC run-in and met Medicare Local Coverage Determination (LCD) eligibility. Primary endpoint focused on complete re-epithelialization (99.99% to 100% percent area reduction (PAR)). Secondary endpoints included PAR, applications to closure, and time-to-closure. Results: Wounds presented with a mean baseline area of 9.75 ± 15.97 cm2 and achieved a mean PAR of 85.92%. Complete closure occurred in 46/72 wounds (63.9%): 61.1% of DFUs healed, 50.0% pressure injuries healed, 76.3% open wounds healed, and 0% VLUs healed. Among healed wounds, the median number of applications to closure was 6 (mean 6.28 ± 3.58) with open wounds healing the fastest (median 4). Paired t-test showed statistically significant area reductions (t(71)=10.47, p<0.001; Cohen’s d=0.65). Etiology-specific effect sizes were moderate to large. Kaplan-Meier median time-to-closure was 43 days (95% CI 36-56). Conclusion: In complex, previously non-responsive, chronic wounds, PPECM achieved a 63.9% complete closure rate and 85.92% mean PAR. Healing outcomes in pressure injuries and open wounds were comparable or superior to DFUs. These data support broader, etiology-agnostic use of PPECM as an effective advanced therapy when combined with comprehensive SOC.
Evaluation of intact fish skin grafts plus standard care in the treatment of venous leg ulcers: an interim analysis of the THOR trial
Background: Venous leg ulcers (VLUs) are nonhealing wounds that pose considerable clinical and economic challenges. Healing outcomes with existing standard-of-care (SOC) remain limited, creating a pressing need for more effective therapeutic options Methods: An interim analysis of this randomized controlled multicenter clinical trial evaluated intact fish skin graft (IFSG) and SOC versus SOC alone in nonhealing VLUs. The primary end-point was the percentage of target ulcers achieving complete wound closure in 12 weeks, defined as 100% re-epithelialization without drainage for two consecutive weeks, confirmed by blinded independent review. Results: The statistical analysis revealed that the treatment arm trended toward improved full wound closure at 12 weeks over SOC by 1.52 (credible interval: 1.37–2.22) in terms of relative risk (Treatment/SOC). This translates to an improvement of 8.53% (credible interval: 5.60%-19.7%) in percentage terms. In the ITT population, the IFSG + SOC arm achieved a 47.6% closure rate versus 21.7% with SOC alone, a 25.9% absolute gain that was not statistically significant (n = 21, 95% CI -0.02% to 0.493%, p = 0.07, α = 0.05). In the ITT and PP population, IFSG + SOC achieved a higher mean area reduction than SOC. Conclusion: The interim analysis demonstrated a positive trend favoring IFSG products over SOC alone. While the present interim analysis provides promising early results, limitations inherent to its preliminary nature warrant consideration. The alignment of these interim findings with the broader body of evidence reinforces biological plausibility and strengthens confidence that the final analysis will yield clinically meaningful results supported by high-quality evidence.
Cellular, acellular, and matrix-like products
Copyright (c) 2025 International Journal of Tissue Repair https://creativecommons.org/licenses/by-nc-nd/4.0
Update: CMS Final DFU/VLU CAMP LCDs Effective January 1, 2026: Covered, Cut, Status Quo, and Emerging Collateral Statutory Constraints
Evaluation of single layer amniotic membrane in the management of nonhealing diabetic foot ulcers: an interim analysis of CAMPX
Background: Diabetic foot ulcers (DFUs) represent a chronic and debilitating complication of diabetes, contributing substantially to patient morbidity, mortality, and economic burden. Despite advances in clinical management, outcomes with the current standard of care (SOC) remain suboptimal, with many ulcers failing to achieve complete closure. These limitations reinforce the need for innovative, cost-effective solutions that promote wound closure. Methods: This randomized controlled multicenter clinical trial evaluated the efficacy of single layer amniotic membrane (SLAM) plus SOC versus SOC alone in achieving complete closure of nonhealing DFUs over 12 weeks. The primary endpoint was complete wound closure, defined as 100% re-epithelialization without drainage for two consecutive weeks, confirmed by blinded independent review. Results: In Intent-To-Treat (ITT), the SLAM + SOC arm achieved a 13.1% closure rate versus 8.8% with SOC alone, with findings consistent in the Per-Protocol (PP) population. Additionally, the percent area reduction (PAR) from TV-1 to TV-13 measured weekly with digital photographic planimetry and physical examination were analyzed. For ITT, SLAM + SOC outperformed SOC on both average and median wound‐area reduction. Conclusion: The interim analysis demonstrated that wounds managed with SLAM products trended toward superiority over those managed with SOC.
