Dehydrated human amnion/chorion membrane allograft with spongy layer to significantly improve the outcome of chronic non-healing wounds.

We investigated the healing effect of a new dehydrated amnion/chorion membrane with a spongy layer over a 30-month period in 32 patients with 53 chronic non-healing wounds of different aetiologies. Wounds with <40% surface reduction after 4 weeks of best wound treatment underwent weekly allograft application by a certified wound specialist based on national guidelines and a standardised protocol until complete healing or definite treatment interruption. The main outcome measure was the percentage of wound surface reduction from baseline calculated using digital planimetry follow-up photographs. Overall, 38 (71.7%) wounds presented a favourable outcome (70%-100% area reduction), with 35 (66%) completely healing over a median time of 77 days (range 29-350 days). Favourable outcomes were observed in 75% of traumatic wounds, surgical wounds, venous leg ulcers and pressure injuries, as well as in 50% of ischaemic wounds. Wounds being present <12 months were significantly more likely to have a favourable outcome than more long-standing wounds (χ2 = 7.799; p = 0.005; OR = 3.378; 95% CI, 1.410-8.092). Thus, treatment with dehydrated amnion/chorion membrane with a spongy layer improves the outcome of non-healing wounds of different aetiologies and, therefore, has to be considered early in the management of refractory wounds.

Unique Usages of Dehydrated Human Amnion Chorion Membrane Allografts in Dermatology.

Dehydrated human amnion chorion membrane (dHACM) allografts are synthetic skin substitutes derived from placental tissue. dHACM allografts are used for replacing lost or damaged dermal tissue, as they contain many of the components found within the extracellular matrix that are beneficial in wound healing. Common uses of dHACM allografts include the healing of diabetic and non-diabetic foot and leg ulcers, decubitus ulcers, and wounds following debridement. While these grafts have been proven to be beneficial in other disciplines of medicine, their potential for use in the field of dermatology is emerging. Current clinical cases and research have shown dHACM allografts to be beneficial in repairing damaged tissue due to dermatologic conditions. They could play a role in the treatment of conditions causing chronic wounds, including dermal scarring or loss, and the repair of fragile skin. Examples of dHACM allograft use in dermatology include cases of pyoderma gangrenosum, Netherton syndrome, and wound healing with Mohs micrographic surgery. This literature review explores the efficacy of using dHACM allografts for the treatment of healing wounds within the field of dermatology. J Drugs Dermatol. 2023;22(12):1228-1231. doi:10.36849/JDD.7115.

Dehydrated human amnion/chorion membrane use in emergent craniectomies shows minimal dural adhesions.

Decompressive craniectomies (DCs) are routinely performed neurosurgical procedures to emergently treat increased intracranial pressure secondary to multiple aetiologies, such as subdural haematoma, epidural haematoma, or malignant oedema in the setting of acute infarction. The DC procedure typically induces epidural fibrosis post-cranial resection, resulting in adherence of the dura to both the brain internally and skin flap externally. This becomes especially problematic in the setting of skull flap replacement for cranioplasty as adherences can lead to bridging vein tear, damage to the underlying brain cortex, and other postoperative complications. Dural adjuvants, which can contribute to decreased rate of adherence formation, can thereby reduce both postoperative cranioplasty complications and operative duration. Dehydrated human amnion/chorion membrane (DHACM) allografts (AMNIOFIX, MIMEDX Group Inc., US) have been shown to reduce the rate of dural scar tissue formation in re-exploration of posterior lumbar interbody fusion operations which require entry into the epidural space. The purpose of this study was to evaluate whether or not the use of DHACM in the setting of emergent craniectomies decreased the rate of dural adhesion formation and subsequent cranioplasty complications. Patients (n=7) who underwent emergent craniectomy and intraoperative placement of DHACM were evaluated during replacement of either an autologous skull cap or a custom-made implant, at which point the degree of adhesions was qualitatively assessed. Placement of DHACM below and on top of the dura resulted in negligible adhesion being found during the defect exposure, and there were no intraoperative complications during cranioplasties. Reported estimated blood loss across the seven patients averaged 64.2ml, total operative time averaged 79.2 minutes, and time dedicated to exposing defect for bone flap placement was <3 minutes.

