Acellular dermal matrix in skin wound healing in rabbits - histological and histomorphometric analyses

Carvalho-Júnior, José da Conceição; Zanata, Fabiana; Aloise, Antônio Carlos; Ferreira, Lydia Masako

doi:10.6061/clinics/2021/e2066

Cited by 11 publications

(7 citation statements)

References 37 publications

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“…Our results reported more significant signs of repair than those reported in a study on the same biomodel using decellularized fetal bovine skin substitute with autologous skin cell suspension [ 69 ], indicating that the wound closed in approximately 42 days after treatment and according to the histological result, the immature epithelium and presence of inflammatory cells in the wound treated with decellularized skin substitute were observed at 28 days. Likewise, the skin repair potential of construct 1 and hADM described here was higher than similar strategies evaluated in different animal models [ 67 , 70 , 71 ]. Although we did not use a positive control such as Integra™ seeded with keratinocytes in our in vivo assay, previous studies have shown that this alternative, evaluated in a porcine biomodel, fails to achieve epithelial stratification [ 72 ], and also produces hyperkeratinized scarring at week 8 of evaluation [ 73 ].…”

Section: Discussionmentioning

confidence: 68%

Bioengineered skin constructs based on mesenchymal stromal cells and acellular dermal matrix exposed to inflammatory microenvironment releasing growth factors involved in skin repair

Correa-Araujo,

Prieto-Abello,

Lara-Bertrand

et al. 2023

Stem Cell Res Ther

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Background Skin tissue engineering is a rapidly evolving field of research that effectively combines stem cells and biological scaffolds to replace damaged tissues. Human Wharton’s jelly mesenchymal stromal cells (hWJ-MSCs) are essential to generate tissue constructs, due to their potent immunomodulatory effects and release of paracrine factors for tissue repair. Here, we investigated whether hWJ-MSC grown on human acellular dermal matrix (hADM) scaffolds and exposed to a proinflammatory environment maintain their ability to produce in vitro growth factors involved in skin injury repair and promote in vivo wound healing. Methods We developed a novel method involving physicochemical and enzymatic treatment of cadaveric human skin to obtain hADM scaffold. Subsequently, skin bioengineered constructs were generated by seeding hWJ-MSCs on the hADM scaffold (construct 1) and coating it with human platelet lysate clot (hPL) (construct 2). Either construct 1 or 2 were then incubated with proinflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α) for 12, 24, 48, 72 and 96 h. Supernatants from treated and untreated constructs and hWJ-MSCs on tissue culture plate (TCP) were collected, and concentration of the following growth factors, bFGF, EGF, HGF, PDGF, VEGF and Angiopoietin-I, was determined by immunoassay. We also asked whether hWJ-MSCs in the construct 1 have potential toward epithelial differentiation after being cultured in an epithelial induction stimulus using an air–liquid system. Immunostaining was used to analyze the synthesis of epithelial markers such as filaggrin, involucrin, plakoglobin and the mesenchymal marker vimentin. Finally, we evaluated the in vivo potential of hADM and construct 1 in a porcine full-thickness excisional wound model. Results We obtained and characterized the hADM and confirmed the viability of hWJ-MSCs on the scaffold. In both constructs without proinflammatory treatment, we reported high bFGF production. In contrast, the levels of other growth factors were similar to the control (hWJ-MSC/TCP) with or without proinflammatory treatment. Except for PDGF in the stimulated group. These results indicated that the hADM scaffold maintained or enhanced the production of these bioactive molecules by hWJ-MSCs. On the other hand, increased expression of filaggrin, involucrin, and plakoglobin and decreased expression of vimentin were observed in constructs cultured in an air–liquid system. In vivo experiments demonstrated the potential of both hADM and hADM/hWJ-MSCs constructs to repair skin wounds with the formation of stratified epithelium, basement membrane and dermal papillae, improving the appearance of the repaired tissue. Conclusions hADM is viable to fabricate a tissue construct with hWJ-MSCs able to promote the in vitro synthesis of growth factors and differentiation of these cells toward epithelial lineage, as well as, promote in a full-thickness skin injury the new tissue formation. These results indicate that hADM 3D architecture and its natural composition improved or maintained the cell function supporting the potential therapeutic use of this matrix or the construct for wound repair and providing an effective tissue engineering strategy for skin repair.