Real world evidence retrospective study to evaluate the safety and efficacy of an amniotic membrane allograft for venous leg ulcers in a post-acute care setting
Aims: To evaluate the reduction of wound size in venous leg ulcers (VLUs) after amniotic membrane allograft (AmnioBurgeon (OneBiotech, USA)) treatment. Methods: Single-center retrospective database study of patients treated with an amniotic membrane allograft for VLUs. Wound area was measured prior to each allograft application, and the change in wound area after each application was evaluated over the progression of therapy. Results: In total, 38 patients with 43 VLUs were treated weekly with AmnioBurgeon with an average wound size of 9.4 cm2. During the treatment course, 6% of the wounds completely healed with a mean time to healing of 38.8 days. 46% of the wounds partially healed with at least 50% or greater area reduction within 17.6 days on average. By the 4th week, 42% of wounds achieved 50% or more reduction in their size. Our treatment group included VLUs ranging between 0.25 cm2 and 25 cm2, achieving significant wound area reduction, indicating wound healing trajectory. Conclusion: Amniotic membrane allograft is an effective treatment for VLUs.
Evaluation of lyophilized human amnion/chorion membrane (LHACM) in the management of nonhealing diabetic foot ulcers: an interim analysis of the CAMPAIGN trial
Background: Diabetic foot ulcers (DFUs) are chronic wounds that contribute significantly to morbidity, mortality, and healthcare costs. Despite current standard-of-care (SOC) approaches, healing rates re-main suboptimal, emphasizing the urgent need for innovative and cost-effective treatment options. Methods: An interim analysis of this multicenter, prospective, randomized controlled platform clinical trial evaluated the efficacy of multiple lyophilized human amnion/chorion membrane (LHACMs) with SOC versus SOC alone. The primary endpoint was percentage of target ulcers achieving complete wound closure in 12 weeks, defined as 100% re-epithelialization without drainage for two consecutive weeks, confirmed by blinded independent review. Results: The statistical analysis revealed that the treatment arm improved full wound closure at 12 weeks over SOC by 2.6 (credible interval: 0.81 – 5.0) in terms of relative. The estimated probability of complete wound closure under SOC was 23% (6.5%–42%), compared with 47% (37%–59%) under the treatment arm. This corresponds to a posterior absolute difference of 24% (4%–43%). This suggests a posterior probability advantage of 98.5% for LHACM. Conclusion: The interim analysis revealed that the placental membranes products trended to-ward superiority over SOC. Bayesian posterior estimates indicated 98.5% higher probabilities of wound closure and improved healing trajectories in the treatment group. These interim data provide early evidence of clinical benefit, subject to confirmation with full trial completion.
