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

Frontiers in Bioengineering and Biotechnology

Bioengineering and Biotechnology

Laure Balasse¹  Françoise Dignat²  Mélanie Vélier²  Julie Véran²  Florence Sabatier²  Chloe Dumoulin²  Laurent Giraudo²  Jérémy Magalon²  Benjamin Guillet³  Romain Appay⁴  Laurent Daniel⁴  Nicolas Macagno⁴  Hugo Caso⁵  Maxime Abellan Lopez⁶  Dominique Casanova⁶  Baptiste Bertrand⁶  Fabien Guillemot⁷  Laurence Hutter⁷  Loïc Hermant⁷  Etienne Pagin⁷  Hélène Riesterer⁷  Laurent Arnaud⁸ 

[1] Aix-Marseille Université, INSERM, Institut National de Recherche Pour l'Agriculture, l'Alimentation et l'Environnement, Centre de Recherche en Cardiovasculaire et Nutrition (C2VN), Marseille, France;Aix-Marseille Université, INSERM, Institut National de Recherche Pour l'Agriculture, l'Alimentation et l'Environnement, Centre de Recherche en Cardiovasculaire et Nutrition (C2VN), Marseille, France;Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France;Aix-Marseille Université, INSERM, Institut National de Recherche Pour l'Agriculture, l'Alimentation et l'Environnement, Centre de Recherche en Cardiovasculaire et Nutrition (C2VN), Marseille, France;Centre Européen de Recherche en Imagerie Médicale (CERIMED), Aix-Marseille Université, Centre National de la Recherche Scientifique, Marseille, France;Anatomy and Pathology Department, INSERM U1263, C2VN, Hôpital de la Timone, Marseille, France;Plastic Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France;Plastic Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France;Aix-Marseille Université, INSERM, Institut National de Recherche Pour l'Agriculture, l'Alimentation et l'Environnement, Centre de Recherche en Cardiovasculaire et Nutrition (C2VN), Marseille, France;Poietis, Pessac, France;Vascular Biology Department, Hôpital de la Timone, AP-HM, Marseille, France;

关键词: skin substitute;    wound healing;    multimodal bioprinting;    laser-assisted bioprinting;    large size;    good manufacturing practice compatible;   

DOI  :  10.3389/fbioe.2023.1217655

 received in 2023-05-05, accepted in 2023-07-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

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 cm2 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.

【 授权许可】

Unknown   
Copyright © 2023 Abellan Lopez, Hutter, Pagin, Vélier, Véran, Giraudo, Dumoulin, Arnaud, Macagno, Appay, Daniel, Guillet, Balasse, Caso, Casanova, Bertrand, Dignat, Hermant, Riesterer, Guillemot, Sabatier and Magalon.