Biomimetic and Biodegradable Adhesive Hydrogels for Tendon Immunomodulation

Abstract

Tendon has a weak intrinsic self-repair and healing ability due to its low cellularity. Following tendon rupture, healing may last over six months and often suffers from post-treatment complications. Variation in healing outcomes may arise from the presence of different cell populations recruited following injury: non-repair models of adult tendon suggest extrinsic cell recruitment, whereas repair models may encourage resident cell recruitment. To further control local cell recruitment throughout the duration of tendon healing, here, a biomimetic, biodegradable tough adhesive hydrogel scaffold is synthesized that can induce the migration and accumulation of M2 (pro-reparative) macrophages locally to the injured tissue. Highly aligned PCL/gelatin nanofibers were embedded onto degradable alginate-polyacrylamide hydrogels to augment the tough and elastic matrix of the hydrogel and promote cell expansion on the scaffolds. This study began investigating the loading and release of SDF-1α, CCL2, and M-CSF from the tough adhesive hydrogels. In vitro studies showed that CCL2 induced macrophage migration and M-CSF promoted M2 macrophage proliferation while discouraging M1 cells. Altogether, this study reports the first degradable, fiber-reinforced tough adhesive hydrogel scaffold for immune cell recruitment, polarization, and proliferation to facilitate tendon healing.