Amniotic Membrane Allograft Research Articles

Total Ankle Arthroplasty Incision Management: What Matters? A Systematic Review

Modern advancements in total ankle arthroplasty techniques and implants have increased the popularity of this treatment for ankle osteoarthritis. The preeminent approach for ankle replacement involves an anterior incision, however, wound complications with this approach provide a persistent challenge to surgeons. The present study was conducted to synthesize current data on ankle replacement wound complications via an anterior approach. A systematic review was completed including studies published from 1993 to present that employed an anterior approach and had precise criteria for wound healing and revisions. Twenty-nine studies, with level 3 to 4 evidence and moderate to serious bias, were included for a total of 6,986 ankle arthroplasties. The rate of wound healing without any complication was 90.38%. Minor dehiscence occurred in 6.00% of cases, while major wounds or infections occurred in 3.62%. Across 2,966 implants, the rate of major wounds or infections decreased from 7.03% before 2013 to 4.75% after 2013 (p = 0.034). Limited comparisons involving simple suture closure to various adjunct wound management techniques including negative pressure wound therapy, 2-octyl cyanoacrylate, platelet-rich plasma, dehydrated human amniotic membrane allograft, non-invasive skin expansion strips, compression wound dressings, tranexamic acid, surgical helmets, tourniquets, ankle arthrodesis, and lateral approach ankle arthroplasty, yielded non-significant differences (p > 0.18). Therefore, contemporary techniques, patient selection, and current implants may be leading to better soft tissue healing. As ankle replacement continues to surge in popularity, further research is needed to evaluate causative factors in successful anterior incision healing. Level of Clinical Evidence3

Impact of Cryopreserved Placental Allografts on Biochemical Recurrence in Prostate Cancer.

Human placental allografts are widely used to promote wound healing. Placental (or amniotic membrane/umbilical cord) allografts are placed along the neurovascular bundles during radical prostatectomy to improve continence and erectile function recovery. It is unknown whether placental allografts impact biochemical recurrence (BCR). This was a single-surgeon retrospective study of 566 robotic radical prostatectomies performed from April 2015 to March 2021. The patients were divided into three groups: the negative control, Brand A, and Brand B. Brand A and Brand B were both cryopreserved amniotic membrane (CAM) allografts. A total of 324 cases were included for BCR Kaplan-Meier and risk-adjusted multivariate analyses (362 for continence analysis). In vitro analyses were performed to determine the effect of CAM allografts on prostate cancer (PCa) cell line growth. For propensity score-matched analysis (adjusting for pre-operative PSA, tumor stage, Gleason Grade, and margin status), (1) the allograft groups did not show differences in time to BCR vs. the negative control group (p = 0.7), and (2) combined allograft treatment groups showed better continence recovery vs. the negative controls (p = 0.01). In vitro, placental allografts reduced PCa cell line growth in co-culture assays. cryopreserved AM allografts (combined or individual brands) did not show a significant effect on BCR but improved continence recovery for PCa patients.

Utilizing Amniotic Membrane Allograft as regenerative therapy for Treating Burns

Burn injuries are prevalent among all age groups and can result from thermal, scald, or electrical sources. Currently, various scaffolds are employed to enhance the healing process and minimize scar formation. Collagen serves as a scaffold, facilitating tissue regeneration and promoting the formation of new blood vessels. Additionally, scaffolds such as amniotic membrane aid in proper epithelialization and scar reduction, boasting unique anti-inflammatory and bacteriostatic properties. In our study, we utilized amniotic membrane allograft as a biological dressing for burn wounds on an adult patient's right thigh.

