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 hyularonic 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 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, or even higher, than that of the tissue culture polystyrene used as 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 have important implications in the repairing of directional tissues, as for example nerve and skeletal muscle.