Human Acellular Dermal Matrices Research Articles

Performance of Human and Porcine Derived Acellular Dermal Matrices in Prepectoral Breast Reconstruction: A Long-term Clinicaland Histologic Evaluation.

Human acellular dermal matrices (ADMs) remain the most used matrices in prosthetic breast reconstruction. However, the availability and cost of ADMs limit their use in prepectoral reconstruction-which requires large amounts of ADM-and alternative matrices are therefore being explored. The aim of this study was to demonstrate the safety and efficacy of human-porcine ADM constructs via clinical outcomes and histologic evidence of graft integration. Consecutive patients undergoing tissue-expander/implant reconstructions with human-porcine ADM constructs were included. Biopsies of both ADMs were obtained at expander/implant exchange and evaluated for cellularization, vascularization, and inflammation. Postoperative complications were retrieved from patient records. Fifty-nine patients met the inclusion criteria. Mean [standard deviation] follow-up was 6.7 [0.56] years; minimum follow-up was 5 years. Any complication rate was 8.6%, including skin necrosis (6.9%), seroma (1.7%), expander/implant exposure (1.7%), and return to the operating room (2.6%). A total of 138 ADM biopsy specimens were obtained from 38 patients at expander/implant exchange. Histologic analyses revealed lower fibroblast infiltration and vascularization and higher inflammatory response in porcine vs human ADM specimens, consistent with published results in nonhuman primates. Despite these differences, there were no cases of graft rejection, capsular contracture, or expander/implant loss. Porcine ADM performs clinically in a similar manner to human ADM, albeit with minor differences in cellular ingrowth and vascularization, suggesting that it may be an alternative to human ADM in prepectoral breast reconstruction.

Vascularization of Human Acellular Dermal Matrices: A Comparative Study in a Nonhuman Primate Model.

Four human acellular dermal matrices (hADMs) were characterized in a nonhuman primate abdominal wall repair model by evaluating host immune response, vascularization, and incorporation into host tissues. AlloDerm™ (electron beam-sterilized hADM [e-hADM]), AlloMax™ (gamma beam-sterilized hADM, freeze-dried [g-hADM-FD]), DermaMatrix™ (hADM, freeze-dried [hADM-FD]), and FlexHD™ (ethanol-treated hADM [EtOH-hADM]) were each implanted in an abdominal wall-bridging defect in nonhuman primates (n = 3 animals/time point, n = 36 animals). Immunohistochemical and histological assessments were conducted on biopsies from each hADM at 1-, 3-, and 6-months postimplantation to assess vascularization (hematoxylin and eosin [H&E], CD31, alpha smooth muscle actin [αSMA], collagen IV), inflammatory/immune response (H&E, CD3, CD20, CD68), and collagen turnover (H&E, matrix metalloproteinase-9 [MMP-9]). MMP-9 immunolabeling was similar among different hADMs at 1 month; however, hADM-FD and EtOH-hADM showed higher total mean MMP-9-immunopositive areas at approximately 16% compared with <1% for e-hADM and g-hADM at 6 months postimplantation. Cells that stained positively for CD68, CD3, and CD20 were generally higher for hADM-FD and EtOH-hADM compared with other hADMs. The mean CD31-immunopositive area, CD31 vessel density, CD31 vessel diameter, and collagen IV-immunopositive area increased over time. Among all the hADM types, e-hADM had the highest mean (±standard deviation [SD]) CD31-immunopositive area at 1.54% ± 1.01%, vessel density at 7.86 × 10-5 ± 3.96 × 10-5 vessels/µm2, and collagen IV-immunopositive area at 2.55% ± 0.73% 1-month postimplantation. The pattern of αSMA immunolabeling varied among the hADMs. Histology showed that overall inflammation was mild at 1 month. Overall fibroblast repopulation and collagen remodeling increased over time from 1 to 6 months postimplantation. Fibroblast infiltration was minimal to mild at 1 month, with e-hADM showing the highest mean (±SD) score at 2.00 ± 0.00 compared with other hADMs. Only hADM-FD was not completely replaced by neotissue formation at 6 months postimplantation. All hADMs promoted vascularization, cell infiltration, and incorporation into host tissue, which were associated with acute inflammation and immune responses, within a 6-month period. A trend toward relatively enhanced early vascularization in e-hADM compared with other hADMs was observed. Immunogenic responses among the hADMs in the present study showed a slight distinction toward more quiescent terminally sterilized hADMs (e-hADM, g-hADM-FD) versus aseptically processed hADMs (EtOH-hADM, hADM-FD).