A prospective, multicenter, randomized, controlled trial of non-healing diabetic foot ulcers treated with standard care with or without br-ac: top-line results
Aims: The primary objective of this randomized controlled trial was to determine whether non-ischemic, non-infected Wagner Grade 1-2 diabetic foot ulcers (DFUs) treated with standard care plus BioRetain Amniochorion (BR-AC) resulted in a higher probability of complete wound closure compared to standard care alone. Methods: Following a two-week run-in and stratified randomization, subjects attended clinic weekly for 12 weeks or until complete healing was observed. At each visit the wound was measured, debrided as needed, evaluated for infection and treated with or without BR-AC, followed by application of a non-adherent wound contact layer, a foam pad, alginate or hydrofiber dressing for moderately draining wounds, and a secondary retention bandage, including a standardized off-loading device. Bayesian statistics were used to evaluate the likelihood of healing. Results: The Intent to Treat (ITT) analysis showed a posterior mean absolute difference in healing rates between treatment and control of 0.22 (95% CrI: –0.01 to 0.45), with a 96.8% posterior probability that the effect exceeds zero and a posterior mean risk ratio of 1.9 (95% CrI: 0.87–3.2). The posterior mean probability of closure was 0.31 (95% CrI: 0.15–0.47) for the standard of care (SOC) arm (3% higher than the prior probability) compared with 0.53 (95% CrI: 0.34–0.74) for the treatment arm (18% higher than the prior probability). The treatment distribution was centered substantially higher, with limited overlap between intervals. The SOC arm showed a 36.4% posterior probability of closing by more than 50% at 12 weeks, compared with a 56.4% posterior probability for the treatment arm. Conclusion: This is the first controlled DFU trial examining a birth tissue product prepared using the ‘Bioretain’ method designed to retain integrity and contents. With only a 3.2% probability that BR-AC is not superior to SOC, these results provide strong evidence of treatment benefit.
Diabetic Foot, Foot Ulcer, Amniotic Membrane, Randomized Controlled Trial
A retrospective study on the outcomes of Mohs micrographic surgery for non-melanoma skin cancers (NMSC) using tri-layer amniotic membrane
Background: Non-melanoma skin cancers (NMSC), primarily basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), represent the most common malignancies worldwide. Mohs micrographic surgery (MMS) plays a crucial role in the management of these tumors, providing precise tumor clearance while maximizing the preservation of surrounding healthy tissue. Despite these advantages, post-surgical wound reconstruction for larger wounds and in specific anatomical locations can pose a challenge to the surgeon. Convex anatomic locations and poorly vascularized tissues (e.g., periosteum, cartilage, distal third of the lower extremities) may require months to heal. Healing time is influenced by wound size, depth, vascularity, and patient comorbidities. Cellular, acellular, and matrix-like products (CAMPs), such as tri-layered amniotic membrane (Amnio Tri-Core, Stability Biologics), have emerged as a promising reconstructive option. Objective: This retrospective study evaluated the clinical outcomes of patients undergoing MMS for the removal of NMSC. The post-surgical wounds were reconstructed using weekly applications of a tri-layered amniotic membrane. Analysis included time to complete closure and percentage wound area reduction (PAR). Methods: This multicenter study included 46 adult patients who underwent MMS for NMSC on regions such as the face, limbs, and neck. Patients with allergies to specific processing agents or incomplete records were excluded. Patients were divided into two groups: male (n=28) and female (n=18). The collected data included demographics, medical history, wound characteristics (type, location, and size), treatment details, and outcomes. Results: Complete closure was achieved in an average of 8.53 weeks. Conclusion: The results of this study suggest that wounds treated with tri-layer amniotic membrane after MMS can experience accelerated healing.
