Cryopreserved Placental Membrane Allograft Reduces the Likelihood of Developing a New or Recurring Foot Ulcer and All-Cause Mortality in Diabetic Patients When Compared with Other Cellular- and Tissue-Based Products.

Objective: To compare outcomes for Medicare patients with diabetic foot ulcer(s) (DFU) receiving cryopreserved placental membrane containing viable cells (vCPM) to other Cellular- and Tissue-Based Products (CTPs). Approach: Patients with DFU and CTP use were selected in Medicare claims (2013-2017) by using a strict definition of DFU with demonstrated diabetes etiology. We compared the effectiveness of vCPM with other CTPs on: (1) reduction of post-treatment ulcer occurrence, and (2) reduction in 1 year mortality. We controlled for selection bias and differential risk characteristics between comparison groups in a two-stage inverse probability treatment weighting model. Results: Overall, 7,869 DFU episodes with CTP use met inclusion criteria: 786 received vCPM, 4,546 received another "cellular" CTP, and 2,537 received "acellular" CTP. For ulcer occurrence, we examined: 30-, 90-, 180-, and 365 days post-treatment. We found a significant reduction in ulcers at each period for vCPM compared with either alternative CTP-results range from a 36.7% percentage point reduction in ulcer occurrence at 30 days compared with cellular CTP, and a 58.5% percentage point reduction at 365 days compared with acellular CTP. Further, the application of vCPM reduces mortality within 1 year by 2.3 percentage points (13-13.8% change) compared with other CTPs. Innovation: This study examines the differences in ulcer occurrence and mortality for Medicare DFU patients receiving vCPM and other CTPs. Our strict DFU definition excludes beneficiaries without foot ulcer with demonstrated diabetes etiology. Conclusion: Among CTPs, vCPM users have reduced ulcer rates (recurrent or new) and reduced all-cause mortality compared with other "cellular" and "acellular" CTPs.

Mesenchymal Stem/Stromal Cells Derived from Human and Animal Perinatal Tissues-Origins, Characteristics, Signaling Pathways, and Clinical Trials.

Mesenchymal stem/stromal cells (MSCs) are currently one of the most extensively researched fields due to their promising opportunity for use in regenerative medicine. There are many sources of MSCs, of which cells of perinatal origin appear to be an invaluable pool. Compared to embryonic stem cells, they are devoid of ethical conflicts because they are derived from tissues surrounding the fetus and can be safely recovered from medical waste after delivery. Additionally, perinatal MSCs exhibit better self-renewal and differentiation properties than those derived from adult tissues. It is important to consider the anatomy of perinatal tissues and the general description of MSCs, including their isolation, differentiation, and characterization of different types of perinatal MSCs from both animals and humans (placenta, umbilical cord, amniotic fluid). Ultimately, signaling pathways are essential to consider regarding the clinical applications of MSCs. It is important to consider the origin of these cells, referring to the anatomical structure of the organs of origin, when describing the general and specific characteristics of the different types of MSCs as well as the pathways involved in differentiation.

Three-dimensional human placenta-like bud synthesized from induced pluripotent stem cells.

Placental dysfunction is related to the pathogenesis of preeclampsia and fetal growth restriction, but there is no effective treatment for it. Recently, various functional three-dimensional organs have been generated from human induced-pluripotent cells (iPSCs), and the transplantation of these iPSCs-derived organs has alleviated liver failure or diabetes mellitus in mouse models. Here we successfully generated a three-dimensional placental organ bud from human iPSCs. The iPSCs differentiated into various lineages of trophoblasts such as cytotrophoblast-like, syncytiotrophoblast-like, and extravillous trophoblast-like cells, forming organized layers in the bud. Placental buds were transplanted to the murine uterus, where 22% of the buds were successfully engrafted. These iPSC-derived placental organ buds could serve as a new model for the study of placental function and pathology.

Regenerative Effects of Hypoxia Primed Flowable Placental Formulation in Muscle and Dermal Injury.