A Histological and Biomechanical Analysis of Human Acellular Dermis (HAD) Created Using a Novel Processing and Preservation Technique.

Large and complex defects requiring reconstruction are challenging for orthopaedic surgeons. The use of human acellular dermal (HAD) matrices to augment large soft tissue defects such as those seen in massive rotator cuff tears, knee extensor mechanism failures and neglected Tendo-Achilles tears has proven to be a valuable tool in surgeons reconstructive armamentarium. Different methods for allograft decellularization and preservation alter the native properties of the scaffold. Traditional processing and preservation methods have shown to have drawbacks that preclude its widespread use. Some of the common issues include inferior biomechanical properties, the risk of rejection, limited customization, difficulty in storing and transporting, the requirement of pre-operative preparation, and last but not the least increased cost. We describe a novel processing and preservation method utilizing a two-step non-denaturing decellularization method coupled with preservation using a water-sequestering agent (glycerol) to remove immunogenic components while retaining biomechanical properties. The efficiency of this novel process was compared with the traditional freeze-drying method and verified by histological evaluation and biomechanical strength analysis. The absence of cellular components and matrix integrity in hematoxylin and eosin-stained glycerol-preserved HAD (gly-HAD) samples compared to freeze-dried HAD (FD-HAD) demonstrated effective yet gentle decellularization. Biomechanical strength analysis revealed that gly-HADs are stronger with an ultimate tensile load to the failure strength of 210 N compared to FD-HAD (124N). The gly-HADs were found to have an optimal suture-retention strength of 126 N. Finally, sterility testing of the resultant grafts was checked to ensure a sterility assurance level of 10-6 to establish implantability. The novel processing and preservation technique is described in this paper to create a Human Acellular Dermis with higher biomechanical strength and superior histological characteristics. The processing and preservation technique ensured high sterility assurance levels to establish implantability.

Improvement in Biocompatibility and Biointegration of Human Acellular Dermal Matrix through Vacuum Plasma Surface Treatment.

Efforts are ongoing to enhance the functionality of human acellular dermal matrices (hADMs), which are extensively utilized in reconstructive surgeries. Among these efforts, plasma treatments, particularly vacuum plasma treatments, have recently emerged in the medical field. This study aims to investigate the efficacy of a vacuum plasma treatment in enhancing the biocompatibility and biointegration of hADMs. Utilizing a plasma activator (ACTILINK reborn, Plasmapp Co., Ltd., Daejeon, Republic of Korea), hADMs were treated and evaluated through in vitro and in vivo analyses. Hydrophilicity changes were gauged by the blood absorption times, while SEM imaging was used to analyze physical surface deformation. Protein adsorption was measured with fluorescently labeled bovine serum albumin and fibronectin. For the in vivo study, mice were implanted with plasma-treated and untreated hADMs, and the post-implantation effects were analyzed through histological and immunofluorescence microscopy. The plasma-treated hADMs demonstrated a significantly enhanced hydrophilicity compared to the untreated samples. SEM imaging confirmed the maintenance of the microroughness after the treatment. The treated hADMs showed a significant reduction in fibronectin adsorption, a critical factor for cellular adhesion. In vivo, the plasma-treated hADMs exhibited reduced capsule formation and enhanced fibroblast infiltration, indicating improved biocompatibility and integration. These findings highlight the potential of a plasma treatment to enhance the performance of hADMs in clinical settings, offering a promising avenue for improving reconstructive surgery outcomes.

Immediate Breast Cancer Reconstruction with or without Dermal Matrix or Synthetic Mesh Support: A Review and Network Meta-Analysis.

The use of acellular dermal matrices (ADMs) and synthetic mesh as part of implant-based breast reconstruction (IBBR) has been widely adopted. The authors investigated the clinical efficacy and safety of human ADM (HADM), xenograft ADM (XADM), and synthetic mesh as part of IBBR in postmastectomy patients as compared with previous standard implant reconstruction techniques using only a submuscular pocket for coverage. A systematic search for randomized controlled trials and observational studies was performed. A frequentist network meta-analysis was conducted using the R packages netmeta and Shiny. Thirty-one of 2375 studies identified met the predefined inclusion criteria. Traditional submuscular placement (no ADM or mesh) had fewer overall complications compared with HADM [OR, 0.51; credible interval (CrI), 0.34 to 0.74], but there was no significant difference between no ADM or mesh and XADM (OR, 0.63; CrI, 0.29 to 1.32) or synthetic mesh (OR, 0.77; CrI, 0.44 to 1.30). No one treatment was superior with regards to implant loss. No ADM or mesh was associated with fewer infectious complications than HADM (OR, 0.6; CrI, 0.39 to 0.89). Both no ADM or mesh (OR, 0.45; CrI, 0.27 to 0.75) and XADM (OR, 0.46; CrI, 0.23 to 0.88) had reduced seroma compared with HADM. Selecting the appropriate IBBR should evaluate effectiveness, adverse events, and cost. Although it is difficult to select a universal ideal IBBR, evaluation using this network analysis may help guide both physicians and patients in their choice of procedure, especially in the case of HADM, which in this study was shown to be significantly predisposed to complications of infection and seroma. Randomized data are required comparing XADM versus synthetic meshes, given the similar risk profiles but significant cost discrepancy between the techniques.