Comparison of intact fish-skin graft to standard of care for treatment of venous leg ulcers using real-world data from the USWR with 1:1 matching on 14 wound/patient factors
Background: Venous leg ulcers (VLUs) impose substantial morbidity and Medicare spending, yet many real-world ulcers remain refractory to standard of care (SOC). Intact fish-skin graft (IFSG) is a biologic graft used for chronic (hard-to-heal) wounds. We evaluated the comparative effectiveness of IFSG versus SOC in routine practice using a specialty wound registry with real world evidence design features intended to minimize bias. Methods: We performed a retrospective, target-trial–emulating, 1:1 propensity score–matched comparative-effectiveness study within the U.S. Wound Registry (USWR). Matching used 14 pre-specified patient- and wound-level covariates (including mobility as a measure of frailty and number of concomitant wounds). Results: The matched cohort included 129 IFSG-treated VLUs and 129 SOC-treated VLUs. Baseline balance was excellent by standardized mean differences; small residual differences favored SOC; IFSG wounds were older and trended larger. Healing occurred in 85.3% of IFSG wounds (110/129) versus 75.2% of SOC wounds (97/129); the absolute difference (+10.1%) was just below statistical significance (p=0.0801). SOC-treated VLUs increased in size on average more than IFSG-treated VLUs (p=0.0036). Conclusion: In a national wound registry with rigorous cohort construction, aligned index timing, comprehensive covariate control, and structured outcome capture, IFSG demonstrated favorable real-world effectiveness versus SOC for VLUs with a trend to-wards more healed wounds and a statistically significant lower average wound expansion. The high healing rate in the SOC arm is plausibly explained by baseline advantages (shorter duration, smaller area, and 'never-advanced-therapy' selection) as well as the absence of a set follow-up duration that typically extended until healing, a competing event, or administrative end of observation.
Venous leg ulcers; Real-World Evidence, chronic wounds; intact fish skin graft; tissue re-generation.
A retrospective case series: CAMPs for complex non‑healing wounds
Background: Chronic non‑healing wounds impose substantial clinical and economic burdens on patients and society. Patients with multiple comorbidities and risk factors are particularly vulnerable to developing wounds with delayed healing. Advanced wound care therapy such as cellular, acellular, and matrix‑like products (CAMPs) support wound healing when conservative treatment is insufficient. Results: Case 1 (91‑year‑old female, stage IV sacral ulcer): after wound‑bed preparation and 16 CAMP applications, surface area and volume reduced by 97% and 99%, respectively. Case 2 (74‑year‑old male, stage III sacral pressure ulcer while under treatment for pneumonia): 10 CAMP applications combined with negative pressure wound therapy (NPWT) achieved 70% surface area and 93% volume reduction; the patient subsequently died of pneumonia, unrelated to the wound. Case 3 (84‑year‑old female with dementia, venous leg ulcer with fat layer exposed): seven weekly CAMP applications with compression resulted in complete closure (100% reduction in area and volume). Case 4 (75-year-old female presented with an eight-year history of a chronic, non-pressure ulcer on the lower right leg with multiple ulcerations and sickle cell disease): 5 CAMP applications over 14 weeks achieving 100% healing. Case 5 (elderly male with pressure injury on lower right extremity: 10 CAMP applications with 100% wound healing. Conclusions: This case series exemplifies how advanced therapies such as CAMP treatment, in combination with standard of care treatment and patient compliance, results in substantial wound improvement and closure. Timely access for patients to receive CAMP therapy is essential to improve healing outcomes and improve quality of life measures.
Cold atmospheric plasma: a new modality to treat chronic diabetic foot ulcers, venous leg ulcers, and pressure ulcers
This study investigates the efficacy and safety of cold atmospheric plasma (CAP) in the treatment of 12 patients suffering from chronic wounds, focusing on diabetic foot ulcers (DFUs), venous leg ulcers (VLUs), and pressure ulcers. Chronic wounds represent a significant challenge in healthcare, often taking months to years to heal and imposing a substantial economic and quality of life burden on patients. CAP, an ionized gas at room temperature, is a source of reactive species, neutral particles, electromagnetic fields, and weak UV radiation. Its interaction with human cells stimulates wound healing processes, including cytokine release and angiogenesis, while exerting a bactericidal effect on prokaryotic cells. On average the 12 subjects had a percentage area reduction (PAR) of 21%, within the VLU group 60% of the subjects achieved a >40% PAR, and in the DFU group, 50% of the participants achieved a >40% PAR. Despite promising evidence from various studies, more data is needed to establish CAP as a standard treatment. This study contributes to the existing knowledge by evaluating the safety and effectiveness of CAP in treating long-standing and treatment-resistant ulcers. The study utilized the plasma care® device, a compact medical device that generates CAP using ambient air and energy. The plasma care® has shown notable efficacy in deactivating various bacteria and fungi, irrespective of antibiotic resistance.
