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Article Dans Une Revue Frontiers in Bioengineering and Biotechnology Année : 2023

In vivo efficacy proof of concept of a large-size bioprinted dermo-epidermal substitute for permanent wound coverage

Résumé

Introduction: An autologous split-thickness skin graft (STSG) is a standard treatment for coverage of full-thickness skin defects. However, this technique has two major drawbacks: the use of general anesthesia for skin harvesting and scar sequelae on the donor site. In order to reduce morbidity associated with STSG harvesting, researchers have developed autologous dermo-epidermal substitutes (DESs) using cell culture, tissue engineering, and, more recently, bioprinting approaches. This study assessed the manufacturing reliability and in vivo efficacy of a large-size good manufacturing practice (GMP)-compatible bio-printed human DES, named Poieskin ® , for acute wound healing treatment. Methods: Two batches (40 cm 2 each) of Poieskin ® were produced, and their reliability and homogeneity were assessed using histological scoring. Immunosuppressed mice received either samples of Poieskin ® ( n = 8) or human STSG ( n = 8) immediately after longitudinal acute full-thickness excision of size 1 × 1.5 cm, applied on the skeletal muscle plane. The engraftment rate was assessed through standardized photographs on day 16 of the follow-up. Moreover, wound contraction, superficial vascularization, and local inflammation were evaluated via standardized photographs, laser Doppler imaging, and PET imaging, respectively. Histological analysis was finally performed after euthanasia. Results: Histological scoring reached 75% ± 8% and 73% ± 12%, respectively, displaying a robust and homogeneous construct. Engraftment was comparable for both groups: 91.8% (SD = 0.1152) for the Poieskin ® group versus 100% (SD = 0) for the human STSG group. We did not record differences in either graft perfusion, PET imaging, or histological scoring on day 16. Conclusion: Poieskin ® presents consistent bioengineering manufacturing characteristics to treat full-thickness cutaneous defects as an alternative to STSG in clinical applications. Manufacturing of Poieskin ® is reliable and homogeneous, leading to a clinically satisfying rate of graft take compared to the reference human STSG in a mouse model. These results encourage the use of Poieskin ® in phase I clinical trials as its manufacturing procedure is compatible with pharmaceutical guidelines.

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hal-04391128 , version 1 (12-01-2024)

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Maxime Abellan Lopez, Laurence Hutter, Etienne Pagin, Mélanie Vélier, Julie Véran, et al.. In vivo efficacy proof of concept of a large-size bioprinted dermo-epidermal substitute for permanent wound coverage. Frontiers in Bioengineering and Biotechnology, 2023, 11, pp.1217655. ⟨10.3389/fbioe.2023.1217655⟩. ⟨hal-04391128⟩
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