Human amniotic membrane modulates collagen production and deposition in vitro

Pathological fibrosis is a significant complication of surgical procedures resulting from the accumulation of excess collagen at the site of repair which can compromise the tissue architecture and severely impede the function of the affected tissue. Few prophylactic treatments exist to counteract this process; however, the use of amniotic membrane allografts has demonstrated promising clinical outcomes. This study aimed to identify the underlying mechanism of action by utilizing relevant models that accurately represent the pathophysiology of the disease state. This study employed a pro-fibrotic in vitro system using TGFβ1 stimulation and macromolecular crowding techniques to evaluate the mechanism by which amniotic membrane allografts regulate collagen biosynthesis and deposition. Following treatment with dehydrated human amnion chorion membrane (DHACM), subsequent RNA sequencing and functional enrichment with Reactome pathway analysis indicated that amniotic membranes are indeed capable of regulating genes associated with the composition and function of the extracellular matrix. Furthermore, macromolecular crowding was used in vitro to expand the evaluation to include both the effects of DHACM and a lyophilized human amnion/chorion membrane (LHACM). DHACM and LHACM regulate the TGFβ pathway and myofibroblast differentiation. Additionally, both DHACM and LHACM modulate the production, secretion, and deposition of collagen type I, a primary target for pathological fibrosis. These observations support the hypothesis that amniotic membranes may interrupt pathological fibrosis by regulating collagen biosynthesis and associated pathways.

PURION® processed human amnion chorion membrane allografts retain material and biological properties supportive of soft tissue repair.

The reparative properties of amniotic membrane allografts are well-suited for a broad spectrum of specialties. Further enhancement of their utility can be achieved by designing to the needs of each application through the development of novel processing techniques and tissue configurations. As such, this study evaluated the material characteristics and biological properties of two PURION® processed amniotic membrane products, a lyophilized human amnion, intermediate layer, and chorion membrane (LHACM) and a dehydrated human amnion, chorion membrane (DHACM). LHACM is thicker; therefore, its handling properties are ideal for deep, soft tissue deficits; whereas DHACM is more similar to a film-like overlay and may be used for shallow defects or surgical on-lays. Characterization of the similarities and differences between LHACM and DHACM was conducted through a series of in vitro and in vivo studies relevant to the healing cascade. Compositional analysis was performed through histological staining along with assessment of barrier membrane properties through equilibrium dialysis. In vitro cellular response was assessed in fibroblasts and endothelial cells using cell proliferation, migration, and metabolic assays. The in vivo cellular response was assessed in an athymic nude mouse subcutaneous implantation model. The results indicated the PURION® process preserved the native membrane structure, nonviable cells and collagen distributed in the individual layers of both products. Although, LHACM is thicker than DHACM, a similar composition of growth factors, cytokines, chemokines and proteases is retained and consequently elicit comparable in vitro and in vivo cellular responses. In culture, both treatments behaved as potent mitogens, chemoattractants and stimulants, which translated to the promotion of cellular infiltration, neocollagen deposition and angiogenesis in a murine model. PURION® processed LHACM and DHACM differ in physical properties but possess similar in vitro and in vivo activities highlighting the impact of processing method on the versatility of clinical use of amniotic membrane allografts.

Tri-layer amniotic membrane allografts: a versatile scaffold for managing acute and hard-to-heal wounds.

Tri-layer amniotic membrane allografts: a versatile scaffold for managing acute and hard-to-heal wounds.

Lyophilised human amniotic membrane allograft modulates cellular activities supportive of wound management.

Lyophilised human amniotic membrane allograft modulates cellular activities supportive of wound management.

Bioengineered Skin for Diabetic Foot Ulcers: A Scoping Review.

Diabetic foot ulcers (DFUs) pose a significant threat to individuals with diabetes mellitus (DM), such as lower limb amputation and severe morbidity. Bioengineered skin substitutes (BSS) are alternatives to traditional interventions for treating DFUs, but their efficacy compared to standard wound care (SWC) or other treatment types, such as allografts, remains unknown. A scoping review of human studies was conducted to identify current approaches in the treatment of DFUs using BSS as compared with other treatment options. Systematic searches in PubMed, Cochrane Library, and Web of Science were conducted to identify comparative studies that enrolled 10 or more patients and evaluated wound healing outcomes (closure, time-to-healing, and area reduction). Database searches isolated articles published from 1 December 2012 to 1 December 2022 and were conducted in accordance with PRISMA-ScR guidelines. The literature search yielded 1312 articles, 24 of which were included for the qualitative analysis. Findings in these studies demonstrated that BSS outperformed SWC in all measured outcomes, suggesting that BSS may be a superior treatment for DFUs. Of the 24 articles, 8 articles compared human amniotic membrane allografts (hAMA) to BSS. Conflicting evidence was observed when comparing BSS and hAMA treatments, highlighting the need for future research.