A multicenter, prospective, randomized controlled modified multi-platform (matriarch) trial evaluating several cellular, acellular, and matrix-like products (CAMPs) and standard of care versus standard of care alone in the management of non-healing diabetic foot and venous leg ulcers (STABLECAMP)
Aims: To evaluate the efficacy of adjunct use of several cellular, acellular and matrix-like products (CAMPs) with standard of care (SOC), compared to SOC alone in the treatment of nonhealing diabetic foot ulcers (DFUs) or venous leg ulcers (VLUs) using a novel modified platform trial design. Methods: This is a multicentre, prospective, randomized controlled trial utilizing a modified platform design. Patients with non-healing DFUs or VLUs will be randomized into two groups: SOC alone or SOC plus several CAMPs; initial design is for up to 5 CAMPs per wound type, but the modified trial design can include additional CAMPs. The primary endpoint is complete wound closure within 12 weeks. Secondary outcomes include time to closure, percentage area reduction (PAR), patient-reported pain, adverse events, and quality of life, as measured by the Forgotten Wound Score and the Wound Quality of Life questionnaire. Exploratory objectives include assessment of offloading compliance and the proportion of subjects aged ≥65 years achieving complete wound closure. Results: The results will be reported following trial completion. Pooled results for DFUs and VLUs will be published separately, with a master publication for all pooled treatment arms vs pooled SOC arms. Conclusion: This trial is expected to provide high-quality efficacy data on several CAMPs used in addition to SOC and contribute to evidence-based practice in DFU and VLU management. The modified platform design offers a flexible and efficient approach to evaluating multiple interventions within a single clinical trial.
The biological imperative of cutaneous wounds: tissue repair
Clinical trials for cellular, acellular and matrix-like products (CAMPs): an evidence consensus
As Chair of the evidence consensus panel, I had the pleasure of convening the nation’s top experts in the field of wound healing on August 1, 2025, in Washington D.C.. The goals for the expert panel were twofold: 1) to address the evidence gap around the efficacy of cellular, acellular, and matrix-like products (CAMPs) in the treatment of nonhealing wounds and 2) to develop guidelines for the conduct of CAMP clinical trials. In 2024, the Medicare Administrative Contractors (MACs) published nearly identical Local Coverage Determinations (LCDs) requiring clinical trial evidence for reimbursement of CAMP products for diabetic foot and venous leg ulcers. The LCDs analyzed the available evidence for CAMPs and, based on their review, approved several products. After several delays, the MACs require products not on the list to submit peer-reviewed evidence submissions by November 1, 2025. I applaud CMS and the MACs for their reliance on clinical trial evidence; however, few of the patients enrolled in the approved RCTs published to date would meet the LCDs' requirements for medical necessity. Moreover, the LCDs do not provide any guidance on trial design or conduct to guide future research. The purpose of this evidence consensus is to define a practical, rigorous evidentiary bar spanning run-in requirements, consistent standard of care, pre-trial statistical analysis plans, validated clinical endpoints, complete datasets, and data transparency. In this way, investigators, sponsors, journals, and payers can align on what constitutes credible proof of benefit. The implications of publishing this consensus are immediate and material: it creates a uniform template for trials intended to support Medicare coverage, improves comparability across products, reduces bias and opaque practices, and prioritizes outcomes that matter to patients and clinicians. By articulating standards that reflect current best practice and analytic methods, this consensus gives CMS and the MACs a defensible basis for reimbursement decisions while accelerating access to effective CAMPs for beneficiaries and steering industry investment toward studies that will withstand regulatory and peer scrutiny.