Comparison of a human acellular dermal matrix and a polypropylene mesh for pelvic floor reconstruction: a randomized trial study in a rabbit model

Non-absorbable polypropylene (PP) meshes have been widely used in surgical reconstruction of the pelvic floor disorders. However, they are associated with serious complications. Human acellular dermal matrices (hADM) have demonstrated safety and efficacy in reconstructive medicine, but their suitability and efficacy at vaginal level is not known. This study compares the biological performance of PP mesh and a newly developed hADM. 20 rabbits were randomized to receive the hADM graft or the PP mesh. Grafts were surgically implanted in the abdominal wall and vagina. After 180 days, grafts were explanted and evaluated. The vaginal mesh extrusion rate was higher in the PP group (33% vs. 0%, p = 0.015). Full integration of the vaginal grafts was more frequent in the hADM group, where 35% of the grafts were difficult to recognize. In the PP group, the vaginal mesh was identified in 100% of the animals (p = 0.014). In PP group, the infiltrates had a focal distribution and were mostly located in the internal part of the epithelium, while in the hADM group, the infiltrates had a diffuse distribution. Additionally, the hADM group also presented more B-lymphocytes and less T-lymphocytes. Biomechanical analysis showed that hADM had lower resistance to stress. Moreover, PP mesh stiffness and elasticity were higher. Then, hADM is associated with fewer clinical complications, as well as better tissue integration. However, it shows greater incorporation into the surrounding native tissue, especially in the vaginal location, undergoing a reduction in its biomechanical properties 6 months after implantation.

Implant-based Breast Reconstruction after Mastectomy for Breast Cancer: A Systematic Review and Meta-analysis.

Background:Women undergoing implant-based reconstruction (IBR) after mastectomy for breast cancer have numerous options, including timing of IBR relative to radiation and chemotherapy, implant materials, anatomic planes, and use of human acellular dermal matrices. We conducted a systematic review to evaluate these options.Methods:We searched Medline, Embase, Cochrane CENTRAL, CINAHL, and ClinicalTrials.gov for studies, from inception to March 23, 2021, without language restriction. We assessed risk of bias and strength of evidence (SoE) using standard methods.Results:We screened 15,936 citations. Thirty-six mostly high or moderate risk of bias studies (48,419 patients) met criteria. Timing of IBR before or after radiation may result in comparable physical, psychosocial, and sexual well-being, and satisfaction with breasts (all low SoE), and probably comparable risks of implant failure/loss or explantation (moderate SoE). No studies addressed timing relative to chemotherapy. Silicone and saline implants may result in clinically comparable satisfaction with breasts (low SoE). Whether the implant is in the prepectoral or total submuscular plane may not impact risk of infections (low SoE). Acellular dermal matrix use probably increases the risk of implant failure/loss or need for explant surgery (moderate SoE) and may increase the risk of infections (low SoE). Risks of seroma and unplanned repeat surgeries for revision are probably comparable (moderate SoE), and risk of necrosis may be comparable with or without human acellular dermal matrices (low SoE).Conclusions:Evidence regarding IBR options is mostly of low SoE. New high-quality research is needed, especially for timing, implant materials, and anatomic planes of implant placement.

Optimization of Novel Human Acellular Dermal Dressing Sterilization for Routine Use in Clinical Practice.

Gamma rays and electrons with kinetic energy up to 10 MeV are routinely used to sterilize biomaterials. To date, the effects of irradiation upon human acellular dermal matrices (hADMs) remain to be fully elucidated. The optimal irradiation dosage remains a critical parameter affecting the final product structure and, by extension, its therapeutic potential. ADM slides were prepared by various digestion methods. The influence of various doses of radiation sterilization using a high-energy electron beam on the structure of collagen, the formation of free radicals and immune responses to non-irradiated (native) and irradiated hADM was investigated. The study of the structure changes was carried out using the following methods: immunohistology, immunoblotting, and electron paramagnetic resonance (EPR) spectroscopy. It was shown that radiation sterilization did not change the architecture and three-dimensional structure of hADM; however, it significantly influenced the degradation of collagen fibers and induced the production of free radicals in a dose-dependent manner. More importantly, the observed effects did not disrupt the therapeutic potential of the new transplants. Therefore, radiation sterilization at a dose of 35kGy can ensure high sterility of the dressing while maintaining its therapeutic potential.