A Multicenter, Randomized, Controlled, Clinical Trial Evaluating Dehydrated Human Amniotic Membrane in the Treatment of Venous Leg Ulcers.

BACKGROUND: This randomized controlled trial evaluated the safety and effectiveness of weekly and biweekly applications of dehydrated human amnion and chorion allograft (dHACA) plus standard of care compared to standard of care alone on chronic venous leg ulcers. METHODS: This open-label randomized controlled trial included patients with chronic venous leg ulcers at eight wound care centers across the United States. The primary endpoint was the proportion of healed ulcers at 12 weeks. Secondary endpoints included the proportion of ulcers achieving 40 percent closure at 4 weeks and the incidence of adverse events. RESULTS: Among 101 patients screened for eligibility, 60 were eligible and enrolled. At 12 weeks, significantly more venous leg ulcers healed in the two dHACA-treated groups (75 percent) than in the standard-of-care group (30 percent) ( p = 0.001) even after adjustment for wound area ( p = 0.002), with an odds ratio of 8.7 (95 percent CI, 2.2 to 33.6). There were no significant differences in the proportion of wounds with percentage area reduction greater than or equal to 40 percent at 4 weeks among all groups. The adverse event rate was 63.5 percent. Among the 38 adverse events, none were graft or procedure related, and all were resolved with appropriate treatment. CONCLUSIONS: dHACA and standard of care, either applied weekly or biweekly, significantly healed more venous leg ulcers than standard of care alone, suggesting that the use of aseptically processed dHACA is advantageous and a safe and effective treatment option in the healing of chronic venous leg ulcers. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Wound repair, safety, and functional outcomes in reconstructive lower extremity foot and ankle surgery using a dehydrated amnion/chorion allograft membrane.

Amniotic membranes are known to be rich in growth factors, cytokines, and matrix proteins, which can help support wound closure and may improve patient outcomes in foot and ankle surgical interventions. In this Institutional Review Board (IRB) approved clinical study, 21 consecutive patients undergoing lower extremity soft tissue and bone reconstruction surgery received dehydrated human amnion and chorion allograft (dHACA) placed as a covering over the deep layers of the surgical wound during closure. Wound healing complications were assessed and American Orthopaedic Foot and Ankle Society (AOFAS) scores were compiled from over a 1-year follow-up period. Summary statistics were calculated for average pain, function, and alignment. The average overall AOFAS pre-treatment score was 35.8 ± 23.0 and the post-treatment score significantly improved to 87.5 ± 6.4 (P = 3.7 × 10-10 ). The pain-score improved from pre-treatment at 10.0 ± 11.0 to post-treatment at 36.7 ± 4.8 (P = 5.0 × 10-5 ). The pre-treatment function score was 18.7 ± 12.9 and at post-treatment increased to 38.5 ± 5.7 (P = 5.8 × 10-5 ). Lastly, the alignment score at pre-treatment was 7.1 ± 4.4 and at post-treatment was 12.4 ± 2.6 (P = .001). These improvements in functional scores were accompanied with clinical observations of reduced surgical complications including a lack of wound dehisance in the cohort. These clinical findings suggest that the application of aseptically processed dHACA may reduce wound complications and as such may aide in clinical improvements in foot and ankle surgical interventions however a larger comparative trial should be considered to validate these initial findings.

Mohs Defect Repair with Dehydrated Human Amnion/Chorion Membrane.