The placental tissue, due to its angiogenic, anti-inflammatory, antioxidative, antimicrobial, and anti-fibrotic properties, has become a compelling source towards a solution for several indications in regenerative medicine. However, methods to enhance and capture the therapeutic properties with formulations that can further the applications of viable placental tissue have not been explored. In this study, we investigated the regenerative effects of a hypoxia primed flowable placental formulation (FPF), composed of amnion/chorion and umbilical tissue, in two in vivo injury models. Laser Doppler data from rodent ischemia hindlimbs treated with FPF revealed significant tissue perfusion improvements compared to control ischemic hindlimbs. To further corroborate FPF's effects, we used a rodent ischemic bipedicle skin flap wound model. FPF treatment significantly increased the rate of wound closure and the quality of wound healing. FPF-treated wounds displayed reduced inflammation and an increase in angiogenesis. Furthermore, quantitative PCR and next-generation sequencing analysis confirmed these changes in the FPF-treated group at both the gene and transcriptional level. The observed modulation in miRNAs was associated with angiogenesis, regulation of inflammatory microenvironment, cell migration and apoptosis, reactive oxygen species generation, and restoring epithelial barrier function, all processes involved in impaired tissue healing. Taken together, these data validate the tissue regenerative properties of the flowable placental formulation configuration tested.

Human placental-derived stem cell therapy ameliorates experimental necrotizing enterocolitis.

Necrotizing enterocolitis (NEC), a life-threatening intestinal disease, is becoming a larger proportionate cause of morbidity and mortality in premature infants. To date, therapeutic options remain elusive. Based on recent cell therapy studies, we investigated the effect of a human placental-derived stem cell (hPSC) therapy on intestinal damage in an experimental NEC rat pup model. NEC was induced in newborn Sprague-Dawley rat pups for 4 days via formula feeding, hypoxia, and LPS. NEC pups received intraperitoneal (ip) injections of either saline or hPSC (NEC-hPSC) at 32 and 56 h into NEC induction. At 4 days, intestinal macroscopic and histological damage, epithelial cell composition, and inflammatory marker expression of the ileum were assessed. Breastfed (BF) littermates were used as controls. NEC pups developed significant bowel dilation and fragility in the ileum. Further, NEC induced loss of normal villi-crypt morphology, disruption of epithelial proliferation and apoptosis, and loss of critical progenitor/stem cell and Paneth cell populations in the crypt. hPSC treatment improved macroscopic intestinal health with reduced ileal dilation and fragility. Histologically, hPSC administration had a significant reparative effect on the villi-crypt morphology and epithelium. In addition to a trend of decreased inflammatory marker expression, hPSC-NEC pups had increased epithelial proliferation and decreased apoptosis when compared with NEC littermates. Further, the intestinal stem cell and crypt niche that include Paneth cells, SOX9+ cells, and LGR5+ stem cells were restored with hPSC therapy. Together, these data demonstrate hPSC can promote epithelial healing of NEC intestinal damage.NEW & NOTEWORTHY These studies demonstrate a human placental-derived stem cell (hPSC) therapeutic strategy for necrotizing enterocolitis (NEC). In an experimental model of NEC, hPSC administration improved macroscopic intestinal health, ameliorated epithelial morphology, and supported the intestinal stem cell niche. Our data suggest that hPSC are a potential therapeutic approach to attenuate established intestinal NEC damage. Further, we show hPSC are a novel research tool that can be utilized to elucidate critical neonatal repair mechanisms to overcome NEC.

Placental Mitochondria Therapy for Cerebral Ischemia-Reperfusion Injury in Mice.