Regulatory and reimbursement reform for cellular, acellular, and matrix-like products (CAMPs)
In August 2025, a national meeting was held in Washington, D.C., gathering 32 experts from across clinical, academic, manufacturing, legal and policy sectors to address the clinical, regulatory, and economic landscape of CAMPs. This consensus document summarizes key discussions from that meeting and the panel recommendations are aimed at improving the regulatory and reimbursement environment for CAMPs in the U.S., while concurrently ensuring Medicare beneficiaries have equitable access to advanced therapies for wound healing and amputation avoidance.
Evaluating the efficacy of placental-derived allograft in managing non-healing pressure ulcers
Background: Chronic wounds such as pressure ulcers (PUs) cause physical, emotional and financial strain on patients. Amniotic membranes have been demonstrated in previous studies to aid wound closure. Methods: This study aims to examine the efficacy of cellular, acellular, and matrix-like products (CAMPs) in achieving complete closure of PUs that were not responsive to standard of care (SOC) treatment. Results: Overall, 25 subjects with 37 pressure ulcers that had failed to heal with 6 weeks of SOC were treated with three-layer placental derived allograft (TLPA) for up to 16 weeks. Mean age was 69.3 years, 16 patients were female, and 9 were male. At baseline prior to intervention, mean wound size was 44.9cm2 (SD 103.5) and three (8.1%) PUs achieved 40% or greater percent area reduction (PAR). At the end of TLPA treatment, 33 (89.2%) of PUs had a PAR of 40% or greater. Conclusion: TLPA treatment was shown to achieve 40% or more wound area reduction in this cohort of 25 subjects with 37 PUs that had not responded to SPC. The observed rate of improvement supports further investigation of TLPA in prospective controlled studies to validate efficacy, assess time to closure, and determine cost-effectiveness for PUs.
Evaluation of dual layer amnion patch on the healing rate of chronic diabetic foot ulcers: an interim analysis of the Med-Maxx SG trial
Background: Diabetes often results in persistent and expensive complications, including diabetic foot ulcers (DFUs), which result in substantial morbidity and mortality. Despite compliance with standard of care (SOC) protocols, healing remains inadequate, emphasizing the need for novel and economically sustainable therapies. Methods: This interim analysis of a multi-center, open label, randomized controlled trial evaluated the efficacy of dual layer amnion patch (DLAP; Amnio-Maxx®, Royal Wound-X, Hackensack, NJ 07601, USA) on chronic DFU closure. Primary endpoints were complete closure at 12-weeks and percentage area reduction (PAR). Interim data were reviewed for this analysis. Fi-nal database lock and quality control checks were pending. Uncertainty was propagated using a Bayesian approach to provide credible estimates despite the provisional data status. Results: Probability of wound closure at week 12 was 4% (94% credible interval: 0.004%-12%) under SOC and 35% (94% CI: 17%-54%) under DLAP, corresponding to an absolute improvement of 31% (94% CI: 12%-48%) and a risk ratio of 41 (94% CI: 1.2 to 115). This indicates a 99.9% posterior probability that DLAP improves wound closure compared with SOC. At week 12, mean PAR was 75% (94% credible interval: 50%-95%) for SOC only, and 73% (94% CI: 47%-95%) for DLAP. The absolute difference in PAR is 2.4% (94% CI: −35%-39%). Conclusion: DFUs treated with DLAP were more likely to reach full closure by week 12. Remaining open wounds were more resistant to shrinkage, resulting in lower mean PAR among non-closers; SOC patients were more frequently “partially healed”, showing large proportional area reductions without closure. Closure and PAR results are consistent and complementary: DLAP increases the probability of full closure, while SOC patients frequently remain partially closed with continued wound area reduction.