Comparison of porcine and human acellular dermal matrix outcomes in wound healing: a deep dive into the evidence.

Acellular dermal matrices (ADM) are a novel graft. The goal of this systematic review is to evaluate the evidence behind differences in human and porcine ADM, irrelevant of manufacturing method, and to determine if there is enough of an evidence base to change clinical practice. An extensive literature search was performed through MEDLINE and Embase with search terms defining a population, intervention and outcome. Title and abstract exclusion were performed with other exclusion criteria. In 191 articles were found after exclusion of duplicates, with only 29 remaining following exclusions. Ten studies were found to have level I and II evidence (I=3, II=8), of which two were histopathological, one was an animal model, one was a systematic review, and six were clinical. The remaining studies were reviewed and considered for discussion, but did not hold high enough standards for medical evidence. Strong clinical evidence already exists for the use of human ADM, but questions of access, cost, and ethics require consideration of a xenograft. Histopathologically, evidence suggests minimal long-term differences between human and porcine ADM, although there is a short acute immune response with porcine ADM. Clinically, there is limited difference in outcomes, with a small range in effect of different ADM preparations. Considering the effectiveness of ADM in wound healing, more high-level research with appropriate statistical analysis to facilitate a future meta-analysis is recommended to justify a transition from human to porcine ADM.

The use of human acellular dermal matrices in advanced wound healing and surgical procedures: State of the art.

Wound closure after post-traumatic injuries and/or localized at peculiar body sites (head-and-neck, oral cavity, legs) are particularly challenging and can often be delayed due to local and systemic factors. In case of deep wounds and/or hard-to-heal wounds, grafting of dermal acellular matrices (ADM) is often needed. Though a great variety of synthetic and semisynthetic dermal and skin equivalents are available, viable human dermis, is still considered the most physiological alternative to replace the loss of autologous dermis, by acting as a physiological scaffold that add structural support to soft tissues. To date, human ADMs (hADMs) have been employed in the reconstruction of skin defects affecting almost all body sites, ranging from visceral sites to the skin and subcutaneous tissues. This review aims to investigate the use of hADM at different body sites and their peculiar advantages. A literature search was using the search terms "acellular dermal matrices", "dermal regeneration", "advances wound healing", "human acellular dermal matrices surgery". A total of 50 out of 150 papers was included. Based on the current body if evidence, hADMs appear to bring several advantages, such as: protection of deep structures (eg, tendons, bones, cartilage and nerves); stimulation of a functional new dermis (rather than a scar); reduction of wound closure time; control of pain and exudate. Finally, hADMs may represent the best treatment option for hard-to-heal wound not only in terms of efficacy and patient satisfaction bout also in terms of sanitary costs, especially across Europe, where hADMs cannot be commercialized as medical devices.

Characterization of Inflammatory and Fibrotic Aspects of Tissue Remodeling of Acellular Dermal Matrix in a Nonhuman Primate Model.

Background:Human acellular dermal matrices (hADMs) are applied in various soft tissue reconstructive surgeries as scaffolds to support tissue remodeling and regeneration. To evaluate the clinical efficacy of hADM implants, it is integral that the hADM does not induce a host chronic inflammatory response leading to fibrotic encapsulation of the implant. In this study, we characterized the inflammatory and fibrosis-related tissue remodeling response of 2 commercial hADM products (SimpliDerm and AlloDerm RTU) in a nonhuman primate model using histology and gene expression profiling.Methods:Eighteen African green monkeys with abdominal wall defects were applied to evaluate the performance of SimpliDerm and AlloDerm RTU implants (N = 3) at 2, 4, and 12-weeks post-implantation. Using histology and gene expression profiling, tissue responses such as implant integration, degradation, cell infiltration, immune response, neovascularization, and pro-fibrotic responses over time were evaluated.Results:SimpliDerm showed a lower initial inflammatory response and slower implant degradation rate than AlloDerm RTU evidenced by histomorphological analysis. These factors led to a more anti-inflammatory and pro-remodeling microenvironment within SimpliDerm, demonstrated by lower TNFα levels and lower expression levels of pro-fibrotic markers, and promoted tissue repair and regeneration by 3-months post-implantation.Conclusions:Overall, histology and gene expression profiling analyses shown in this study demonstrated an effective model for analyzing hADM performance in terms of host inflammatory and fibrotic response. Further studies are warranted to fully evaluate the utility of this novel hADM in the clinical setting and verify the prognosis of our pre-clinical analysis model.

