Allogeneic Acellular Dermal Matrix Research Articles

Application of Allogeneic Human Acellular Dermal Matrix Reduces the Incidence of Fistula in Hypospadias Repair.

BackgroundUrethrocutaneous fistula is one of the most common complications arising from hypospadias surgery. The purpose of our study was to investigate the effectiveness and safety of allogeneic human acellular dermal matrix (HADM) application as a means of preventing the occurrence of urethrocutaneous fistula following hypospadias surgery.MethodsThis is a non-randomized study of 219 cases (out of 270 patients with hypospadias) which satisfied inclusion and exclusion criteria. These patients were divided into two groups: 101 HADM patients, and 118 control patients (who did not receive HADM). In the control group, 77 boys were treated by single-stage urethroplasty (TIP) and 41 underwent staged urethroplasty (Thiersch-Duplay). In the HADM group, 59 boys underwent the TIP and 42 underwent the Thiersch-Duplay. In the postoperative period, we recorded the incidence of infection, urethrocutaneous fistula, and urethral stricture complications in these two groups of patients. The effectiveness and safety of HADM in preventing urethrocutaneous fistula following hypospadias surgery were evaluated according to these indicators.ResultsIn the control group, following the operation there were 16 cases of infection, 38 cases of urethrocutaneous fistula after extubating, and 5 cases of urethral stricture. In the HADM group, there were 19 cases of postoperative infection, 12 cases of urethrocutaneous fistula after extubating, and 5 children with urethral stricture. In comparing the two groups, it was found that the postoperative infection rate (13.6 vs. 18.8%) and the incidence of urethral stricture (4.2 vs. 5.0%) were not statistically significant (P > 0.05), while the postoperative urethrocutaneous fistula rate (32.2 vs. 11.9%) was statistically significant (P < 0.001).ConclusionIt is found that HADM application can significantly reduce the incidence of urethrocutaneous fistula complications, without increasing the risk of infection and urethral stricture.

Clinical Efficacy of Gingival Thickening Following the Use of Allogeneic Acellular and Xenogeneic Collagen Matrix: A 12-Month Randomized Clinical Trial.

This randomized controlled clinical trial with a 1-year follow-up evaluated gingival thickness changes around teeth after use of dermal allograft and xenograft matrix. A total of 116 teeth (19 patients) were separated into two groups. One group received xenogeneic collagen matrix (n = 48), while the other received allogeneic acellular dermal matrix (n = 68) via a coronally advanced flap (CAF). Gingival thickness (GT), keratinized gingival width (KGW), pocket depth (PD), and clinical attachment loss (CAL) were measured on the day of surgery (baseline) and at 3 weeks, 2 months, 6 months, and 1 year postoperative. The two groups were compared using repeated-measures ANOVA (P < .05). The mean GT at 1 year was 1.59 ± 0.31 mm in the xenogeneic group and 1.63 ± 0.33 mm in the allogeneic group (P = .60). The mean change in GT was 1.08 mm in the xenogeneic group and 1.13 mm in the allogeneic group, which was clinically relevant and statistically significant compared to baseline values (P < .001). However, changes in GT were not significantly different between the two groups at any time point (P > .05). The GT increased in all cases treated with allogeneic and xenogeneic enriched collagen matrix. Both soft tissue substitutes were equally effective in acheiving optimal GT.

Effects of allogenic acellular dermal matrix combined with autologous razor-thin graft on hand appearance and function of patients with extensive burn combined with deep hand burn.