Evaluation of acellular human dermis graft on the healing rate of chronic diabetic foot ulcers: an interim analysis of the Derm-Maxx trial
Background: Diabetic foot ulcers (DFUs) remain a chronic and costly complication of diabetes, associated with morbidity and mortality. Healing outcomes are often suboptimal, despite compliance with standard of care (SOC) protocols, highlighting the need for innovative and cost-effective therapeutic approaches. Methods: This interim analysis of a multi-center, open label, randomized controlled trial evaluated the efficacy of acellular human dermis graft (AHDG; Derm-Maxx™, Royal Wound-X, Hackensack, NJ 07601, USA) on chronic DFU closure. Primary endpoints were complete closure at 12-weeks and percentage area reduction (PAR). Interim data were reviewed for this analysis. Final database lock and quality control checks were pending. Uncertainty was propagated using a Bayesian approach to provide credible estimates despite the provisional data status. Results: The probability of wound closure at week 12 was 19% (94% credible interval: 6.3%-32%) with SOC, and 45% (94% CI: 33%-57%) with AHDG, representing an absolute improvement of 27% (94% CI: 13%-41%) and a risk ratio of 2.8 (94% CI: 1.2 to 4.9). This indicates a 99.9% posterior probability that AHDG improves closure compared with SOC. At week 12, mean PAR was 85% (94% credible interval: 72%-97%) for SOC only wounds versus 66% (94% CI: 38%-91%) for wounds in the AHDG arm. The absolute difference in PAR is 19% (94% CI: 12%-49%). Conclusion: Wounds in the AHDG arm were more likely to achieve complete closure by week 12. Remaining open wounds exhibited slower closure, resulting in lower mean PAR among non-closers. Additionally, wounds in the SOC group more frequently remained “partially closed,” with continued but incomplete area reduction. Closure and PAR outcomes are consistent and complementary, indicating that AHDG enhances the likelihood of complete wound closure in comparison to SOC only.
Real-world evaluation of cellular, acellular, and matrix-like products for pressure ulcers in the post-acute setting
Objective: To evaluate the real-world effectiveness of cellular, acellular, and matrix-like products (CAMPs) compared with standard of care (SOC) in promoting pressure ulcer (PU) healing among patients treated in post-acute settings. Method: This observational comparative effectiveness study analyzed de-identified data from the LiftOff Registry, a national database encompassing more than 18,000 patients and 23,000 pressure ulcers (PUs) treated in long-term acute care hospitals and skilled nursing facilities. Wounds receiving CAMPs + SOC were compared with those managed with SOC alone. Bayesian propensity score methods were applied to reduce confounding and achieve covariate balance across key demographic and clinical variables. All Bayesian models were implemented in Python 3.12 using PyMC, with the Bayesian Model-Building Interface (Bambi) for model specification and ArviZ for posterior diagnostics and visualization. Healing—defined as complete re-epithelialization or closure—was modeled using Bayesian logistic regression with study arm and baseline wound stage as predictors, summarized as posterior means and 95% credible intervals (CrI). Results: Before matching, the SOC cohort included 9,356 patients (14,740 wounds), while the CAMPs cohort included 136 patients (190 wounds). After Bayesian matching, 375 wounds were retained (190 treatment; 185 SOC), with comparable distributions of age, diabetes prevalence, and baseline wound area (mean: 23.2cm² versus 24.4cm²). Most wounds were classified as Stage 3 or 4. The posterior mean average treatment effect (ATE) was 0.16 (95% CrI, 0.15 –0.18), representing a 16-percentage-point improvement in ATE with CAMPs versus SOC, or approximately a 50 point increase in percentage terms. Conclusion: The use of CAMPs in post-acute settings was associated with a significant and credible improvement in PU healing compared with SOC. These real-world findings support the integration of CAMPs into post-acute wound management protocols to enhance outcomes for patients with complex or non-healing wounds.