In VivoComparison of Three Human Acellular Dermal Matrices for Breast Reconstruction

Acellular dermal matrices (ADMs) have become popular in implant-based breast reconstruction. The aim of this study was to compare three commonly used ADM products in vivo in an animal model. The nucleic acid content (residual double-stranded DNA) and the levels of the remaining growth factors after decellularization were measured for each ADM. Cytocompatibility with ADMs was documented using NIH 3T3 mouse fibroblast cells. In vivo, the implanted ADMs were histologically evaluated at 1, 2, 3, and 6 months (n=5) using male 8-week-old Sprague-Dawley rats. Fibroblasts grew in the SureDerm HD and DermACELL with no cytotoxicity. In a rat model, SureDerm HD and DermACELL incorporated more readily into the surrounding host tissue, as measured by rapid cell influx and collagen deposition, and showed more delayed tissue remodeling with decreased matrix metalloproteinases levels compared to AlloDerm. SureDerm HD and DermACELL can be used as biological materials for breast reconstruction.

Complication Rate of Prepectoral Implant-based Breast Reconstruction Using Human Acellular Dermal Matrices.

Background:Implant-based breast reconstruction (IBR) is currently the most frequently performed reconstructive technique post mastectomy. Even though submuscular IBR continues to be the most commonly used technique, mastectomy technique optimization, the possibility to check skin viability with indocyanine green angiography, the enhanced propensity of patients undergoing prophylactic mastectomies, and the introduction of acellular dermal matrices (ADMs) have paved the way to the rediscovery of the subcutaneous reconstruction technique. The aim of this article is to update the complication rate of immediate and delayed prepectoral IBR using human ADMs (hADMs).Methods:A literature search, using PubMed, Medline, Cochrane, and Google Scholar database according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, was conducted to evaluate complication rates of prepectoral implant–based reconstructions using hADMs. The following MeSH terms were used: “prepectoral breast reconstruction acellular dermal matrix,” “prepectoral breast reconstruction ADM,” “human ADM breast reconstruction,” and “human acellular dermal matrix breast reconstruction” (period: 2005–2020; the last search took place on April 2, 2020).Results:This meta-analysis includes 1425 patients (2270 breasts) who had undergone immediate or delayed prepectoral IBR using different types of hADMs. The overall complication rate amounted to 19%. The most frequent complication was represented by infection (7.9%), followed by seroma (4.8%), mastectomy flap necrosis (3.4%), and implant loss (2.8%).Conclusions:The overall complication rate was 19%. The most frequent complications were infection, seroma, and mastectomy flap necrosis, while capsular contracture was rare.

Human Acellular Dermal Matrices Fabricated By Various Processes Elicit Diverse Host Responses in a Primate Model