The aim of the study was to observe the effect of allogeneic acellular dermal matrix (ADM) combined with autologous razor‐thin graft on the appearance and function of hands in patients with extremely large area burns combined with deep hand burns. Sixty‐four patients with severe burn combined with deep burn of the hand in our hospital from August 2015 to August 2019 were selected as the study subjects. All patients were randomly divided into the study group (32 cases, given allogeneic ADM combined with autologous razor‐thin graft) and the control group (32 cases, given autologous scar tissue combined with autologous razor‐thin graft). Hand appearance, wound healing, wound contraction, hand function, and quality of life were compared between the two groups at 3 and 6 months after treatment. The vascular distribution, skin thickness, and flexibility scores of the two groups 6 months post operation were lower than those of the 3 months post operation (P < .05). At 6 months after operation, there were significant differences in blood vessel distribution, skin thickness, flexibility, and colour between the two groups (P < .05). The wound healing rate and wound contraction rate of the two groups at 6 months after operation were higher than those at 3 months after operation (P < .05). The wound healing rate of the study group was higher than that of the control group (P < .05), but there was no significant difference in the wound contraction rate between the two groups. Hand function was better in both groups 6 months after operation than 3 months after operation (P < .05). The hand function of the experimental group was better than that of the control group at 3 and 6 months after operation (P < .05). The quality of life in the two groups at 6 months after operation was significantly higher than that at 3 months after operation, and the quality of life in the study group was consistently higher than that in the control group (P < .05). Allogeneic ADM combined with razor‐thin graft in the treatment of patients with extensive burns and deep hand burns can effectively restore the shape and function of the hand, which is conducive to wound healing and improve the quality of life of patients, and it is worthy of wide clinical application.

The Clinical Effects of Utilizing Allogeneic Acellular Dermal Matrix in the Surgical Therapy of Anterior Urethral Stricture

Objective: The aim of this study was to estimate the clinical effects of allogeneic acellular dermal matrix (ADM) in the surgical therapy of anterior urethral stricture (AUS). Methods: We retrospectively collected the clinical data of 49 patients with AUS who underwent urethral repair surgery with ADM in the Department of Urology of the Peking University People’s Hospital, and in the First Affiliated Hospital of the People’s Liberation Army, from September 2015 to January 2019. The changes in urine flow rate and conditions of urethral mucosal coverage were observed as well as complications and outcomes, and statistical analysis was performed. Results: The average maximum urine flow rates at the 1st, 6th, and 12th month post-surgery were 16.3 ± 1.5, 15.0 ± 1.9, and 14.6 ± 2.1 mL/s, respectively. These values were significantly higher than the preoperative maximum urine flow rate, 1.3 ± 0.5 mL/s (p < 0.05). Cystoscopy was performed in 11 patients 12 months after surgery, with microscopic assessment revealing good urethral epithelial mucosal coverage. Only 2 patients developed infection 2–4 weeks after surgery, while 7 patients developed noninfective urethral restricture 6–10 months after surgery and 1 patient developed urinary fistula 5 months after surgery. All of these statuses improved after receiving appropriate treatment. Conclusions: Use of ADM represents a new option for the surgical management of AUS repair and reconstruction, with positive clinical effects. In addition, it has the advantages of convenient for operation procedures and access, with no need for additional sampling surgery.

Clinical effectiveness of simultaneous reconstructions of multiple joint scar contracture deformity of limb

