Résumé
Background: While collagen-based gels are the dermal substitutes par excellence, their lack of mechanical stability to withstand the rapid cell-mediated contraction remains a major problem, potentially leading to undesirable and excessive scarring, impaired tissue function and poor cosmesis. In this work, we aim to produce a hybrid substitute based on collagen and a polymeric scaffold to minimize the fast contraction that usually limits the performance of dermal equivalents.Particularly, we investigated i) the formulation of a collagen gel template to host normal human dermal fibroblasts (NHDF), ii) the synthesis/processing of a reinforcing polymeric scaffold and iii) the integration of both parts (gel + polymer) to evaluate the contraction of the final construct and the change of properties over time.Materials & Methods: A collagen gel contraction assay was used to quantify the size change of gels or hybrid constructs; their nanostructure was evaluated with scanning electron microscopy (SEM) and their rheological properties with vibration-based technologies. Home-made polymers were characterized likewise and their degradation in vitro was followed for at least 45 days. The mechanical and cellular responses, as well as the interface and stability of the collagen-polymer association were also evaluated.Results: We first optimize collagen formulations that allowed the viability, proliferation and homogeneous distribution of NHDF across the gels. These gel templates rapidly shrank due to cell-remodelling in the first 14 days (particularly in the first 7), correlating with the increase of their elastic modulus (G’) and the reduction of their thickness. Then, we processed several polymers into macroporous structures that showed 1) greater mechanical strength than collagen and 2) progressive degradation (up to 45% loss of the initial molecular weight in 45 days) while gaining brittleness (hence prone to disintegration). Next, we prepared hybrid constructs that exhibited at least a three-fold increase in G’ compared to gel controls, permitting a gradual and restrained contraction of the collagen composite.Conclusions: The rapid contraction of seeded collagen gels can be minimized by using reinforcing degradable polymers; the extent of contraction (and degradation) is driven by the polymer’s nature and/or shaping process. These promising Results open the door to the development of skin engineering strategies that overcome contraction and scarring issues.