Human Placental Membranes Research Articles

Retention processed placental membrane versus standard of care in treating diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are a severe complication for diabetic patients, significantly impacting patient quality of life and healthcare system efficiency. Traditional standard of care (SOC) treatments are inadequate for many patients, necessitating the use of advanced wound care products, such as human placental membranes. We studied a real-world population of large, hard-to-heal and complicated wounds, otherwise under-studied in the wound care literature. To this end, we conducted a retrospective cohort analysis to compare the effectiveness of a human placental amnion/chorion membrane product using retention-based processing (RE-AC) and SOC in managing chronic DFUs. During the study period of September 2021 through April 2024, we collected retrospective observational data from electronic health records of 21 patients treated with RE-AC at three outpatient wound care centres. Additionally, 21 control SOC patients were matched from a wound registry using Coarsened Exact Matching. Patients were categorized into two cohorts based on whether they received RE-AC or SOC. Key metrics included wound size progression and wound closure. The analysis employed Bayesian regression and Hurdle Gamma Analysis of Covariance models. Despite their rather large size (average of 13.8 cm2), our results indicated that RE-AC achieved almost a 10% higher expected wound closure rate compared to SOC at 12 weeks (8.53% [credible interval: 5.60%-10.7%]). Further, for wounds that did not close, RE-AC resulted in a 93.6% (credible interval: 147.7%-41.6) improvement in expected Percent Area Reduction over the SOC group at 12 weeks. We noted that on average, SOC wounds stalled or grew larger. In terms of a risk ratio comparing the study group with SOC, we found a 52% benefit in the RE-AC group (RR = 1.52). The findings suggest that even with larger DFUs, R-AC is superior to SOC for wound closure and expected Percent Area Reduction by 12 weeks. This benefit likely leads to reduced treatment costs, optimized resource utilization and improved outcomes in the DFU patient population; ultimately resulting in improved patient care.

Assessing placental membrane treatment efficiency in diabetic foot ulcers: Processing for retention versus lamination.

Diabetic foot ulcers are a severe complication in diabetic patients, significantly impact healthcare systems and patient quality of life, often leading to hospitalization and amputation. Traditional Standard of Care (SOC) treatments are inadequate for many patients, necessitating advanced wound care products (AWCPs) like human placental membranes. This study conducts a retrospective analysis to compare the effectiveness of two human placental membrane products, retention-processed amnion chorion (RE-AC) and lamination-processed amnion chorion (L-AC) in managing chronic diabetic foot ulcers (DFUs). The study collected retrospective observational data from electronic health records (EHRs) of patients treated for DFU at three outpatient wound care centers. Patients were categorized into two cohorts based on the treatment received. Key metrics included wound size progression and the number of product applications. The analysis employed Bayesian estimation, utilizing an analysis of covariance model with a Hurdle Gamma likelihood. We found that RE-AC achieved a marginally higher expected Percent Area Reduction (xPAR) in DFUs compared to L-AC at 12 weeks (67.3% vs. 52.6%). RE-AC also required fewer applications, suggesting greater efficiency in general wound closure. Probability of full wound closure was similar in both groups (0.738 vs 0.740 in RE-AC and L-AC, respectively). The findings suggest that while L-AC might be slightly more effective in complete ulcer healing, RE-AC offers overall better treatment efficiency, especially in reducing the frequency of applications. This efficiency can lead to improved patient comfort, reduced treatment costs, and optimized resource utilization in healthcare settings.

Epicardial placement of human placental membrane allografts in coronary artery bypass graft surgery is associated with reduced postoperative atrial fibrillation: a pilot study for a future multi-center randomized controlled trial

