Hydrogel-filled tubular scaffolds for directional tissue regeneration combining shape-memory polyester blends with hyaluronic acid click-hydrogels

Abstract

A clinical need still exists for advanced therapeutics to improve the recovery of patients suffering from large-gap peripheral nerve injuries (PNI). In this study, tubular constructs of submicrometric thickness (<1 µm) are prepared using shape-memory 50 : 50, 70 : 30 and 90 : 10 poly(lactic acid) (PLA)/polycaprolactone (PCL) blends, which are filled with a hyaluronic acid (HA)-based hydrogel. The hydrogel is crosslinked in situ by click chemistry using a 3-arm alkyne-functionalized polyethylene glycol and thiol-modified HA. The Young's moduli of the hydrogels confined inside the different cylindrical constructs are similar to that of the free hydrogel, the tubular shell mainly affecting the tensile strength and deformability. On the other hand, cell adhesion and proliferation assays demonstrate that the cytocompatibility of the blends, the hydrogel and the filled tubular constructs is similar to or even higher than that of the tissue culture polystyrene used as the control. Furthermore, the scaffold derived from the 70 : 30 PLA/PCL blend provides a 3D cell-friendly mechanical environment that promotes the directional migration of cells towards the confined hydrogel. The engineered scaffolds may have important implications in the repairing of directional tissues.

This publication is part of the I + D + i project PID2021-125767OB-I00 and CEX2023-001300-M funded by MCIN/AEI/10.13039/501100011033 and, as appropriate, by “ERDF A way of making Europe” and European Union Next Generation EU. The authors are thankful to the Agència de Gestió d'Ajuts Universitaris i de Recerca (2021 SGR 00387) for financial support. A. H.-Y. is thankful to the MCIN/AEI for a FPI Fellowship. M. M. P.-M. thanks the Ministerio de Ciencia, Innovación y Universidades for the Junior Beatriz Galindo Award (BG20/00216). Support for the research of C. A. was also received through the prize “ICREA Academia” for excellence in research funded by the Generalitat de Catalunya.

Peer Reviewed

Postprint (published version)