PURPOSE: An assortment of human acellular dermal matrices (HADMs), manufactured using a variety of decellularization and antiseptic protocols, are commercially available and used for various surgical applications. Although several studies in the literature have made direct comparison among multiple HADMs, few have linked in vivo biologic host response to tissue manufacturing method or resulting out-of-package biochemical and biomechanical attributes of the matrix. Here, we aim to evaluate 5 distinctly processed and disinfected HADMs in a nonhuman primate. MATERIALS AND METHODS: African Green monkeys were implanted either subcutaneously on the back with two, 1 × 1 cm pieces each of electron-beam irradiated HADM (AlloDerm/e-HADM) and gamma-irradiated HADM (DermACELL/g-HADM) for 1 month, or in the dynamically loaded site of the ventral abdominal wall with one, larger 3 × 7 cm piece of either electron-beam irradiated HADM (AlloDerm/e-HADM), freeze-dried gamma-irradiated HADM (AlloMax/g-HADM-FD), ethanol-stored aseptically processed HADM (Flex HD/EtOH-HADM), or freeze-dried aseptically processed HADM (DermaMatrix/HADM-FD) for either 1, 3, or 6 months. All HADM samples were harvested at the specified time points and evaluated histologically for cellular ingrowth, vascularity, and inflammatory response, whereas dynamically loaded HADM samples were additionally evaluated for regenerative response as judged by HADM–host interface integration and neo-collagen alignment. Host response established in these NHP models was compared with out-of-package in vitro mechanical properties as well as in vitro attributes established in previous studies. RESULTS: Out-of-package, e-HADM had significantly higher tensile strength (379.4 ± 26.2N) than g-HADM, EtOH-HADM, HADM-FD, and g-HADM-FD (233.2 ± 33.1N, 233.1 ± 126.2N, 211.6 ± 18.6N, and 104.0 ± 17.8N, respectively). In previous benchtop studies, e-HADM had also been found to have ultrastructural characteristics, acid-soluble collagen content, and degree of susceptibility to digestion by collagenase more similar to native tissues than g-HADM, EtOH-HADM, or g-HADM-FD.1 Subcutaneously implanted g-HADM samples demonstrated substantially greater inflammatory host response than e-HADM as determined through hematoxylin and eosin histologic analysis and immunohistochemically via anti–CD-68 antigen presence at 1-month implantation. In the dynamically loaded model, a greater inflammatory infiltrate was evident histologically and immunohistochemically (CD-68/CD-3/CD-20) for g-HADM-FD, EtOH-HADM, and HADM-FD, as compared with e-HADM. Subsequently, degree of HADMs to resist in vivo contraction and extent of incorporation was greater grossly for e-HADM than other HADMs and was supported by histologic fibroblast cell infiltration at the HADM–primate tissue interface. Likewise, collagen fibers could be observed to align linearly in the direction of dynamic forces for e-HADM, whereas other HADMs in the study tended to demonstrate a scar-like morphology histologically. Vascularization/integration was shown to increase in terms of vessel number and relative size for e-HADM and was generally not inflammation-associated, whereas g-HADM-FD, EtOH-HADM, and HADM-FD vessels were either less evident or associated with areas predominated by inflammatory cell infiltration. CONCLUSIONS: The data presented here appear to demonstrate a relationship between in vivo host response to HADMs in a nonhuman primate and benchtop attributes of these differently processed HADMs. Maintenance of structural, biochemical, and mechanical attributes of HADM products appears to be crucial for positive host response in terms of cellular infiltration and vascularization, leading to improved incorporation with low inflammatory characteristics. REFERENCE: 1. Sandor M, Leamy P, Assan P, et al. Relevant in vitro predictors of human acellular dermal matrix-associated inflammation and capsule formation in a nonhuman primate subcutaneous tissue expander model. Eplasty. 2017;17:e1.

Acellular Dermal Matrix, Smooth Tissue Expanders, and Betadine: Histologic Assessment in a Primate Model

INTRODUCTION: It is known that an overabundance of pathogens in the setting of prosthetic breast devices can lead to infection, prolonged inflammation, and capsular contracture. As such, there has been increasing emphasis on the use of aseptic techniques that include antimicrobial irrigation solutions such as Betadine. The increasing use of human acellular dermal matrices (HADM) and prosthetic devices have raised questions as to whether exposure of the implant or tissue expander (TE) to Betadine may lead to deleterious effects related to HADM incorporation. The aim of this study was to determine if exposure of HADM to a Betadine-saturated TE would affect the corresponding biological response. METHODS: Samples (1.5 × 1.5 cm) cut from custom-made smooth silicone TEs (Allergan plc) were soaked in 100% Betadine for 2 minutes, without a subsequent saline rinse, or soaked in control saline alone, and then sutured to equivalently sized HADM samples (AlloDerm, Allergan plc) to form an HADM:TE construct. Eighteen African Green monkeys were each implanted subcutaneously with a pair of Betadine and saline-treated HADM:TE constructs and evaluated for overall biologic response to Betadine treatment following implantation at 2 or 4 weeks as demonstrated by hematoxylin and eosin histologic staining and using a subjective scoring scale (0–9) inclusive of recellularization, neovascularization, and inflammatory responses. The presence of individual cell types involved in inflammation (eosinophils, lymphocytes, neutrophils, histiocytes, foreign body giant cells) and HADM remodeling (fibroblasts) was also evaluated based on hematoxylin and eosin histologic staining (0–3 scoring scale) and in some cases corroborated by immunohistochemical staining (CD-3, CD-20, CD-68). Betadine-treated constructs were compared at 2-week (n = 9) and 4-week (n = 9) implantation to saline control-treated constructs with no exposure to Betadine also at 2-week (n = 9) and 4-week (n = 9) implantation. RESULTS: Overall biologic response to the HADM in the presence of Betadine or saline control was similar at 2-week implantation, scoring 5.6 ± 0.5 and 5.3 ± 0.9, respectively (P = 0.41) and remained similar at 4 weeks, scoring 4.6 ± 1.0 and 4.2 ± 0.8, respectively (P = 0.46). Although the presence of individual inflammatory cell types appeared to trend higher in the saline control group than in the Betadine-treated group at 2 weeks, the difference was not statistically significant, and the trend did not persist at 4 weeks. Likewise, differences in HADM fibroblast infiltration were not significant between Betadine-treated and control groups. However, the presence of fibroblasts within the implanted HADM did increase over time between 2 and 4 weeks, for both the Betadine-treated (increase from 1.0 ± 0.9 to 1.8 ± 1.0) and saline control groups (increase from 1.4 ± 0.9 to 1.8 ± 0.8), indicative of ongoing HADM incorporation. CONCLUSIONS: The data suggest that exposure of the HADM to a Betadine-treated TE did not negatively impact the host response to the implanted HADM in terms of inflammation, vascularization, recellularization, or overall HADM incorporation.