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Section: Discussionmentioning

confidence: 68%

Bioengineered skin constructs based on mesenchymal stromal cells and acellular dermal matrix exposed to inflammatory microenvironment releasing growth factors involved in skin repair

Correa-Araujo,

Prieto-Abello,

Lara-Bertrand

et al. 2023

Stem Cell Res Ther

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“…In a pre-clinical study, Li et al, showed that tilapia-skin ADM promoted wound healing by inducing angiogenesis and epithelialization [ 14 ]. In addition, greater skin wound healing was observed in rabbit models when ADM was used [ 40 ]. The beneficial effects of ADM in wound healing were also observed in other studies of animal models [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Fetal Bovine Acellular Dermal Matrix Seeded with Wharton’s Jelly Mesenchymal Stem Cells for Healing Full-Thickness Skin Wounds

Mansour

Hasanzadeh

Abasi

et al. 2023

Genes

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The treatment of full-thickness skin wounds is a problem in the clinical setting, as they do not heal spontaneously. Extensive pain at the donor site and a lack of skin grafts limit autogenic and allogeneic skin graft availability. We evaluated fetal bovine acellular dermal matrix (FADM) in combination with human Wharton’s jelly mesenchymal stem cells (hWJ-MSCs) to heal full-thickness skin wounds. FADM was prepared from a 6-month-old trauma-aborted fetus. WJ-MSCs were derived from a human umbilical cord and seeded on the FADM. Rat models of full-thickness wounds were created and divided into three groups: control (no treatment), FADM, and FADM-WJMSCs groups. Wound treatment was evaluated microscopically and histologically on days 7, 14, and 21 post-surgery. The prepared FADM was porous and decellularized with a normal range of residual DNA. WJ-MSCs were seeded and proliferated on FADM effectively. The highest wound closure rate was observed in the FADM-WJMSC group on days 7 and 14 post-surgery. Furthermore, this group had fewer inflammatory cells than other groups. Finally, in this study, we observed that, without using the differential cell culture media of fibroblasts, the xenogeneic hWJSCs in combination with FADM could promote an increased rate of full-thickness skin wound closure with less inflammation.

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“…Most patients began wound management by undergoing vascular examinations immediately before or immediately after hospitalisation with sharp debridement in the absence of blood flow abnormalities. In the case of impaired blood flow, wound management was initiated at 3–4 weeks after implementing percutaneous transluminal angioplasty at a time when reperfusion injury was minimized, 24 , 25 which was found to be at an average of 20.34 days after initiating wound management. It was worth noting that it took an average of 12.68 days to be discharged from the hospital when using a micronized ADM and that treatment was terminated after an average of 66.40 days on an outpatient basis.…”

Section: Discussionmentioning

confidence: 99%

A long‐term follow‐up study of diabetic foot ulcer using micronized acellular dermal matrix

Byeon

Hwang

Choi

et al. 2022

International Wound Journal

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Treating a diabetic foot ulcer (DFU) extending to the tendon or bone can be a challenge for physicians. Recent studies have shown positive results of micronized acellular dermal matrix (ADM) treatment for treating DFU. However, studies on such ADM with a long‐term follow‐up are rare. Thus, the objective of this study was to retrospectively analyse patients treated with micronized ADM with a long‐term follow‐up to assess the effectiveness of the treatment and determine the recurrence rate. The rate of success of complete healing was 62.96% and the time of complete healing was 86.96 days in this study. The recurrence rate of DFUs was 41.17% in the overall group. However, it was only 23.52% in the micronized ADM group. The average duration of recurrence was 720.50 ± 505.12 days. The recurrence rate was 50% in weight bearing areas such as the plantar and heel. It was 12.5% in toes and non‐weight bearing areas. In conclusion, micronized ADM can be used to effectively treat DFUs that have invaded ligaments or bones. A close follow‐up of weight bearing area wounds will allow us to identify and treat recurrence early.

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Acellular dermal matrix in skin wound healing in rabbits - histological and histomorphometric analyses

Cited by 11 publications

References 37 publications

Bioengineered skin constructs based on mesenchymal stromal cells and acellular dermal matrix exposed to inflammatory microenvironment releasing growth factors involved in skin repair

Bioengineered skin constructs based on mesenchymal stromal cells and acellular dermal matrix exposed to inflammatory microenvironment releasing growth factors involved in skin repair

The Effect of Fetal Bovine Acellular Dermal Matrix Seeded with Wharton’s Jelly Mesenchymal Stem Cells for Healing Full-Thickness Skin Wounds

A long‐term follow‐up study of diabetic foot ulcer using micronized acellular dermal matrix

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