BACKGROUND AND PURPOSE: There is an urgent need to develop adjunct therapies that can be added onto reperfusion for acute ischemic stroke. Recently, mitochondrial transplantation has emerged as a promising therapeutic approach for boosting brain tissue protection. In this proof-of-concept study, we investigate the feasibility of using placenta as a source for mitochondrial transplantation in a mouse model of transient focal cerebral ischemia-reperfusion. METHODS: Mitochondria-enriched fractions were isolated from cryopreserved mouse placenta. Mitochondrial purity and JC1 membrane potentials were assessed by flow cytometry. Adenosine triphosphate and mitochondrial proteins were measured by luminescence intensity and western blot, respectively. Therapeutic efficacy of mitochondrial fractions was assessed in a mouse model of transient focal cerebral ischemia-reperfusion. RESULTS: Flow cytometry analysis demonstrated that about 87% of placental mitochondria were viable and maintained JC1 membrane potentials after isolation. Placental mitochondrial fractions contained adenosine triphosphate equivalent to mitochondrial fractions isolated from skeletal muscle and brown fat tissue. Normalized mitochondrial antioxidant enzymes (glutathione reductase, MnSOD [manganese superoxide dismutase]) and HSP70 (heat shock protein 70) were highly preserved in placental mitochondrial fractions. Treatment with placental mitochondrial fractions immediately after reperfusion significantly decreased infarction after focal cerebral ischemia in mice. CONCLUSIONS: Cryopreserved placenta can be a feasible source for viable mitochondrial isolation. Transplantation with placental mitochondria may amplify beneficial effects of reperfusion in stroke.

Placental membrane grafts for urethral replacement in a rabbit model: a pilot study.

PURPOSE: Several graft materials are available for use in the treatment of urethral stricture disease. Placental membrane is being used in a variety of settings as a graft in wound healing and tissue repair. We aim to evaluate the effect of implanting decellularized human placental membrane into rabbit urethras. METHODS: Dorsal onlay graft urethroplasty using prepared human placental membrane was performed in 10 New Zealand White rabbits (Oryctolagus cuniculus). After 3 months, the rabbits underwent cystourethroscopy to evaluate urethral patency. The rabbits were then euthanized and the urethras examined for pathological findings. RESULTS: All urethroplasties were performed without complication. There were no observed episodes of urinary retention, infection, or renal failure. Urethral patency was achieved in all rabbits 3 months postoperatively. Urothelial replacement of the placental membrane graft was observed in all rabbits without malignant transformation. CONCLUSION: Dorsal onlay urethroplasty using decellularized human placental membrane can safely be performed in a rabbit model. This pilot study demonstrated urothelial replacement of human placental membrane in the rabbit urethra without stricture formation. Placental membrane is a promising biomaterial for urethral reconstruction.

Nonoperative Applications of Placental Tissue Matrix in Orthopaedic Sports Injuries: A Review of Literature.

OBJECTIVE: Recently, various amniotic tissue and placental-based tissue matrix (PTM) products have become increasingly available as a nonoperative treatment for tendinopathies and orthopaedic sports injuries. The aim of this review was to evaluate: (1) safety and efficacy of nonoperative use of PTM products, in acute and chronic tendon injuries and (2) the commercially available tissue options to better understand their differences. DATA SOURCES: A comprehensive literature search was performed. Inclusion criteria were studies reporting on: (1) nonoperative uses of PTM therapy in sports injuries; and (2) clinical outcomes; in (3) human subjects. We excluded: (1) animal studies; (2) basic science studies; (3) non-English language literature; (4) review articles; and (5) duplicate studies. In addition, to determine the various product formulations, their tissue contents, and indications for use, we searched publicly available website content, marketing literature, and Food and Drug Administration (FDA) registration documents. MAIN RESULTS: Current evidence investigated various PTM products for the treatment of various tendon injuries with demonstrated efficacy mainly in the short term with follow-up ranging between 6 weeks and 3 months. In addition, across all studies, no specific adverse events were reported. Substantial differences exist among the currently available products due to variations in their tissue source, formulations, processing methods, method of sterilization, preservation, and storage, indications for use, and FDA regulation. CONCLUSIONS: Placental- and amniotic membrane-derived tissues seem to be safe for the nonoperative treatment of tendinopathies. However, several factors may affect the efficacy and safety profile of these products, and the orthopaedic surgeons should be aware of the differences.

A Prospective, Single-center, Open-label Case Series Evaluating the Clinical Outcomes of Lyopreserved Placental Membrane Containing Viable Cells in the Treatment of Chronic Wounds.

