AUTHOR=Abellan Lopez Maxime , Hutter Laurence , Pagin Etienne , Vélier Mélanie , Véran Julie , Giraudo Laurent , Dumoulin Chloe , Arnaud Laurent , Macagno Nicolas , Appay Romain , Daniel Laurent , Guillet Benjamin , Balasse Laure , Caso Hugo , Casanova Dominique , Bertrand Baptiste , Dignat Françoise , Hermant Loïc , Riesterer Hélène , Guillemot Fabien , Sabatier Florence , Magalon Jérémy
TITLE=In vivo efficacy proof of concept of a large-size bioprinted dermo-epidermal substitute for permanent wound coverage
JOURNAL=Frontiers in Bioengineering and Biotechnology
VOLUME=11
YEAR=2023
URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2023.1217655
DOI=10.3389/fbioe.2023.1217655
ISSN=2296-4185
ABSTRACT=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.