Importance: Reconstructing cosmetically sensitive defects in an aging population undergoing multiple Mohs micrographic surgeries (MMS) may be addressed with alternatives to surgery. Objective: Patients undergoing MMS with defect reconstruction in visually prominent areas receiving placental allograft were compared with traditional autologous tissue-based procedures-flaps and full-thickness skin grafts (FTSG). Design, Setting, and Participants: This retrospective case-control study evaluated patients who underwent MMS for removal of a basal or squamous cell carcinoma with same-day repair. Main Outcomes and Measures: The primary endpoint was the incidence and comparison of postoperative morbidity. Risk for developing medical or cosmetic sequelae was determined through multivariate logistic regression. Results: The study population consisted of 143 propensity score-matched pairs (n = 286) with moderate- to high-risk defects on the face, head, and neck. Compared with autologous tissue, placental allograft cases were associated with significantly lower risk for infection (p = 0.004), poor scar cosmesis (p < 0.0001), scar revision (p < 0.0001), or reoperation (p = 0.0007). Conclusions and Relevance: Postoperative complication rates for placental reconstructions did not exceed those demonstrated by autologous tissue counterparts, indicating this is a safe alternative to flap and FTSG in cosmetically sensitive repairs.

Dehydrated Human Amnion-Chorion Membrane (Placenta) Reinforcement of Esophagectomy Anastomosis.

An anastomotic leak is a potentially fatal complication after esophagectomy. This report describes the use of a dehydrated human amnion-chorion membrane (dHACM) placenta allograft patch for reinforcement of an esophageal anastomosis. The anastomotic technique was a modified Orringer procedure through a right thoracotomy (Ivor Lewis procedure). The anastomosis was reinforced with dHACM placenta allograft. Use of the allograft prevented anastomotic leaks and loss of gastrointestinal integrity. Early results are promising.

Micronized Dehydrated Human Amnion/Chorion Membrane Injection in the Treatment of Chronic Achilles Tendinitis.

Background: Human amniotic membrane contains growth factors and cytokines that promote epithelial cell migration and proliferation, stimulate metabolic processes that lead to collagen synthesis, and attract fibroblasts, while also reducing pain and inflammation. Randomized studies have shown effectiveness of micronized dehydrated human amnion/chorion membrane (mdHACM) allograft injection in treatment of plantar fasciitis. We present our experience and short-term outcomes with using mdHACM injection as a treatment for Achilles tendinopathy. Methods: Retrospective case series of patients with Achilles tendinopathy treated with mdHACM by a single physician. Participants had at least two follow-up visits within 45 days of mdHACM injection. Outcomes examined included change in reported level of pain during the 45-day observation period and treatment-associated adverse events. Results: Follow-up data were available for 32 mdHACM-treated patients. At treatment initiation, 97% of patients reported severe (66%) or moderate (31%) pain. At the first follow-up visit (mean ± SD of 8.1 ± 2.7 days postinjection), 27 patients (84%) reported improvement in pain levels, although 37% of patients continued to report severe (6%) or moderate (31%) pain. At the second follow-up visit (mean ± SD of 23.1 ± 6.2 days postinjection), no patients reported severe pain and one reported moderate pain. Within 45 days of mdHACM injection, complete symptom resolution was reported by 66% of treated patients (n = 21), with the remaining 34% (n = 11) reporting symptom improvement but not complete resolution. Two patients reported calf or quadricep pain or tightness after injection. Conclusions: In our experience, mdHACM injection reduced or eliminated pain in all 32 patients with follow-up data.

Human Amnion Chorion Membrane Allografts in the Treatment of Chronic Diabetic Foot Ulcers: A Literature Review.

OBJECTIVE: To discuss human amnion chorion (placental) membrane allograft (HACMA) use for the treatment of chronic diabetic foot ulcers (DFUs) and to evaluate the effectiveness, cost, and product waste of this therapy. DATA SOURCES: PubMed, Cochrane, and OVID databases. STUDY SELECTION: Twenty-four articles pertaining to HACMA and DFUs published from 2016 to 2020 were selected. DATA EXTRACTION: The data collected included type of wound care product, study design, study size, baseline size of DFU, cost, product wastage, number of applications, and wound healing outcomes. DATA SYNTHESIS: Human amnion chorion membrane allografts in the treatment of chronic DFUs have led to a reduction in healing time and increased the overall percentage of healing, making them more effective in treating DFUs compared with standard of care. These products are offered in multiple sizes with various shelf lives and methods of storage, making them accessible, easy to use, less wasteful, and lower in cost compared with other commercially available products. Promising evidence demonstrates that HACMAs are beneficial in treating complex, high-grade DFUs with exposed tendon or bone. CONCLUSIONS: Human amnion chorion membrane allografts are effective in treating chronic DFUs with a greater percentage of complete wound closure and a reduction in healing time versus standard of care.