INTRODUCTION: Cryopreserved placental membrane containing viable cells (vCPM) in conjunction with standard of care (SOC) has shown clinical effectiveness in several studies for the management of acute and chronic wounds. Recently, a new lyophilization technique has been developed that allows viable tissues to be stored at room temperature as a structural and functional equivalent to vCPM. OBJECTIVE: This case series evaluates the clinical outcomes of a lyopreserved placental membrane containing viable cells (vLPM) for the management of chronic wounds of various etiologies. MATERIALS AND METHODS: Eleven patients (11 wounds: 5 diabetic foot ulcers, 5 venous leg ulcers, and 1 pressure ulcer) received weekly vLPM applications adjunct to SOC. RESULTS: By week 12 of treatment, 63.6% (7/11) of patients achieved complete wound closure, with a mean time to closure of 47.1 days and a mean of 6 vLPM applications. Further, there were no adverse events attributed to vLPM. CONCLUSIONS: This is the first case series reporting the clinical outcomes of vLPM for the management of chronic wounds. Results of this study demonstrate similar closure rates to those previously reported for vCPM. These results suggest potential clinical equivalence between the 2 formulations, with vLPM providing the added convenience of long-term room-temperature storage (current shelf life of 12 months).

Decellularized bovine placentome for portacavally-interposed heterotopic liver transplantation in rats.

Scaffolds from healthy placentae offer advantages for tissue engineering with undamaged matrix, associated cytoprotective molecules, and embedded vessels for revascularization. As size disparities in human placenta and small recipients hamper preclinical studies, we studied alternative of bovine placentomes in smaller size ranges. Multiple cow placentomes were decellularized and anatomical integrity was analyzed. Tissue engineering used inbred donor rat livers. Placentomes were hepatized and immediately transplanted in rats with perfusion from portal vein and drainage into inferior vena cava. Cows yielded 99 ±â€¯16 placentomes each. Of these, approximately 25% had 3 to 9 cm diameter and 7 to 63 ml volume, which was suitable for transplantation. After decellularization, angiography and casts documented 100% of vessels and vascular networks were well-perfused without disruptions or leaks. The residual matrix also remained intact for transplantation of placentomes. Perfusion in transplanted placentomes was maintained over up to 30 days. Liver tissue reassembled with restoration of hepatic acinar and sinusoidal structure. Transplanted tissue was intact without apoptosis, or necrosis. Hepatic functions were maintained. Preservation of hepatic homeostasis was verified by cytofluorimetric analysis of hepatocyte ploidy. The prevalence in healthy and transplanted liver of diploid, tetraploid and higher ploidy classes was similar with 57%, 41% and 2% versus 51%, 46.5% and 2.6%, respectively, p = 0.77, ANOVA. CONCLUSIONS: Cow placentomes will allow therapeutic development with disease models in small animals. This will also advance drug or toxicology studies. Portasystemic interposition of engineered liver will be particularly suitable for treating hepatic insufficiencies (metabolic, secretory or detoxification needs), including for children or smaller adults.

Stage IV Perineal Pressure Ulcers in Immobile Patients Treated With Surgical Flap Closure Augmented With Cryopreserved Placental Membrane Containing Viable Cells.

INTRODUCTION: Surgical closure of late-stage pressure ulcers (PUs) poses challenges in the immobilized population due to the high rate of complications, including infection, dehiscence, and recurrence. Muscle flap closure is the standard treatment for chronic, late-stage (stage 4) PUs, characterized by the European Pressure Ulcer Advisory Panel and National Pressure Ulcer Advisory Panel as full-thickness tissue loss with exposure of bone, tendon, or muscle. OBJECTIVE: The aim of this study is to evaluate the outcomes associated with the use of a cryopreserved placental membrane containing viable cells (vCPM) graft for the augmentation of surgical flap closure in nonhealing perineal ulcers. MATERIALS AND METHODS: Four paraplegic patients (2 men, 2 women; average age, 61 years; range, 44-77 years) with stage IV PUs (ischial, gluteal, and sacral areas) with a mean duration of 4 years (range, 0.5-10 years) received muscle flap closure augmented with vCPM. Following surgical debridement, vCPM was placed between the wound bed and muscle flap closure prior to skin closure. Patients were kept offloaded in fluid-air beds for 6 weeks followed by a gradual return to mobilization. RESULTS: All 4 patients achieved complete wound closure in an average of 7 weeks (range, 6-8 weeks) without complications or recurrence. All patients demonstrated complete take of the muscle flap and maintained their closed wounds for an average follow-up of 12 months. CONCLUSIONS: Preliminary clinical results indicate vCPM supports surgical wound closure of chronic perineal PUs in immobile, high-risk patients. In an effort to decrease postoperative recovery time and reduce complications, vCPM may be beneficial for patients undergoing perineal muscle flap closure.

