The challenge of finding an adapted scaffold for ligament tissue engineering remains unsolved after years of researches. A technology to fabricate a multilayer braided scaffold with flexible and elastic poly (l-lactide-co-caprolactone) (PLCL 85/15) has been recently pioneered by our team. In this study, polyelectrolyte multilayer films (PEM) with poly-l-lysine (PLL)/ hyaluronic acid (HA) were deposited on this scaffold. After PEM modification, polygonal (PLL) and particle-like (HA) structures were present on the braided scaffold with no significant variation of fibers Young's modulus. Wharton's jelly mesenchymal stem cells (WJ-MSC) and bone marrow mesenchymal stem cells (BM-MSC) showed good metabolic activity on scaffolds. They presented a spindled shape along the fiber longitudinal direction, and crossed the fibers to form cell bridges. Collagen type I, collagen type III, and tenascin-C secreted by MSCs were detected on day 14. Moreover, one-layer modified scaffold presented increased chemotaxis. As a conclusion, our results indicate that this braided PLCL scaffold with one-layer PEM modification shows inspiring potential with satisfying mechanical properties and biocompatibility. It opens new perspectives to incorporate growth factors within PEM-modified braided PLCL scaffold for ligament tissue engineering and to recruit endogenous cells after implantation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3042-3052, 2018.

(1) Background: A suitable scaffold with adapted mechanical and biological properties for ligament tissue engineering is still missing. (2) Methods: Different scaffold configurations were characterized in terms of morphology and a mechanical response, and their interactions with two types of stem cells (Wharton’s jelly mesenchymal stromal cells (WJ-MSCs) and bone marrow mesenchymal stromal cells (BM-MSCs)) were assessed. The scaffold configurations consisted of multilayer braids with various number of silk layers (n = 1, 2, 3), and a novel composite scaffold made of a layer of copoly(lactic acid-co-(e-caprolactone)) (PLCL) embedded between two layers of silk. (3) Results: The insertion of a PLCL layer resulted in a higher porosity and better mechanical behavior compared with pure silk scaffold. The metabolic activities of both WJ-MSCs and BM-MSCs increased from day 1 to day 7 except for the three-layer silk scaffold (S3), probably due to its lower porosity. Collagen I (Col I), collagen III (Col III) and tenascin-c (TNC) were expressed by both MSCs on all scaffolds, and expression of Col I was higher than Col III and TNC. (4) Conclusions: the silk/PLCL composite scaffolds constituted the most suitable tested configuration to support MSCs migration, proliferation and tissue synthesis towards ligament tissue engineering.