BackgroundPost-operative atrial fibrillation (POAF) occurs in up to 40% of patients following coronary artery bypass grafting (CABG) and is associated with a higher risk of stroke and mortality. This study investigates how POAF may be mitigated by epicardial placement of aseptically processed human placental membrane allografts (HPMAs) before pericardial closure in CABG surgery. This study was conducted as a pilot feasibility study to collect preliminary for a forthcoming multi-center randomized controlled trial.MethodsThis retrospective observational study of patients undergoing CABG surgery excluded patients with pre-operative heart failure, chronic kidney disease, or a history of atrial fibrillation. The “treatment” group (n = 24) had three HPMAs placed epicardially following cardiopulmonary bypass decannulation but before partial pericardial approximation and chest closure. The only difference in clinical protocol for the control group (n = 54) was that they did not receive HPMA.ResultsHPMA-treated patients saw a significant, greater than four-fold reduction in POAF incidence compared to controls (35.2–8.3%, p = 0.0136). Univariate analysis demonstrated that HPMA treatment was associated with an 83% reduction in POAF (OR = 0.17, p = 0.0248). Multivariable analysis yielded similar results (OR = 0.07, p = 0.0156) after controlling for other covariates. Overall length of stay (LOS) between groups was similar, but ICU LOS trended lower with HPMA treatment (p = 0.0677). Post-operative inotrope and vasopressor requirements were similar among groups. There was no new-onset post-operative heart failure, stroke, or death reported up to thirty days in either group.ConclusionsEpicardial HPMA placement can be a simple intervention at the end of CABG surgery that may provide a new approach to reduce post-operative atrial fibrillation by modulating local inflammation, possibly reducing ICU and hospital stay, and ultimately improving patient outcomes.

Characterization of a full-thickness decellularized and lyophilized human placental membrane for clinical applications.

Allografts derived from live-birth tissue obtained with donor consent have emerged as an important treatment option for wound and soft tissue repairs. Placental membrane derived from the amniotic sac consists of the amnion and chorion, the latter of which contains the trophoblast layer. For ease of cleaning and processing, these layers are often separated with or without re-lamination and the trophoblast layer is typically discarded, both of which can negatively affect the abundance of native biological factors and make the grafts difficult to handle. Thus, a full-thickness placental membrane that includes a fully-intact decellularized trophoblast layer was developed for homologous clinical use as a protective barrier and scaffold in soft tissue repairs. Here, we demonstrate that this full-thickness placental membrane is effectively decellularized while retaining native extracellular matrix (ECM) scaffold and biological factors, including the full trophoblast layer. Following processing, it is porous, biocompatible, supports cell proliferation in vitro, and retains its biomechanical strength and the ability to pass through a cannula without visible evidence of movement or damage. Finally, it was accepted as a natural scaffold in vivo with evidence of host-cell infiltration, angiogenesis, tissue remodelling, and structural layer retention for up to 10 weeks in a murine subcutaneous implant model.

Cisgender Cellular Tissue-Based Products Improve Wound Healing

Neither the CTP sex effect of female CTP derived from cryopreserved human placental membranes, nor male CTP bioengineered from living human keratinocytes and foreskin fibroblasts has been described. Healing in wounds was examined to establish the CTP sex’ s role in both males and females. Cisgender CTP wounds had better closure. Overall, male PC, PC-End, and CC rates over time were better than female rates. Outcomes were affected by access, etiology, and follow-up.

The Human Placental Amniotic Membrane Mesenchymal-Stromal-Cell-Derived Conditioned Medium Inhibits Growth and Promotes Apoptosis of Human Cholangiocarcinoma Cells In Vitro and In Vivo by Suppressing IL-6/JAK2/STAT3 Signaling.

Mesenchymal stromal cells (MSCs) have recently been shown to play an important role in the growth and progression of many solid tumors, including cholangiocarcinoma (CCA). The human placental amniotic membrane (hPAM) is one of the most favorable sources of MSCs due to its availability and non-invasive harvesting procedure. However, the role of human placental amniotic membrane mesenchymal stromal cells (hPAMSCs) in the growth and progression of human CCA has not yet been determined. This study investigates the effects of conditioned medium derived from hPAMSCs (PA-CM) on the properties of three human CCA cell lines and explores possible mechanisms of action. Varying concentrations of PA-CM were used to treat CCA cells to determine their effects on the proliferation and apoptosis of CCA cells. The results showed that PA-CM inhibited the proliferation and colony-forming capacity of KKU100, KKU213A, and KKU213B cells. PA-CM also promoted the apoptosis of these CCA cells by causing the loss of mitochondrial membrane potential. Western Blotting confirmed that PA-CM induced CCA cell apoptosis by increasing the levels of the Bax/Bcl-2 ratio, cleaved caspase 3, and cleaved PARP, possibly by inhibiting the IL-6/JAK2/STAT3 signaling pathway. Moreover, our in vivo study also confirmed the suppressive effect of hPAMSCs on CCA cells by showing that PA-CM reduced tumor volume in nude mice transplanted with human CCA cells. Taken together, our results demonstrate that PA-CM has potent tumor-suppressive effects on human CCA cells and could potentially be used in combination with chemotherapy to develop a more effective treatment for CCA patients.