Prospective study of cryopreserved placental tissue wound matrix in the management of chronic venous leg ulcers.

OBJECTIVE: Chronic venous leg ulcers (VLUs) affect up to 2% of the general population, resulting in a significant socioeconomic burden. Placental tissue that contains mesenchymal stem cells and active growth factors has been shown to be beneficial in healing of chronic wounds. We compared the efficacy of a human viable wound matrix (hVWM) of cryopreserved placental tissue for the treatment of refractory VLUs with standard therapy. METHODS: This prospective single-center open-label single-arm study enrolled patients with Clinical, Etiology, Anatomy, and Pathophysiology clinical class C6 VLUs. The ulcers of all enrolled patients had failed to heal after a trial of standard therapy of at least 12 weeks, which included weekly multilayer compression therapy along with local wound care. The same patients subsequently received application of hVWM (Grafix; Osiris Therapeutics, Columbia, Md) every 1 to 2 weeks in addition to standard therapy. Healing with hVWM therapy was then compared with standard therapy, with each patient serving as his own control. RESULTS: There were 30 VLUs in 21 consecutive eligible patients who were enrolled in the study. All patients were men with an average age of 67 years (standard deviation [SD], ±10.8 years), and the average area of venous ulcers before hVWM initiation was 12.2 cm2 (SD, ±14.6 cm2; range, 3.3-12.3 cm2). Duplex ultrasound confirmed superficial or deep system venous reflux in all patients. Complete ulcer healing was achieved in 53% (16/30) of VLUs refractory to standard therapy after application of hVWM. There was a mean reduction in wound surface area by 79% (SD, ±27.3%; P < .001 compared with standard therapy) after a mean treatment time of 10.9 weeks. Eighty percent of VLUs were reduced in size by half compared with 25% with standard therapy (P < .001). The mean rate of reduction in ulcer area after hVWM applications was 1.69% per day vs 0.73% per day with standard therapy (P = .01). CONCLUSIONS: Cryopreserved placental tissue (hVWM) improves healing processes to achieve complete wound closure in a significant proportion of chronic VLUs refractory to standard therapy. Adjunctive therapy with hVWM provides superior healing rates in refractory VLUs.

Allogeneic Skin Substitutes Versus Human Placental Membrane Products in the Management of Diabetic Foot Ulcers: A Narrative Comparative Evaluation of the Literature.

Outcomes following standard wound care (SWC) for diabetic foot ulcers (DFUs) remain suboptimal. Supplementing SWC with tissue engineered allogeneic cellular wound therapies represents an emerging treatment strategy. This review aimed to evaluate the efficacy and safety of allogeneic skin substitutes and human placental membrane allografts in the management of DFUs. Ovid MEDLINE and Embase databases were searched from inception to October 2017. Any randomized controlled trial (RCT) with an allogeneic skin substitute or placental membrane allograft intervention group was included. Our primary outcome measure was the proportion of completely healed ulcers. Secondary outcome measures included time to complete wound healing and local adverse event rates. Each study was assessed for risk of bias and the quality of evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Moderate quality evidence from 11 included RCTs demonstrated that both allogeneic cellular approaches improve the proportion of completely healed ulcers at 6 and 12 weeks. One RCT showed that a placental membrane allograft was superior to an allogeneic skin substitute, although this has yet to be repeated in other studies. The addition of allogeneic cellular wound products to SWC improves DFU outcomes. Further studies are required to conclusively establish if placental membrane allografts are superior to allogeneic skin substitutes.