Objective: To explore the clinical effects of simultaneous reconstruction of multiple joint scar contracture deformity of limb. Methods: From January 2010 to June 2018, 24 patients with multiple joint scar contracture deformity of the same limb were reconstructed in simultaneous operations in Xiangya Hospital of Central South University, including 16 males and 8 females, aged 3-42 years, with 15 patients having deformities in the upper limbs and 9 patients having deformities in the lower limbs. One operation was performed to repair contracture deformity of axillary fossa and elbow in 3 patients, cubital fossa and palmar of wrist in 4 patients, cubital fossa and hand in 5 patients, palmar of wrist, palm, and palmar of finger in 3 patients, groin and medial knee in 2 patients, popliteal fossa and posterior ankle in 1 patient, and anterior ankle and dorsum of foot in 6 patients. After the release of various joint scar contractures, the area of skin defect was 140 to 580 cm(2). Autologous full-thickness skin grafts were used in 7 patients, autologous medium-thickness skin grafts were used in 4 patients, autologous full-thickness skin grafts combined with local skin flaps were used in 9 patients, and allogeneic acellular dermal matrix and autologous thin skin grafts were used in 4 patients. Comprehensive measures for rehabilitation were taken and the survival of the skin graft was observed after operation. Six months to eight years after the operation, all the patients were followed up for the functions of the affected limbs, among which the functions of the upper limbs were evaluated according to the trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association. The joint mobility, walking, and squatting function of lower extremity were examined after operation. Recurrence of contractures in all the affected limbs and reoperation were recorded. Results: The grafts survived after operation in 22 patients. Two patients had necrosis in small full-thickness skin area, of which one was healed by skin grafting after debridement, and the other one was healed after dressing changes. The deformity of scar contracture at each repaired joint was completely or partially corrected. During a follow-up for 6 to 96 months, the upper limb functions of 15 patients were rated excellent in 12 patients and good in 3 patients. Among the 9 patients of lower limb scar contractures, except for one 3-year-old child who experienced recurrence of medial knee scar contracture and underwent surgical release and skin grafting 5 years later, the remaining 8 patients basically recovered normal joint functions with pretty good outcomes. Conclusions: For continuous scar contracture deformity of multiple joints of the same limb, simultaneous surgical release and skin grafting can reduce operation frequency and obtain better outcomes of surgical operation.

Preparation and processing of human allogenic dermal matrix for utilization in reconstructive surgical procedures.

This articlepresents the development of anovel preparation and processing methodas well as indication for clinical applications of human allogeneic acellular dermal matrix, which was developed originally in the Central Tissue Bank (CTB) for use in burn medicine and reconstructive surgery. Acellular dermal matrix (ADM) isa biological material assigned for utilization inseveral surgical procedures due to its unique structure and advantageous properties. The article focuses on a novel preparation and processing method developed by CTB, which differs in its impact on the structure, biological and biomechanical properties of the final ADM compared to the wide range of commercially available ADM products and currently available ADM products of other tissue banks. The ubiquitous acellular allogeneic dermal collagen matrix is the main substance participating in advantageous properties facilitating the use of ADM in numerous indications from dermal replacement and soft tissue augmentation to more extensive surgical reconstructive procedures. Dermal substitutes play an essential role in the reconstruction of full-thickness skin defects, both in acute and chronic wounds, defects of fasciae, peritoneum, etc., and there is a strong evidence that they can improve the final scar quality as well. Differencesin preparation methods of ADMs are recently causing concerns among surgeons utilizing the ADMs. We present three different cases with favourable outcomes by using human acellular ADM grafts. Although ADMs did not fulfil all of the requirements for an ideal dermal substitute, their applications have been advanced for diverse indications in soft tissue reconstructions and augmentations. Early revascularization of the allografts reduces bacterial contamination. Research and development of new generation of acellular dermal matrices with incorporated autologous in vitro cultured cells will likely yield new products and give new hope for continued improve-ments in functional and cosmetic outcomes (Fig. 9, Ref. 60).

Tissue Reactions to Heterogenic and Allogeneic Acellular Dermal Matrix Mesh Placed in the Vesicovaginal Space in a Rabbit Model

Background and Aim: This study is aimed at investigating the tissue reactions of heterogenic and allogeneic acellular dermal matrix (ADM) mesh implanted in the vesicovaginal space in a rabbit model. Methods: Twenty eight rabbits were implanted with heterogenic or allogeneic mesh, respectively, in the vesicovaginal space, and 4 served as the no-implantation control group. Rabbits were sacrificed at 7, 30, and 90 days after implantation. Histopathological study and immunohistochemical examination for collagen were performed. Results: Heterogenic but not allogeneic mesh was identifiable at 90 days. In the allogeneic group, neovascularization was observed from day 7 after implantation. A chronic inflammatory reaction was noted in the heterogenic group at 30 days that decreased at 90 days. Inflammation was less in the allogeneic group, but giant cells and fibroblasts were present. With respect to collagen, the heterogenic mesh remained structurally unchanged at 90 days, while new collagen fibers were observed in the allogeneic group from day 7. Conclusion: The immunological outcomes of heterogenic and allogeneic ADM mesh are different. Heterogenic mesh induces a chronic inflammatory reaction at day 30 after implantation, and maintains its original form longer. Allogeneic mesh is associated with new collagen generation, but degrades earlier.