Epicardial placement of human placental membrane protects from heart injury in a swine model of myocardial infarction.

Cardiac ischemic reperfusion injury (IRI) is paradoxically instigated by reestablishing blood-flow to ischemic myocardium typically from a myocardial infarction (MI). Although revascularization following MI remains the standard of care, effective strategies remain limited to prevent or attenuate IRI. We hypothesized that epicardial placement of human placental amnion/chorion (HPAC) grafts will protect against IRI. Using a clinically relevant model of IRI, swine were subjected to 45 min percutaneous ischemia followed with (MI + HPAC, n = 3) or without (MI only, n = 3) HPAC. Cardiac function was assessed by echocardiography, and regional punch biopsies were collected 14 days post-operatively. A deep phenotyping approach was implemented by using histological interrogation and incorporating global proteomics and transcriptomics in nonischemic, ischemic, and border zone biopsies. Our results established HPAC limited the extent of cardiac injury by 50% (11.0 ± 2.0% vs. 22.0 ± 3.0%, p = 0.039) and preserved ejection fraction in HPAC-treated swine (46.8 ± 2.7% vs. 35.8 ± 4.5%, p = 0.014). We present comprehensive transcriptome and proteome profiles of infarct (IZ), border (BZ), and remote (RZ) zone punch biopsies from swine myocardium during the proliferative cardiac repair phase 14 days post-MI. Both HPAC-treated and untreated tissues showed regional dynamic responses, whereas only HPAC-treated IZ revealed active immune and extracellular matrix remodeling. Decreased endoplasmic reticulum (ER)-dependent protein secretion and increased antiapoptotic and anti-inflammatory responses were measured in HPAC-treated biopsies. We provide quantitative evidence HPAC reduced cardiac injury from MI in a preclinical swine model, establishing a potential new therapeutic strategy for IRI. Minimizing the impact of MI remains a central clinical challenge. We present a new strategy to attenuate post-MI cardiac injury using HPAC in a swine model of IRI. Placement of HPAC membrane on the heart following MI minimizes ischemic damage, preserves cardiac function, and promotes anti-inflammatory signaling pathways.

Evaluation of colonic anastomosis healing using hybrid nanosheets containing molybdenum disulfide (MOS2) scaffold of human placental amniotic membrane and polycaprolactone (PCL) in rat animal model.

Anastomosis is a standard technique following different conditions such as obstruction, tumor, and trauma. Obstruction, adhesion, or anastomosis leakage can be some of its complications. To improve healing and prevent postoperative complications, we design a hybrid scaffold containing acellular human amniotic membranes and polycaprolactone-molybdenum disulfide nanosheets for colon anastomosis. The animal model of colocolonic anastomosis was performed on two groups of rats: control and scaffold. The hybrid scaffold was warped around the anastomosis site in the scaffold group. Samples from the anastomosis site were resected on the third and seventh postoperative days for histopathological and molecular assessments. Histopathologic score and burst pressure had shown significant improvement in the scaffold group. No mortality and anastomosis leakage was reported in the scaffold group. In addition, inflammatory markers were significantly decreased, while anti-inflammatory cytokines were increased in the scaffold group. The result indicates that our hybrid scaffold is a proper choice for colorectal anastomosis repair by declining postoperative complications and accelerating healing.

The Use of a Dehydrated Complete Human Placental Membrane Allograft for Mohs Surgical Defects of the Nose.

Repair options for Mohs surgical defects include primary closure, flap or graft, or healing by second intention. These options may not be optimal in all cases. A dehydrated complete human placental membrane (dCHPM) allograft may serve as an alternative repair option. To assess the aesthetic and functional outcomes of an alternative repair technique for Mohs surgical defects of the nose. Twenty patients with Mohs surgical defects of the nose repaired with a dCHPM allograft were retrospectively identified. Photographs were used to demonstrate surgical technique and outcomes. Two blinded observers evaluated final outcomes using the Patient and Observer Scar Assessment Scale. Observers rated the scar outcome a combined mean score of 8.4 ± 3.2 (scale 5-50). Patients rated their outcomes a mean of 12.6 ± 7.4 (scale 6-60). The mean "Overall Opinion score" was 2.5 ± 1.8 by patients and 1.9 ± 1.3 by observers (scale 1-10). This was a single institution study with a small sample size. Our study demonstrates that dCHPM allografts are a viable alternative repair option for Mohs surgical defects of the nose.