Patient-Reported Outcomes and Aesthetic Results after Immediate Breast Reconstruction Using Human Acellular Dermal Matrices: Results of a Multicenter, Prospective, Observational NOGGO-AWOGyn Study

Background: With the increased use of acellular dermal matrices (ADMs) in implant-based breast reconstructions (IBBRs), the evaluation of patient-reported outcomes becomes more important. Methods: Patients who underwent an immediate human ADM-assisted, submuscular IBBR were included in this noninterventional, multicenter, prospective cohort study. Patients with primary reconstruction (cohort A) and patients with a revision surgery after capsular fibrosis (cohort B) were followed up for 12 months after surgery. Quality of life (EORTC BR-23) and patient and surgeon satisfaction scores (1 [“very satisfied”] to 6 [“not satisfied”]) with the outcome and the aesthetic result evaluated by 2 independent, external experts were assessed. Results: Eighty-four patients were enrolled in the study. The mean patient satisfaction score was 2.1 ± 0.8, with higher satisfaction in cohort B (p = 0.041). The score did not change significantly during the follow-up (p = 0.479). The mean satisfaction score of the surgeons was 2.0 ± 0.7; it was also higher in cohort B (p = 0.016) and showed no changes over time (p = 0.473). The mean aesthetic result was 2.2 ± 0.7. 92.9% of the patients completed at least 1 quality of life questionnaire. Body image and sexual functioning increased during follow-up. One year after surgery, the mean scores were 77.2 ± 22.5 and 44.7 ± 27.3, respectively. Conclusion: The level of satisfaction among patients and surgeons and the score of the aesthetic result were constantly high among patients after ADM-assisted IBBR. Higher satisfaction scores could be observed after revision surgery caused by capsular fibrosis (cohort B) compared to primary reconstruction (cohort A). Quality of life increased during the first year after surgery.

Acellular Dermal Matrix Tissues in Genitourinary Reconstructive Surgery: A Review of the Literature and Case Discussions.

There have been major advancements in the field of urologic reconstruction and gender-affirming surgeries over the past 10years. These operations have become increasingly complex involving multiple revisions, with limited healthy native tissue availability. Grafts are frequently needed when a patient's own tissue is expected to have poor wound-healing properties. To reduce the morbidity associated with autologous grafts and complications associated with synthetic grafts, acellular dermal matrices (ADMs) can be used as substitutes in genitourinary surgery as they demonstrate decreased immunogenicity and retaine structural integrity. The purpose of this review is to describe the importance and potential uses of ADMs by reviewing the literature and highlighting key examples of our institution's expanded application of ADM grafts in genitourinary reconstruction. We performed a literature review for the use of ADMs in genitourinary surgery including the search terms acellular dermal matrix, alloderm, extracellular matrix, penis, penile reconstruction, intrapenile prosthesis, phalloplasty, neophallus, urethroplasty, artificial urinary sphincters, Peyronie's disease, and urology. We highlight 5 representative genitourinary reconstructive cases performed at this institution where ADMs contributed to surgical success. Genitourinary reconstructive surgeries that have used ADMs in the literature included neophallus construction for gender affirmation, phalloplasty for trauma, penile augmentation, and plaque excision and grafting for Peyronie's disease. Biomechanical studies across different graft types are limited in genitourinary applications. Initial studies using ADMs indicate benefits of limited inflammatory response, finite elasticity, and substantial tensile strength, acceptably mimicking properties of the native tissue. Our experience and the current literature suggest that human ADM is a valuable option for tunica albuginea replacement, but its use to support free grafts should be cautioned secondary to graft take. Haney NM, Huang MM, Liu JL, etal. Acellular Dermal Matrix Tissues in Genitourinary Reconstructive Surgery: A Review of the Literature and Case Discussions. Sex Med Rev 2021;9;488-497.