Own Experience From The Use Of A Substitute Of An Allogeneic Acellular Dermal Matrix Revitalized With In Vitro Cultured Skin Cells In Clinical Practice.

As a result of the removal of cells from human allogeneic dermis, a collagen scaffold is obtained, which can be populated de novo with autologous/allogeneic skin cells and transplanted onto the area of skin loss. The optimal method for production of acellular dermal matrices (ADM) has been selected. Three female patients (a mean age of 54 years) were subjected to the transplantation of either autologous or allogeneic keratinocytes and fibroblasts into the holes of acellular dermal matrix (ADM) mesh graft. The method for burn wound treatment based on the use of a viable dermal-epidermal skin substitute (based on ADM and in vitro cultured fibroblasts and keratinocytes) may be the optimal method of burn treatment.

Application of composite skin grafts consisting of allogeneic acellular dermal matrix and autologous scalp to the repair of defects after excision of giant pigmented nevi in children

Objective To evaluate the efficacy of composite skin grafts consisting of allogeneic acellular dermal matrix and autologous scalp in the repair of defects after excision of giant pigmented nevi in children.Methods Eighteen children with giant pigmented nevi were included in this study.All the patients received excision of giant pigmented nevi.The defects were repaired using composite skin grafts consisting of allogeneic acellular dermal matrix and autologous razor-thin scalp grafts in 10 children from June 2009 to October 2012 (test group),and using autologous thin or intermediate-thickness skin grafts in 8 children from March 2006 to May 2009 (control group).Donor site healing time,skin graft survival rate,and the degree of scar proliferation were compared between the two groups.Results Significant differences were observed at donor sites between the test group and control group in healing time ((5.31 ± 1.45) vs.(11.63 ± 1.69) days,P ＜ 0.05) and scar score (1.62 ± 0.38 vs.6.38 ± 0.58,P ＜ 0.05).At recipient sites,the survival rate of skin grafts was similar between the test group and control group ((94.44 ± 2.56)％ vs.(95.13 ± 3.13)％,P ＞ 0.05),while scar score was significantly different (5.38 ±0.62 vs.8.40 ± 0.41,P ＜ 0.05).Conclusion Composite skin grafts consisting of allogeneic acellular dermal matrix and autologous scalp appear to be a good option for the repair of defects after excision of giant pigmented nevi in children,with minor donor-site injuries and satisfying cosmetic and functional outcomes at recipient sites. Key words: Nevus; Child; Skin transplantation; Dermis

Correction of penile curvature by allogeneic acellular dermal matrix

Objective To evaluate the effect of lengthening the short-side albuginea of the bending penis by the allogeneic acellular dermal matrix ( Allo-ADM ) for the treatment of penile curvature.Methods From Jun 2007 to Jun 2010,18 patients with penile curvature due to malformation of the albuginea cavernous body were treated.The age of the patients ranged from 15 to 26 years (mean,20 years).Twelve patients were married.The curvature degree ranged from 30° to 80° (mean,55°).There were 17cases of single curvature and 1 case of complex curvature.The grafts ( Allo-ADM ) of different sizes were sutured to the albuginea at the curvatus side of the penis according to the extent of penile curvature through a circumcision incision.The extent of penile curvature and complications were evaluated postoperatively.Results Penile curvature was corrected in all 18 patients after the operation.No infection,hematoma and abnormal erection occurred postoperatively. No erectile dysfunction and penile re-curvature was observed during the follow-up period of 3 to 24 months. Conclusion Lengthening the short-side albuginea of the bending penis by Allo-ADM could be a safe and effective way to correct penile curvature. Key words: Allogeneic acellular dermal matrix; Penile curvature; Albuginea; Transplantation, homologous