Repair of facial dog bite wound utilizing cryopreserved umbilical cord allograft.

In the United States, craniofacial injuries are the most frequently observed traumas in the pediatric population. Human birth tissue products contain growth factors, cytokines, and signaling molecules that can be potentially harnessed for tissue regeneration and wound healing. A cryopreserved ultra-thick amniotic membrane (AM) allograft wound dressing was used in a patient with significant facial soft tissue loss due to a dog bite injury. This is a single case report of a pediatric patient. After obtaining IRB exemption, operative and postoperative clinic notes were reviewed. A 10-year-old female presented to the emergency department after suffering a dog bite to her left cheek and upper lip, resulting in tissue loss. A cryopreserved ultra-thick AM allograft was used to cover the area of tissue loss as part of surgical reconstruction. The patient was followed up at 1 week, 3 weeks, 4 months, and 1 year after the graft was placed, and rapid healing and full epithelialization were achieved in addition to scar contracture due to wound location. In the setting of acute trauma and tissue loss, human birth tissue was found to promote epithelialization and regenerative healing of facial tissues.

Urethral reconstruction using amniotic membrane allograft in hereditary androgen insensitivity syndrome: a case series

Abstract Partial androgen insensitivity syndrome is a rare X-linked disorder. While most cases are sporadic, familial cases are less frequent. The management of this syndrome follows a multidisciplinary approach involving hormone substitution, psychological counseling, and surgical procedures. We present a case series of three young siblings with familial partial androgen insensitivity syndrome who presented with a female phenotype. All of them were managed with hormonal treatment for 6 months followed by surgical reconstruction. The operative procedure involved phalloplasty and urethroplasty using amniotic membrane transplant, which is considered a novel technique in this group of patients. No intraoperative or postoperative complications were observed and good results were achieved within 2 years of follow-up.

The Preparation and Clinical Efficacy of Amnion-Derived Membranes: A Review.

Biological tissues from various anatomical sources have been utilized for tissue transplantation and have developed into an important source of extracellular scaffolding material for regenerative medicine applications. Tissue scaffolds ideally integrate with host tissue and provide a homeostatic environment for cellular infiltration, growth, differentiation, and tissue resolution. The human amniotic membrane is considered an important source of scaffolding material due to its 3D structural architecture and function and as a source of growth factors and cytokines. This tissue source has been widely studied and used in various areas of tissue repair including intraoral reconstruction, corneal repair, tendon repair, microvascular reconstruction, nerve procedures, burns, and chronic wound treatment. The production of amniotic membrane allografts has not been standardized, resulting in a wide array of amniotic membrane products, including single, dual, and tri-layered products, such as amnion, chorion, amnion-chorion, amnion-amnion, and amnion-chorion-amnion allografts. Since these allografts are not processed using the same methods, they do not necessarily produce the same clinical responses. The aim of this review is to highlight the properties of different human allograft membranes, present the different processing and preservation methods, and discuss their use in tissue engineering and regenerative applications.

The Therapeutic Efficacy of Freeze-Dried Human Amniotic Membrane Allograft Gel for Diabetic Foot Ulcers: A Phase-1 Clinical Trial.