A systematic review with semi-quantitative synthesis and GRADE qualification of the effectiveness of a keratin-based matrix in treating hard-to-heal wounds
Background: Hard-to-heal wounds impose substantial morbidity, cost, and, in the case of diabetic foot ulcers, elevated mortality risk. Venous leg ulcers (VLUs) and variants of epidermolysis bullosa (EB) likewise impose major chronic-disease burden and healthcare cost. Keratin biomaterials derived from wool have demonstrated regenerative potential by stimulating keratinocyte activation and collagen synthesis. Objective: To systematically assess the clinical efficacy and certainty of evidence for a wool-derived keratin-based matrix (KBM) (Keramatrix [Q4165], Biowound Solutions Inc., Las Vegas, NV, USA), a 510(k) U.S. Food and Drug Administration (FDA) approved product with cleared indications, and related keratin biomaterials in the management of hard-to-heal wounds, using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Methods: Literature from 2006–2025, including a randomized controlled trial (RCT), prospective cohorts, and case-series data, was extracted into a master evidence table. Studies were assessed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) and evaluated across five GRADE domains with appropriate downgrading and upgrading factors. Data were synthesized narratively and semi-quantitatively, with directional summaries of epithelialization and closure outcomes rather than formal meta-analytic pooling due to heterogeneity among studies.Results: Thirty-two studies (n≈700 human wounds) were identified: one RCT (High certainty), six comparative or cohort studies (Moderate), fifteen case series, and ten case reports or preclinical studies (Low–Very Low). Across seven comparative studies (n≈400 wounds), keratin-based matrix (KBM) treated groups achieved 60–80 % complete or ≥ 50 % partial closure by 8–12 weeks versus 25–40 % among controls (approximate RR 1.97; 95 % CI 1.2–3.2). This finding, based on a fixed-effect inverse-variance summary of study-level risk ratios, reflects a semi-quantitative directional effect rather than a formal meta-analysis. Owing to heterogeneity of endpoints, this estimate is reported as a semi-quantitative directional effect rather than a formal meta-analysis. Uncontrolled series reported similar healing rates in treated wounds without formal comparators. No serious adverse events were reported. Conclusion: Using formal GRADE qualification, the KBM used in these studies demonstrate consistent clinical efficacy and favorable safety across diabetic foot ulcers, venous leg ulcers, and epidermolysis bullosa. Evidence certainty is moderate overall, driven by one high-certainty RCT and multiple concordant cohort studies. The findings support CMS formulary inclusion of Keramatrix as a reasonable and necessary adjunctive therapy following failure of standard of care techniques. Ongoing real-world data continue to corroborate and expand these findings across diverse care settings. Certainty of Evidence: Overall Moderate.
Full thickness placental membrane allograft for diabetic foot ulcers: two clinical cases from the TIGERCAMP clinical trial
Background: Diabetic foot ulcers (DFUs) are chronic wounds often marked by delayed epithelialization and limited response to standard of care (SOC) procedures. Their persistence substantially impairs quality of life and are associated with 50-60% infection rates and around 30% 5-year mortality rates, highlighting the need for new cost-effective strategies. Methods: This case series evaluated two subjects with chronic DFUs evaluated at 2 sites between April 2025 and July 2025. Offloading was provided with a removable walker boot. Subjects had target ulcers between >1.0 cm2 and 20.0 cm2 at enrollment that had not closed after 4 weeks of SOC. Subjects received a weekly application of a full-thickness placental membrane allograft (FT; caregraFT™, Tiger Wound Care Medical, LLC, Conshohocken, PA, USA) combined with standard care (sharp debridement, offloading, and moisture balance) in an ongoing randomized con-trolled modified platform trial. Results: The two patients were between the ages of 79 and 86, one female and one male. One patient reached ≥50%, ≥75%, and ≥90% PAR by Weeks 1, 3, and 6, respectively, with complete closure at Week 9. The other subject reached ≥50%, ≥75%, and ≥90% PAR by Weeks 2, 4, and 5, respectively, with complete closure at Week 8. Both wounds were confirmed closed in subsequent closure confirmation visits. No product related adverse events were reported. Conclusion: These cases demonstrate the potential of FT allografts in aiding SOC to improve wound closure rates of DFUs in older patients with both hard-to-heal and newly diagnosed chronic wounds. These results highlight the importance of continued clinical evaluation through controlled studies aimed at confirming both the wound care benefits and the potential for reducing overall healthcare costs.