Distribution of an analgesic palmitoylethanolamide and other N-acylethanolamines in human placental membranes.

Human amniotic and amniochorionic membranes (AM, ACM) represent the most often used grafts accelerating wound healing. Palmitoylethanolamide, oleoylethanolamide and anandamide are endogenous bioactive lipid molecules, generally referred as N-acylethanolamines. They express analgesic, nociceptive, neuroprotective and anti-inflammatory properties. We assessed the distribution of these lipid mediators in placental tissues, as they could participate on analgesic and wound healing effect of AM/ACM grafts. Seven placentas were collected after caesarean delivery and fresh samples of AM, ACM, placental disc, umbilical cord, umbilical serum and vernix caseosa, and decontaminated samples (antibiotic solution BASE 128) of AM and ACM have been prepared. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used for N-acylethanolamines analysis. N-acylethanolamines were present in all studied tissues, palmitoylethanolamide being the most abundant and the anandamide the least. For palmitoylethanolamide the maximum average concentration was detected in AM (350.33 ± 239.26 ng/g), while oleoylethanolamide and anandamide were most abundant in placenta (219.08 ± 79.42 ng/g and 30.06 ± 7.77 ng/g, respectively). Low levels of N-acylethanolamines were found in serum and vernix. A significant increase in the levels of N-acylethanolamines (3.1-3.6-fold, P < 0.001) was observed in AM when the tissues were decontaminated using antibiotic solution. The increase in decontaminated ACM was not statistically significant. The presence of N-acylethanolamines, particularly palmitoylethanolamide in AM and ACM allows us to propose these lipid mediators as the likely factors responsible for the anti-hyperalgesic, but also anti-inflammatory and neuroprotective, effects of AM/ACM grafts in wound healing treatment. The increase of N-acylethanolamines levels in AM and ACM after tissue decontamination indicates that tissue processing is an important factor in maintaining the analgesic effect.

Myoglobin expression by alternative transcript in different mesenchymal stem cells compartments

BackgroundThe metabolic phenotype of stem cells is increasingly recognized as a hallmark of their pluripotency with mitochondrial and oxygen-related metabolism playing a not completely defined role in this context. In a previous study, we reported the ectopic expression of myoglobin (MB) in bone marrow-derived hematopoietic stem/progenitor cells. Here, we have extended the analysis to mesenchymal stem cells (MSCs) isolated from different tissues.MethodsMSCs were isolated from human placental membrane, mammary adipose tissue and dental pulp and subjected to RT-PCR, Western blotting and mass spectrometry to investigate the expression of MB. A combination of metabolic flux analysis and cyto-imaging was used to profile the metabolic phenotype and the mitochondria dynamics in the different MSCs.ResultsAs for the hematopoietic stem/progenitor cells, the expression of Mb was largely driven by an alternative transcript with the protein occurring both in the monomer and in the dimer forms as confirmed by mass spectrometry analysis. Comparing the metabolic fluxes between neonatal placental membrane-derived and adult mammary adipose tissue-derived MSCs, we showed a significantly more active bioenergetics profile in the former that correlated with a larger co-localization of myoglobin with the mitochondrial compartment. Differences in the structure of the mitochondrial network as well as in the expression of factors controlling the organelle dynamics were also observed between neonatal and adult mesenchymal stem cells. Finally, the expression of myoglobin was found to be strongly reduced following osteogenic differentiation of dental pulp-derived MSCs, while it was upregulated following reprogramming of human fibroblasts to induce pluripotent stem cells.ConclusionsEctopic expression of myoglobin in tissues other than muscle raises the question of understanding its function therein. Properties in addition to the canonical oxygen storage/delivery have been uncovered. Finding of Mb expressed via an alternative gene transcript in the context of different stem cells with metabolic phenotypes, its loss during differentiation and recovery in iPSCs suggest a hitherto unappreciated role of Mb in controlling the balance between aerobic metabolism and pluripotency. Understanding how Mb contributes through modulation of the mitochondrial physiology to the stem cell biology paves the way to novel perspectives in regenerative medicine as well as in cancer stem cell therapy.Graphical abstract