Diabetic foot ulcers (DFUs) are classified as hard-to-heal wounds, which occur in approximately 15% of diabetic patients. Several interventions have shown efficacy in reducing the risk of amputation among patients with DFU, including timely diagnosis and management of infection and ischemia, debridement of necrotic tissues, reducing mechanical pressure on ulcers, and patient education. One major challenge in the management of DFUs is optimizing wound care to improve healing outcomes. Recently, interdisciplinary approaches proposed a new generation of wound dressing which increased efficacy and significantly decreased the healing time. The current study assessed the healing characteristics of chronic DFUs treated with lyophilized amniotic membrane gel (LAMG) in combination with standard care, versus a placebo hydrogel with standard care. In total, 18 patients (8 male, 10 female) were randomly assigned to the control group, which received standard care and a gelatin scaffold (placebo), or the intervention group, which received standard care along with LAMG. We evaluated the reduction in wound size and assessed the patient's health-related quality of life over 9 weeks. In the LAMG group (n = 9) and the Placebo group (n = 9), the wounds were reduced in size by a mean of 73.4% ± 15.3% and 13.1% ± 10.1%, respectively (P = .008). Patients treated with LAMG demonstrated significant improvements in the scores related to physical function, physical limitation, physical pain, general health, social function, emotional problems, and energy levels compared to the control group. The findings of this study indicate that using the LAMG with standard care significantly enhances wound healing.

Processing and Use of Radiation Sterilized Human Amniotic Membrane Allografts as Biological Dressings of Wounds in Children: A Review

Radiation sterilized human amniotic membrane allografts are used as biological dressing of wounds in rehabilitative surgery. The amniotic membrane is used in many different clinical situations such as: heat burn, chemical burns, diabetic wound/ diabetic foot ulcer, leprotic ulcer, abdominal wall reconstruction, pterigium removal site, peripheral corneal ulcer, in the management of pressure sore, etc.Non-viable lyophilized/oven-dried radiation sterilized amniotic membrane allografts could be processed for utilization as temporary biological dressing of wounds. The allografts used clinically should not be the carriers of germs or a source of infection. Human chorio-amniotic membranes collected for processing as tissue allografts to be used as biological dressings were reported to be contaminated with microorganisms such as species of Staphylococcus, Micrococcus, Bacillus and Pseudomonas.However, oven dried (40ºC) or freeze dried (-50ºC) human amniotic membranes were found to be sterilized by irradiation with the dose of 25 kiloGray (kGy) of gamma radiation.Careful screening and selection of tissue donors, proper processing and gamma radiation sterilization of human amniotic membranes minimize the risk of disease transmission to recipients through allografts.
 DS (Child) H J 2021; 38(1): 49-55

Quantification of Analgesic and Anti-Inflammatory Lipid Mediators in Long-Term Cryopreserved and Freeze-Dried Preserved Human Amniotic Membrane.

The aim of this study was to compare concentrations of endogenous N-acylethanolamine (NAE) lipid mediators-palmitoylethanolamide (PEA), oleoylethanolamide (OEA), and anandamide (AEA)-in fresh, decontaminated, cryopreserved, and freeze-dried amniotic membrane (AM) allografts, thereby determining whether AM's analgesic and anti-inflammatory efficiency related to NAEs persists during storage. The concentrations of NAEs were measured using ultra-high-performance liquid chromatography-tandem mass spectrometry. Indirect fluorescent immunohistochemistry was used to detect the PEA PPAR-α receptor. The concentrations of PEA, OEA, and AEA were significantly higher after decontamination. A significant decrease was found in cryopreserved AM compared to decontaminated tissue for PEA but not for OEA and AEA. However, significantly higher values for all NAEs were detected in cryopreserved samples compared to fresh tissue before decontamination. The freeze-dried AM had similar values to decontaminated AM with no statistically significant difference. The nuclear staining of the PPAR-α receptor was clearly visible in all specimens. The stability of NAEs in AM after cryopreservation was demonstrated under tissue bank storage conditions. However, a significant decrease, but still higher concentration of PEA compared to fresh not decontaminated tissue, was found in cryopreserved, but not freeze-dried, AM. Results indicate that NAEs persist during storage in levels sufficient for the analgesic and anti-inflammatory effects. This means that cryopreserved AM allografts released for transplant purposes before the expected expiration (usually 3-5 years) will still show a strong analgesic effect. The same situation was confirmed for AM lyophilized after one year of storage. This work thus contributed to the clarification of the analgesic effect of NAEs in AM allografts.