A dehydrated, aseptically-processed human amnion/chorion allograft accelerates healing in a delayed murine excisional wound model.

Since chronic, non-healing wounds represent an increasing source of economic and temporal burden for patients who suffer from them and healthcare professionals that treat them, therapeutic modalities that promote closure of delayed and non-healing wounds are of utmost importance. Recent clinical results of allografts derived from amnion and chorion placental layers encourage further investigation of the mechanisms underlying clinical efficacy of these products for treatment of wounds. Here, we utilized a diabetic murine splinted excisional wound model to investigate the effects of a dehydrated human amnion/chorion-derived allograft (dHACA) on delayed wound healing, as well as the effects of dehydrated allograft derived solely from amnion tissue of the same donor. We examined wound healing by histological endpoint analysis, and we assessed other parameters relevant to functional wound healing in the wound bed including angiogenesis, macrophage phenotypes, proliferative activity, and gene expression. Herein we demonstrate that application of dHACA to a murine diabetic model of delayed wound progression results in better macroscale wound resolution outcomes, including rate of closure, compared to unaided wound progression, while dehydrated human amnion allograft (dHAA) fails to improve outcomes. Improved gross wound resolution observed with dHACA was accompanied by increased granulation tissue formation, proliferation and vascular ingrowth observed in the wound bed, early macrophage polarization towards anti-inflammatory phenotypes, and downregulation of pro-fibrotic gene expression. Overall, our data suggest that improvements in the rates of delayed wound closure observed from combined amnion/chorion allografts are associated with modulation of critical cellular and tissue processes commonly found to be dysregulated in delayed healing wounds, including proliferation, vascularization, inflammation, and re-epithelialization.

Micronized Dehydrated Human Amnion Chorion Membrane Injection in the Treatment of Knee Osteoarthritis-A Large Retrospective Case Series.

Osteoarthritis (OA) of the knee is a leading cause of chronic pain and disability in the United States. Current treatment options primarily target OA symptoms reserving surgical intervention and knee replacement for those who fail conservative measures. With average age of patients with knee OA decreasing, regenerative treatment approaches to reduce symptoms, increase quality of life, and delay the need for surgical intervention are increasingly sought. Human amniotic membrane contains growth factors and cytokines, which promote epithelial cell migration and proliferation, stimulate metabolic processes leading to collagen synthesis, and attract fibroblasts, while also reducing pain and inflammation. Micronization of the tissue allows for suspension in normal saline and injection. We conducted a retrospective review of 100 knees treated for symptomatic OA with micronized dehydrated human amnion/chorion membrane (mdHACM) and followed for 6 months. Our purpose is to present our experience and patient outcomes. Data were abstracted from electronic medical records of 82 consecutive OA patients (100 knees) injected with 100 mg mdHACM. Patient age, gender, adverse events and routinely collected Knee Injury and Osteoarthritis Outcome Score (KOOS) were evaluated. Effectiveness of mdHACM treatment was measured by serial KOOS at baseline, and posttreatment at 6 weeks, 3, and 6 months. Overall mean KOOS for the cohort was 40 at baseline, improving to 52, 62, and 65 at 6 weeks, 3 months, and 6 months post-mdHACM injection. Percent increases were 32, 56, and 65%, respectively. Quality of life and sports/recreation domains improved by 111 and 118%, respectively, at 6 months. Pain scores improved by 67% at 6 months. All scores improved throughout the observation period. The most common adverse event was pain after injection lasting 2 to 7 days, observed in 68% of cases. This represents the largest single-physician experience with mdHACM for treatment of knee OA reported to date. Injectable mdHACM appears to be a potentially useful treatment option for knee OA patients. Controlled studies are underway to confirm these observations.

Aloinjerto de membrana amniótica en úlceras por presión / Amniotic membrane allograft in pressure ulcers

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Effectiveness and safety of human amnion/chorion membrane therapy for diabetic foot ulcers: An updated meta-analysis of randomized clinical trials.