Surgical Application of Viable Cryopreserved Placental Membrane for the Treatment of Chronic Wounds in 12 High-risk Patients.

Treatment of lower extremity ulcers remains a challenge to physicians and surgeons. These wounds lead to an increased risk of amputation and increased mortality rate and must be treated aggressively, in many cases requiring surgical debridement, to prevent these complications. The objective of this retrospective case series is to evaluate the safety and efficacy of a viable cryopreserved placental membrane (vCPM) in 12 patients with 16 wounds of mixed etiologies when surgically debrided and augmented with vCPM 1 time, followed by standard of care (nonadherent dressing, gauze, and compression) until healed. The results of this case series demonstrate that the surgical application of vCPM can be used as an alternative treatment for high-risk patients with chronic lower extremity wounds.

Experience in Using Fetal Membranes: The Present and New Perspectives.

INTRODUCTION: The placenta is an accessible source of tissues for transplantation. Placental transplants have been used in wound treatment because of the basic function of the placenta and its nutritious properties and structure. PATIENTS AND METHODS: The aim of this work is to present the clinical usage of fetal membranes, including human amnion, on the basis of the burn treatment center's experience. The clinical use of amnion and different types of placental transplants are described. The initial results of research work within the MEDPIG project are presented regarding the application of placenta from transgenic pigs as a source of tissues for transplantation. RESULTS: From August 2011 to March 2017, 252,592 cm2 of biostatic human amnion transplants were prepared in our tissue bank. During this period they were transplanted to 528 patients, including 10 patients with Lyell syndrome. Initial studies were conducted in which placentas were collected from 5 transgenic pigs and 27,426 cm2 of amniotic grafts were prepared from them. DISCUSSION: The authors' own experience as well as the literature confirm the extraordinary efficiency of transplants prepared from placental tissues, especially from the amniotic membrane. CONCLUSIONS: The clinical effects confirm the effectiveness of using human amnion in wound treatment. Amniotic transplant is a new treatment standard in toxic epidermal necrolysis TEN (Lyell's syndrome), which has found confirmation in very good clinical outcomes. The collected placentas from transgenic animals enabled the preparation of significantly more grafts than in the case of human material, which is a great advantage of this source of placenta over human tissues.

Open-label Extension Phase of a Chronic Diabetic Foot Ulcer Multicenter, Controlled, Randomized Clinical Trial Using Cryopreserved Placental Membrane.

OBJECTIVE: The results of the single-arm, open-label extension phase of the Grafix (cryopreserved placental membrane; CPM; Osiris Therapeutics, Inc, Columbia, MD) multicenter, blinded, randomized, controlled clinical trial for chronic diabetic foot ulcers (DFUs) is reported. MATERIALS AND METHODS: Twenty-six patients in the standard wound care (SWC) arm whose DFUs did not close in the blinded phase chose to receive weekly applications of the CPM in an open-label extension phase. RESULTS: In the extension phase, 17 (65.4%) patients closed their wounds in a median of 34 days and 3 visits. There were fewer total adverse events (AEs) (24 CPM vs. 52 SWC) and index wound-related infections (5 CPM vs. 12 SWC) during the CPM application compared with the number of AEs for the same patients during the SWC treatment in the blinded phase of the trial. CONCLUSIONS: These results corroborate the benefits of this CPM combined with SWC over SWC alone for chronic DFUs previously reported for the blinded randomized phase of the trial, which directly relate to lower health care costs.

A multicenter, randomized, single-blind trial comparing the efficacy of viable cryopreserved placental membrane to human fibroblast-derived dermal substitute for the treatment of chronic diabetic foot ulcers.