ヒト無細胞真皮マトリックスを担体とした複合型培養粘膜の開発 : 熱傷創への予備的臨床応用(杏林大学学位論文要旨および審査要旨)

ヒト無細胞真皮マトリックスを担体とした複合型培養粘膜の開発 : 熱傷創への予備的臨床応用(杏林大学学位論文要旨および審査要旨)

Development of a tissue-engineered human oral mucosa equivalent based on an acellular allogeneic dermal matrix: A preliminary report of clinical application to burn wounds

Tissue-engineered skin equivalents composed of epidermal and dermal components have been widely investigated for coverage of full-thickness skin defects. We developed a tissue-engineered oral mucosa equivalent based on an acellular allogeneic dermal matrix and investigated its characteristics. We also tried and assessed its preliminary clinical application. Human oral mucosal keratinocytes were separated from a piece of oral mucosa and cultured in a chemically-defined medium. The keratinocytes were seeded on to the acellular allogeneic dermal matrix and cultured. Histologically, the mucosa equivalent had a well-stratified epithelial layer. Immunohistochemical study showed that it was similar to normal oral mucosa. We applied this equivalent in one case with an extensive burn wound. The equivalent was transplanted three weeks after the harvest of the patient's oral mucosa and about 30% of the graft finally survived. We conclude that this new oral mucosa equivalent could become a therapeutic option for the treatment of extensive burns.

Symposium i‐2. pathophysiology and treatment of pressure ulcer Moderated by Toshimasa Asahara: Sterilized Acellular Allogeneic Dermal Matrix for Scaffold of Cultured Composite Skin

Aim: Acellular Allogeneic Dermal Matrix ADM has been used for scaffold of cultured composite skin. However, possibility of disease transmission by ADM remains as its potential risk. So it is important to reduce the risk by ADM transplantation the purpose of this study was to evaluate whether ADM could be used as a scaffold of cultured composite skin safely.Method: Four different kinds of methods were used for sterilization, such as 98% glycerol, Pasteurization, Gamma irradiation, and ethylene oxide gas sterilization (EOG). Histological, immunohistochemical and electrophoretic (SDS‐PAGE) properties were evaluated. The property as a scaffold of cultured composites skin was evaluated using normal human cultured keratinosytes.Results: Four methods did not induce apparent collagen degradation of ADM on SDS‐PAGE. However, damage of basement membrane structure was observed by ADM treated with Pasteurization, Gamma irradiation, and EOG histological. These three methods also resulted in the poor regeneration of the epidermal layer in cultured composite skin.Conclusion: The results suggested that glycerol treatment was found to be the best method of ADM sterilization as far as its scaffold was concerned.

Characterization of Acellular Allogeneic Dermal Matrix Treated with Various Disinfecting and Sterilizing Methods

Characterization of Acellular Allogeneic Dermal Matrix Treated with Various Disinfecting and Sterilizing Methods

Tissue-engineered skin. Current status in wound healing.

