Cultured epithelial autografts: diving from surgery into matrix biology

Raghunath, Michael; Meuli, M.

doi:10.1007/s003830050188

Cited by 6 publications

(7 citation statements)

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“…Unfortunately, cultured epithelial autografts remain fraught with considerable problems when used for the coverage of deep skin defects, including graft fragility, poor take, instability of healed grafts, and unsatisfactory long-term functional and aesthetic results. 2,[7][8][9] The clinical introduction of nowadays widely used dermal regeneration templates [e.g., Integra Dermal Regeneration Template (Integra LifeSciences Corp., Plainsboro, N.J.), Matriderm (MedSkin Solutions Dr. Suwelack AG, Billerbeck, Germany)] has pushed the frontiers further, carrying the potential for improved functional and aesthetic results, yet such templates still require coverage with an overlying autologous split-thickness skin graft. 10 In the early 1990s, the first cultured autologous dermo-epidermal skin substitute, developed by Hansbrough et al, was successfully applied clinically for "compassionate use" in severe burns, 11 and has more recently been investigated in a clinical trial setting.…”

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confidence: 99%

A Cultured Autologous Dermo-epidermal Skin Substitute for Full-Thickness Skin Defects: A Phase I, Open, Prospective Clinical Trial in Children

Meuli

Hartmann-Fritsch

Hüging³

et al. 2019

Plastic &Amp; Reconstructive Surgery

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BACKGROUND: The management of deep partial-thickness and full-thickness skin defects remains a significant challenge. Particularly with massive defects, the current standard treatment, splitthickness skin grafting, is fraught with donor-site limitations and unsatisfactory long-term outcomes. A novel, autologous, bioengineered skin substitute was developed to address this problem. METHODS: To determine whether this skin substitute could safely provide permanent defect coverage, a phase I clinical trial was performed at the University Children's Hospital Zurich. Ten pediatric patients with acute or elective deep partial-or full-thickness skin defects were included. Skin grafts of 49 cm were bioengineered using autologous keratinocytes and fibroblasts isolated from a patient's small skin biopsy specimen (4 cm), incorporated in a collagen hydrogel. RESULTS: Graft take, epithelialization, infection, adverse events, skin quality, and histology were analyzed. Median graft take at 21 days postoperatively was 78 percent (range, 0 to 100 percent). Healed skin substitutes were stable and skin quality was nearly normal. There were four cases of hematoma leading to partial graft loss. Histology at 3 months revealed a wellstratified epidermis and a dermal compartment comparable to native skin. Mean follow-up duration was 15 months. CONCLUSIONS: In the first clinical application of this novel skin substitute, safe coverage of skin defects was achieved. Safety and efficacy phase II trials comparing the novel skin substitute to split-thickness skin grafts are ongoing. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

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mentioning

confidence: 99%

A Cultured Autologous Dermo-epidermal Skin Substitute for Full-Thickness Skin Defects: A Phase I, Open, Prospective Clinical Trial in Children

Meuli

Hartmann-Fritsch

Hüging³

et al. 2019

Plastic &Amp; Reconstructive Surgery

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“…When CEA sheets are applied, whether the sheet will take also raises a question. The earlier literature reported the engraftment rate as 15-65%, depending on the individual technique and the grafted parts of the body (21,(23)(24)(25)(26)(27)(28)(29). The subsequent engraftment rate may be even lower if the wound becomes contaminated with bacteria, which may cause nearly complete loss of the CEA sheets (18,30).…”

Section: Single Sheet Of Epidermal Cellsmentioning

confidence: 93%

Epidermal cells delivered for cutaneous wound healing

Wang

Sun

Wang

et al. 2010

Journal of Dermatological Treatment

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Re-epithelialization is the first and most important step in cutaneous wound healing. The vital role of epidermal cells, or keratinocytes, in accelerating wound healing has long been established. The technique of delivering the cultured and uncultured epidermal cells to the wound bed takes a variety of forms including cultured epithelial autografts (CEAs), tissue-engineered skin equivalent, epidermal suspension and microbead-loaded composite. These techniques, together with the keratinocyte culturing method and scaling up equipment, are still the ongoing research. Application of these techniques also bears direct impact on the outcome of the wounded patients. Best understanding of the delivery technique and its relationship with the culturing method and delivery vehicle could benefit not only the wounded patient but also the development of tissue-engineered skin equivalent.

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“…The earlier literature data of multicenter trials reported a high engraftment rate of cultured CEA, whereas later on others and especially single center experiences with a larger number of CEA grafted patients reported considerably lower take rates (between 15% and 65%) [24,25,30,53,81,94,98,101,116,128,129]. The true "take rate" derived from cumulative literature metaanalysis may therefore reach an average value of only 50% or less [40].…”

Section: Conventional "Sheet Graft" (Cea) Skin Substitutesmentioning

confidence: 99%

Tissue engineering of cultured skin substitutes

et al. 2005

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Skin replacement has been a challenging task for surgeons ever since the introduction of skin grafts by Reverdin in 1871. Recently, skin grafting has evolved from the initial autograft and allograft preparations to biosynthetic and tissue-engineered living skin replacements. This has been fostered by the dramatically improved survival rates of major burns where the availability of autologous normal skin for grafting has become one of the limiting factors. The ideal properties of a temporary and a permanent skin substitute have been well defined. Tissue-engineered skin replacements: cultured autologous keratinocyte grafts, cultured allogeneic keratinocyte grafts, autologous/allogeneic composites, acellular biological matrices, and cellular matrices including such biological substances as fibrin sealant and various types of collagen, hyaluronic acid etc. have opened new horizons to deal with such massive skin loss. In extensive burns it has been shown that skin substitution with cultured grafts can be a life-saving measure where few alternatives exist. Future research will aim to create skin substitutes with cultured epidermis that under appropriate circumstances may provide a wound cover that could be just as durable and esthetically acceptable as conventional split-thickness skin grafts. Genetic manipulation may in addition enhance the performance of such cultured skin substitutes. If cell science, molecular biology, genetic engineering, material science and clinical expertise join their efforts to develop optimized cell culture techniques and synthetic or biological matrices then further technical advances might well lead to the production of almost skin like new tissue-engineered human skin products resembling natural human skin.

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Cultured epithelial autografts: diving from surgery into matrix biology

Cited by 6 publications

References 0 publications

A Cultured Autologous Dermo-epidermal Skin Substitute for Full-Thickness Skin Defects: A Phase I, Open, Prospective Clinical Trial in Children

A Cultured Autologous Dermo-epidermal Skin Substitute for Full-Thickness Skin Defects: A Phase I, Open, Prospective Clinical Trial in Children

Epidermal cells delivered for cutaneous wound healing

Tissue engineering of cultured skin substitutes

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