Lateral epicondylitis: comparing ultrasound-guided tenotomy with or without amniotic membrane allograft injection.

Aim: To evaluate the clinical response to augmenting ultrasound-guided tenotomy (USGT) with an amniotic membrane (AM) allograft injection. Design: Retrospective study. Materials& methods: Subjects underwent either a USGT (N=16) or a combined USGT plus AM injection (N=14). Results: Both groups demonstrated a significant reduction in pain from baseline starting after 2 weeks in the USGT plus AM group (p=0.036) and after 8 weeks in the USGT group (p=0.021). The reduction in pain was sustained for the entire duration of the study (52weeks). There was no significant difference in pain levels at 26- or 52-week follow-up or patient satisfaction between the two groups. Conclusion: USGT with or without AM allograft injections results in a significant reduction in pain with high patient satisfaction.

Novel Application of Umbilical Cord Flowable Tissue Allografts in Sacral Decubitus Ulcers: A Case Study

Each year, thousands of patients suffer from sacral decubitus ulcers, also known as pressure ulcers or sores. The current standard of care for sacral decubitus ulcer treatment is expensive and suboptimal, ranging in cost from a 15-dollar tube of Neosporin Ointment to 240,000 dollars for a skin flap surgery. Grade II pressure sores inevitably progress to stage III and IV if not addressed aggressively and early. Late-stage pressure sores present a unique challenge to physicians, particularly when they are deep, tunneling, and have tendon or bone involvement, as is the case for the two patients in this case study. The first patient in this study (referred to as patient 1) was afflicted with a mid-sacral pressure sore with exposed tendon, bone, and tunneling of ten years duration. The second patient in this study (referred to as patient 2) suffered from an ischial pressure sore with exposed tendon, bone, and tunneling for 30 months duration. Both patients exhausted conservative measures, including wound vac placement, oral and IV antibiotic treatment, multiple episodes of sharp debridement, wet-to-dry dressings, silver sulfadiazine dressings, and dehydrated amniotic membrane allograft placements. After failing conservative management, both patients received several applications of Wharton’s Jelly, a Mesenchymal Connective Tissue allograft (MCT), to accelerate wound closure. Conservative management, including sharp debridement, oral antibiotics, and electrical stimulation, was used in conjunction with the WJ allograft applications. At the time of consultation with Dr. Michael Lavor, both patients had Sacral Decubitus Ulcers (SDU) classified as Stage IV with tissue loss and involvement of bone or tendon, according to the National Pressure Ulcer Advisory Panel (NPUAP). After eight months of standardized wound care treatment combined with six Wharton’s Jelly allograft applications, both patients had wounds showing over 90% contraction in depth, tunneling, and diameter. This case study demonstrates a precedent for applying Wharton’s Jelly allografts in late-stage sacral decubitus ulcers with associated tunneling in combination with standard of care. Future research efforts with Wharton’s Jelly allografts applied to recalcitrant wounds may be directed at the frequency and combination of procedural techniques that best promote granulation tissue formation and volumetric contracture of deep wounds by secondary intention.

Application of Amniotic Membrane Allograft in the Treatment of Foot and Ankle Pathologies: A Review of the Basic Science and Clinical Evidence

Application of Amniotic Membrane Allograft in the Treatment of Foot and Ankle Pathologies: A Review of the Basic Science and Clinical Evidence

Plantar fasciitis: a comparison of ultrasound-guided fasciotomy with or without amniotic membrane allograft injection.