Human amnion/chorion membrane therapy has shown advantages in the management of diabetic foot ulcers and its effectiveness has been evaluated in the systematic reviews and meta-analyses. However, the number of patients included in the previous literatures was small and the safety profile of human amnion/chorion membrane therapy was not concerned. Therefore, we conducted an updated meta-analysis to better understand the effectiveness and safety of human amnion/chorion membrane therapy for diabetic foot ulcers. The PubMed, Embase, Cochrane Library, and ClinicalTrial.gov databases were searched for any randomized clinical trials comparing human amnion/chorion membrane therapy and standard therapy in the treatment of diabetic foot ulcers. Ulcer healing rate was considered as the primary outcome and the secondary outcomes mainly included mean time to ulcer healing and adverse events. Nine RCTs with 541 patients were included. Compared with merely standard therapy, human amnion/chorion membrane therapy plus standard therapy improved the ulcer healing rates at 6 weeks (RR = 3.50, 95% CI: 2.35-5.21), 12 weeks (RR = 2.09, 95% CI: 1.53-2.85) and 16 weeks (RR = 1.70, 95% CI: 1.25-2.30), and also shortened the healing time (MD = -4.58, 95% CI: -5.70 to -3.46). Meanwhile, no significant difference was observed in the number of patients with adverse events (RR = 0.56, 95% CI: 0.31-1.03) between two groups. This meta-analysis suggests that human amnion/chorion membrane therapy as an adjuvant treatment could promote the healing of diabetic foot ulcers and has a safety profile. More evidence from large high-quality randomized clinical trials with long follow-up duration are in urgent need to further confirm our findings.

Dehydrated human amnion and chorion allograft versus standard of care alone in treatment of Wagner 1 diabetic foot ulcers: a trial-based health economics study.

AIMS: The aim of this health economics study was to estimate the cost-utility of an aseptically processed, dehydrated human amnion and chorion allograft (dHACA) plus standard of care (SOC) (group 1) versus SOC alone (group 2) based on a published randomized controlled trial in which patients who had an eligible Wagner 1 diabetic foot ulcer wound were randomized to either of these treatments. MATERIALS AND METHODS: A Markov microsimulation was used to project trial results out to a 1-year horizon time with a third-party payer perspective. The starting health state was an unhealed non-infected ulcer with other health states of healed ulcer, infected non-healed ulcer, cellulitis, osteomyelitis, and absorbing states of dead or amputation. All patients started with unhealed non-infected ulcers at cycle 0. Costs were incurred by patients for procedures at hospital outpatient wound care provider-based departments (PBDs) and hospitals (if complications occurred) and were calculated using time-based activity costing methods. Effectiveness units were quality-adjusted life years (QALYs) computed from literature utility values. One-way and probabilistic sensitivity analysis (PSA) were also conducted. RESULTS: After 1 year, the calculated incremental cost-effectiveness ratio (ICER) for group 1 versus group 2 was -$4,373 with group 1 (dHACA) being dominant over group 2 (SOC). PSA demonstrated that group 1 had 69.2% lower cost values with increased positive incremental effectiveness for 94.9% of values. A willingness to pay (WTP) curve showed that about 92% of interventions were cost effective for group 1 when $50,000 was paid. CONCLUSIONS: The results of this study demonstrated that dHACA added to SOC compared to SOC alone was extremely cost-effective in the defined trial population.

Application of Dried Human Amnion Graft to Improve Post-Prostatectomy Incontinence and Potency: A Randomized Exploration Study Protocol.