Viability of Amnion-Chorion membrane with the trophoblast layer in augmented posterior extraction sockets

Augmentation of the extraction sockets with bone and a membrane prior to dental implants insertion has been an integral part of the dental practice due to the advantages of providing adequate hard and soft tissue support essential for the implant emergence profile. Several bone graft materials and membranes have been recommended for the socket preservation however most of the commercially available resorbable membranes dissolve prematurely when exposed resulting in loss of the graft material. With the introduction of the human placental membranes into the dental field expedited wound healing was demonstrated even when exposed due to the abundance of growth factors. In this study Amniotic membrane which processed in a way to preserve the trophoblast layer has been tested on top of augmented extraction sockets . Clinically this membrane was easier to handle due to the increased thickness as a result of combining amnion chorion and trophoblast layer , it has also shown expedited healing through tissue formation on top of the bone graft mass as soon as two weeks. The histological examination demonstrated a considerable layer of fully matured epithelized tissue covering the bone in a short period of time. The results confirmed the viability of the Amnion Chorion and trophoblast membrane in generating epithelized tissue is a short period of time when used in covering bone grafts in extraction sockets.

Evaluating the efficacy of human placental amnion membrane in combination with modified coronally advanced flap technique in the management of gingival recession: An interventional study

Aims and objectives: A common problem experienced by adults is the recession of the gingiva resulting in unpleasant appearance of their teeth. There are various techniques to achieve the gingival recession coverage (GRC). But, only few techniques such as connective tissue grafts, coronally advanced flap technique (CAF) have been proved effective in achieving 100% recession coverage. The present study aims at evaluating the efficacy of amnion membrane along with CAF in the management of GRC. Materials and methods: A total number of 10 patients with class I or class II gingival recession were included in the study. The clinical parameters such as Probing depth (PD), clinical attachment level (CAL), thickness of attached gingiva (TAG), width of keratinized gingiva (WKG), height of gingival recession (HGR), percentage of recession coverage (PRC) and recession coverage esthetic score (RCES) were measured at baseline, 3 months and 6 months post-operatively. The patients were treated using amnion membrane in combination with modified coronally advanced flap technique (MCAF). Results: The patients showed statistically significant improvement in all the clinical parameters at the 3 months and 6 months follow-up visit. 97.8% CRC was observed by the end of 6 months. Moreover, the RCES showed remarkable esthetic outcome at the post-operative 6 months visit. Conclusion: Modified coronally advanced flap technique produces excellent clinical outcomes in terms of GRC. The use of amnion membrane aids in faster healing and improves the TAG which is an important aspect for the long term stability of the results obtained. Keywords Amnion membrane, Coronally advanced flap, Gingival recession, Guided tissue regeneration, Recession coverage

Effectiveness of Amnion on Chronic Wounds Vs Saline Dressing

Introduction: Chronic wounds have deleterious effects on patient health and quality of life. Human placental membranes consist of amnion and chorion which are conjoined and avascular structures. These membranes have abundant growth factors and cytokines and extracellular matrix which can induce angiogenesis and dermal fibroblast proliferation and recruit mesenchymal stem cells involved in wound repair supplying an ideal environment for wound closure.&#x0D; Aims &amp; Objectives: To compare the effectiveness of human amnion vs. normal saline dressing in chronic wounds.&#x0D; Place and duration of study: This study was conducted at Shaikh Zayed Medical Complex for a period of 6 months.&#x0D; Material &amp; Methods: This randomized control trial was carried out in the Department of Plastic Surgery at Shaikh Zayed Hospital, Lahore from 20-08-2019 to 20-02-2020. 60 patients of both genders,18 - 65 years of age having ulcers of more than six weeks duration and larger than 10 x 10 cm were inducted using non -probability consecutive sampling technique. They were divided into two groups of 30 patients each. Group A (Amnion) and Group B (Saline Dressing). Patients were assessed pre-treatment, wound dressings applied daily and followed up for 6 weeks for efficacy of dressing based on reduction in wound size and its relation to wound chronicity. Data was entered and analyzed using SPSS version 20.&#x0D; Results: There were 27 (90%) male and only 3 (10%) females patients in group A and 21 (70%) male and 9 (30%) females patients in group B. Mean age of the patients was 45.60±12.51 years for group A and 44.20±11.65 years for group B. 27 (90%) patients demonstrated good efficacy of treatment at six weeks in group A as compared to 5 (17%) patients in group B which is statistically significant (P 0.041). Significant healing was noted in amnion treated chronic wounds of up to 21 weeks duration.&#x0D; Conclusion: Our randomized control trial shows that amniotic membrane dressing are beneficial in the treatment of chronic wounds as compared to normal saline dressings.

Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment.

Venous leg ulcers (VLUs) are one of the most common ulcers of the lower extremity. VLU affects many individuals worldwide, could pose a significant socioeconomic burden to the healthcare system, and has major psychological and physical impacts on the affected individual. VLU often occurs in association with post-thrombotic syndrome, advanced chronic venous disease, varicose veins, and venous hypertension. Several demographic, genetic, and environmental factors could trigger chronic venous disease with venous dilation, incompetent valves, venous reflux, and venous hypertension. Endothelial cell injury and changes in the glycocalyx, venous shear-stress, and adhesion molecules could be initiating events in VLU. Increased endothelial cell permeability and leukocyte infiltration, and increases in inflammatory cytokines, matrix metalloproteinases (MMPs), reactive oxygen and nitrogen species, iron deposition, and tissue metabolites also contribute to the pathogenesis of VLU. Treatment of VLU includes compression therapy and endovenous ablation to occlude the axial reflux. Other interventional approaches such as subfascial endoscopic perforator surgery and iliac venous stent have shown mixed results. With good wound care and compression therapy, VLU usually heals within 6 months. VLU healing involves orchestrated processes including hemostasis, inflammation, proliferation, and remodeling and the contribution of different cells including leukocytes, platelets, fibroblasts, vascular smooth muscle cells, endothelial cells, and keratinocytes as well as the release of various biomolecules including transforming growth factor-β, cytokines, chemokines, MMPs, tissue inhibitors of MMPs (TIMPs), elastase, urokinase plasminogen activator, fibrin, collagen, and albumin. Alterations in any of these physiological wound closure processes could delay VLU healing. Also, these histological and soluble biomarkers can be used for VLU diagnosis and assessment of its progression, responsiveness to healing, and prognosis. If not treated adequately, VLU could progress to non-healed or granulating VLU, causing physical immobility, reduced quality of life, cellulitis, severe infections, osteomyelitis, and neoplastic transformation. Recalcitrant VLU shows prolonged healing time with advanced age, obesity, nutritional deficiencies, colder temperature, preexisting venous disease, deep venous thrombosis, and larger wound area. VLU also has a high, 50–70% recurrence rate, likely due to noncompliance with compression therapy, failure of surgical procedures, incorrect ulcer diagnosis, progression of venous disease, and poorly understood pathophysiology. Understanding the molecular pathways underlying VLU has led to new lines of therapy with significant promise including biologics such as bilayer living skin construct, fibroblast derivatives, and extracellular matrices and non-biologic products such as poly-N-acetyl glucosamine, human placental membranes amnion/chorion allografts, ACT1 peptide inhibitor of connexin 43, sulodexide, growth factors, silver dressings, MMP inhibitors, and modulators of reactive oxygen and nitrogen species, the immune response and tissue metabolites. Preventive measures including compression therapy and venotonics could also reduce the risk of progression to chronic venous insufficiency and VLU in susceptible individuals.

Intermediate layer contribution in placental membrane allografts.