Aim: The purpose of this study was to evaluate the clinical response to augmenting an ultrasound-guided percutaneous plantar fasciotomy (UGPF) with an amniotic membrane (AM) allograft injection. Design: Retrospective, single-center, matched, case-controlled study. Methods: Patients underwent either an UGPF (n=15) or a combined UGPF and AM injection (n=16). Results: The UGPF plus AM group demonstrated a significant reduction in pain (p=0.02) from baseline at the short-term follow-up, but there was no significant difference in pain or patient satisfaction between groups at the 52-week follow-up. Conclusion: Both groups demonstrated a significant reduction in pain and high level of patient satisfaction, but the combination of UGPF with an AM injection may provide a greater reduction in pain earlier in the post-operative period.

Application of Amniotic Membrane Allografts in Advanced Venous Leg Ulcer: A Case Study and Literature Review

Chronic Venous Insufficiency (CVI) is a lifelong, moribund and debilitating disease process with tremendous personal and financial costs. At its core, CVI involves blood pooling in the lower extremities secondary to inadequate venous blood return, resulting in venous hypertension and incompetence of the one-way valves in the lower extremity veins. As venous circulation slows, metabolic demands of the cells in the lower extremities increase, leading to stasis dermatitis, infection, cellular death, and venous ulceration. This case study aims to report the efficacy of Dehydrated Amniotic Membrane Allograft (DAMA) applications to a chronic right lateral ankle ulcer resulting from chronic venous insufficiency. The patient in this study received DAMA applications weekly for six weeks. Upon examination at the initial application, the wound was wet and macerated due to drainage with significant hemosiderosis and lipodermatosclerosis consistent with a Venous Clinical Severity Score (VCSS) of 2. Upon inspection at the final visit, the wound was closed, with a VCSS of 0. This case study demonstrates that the application of DAMA has the potential to act as an effective barrier to cover and accelerate wound closure time. Future non randomized and randomized controlled trials may further establish standardized protocols for DAMA application in venous ulceration, help create treatment algorithms to predict wound closure endpoints, and encourage innovation that may further accelerate healing time.

Chronic Plantar Fasciitis: Comparison of Ultrasonic Guided Percutaneous Fasciotomy vs New Technique Combining Fasciotomy with Amniotic Membrane Allograft

Category: Basic Sciences/Biologics Introduction/Purpose: Plantar fasciitis is a common condition affecting approximately one in ten people in their lifetime. Treatment is typically conservative and symptoms are self-limiting. Operative treatment is indicated in recalcitrant cases. Minimally-invasive partial plantar fasciotomy can be performed using ultrasound-guided percutaneous techniques and is an attractive alternative to traditional surgery. Methods: A retrospective review was performed on consecutive patients who underwent either an ultrasound-guided fasciotomy or a combined percutaneous fasciotomy with a flowable amniotic matrix allograft. All ultrasound-guided percutaneous fasciotomy procedures were performed using the Tenex TX2 cutting device. Human amniotic allograft consisted of an injection of 0.5 mL of a flowable placental tissue matrix. Outcomes were assessed at short-term (2, 8, and 16 weeks) and long-term follow-up (26 and 52 weeks). Results: Both groups demonstrated a significant reduction in pain from baseline after the respective interventions and demonstrated a high level of patient satisfaction. The only significant difference in the 2 groups was at short-term follow-up in which the percutaneous fasciotomy with the amniotic membrane allograft (n=12) showed a statistically-significant reduction (p<0.05) in pain when compared to the fasciotomy alone group (n=11). There was no difference between the 2 groups at long- term follow-up. Conclusion: Treatment of chronic plantar fasciitis using ultrasound-guided fasciotomy is an attractive alternative to traditional surgery. Ultrasound-guided fasciotomy did improve pain from baseline with high level of patient satisfaction. Furthermore, the combination of percutaneous fasciotomy with a flowable amniotic matrix allograft may provide a greater reduction in pain earlier in the post-operative period, but does not seem to alter the long-term outcome of the procedure. More subjects are needed to possibly detect long-term effects.