Randomized controlled clinical trials, the gold standard to determine treatment efficacy against control, have demonstrated advantages of skin substitutes for the treatment of chronic diabetic foot ulcers in comparison to standard of care. However, randomized controlled clinical trials comparing efficacy between two or more skin substitutes are very limited. With growing numbers of new skin substitutes, such studies are essential for treatment and policy-making decisions by wound care providers and payers. In this study, we analyzed clinical outcomes and product cost between a viable cryopreserved placental membrane (vCPM) and a human fibroblast-derived dermal substitute (hFDS) for the treatment of chronic diabetic foot ulcers in a prospective, multicenter, single-blind study. The outcomes of 62 patients were analyzed: 31 patients in the vCPM treatment group and 31 patients in the hFDS treatment group. Utilizing a non-inferiority trial design and the established treatment regimen of 8 applications for hFDS, we demonstrated that vCPM was not inferior to hFDS for the proportion of patients achieving complete wound closure (9.68, 90% CI: [10.67, 28.94]). However, preliminary findings show that vCPM may have better outcomes for wounds ≤ 5 cm2 : 81.3% (13/16) of wounds in the vCPM group vs. 37.5% (6/16) of wounds in the hFDS group reached complete closure at the end of treatment (p = 0.0118). A preliminary product cost analysis for wounds ≤ 5 cm2 may show significant savings for patients treated with vCPM. Average per-patient costs during the course of treatment were $3,846 and $7,968 (p < 0.0001) for vCPM and hFDS patients, respectively. These results may be used as guidance to wound care providers and payers.

Human placental membrane as a wound cover for chronic diabetic foot ulcers: a prospective, postmarket, CLOSURE study.

OBJECTIVE: To evaluate the safety and efficacy of a chorioamniotic allograft, used as a wound cover for chronic foot ulcers, in patients with diabetes. METHODS: A multicentre, prospective, postmarket study where eligible patients received up to 11 weekly wound cover applications. Computerised planimetry was used to calculate the diabetic foot ulcer (DFU) area each week. The primary endpoint of the study was wound closure assessment. Secondary endpoints included DFU recurrence and morbidity. RESULTS: A total of 63 patients with 64 ulcers were enrolled, after successful completion of a two-week run-in period. Patients were predominantly male and had risk factors for delayed healing. Mean baseline DFU area was 3.8cm2 (standard deviation (SD): 4.8). After 12 weeks, a total of 19 (40%) DFUs had closed. Results varied by size category, 'small' (≤2.0cm2), 'medium' (>2.0-4.0 cm2), and 'large' (>4.0-25.0 cm2), with higher percentage closure in the 'small' DFU group, compared with the 'medium' and 'large' DFUs (57%, 33%, and 10%, respectively). Of those DFUs that closed, the average closure time was 6.5 weeks. There were no unanticipated adverse events. CONCLUSION: Known risk factors for healing, including DFU size, location and duration, affected the outcomes. However, the results are in line with the literature and support the use of the chorioamniotic allograft in chronic and complex cases.

The Role of Placental Membrane Allografts in the Surgical Treatment of Tendinopathies.

Placental membrane grafts have long been used in the realms of wound care and ophthalmology to assist in the healing cascade. Recently, surgeons have started to implant placental membrane grafts in a wide variety of foot and ankle surgeries to take advantage of their many touted benefits. The application of placental membrane grafts for cases of lower extremity tendinopathy is detailed in this article.

Treatment of gingival recession using a coronally-advanced flap procedure with or without placental membrane.

AIM: The aim of the present study was to compare the treatment of gingival recession defects using a coronally-advanced flap procedure with or without placental membrane. METHODS: Sixty teeth in 15 patients with single and multiple Miller's class I and II gingival recession defects bilaterally in the anterior and premolar region of the maxilla and mandible were divided into two groups. In group I (control), 30 recession defects were treated with coronally-advanced flap alone using Zucchelli's technique. In group II (test), 30 recession defects were treated with coronally-advanced flap along with placental membrane. Probing depth, height of the gingival recession (HGR), clinical attachment level (CAL), width of the gingival recession, and width of the keratinized tissue (WKT) were recorded at baseline and 3 and 6 months after the surgical procedures. RESULTS: There was a statistically-significant reduction in the HGR, gain in the CAL, and WKT in group II compared to group I. CONCLUSION: Coronally-advanced flap with placental allograft provides a reliable technique for root coverage when compared to coronally-advanced flap alone.