INTRODUCTION: Incontinence (up to 20%) and erectile dysfunction (up to 70%) occur frequently after radical prostatectomy (RP) in patients with localized prostate cancer. Human amniotic membrane (HAM) can improve tissue regeneration and functional outcome after RP owing to the growth factors and unique immune tolerance. Preliminary studies showed the potential value of HAM in the reconstruction of the urinary tract and nerve protection during RP. METHODS: A protocol is developed for a prospective, randomized, single-blind, single-surgeon, placebo-controlled exploration study of the efficacy and safety of dehydrated human amnion membrane placed around the neurovascular bundle (NVB) and vesicourethral anastomosis (VUA) during RP for the treatment of localized prostate cancer. Eligible for inclusion are patients with localized prostate cancer, requiring a surgical procedure and exclusion of preoperative incontinence and erectile dysfunction. The patients are randomized 1:1 to HAM vs. placebo and blinded during the study period. According to the T test with an alpha of 0.05 and a power of 80% and expecting a dropout of 20% of the patients, an adjusted sample size per arm of 164 patients is required. PLANNED OUTCOMES: The primary outcome is a postoperative continence measured as 24-h pad test up to 12 months postoperatively. Secondary outcomes are potency, time of postoperative catheter removal, postoperative complications, and biochemical recurrence. The protocol for this randomized exploration study defines the conditions to assess the efficacy and safety of HAM application during RP in order to improve the postoperative functional outcome. This trial should pave the way for future studies of tissue engineering in an effort to reduce the morbidity of RP. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT03864939.

Use of dehydrated human amnion chorion membrane allograft on infected ruptured arteriovenous fistula: revision and closure.

OBJECTIVE: Over two million individuals worldwide, with end-stage renal disease (ESRD), depend on dialysis therapy or a kidney transplant for survival. Every haemodialysis patient requires vascular access. The arteriovenous fistula (AVF) is preferred for long-term hemodialysis vascular access due to long-term primary patency rates. Given the limited options for haemodialysis access and placement, preservation of existing AVF sites is always a clinical priority. This case report describes a novel approach to wound closure with the application of dehydrated amnion chorion human membrane (dHACM) at an AVF surgical site known to be complicated with issues of scarring and tissue breakdown. The patient was treated successfully with the imperative preservation of his AVF given that he had few other vascular access options.

A mechanistic evaluation of the angiogenic properties of a dehydrated amnion chorion membrane in vitro and in vivo.

Angiogenesis is essential for the successful repair of tissues; however, in many chronic conditions, angiogenesis is inhibited. Placental tissues have been shown to illicit an angiogenic response both in vitro and in vivo, and the angiogenic properties of these tissues likely contribute to observed clinical outcomes. Although there is some work describing the angiogenic effects of these tissues, comparatively little has been done to determine the possible mechanisms responsible for this effect. The purpose of this study was to conduct a thorough evaluation of a commercially available dehydrated amnion chorion membrane to better understand how these tissues may promote angiogenesis. The proteomic content of this tissue was evaluated using a high throughput proteomic microarray, and then the effects of these grafts were evaluated in vivo using subcutaneous gelfoam sponge implants containing conditioned media (CM) from the graft. Human microvascular endothelial cells were then used to determine how released factors effect migration, proliferation, gene expression, and protein production in vitro. Finally, to elucidate potential signaling-pathways through which tissue-derived factors act to induce pro-angiogenetic phenotypes in endothelial cells in vitro, we performed a global analysis of both serine/threonine and tyrosine kinase activity. Kinomic and proteomic data were then combined to generate protein-protein interaction networks that enabled the identification of multiple growth factors and cytokines with both pro- and anti-angiogenetic properties. In vivo, the addition of CM resulted in increased CD31 and αSMA staining and increases in pro-angiogenic gene expression. In vitro, CM resulted in significant increases in endothelial proliferation, migration, and the expression of granulocyte-macrophage colony-stimulating factor, hepatocyte growth factor, and transforming growth factor beta-3. Integrated kinomic analysis implicated ERK1/2 signaling as the primary pathway activated following culture of endothelial cells with dehydrated amnion/chorion membrane (dACM) CM. In conclusion, dACM grafts triggered pro-angiogenic responses both in vitro and in vivo that are likely at least partially mediated by ERK1/2 signaling.

Amnion Applications in the Foot and Ankle.

Amnion and chorion products show great promise and have real potential to be mainstays of treatment for chronic, nonhealing wounds. Although amniotic products do carry a cost, the decrease in time to healing, with the assumed subsequent decrease in complication and infection rates, should also be taken into consideration. These products, with their unique biologic potential and availability in the clinical setting, may prove to be beneficial in a vast array of podiatric surgical applications.