A comparison of patient-reported outcomes between Alloderm and Dermacell in immediate alloplastic breast reconstruction: A randomized control trial

Alloderm and Dermacell are the two leading human acellular dermal matrices (ADM) in immediate breast reconstruction (IBR). Despite differences in sterility, consistency, thickness and cost, there are no comparative trials to date to compare patient-reported outcome measures (PROM) between the two products. The purpose of this study was to determine if there was a difference in patient-reported outcomes (as measured by the BREAST-Q) between patients reconstructed with Alloderm and Dermacell. A single center, open-label, randomized control trial of patients undergoing IBR with an implant for breast cancer or breast cancer prophylaxis was performed. Patients were randomized to either Alloderm or Dermacell. Baseline demographic data were compared, and linear mixed models were used to identify associations with BREAST-Q over time. Between June 2016 and October 2018, 62 patients were randomized into two groups, 31(50%) Alloderm and 31(50%) Dermacell. Of these, 23(74%) patients in the Alloderm group and 27(87%) patients of the Dermacell group filled out BREAST-Q questionnaires. Baseline BREAST-Q scores with respect to satisfaction with breasts, psychosocial well-being, sexual well-being, and physical well-being were similar between groups (p>0.05). At 3 months postoperatively, the Alloderm group had a statistically significant improvement with respect to satisfaction with breasts (67 vs 53, p = 0.03), satisfaction with overall results (85 vs 61, p = 0.003), satisfaction with the surgeon (89 vs 67, p = 0.01), and satisfaction with information provided (74 vs 59, p = 0.02). At 12 months postoperatively, there were no statistically significant differences in PROM between groups (p>0.05). We report the first randomized controlled trial to date comparing patient-reported outcomes of the two most commonly used ADMs in IBR in Canada. Although a short-term analysis favors the use of Alloderm, there does not appear to be any difference in outcomes between the two products in the longer term.

Alloderm and Cortiva Have Similar Perioperative Wound Complications in Abdominal Wall Reconstruction

BackgroundAlthough controversial, the use of acellular dermal matrices (ADMs) for abdominal wall reconstruction (AWR) is increasing. There are now many different ADMs available, but there is a lack of studies directly comparing ADMs in terms of outcomes. Materials and methodsA retrospective chart review was performed to compare perioperative wound complications (up to 120 d postoperatively) between patients who underwent AWR with the human noncrosslinked ADMs Alloderm or Cortiva from January 2012 to March 2020. Surgical technique uniformly consisted of open component separation, onlay implantation of ADM, and progressive tension suture fixation of ADM. ResultsAfter exclusions, 53 patients were in the Alloderm group, and 29 patients were in the Cortiva group. The overall perioperative wound complication rate between Alloderm (51.92%) and Cortiva (72.41%) was not significantly different (P = 0.09921). The average follow-up for Alloderm was 76.69 ± 29.52 d and for Cortiva was 66.93 ± 35.16 d (P = 0.2088). There were no cases that required explantation of ADM. ConclusionsGiven the similar perioperative wound complication profiles, the more cost-effective ADM may be a consideration for use in AWR. The fact that there were zero instances of ADM explantation also supports the use of ADM in these high-risk cases.

Transplantation of a New Biological Product in Rare Diseases, Such as Epidermolysis Bullosa: Response and Clinical Outcome

BackgroundEpidermolysis bullosa (EB) is a phenotypically diverse group of hereditary blistering disorders involving mutations in 20 different genes. Those debilitating disorders are currently incurable; however, there are a number of promising preclinical trials, where some treatments already approach the stage of early clinical trial. In this paper we introduce a novel surgical approach to the treatment of EB-induced ulcerations.The purpose of our study was to evaluate the safety and efficacy of a new biological dressing in the form of an allogenic human skin equivalent graft before using multipotent stem cells, classified as an advanced therapy medicinal product. MethodsImplanted human acellular dermal matrices were prepared from the superficial layers of donated human skin. Scaffold sterilization was conducted via irradiation with the use of a linear electron accelerator. Following water-knife debridement, wounds were surgically covered with accordingly prepared grafts and dressed in burn-injury fashion. Subsequently, the wounds were monitored for infection and viability. ResultsOur data indicate that grafting as a potential new medicinal product was safe and effective in patients with rare diseases, such as EB, and may be used for stem cells to create new Advanced Therapy Medicinal Products. During a 200-day follow-up, we proved the safety of using human scaffolds (allogeneic graft) by observing no apparent infection or necrosis. Instead, we noted fewer required dressing changes, promoted wound healing, pain reduction, and an overall improvement in the quality of life in patients with EB. ConclusionThe protocol for grafting allogenic acellular epidermal sheets is the most promising treatment for severely affected skin areas in EB patients to date.