Placental membrane (PM) allografts are commonly used to treat chronic wounds. Native PM is composed of an amnion, chorion, and intermediate layer (IL) that contain matrix structures and regulatory components beneficial in wound healing. Historically, commercially available allografts were composed of only one or two layers of the PM. To maximize the conserved material in PM allografts, a dehydrated complete human placental membrane (dCHPM) allograft processed using the Clearify™ process was developed. Histological and proteomic characterization comparing dCHPM allografts with native PM demonstrated that the majority of matrix structures and regulatory proteins are retained in dCHPM allografts through processing. To evaluate the importance of maintaining the entire intact PM and the contribution of the IL, the structural and proteomic makeup of the IL was compared with that of dCHPM allografts. This is the first known characterization of regulatory proteins in the IL. Results demonstrate that the IL contains over 900 regulatory and signaling components, including chemokines, growth factors, interleukins, and protease inhibitors. These components are key regulators of angiogenesis, neurogenesis, osteogenesis, inflammation, tissue remodeling, and host defense. The results show that the proteomic composition of the IL is consistent with that of the entire dCHPM allograft. Although further investigation is required to fully understand the contribution of the IL in PM allografts, these results demonstrate that the IL contains structural and regulatory proteins that can enhance the barrier and wound healing properties of PM allografts.

Glycoanalysis of the placental membrane glycoproteins throughout placental development

Structural changes of glycans are observed in different (patho)physiological conditions. Human placental membrane (glyco)proteins were isolated from the first and third trimester placentas of mothers at different ages. By using lectin microarray, we demonstrated that the placental membrane N-glycome contains several N-glycan groups: high mannose, asialylated and sialylated biantennary moieties, bisected, core fucosylated, fucosylated at other positions (bearing terminal and/or antennary Fuc), α2-6 and α2-3 sialylated structures. Employing MALDI-TOF MS enabled identification of over sixty different N-glycan structures in all samples, with 17 moieties exceeding the relative abundance of 2%. The major MS peaks originated from: 1) biantennary complex type N-glycan with a bisecting GlcNAc residue and 2) a core Fuc paucimannosidic and high mannose type structures M3-M9. Age of mothers and the stage of placental development affected N-glycome. The work presented in this article is the first comprehensive mass spectrometric study of the N-glycome of human placental membrane proteins. Our results may be seen as the baseline which can serve for future MALDI MS profiling of the placental membrane N-glycome in different pathophysiological conditions.

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

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. 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. 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. 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.

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.

A quality improvement pilot assessment of the safety and associated outcomes of a viable cryopreserved umbilical tissue allograft as an adjunct surgical wrap in peroneus brevis tendon repair.

Surgical tendon repairs of the lower extremity are frequently associated with post-operative (post-op) risks that result in poor patient outcomes. Initially, increased pain levels may contribute to extended post-op rehabilitation while the development of tissue adhesions and fibrosis limit long-term functionality through reduced range of motion. Several surgical methods describing incorporation of various augmentative graft materials in tendon repair exist. However, reports demonstrating technique and both short- and long-term patient outcomes are lacking. Recently, advances in tissue preservation technology have led to the commercialization of human placental allografts. Of these available allogeneic biomaterials, the components found in human placental membranes may provide anti-inflammatory, antimicrobial, anti-adhesive, and antifibrotic properties to benefit surgical outcomes.Here, the authors introduce and technically describe the use of a viable cryopreserved umbilical tissue (vCUT) (Stravix, Osiris Therapeutics, Inc., Columbia, MD) as a complementary surgical wrap in primary tendon repair, with particular focus on the peroneus brevis. A pilot study was undertaken to assess the safety and potential for secondary rehabilitative outcomes associated with the use of vCUT in 5 tendon repair cases. The use of vCUT as a surgical tendon wrap was evaluated via the following primary endpoints at post-op day 7:1. presence of erythema, tenderness, heat and/or swelling;2. pain score;3. patient use of narcotic medication; and4. the development of adverse events during any point during the post-op course, defined in this study as dehiscence, confirmed infection, fluid collection or drainage.Secondary investigative endpoints included clinical and rehabilitative outcome measures for comparative pain reduction and transition times to both controlled ankle movement (CAM) boot and normal shoe ambulation.All patients were followed for an average of 24.15 months (range 16.75–26.5 months) after surgery. For primary safety measures, erythema, tenderness, drainage, heat, and swelling was absent in all 5 surgical sites. None of the patients required post-op use of narcotics past day 7. The potential for long-term rehabilitative improvement with adjunct use of vCUT was also demonstrated through reduced pain and reduced transition times to functional and non-assisted ambulation in normal shoewear as compared to historical controls managed without vCUT.This surgical technique is simple and safe for patients and preliminary findings have demonstrated favorable clinical and rehabilitative outcomes over historically observed controls.