Tissue-engineered skin is a significant advance in the field of wound healing and was developed due to limitations associated with the use of autografts. These limitations include the creation of a donor site which is at risk of developing pain, scarring, infection and/or slow healing. A number of products are commercially available and many others are in development. Cultured epidermal autografts can provide permanent coverage of large area from a skin biopsy. However, 3 weeks are needed for graft cultivation. Cultured epidermal allografts are available immediately and no biopsy is necessary. They can be cryopreserved and banked, but are not currently commercially available. A nonliving allogeneic acellular dermal matrix with intact basement membrane complex (Alloderm) is immunologically inert. It prepares the wound bed for grafting allowing improved cultured allograft 'take' and provides an intact basement membrane. A nonliving extracellular matrix of collagen and chondroitin-6-sulfate with silicone backing (Integra) serves to generate neodermis. A collagen and glycosaminoglycan dermal matrix inoculated with autologous fibroblasts and keratinocytes has been investigated but is not commercially available. It requires 3 to 4 weeks for cultivation. Dermagraft consists of living allogeneic dermal fibroblasts grown on degradable scaffold. It has good resistance to tearing. An extracellular matrix generated by allogeneic human dermal fibroblasts (TransCyte) serves as a matrix for neodermis generation. Apligraf is a living allogeneic bilayered construct containing keratinocytes, fibroblasts and bovine type I collagen. It can be used on an outpatient basis and avoids the need for a donor site wound. Another living skin equivalent, composite cultured skin (OrCel), consists of allogeneic fibroblasts and keratinocytes seeded on opposite sides of bilayered matrix of bovine collagen. There are limited clinical data available for this product, but large clinical trials are ongoing. Limited data are also available for 2 types of dressing material derived from pigs: porcine small intestinal submucosa acellular collagen matrix (Oasis) and an acellular xenogeneic collagen matrix (E-Z-Derm). Both products have a long shelf life. Other novel skin substitutes are being investigated. The potential risks and benefits of using tissue-engineered skin need to be further evaluated in clinical trials but it is obvious that they offer a new option for the treatment of wounds.

Xenogeneic acellular dermal matrix as a dermal substitute in rats.

Acellular dermal matrix (ADM) has been used as a dermal substitute for the treatment of deep burns, but the availability of cadaver skin for the production of ADM is limited. The usefulness of porcine ADM as a xenogeneic dermal substitute in rats was studied. With the use of Dispase II (Boehringer Mannheim, Indianapolis, Ind) and Triton X-100 (US Biochemicals, Cleveland, Ohio), xenogeneic ADM was prepared from commercially available, cryopreserved porcine skin, and allogeneic ADM from the rats was also prepared. Four full-thickness injuries 225 mm2 in size were created on the dorsum of each rat. One of these wounds was treated with xenogeneic ADM and 1 was treated with allogeneic ADM, and immediately a 0.005-in thick split-thickness skin graft was placed over the ADM. The other 2 wounds were covered with 0.005- or 0.017-in thick split-thickness skin grafts alone. The wounds were evaluated macro- and microscopically 10, 14, 20, and 30 days after grafting. At 30 days after grafting, contraction of the wounds that contained xenogeneic ADM was significantly greater than that of the wounds that contained allogeneic ADM. Graft take was poor in the wounds that contained xenogeneic ADM at 14 days after surgery and moderately good in those that contained allogeneic ADM. The use of thick autografts resulted in the best wound healing, whereas the use of thin autografts resulted in considerable wound contraction. Allogeneic ADM diminished this contraction, but wound healing was significantly worsened when xenogeneic ADM was used.

Dispase/detergent treated dermal matrix as a dermal substitute

A method for preparing acellular allogeneic dermal matrix (ADM) and its effectiveness as a dermal substitute are described. Treatment of rat skin with Dispase followed by Triton X-100 completely removed cellular components from the dermis. Subcutaneously implanted ADM evoked no immunological reaction and 20 weeks after implantation, the size of the implanted ADM was reduced to about 60 per cent of its original area. ADM became completely vascularized within 2 weeks after implantation into full thickness skin defects in the rat and inhibited extensive wound contracture. A second layer of ADM placed onto the implanted ADM served as an excellent dressing, providing mechanical protection and permitting vascularization of the underlying implant. Onlay skin autografts placed onto vascularized allogeneic ADM showed good survival when the skin was grafted more than 1 week after ADM implantation. Dispase/detergent treated ADM derived from animal or human skin may be useful in full thickness skin defects providing a vascularized bed for subsequent epidermal coverage.