Kartogenin-loaded polyvinyl alcohol/nano-hydroxyapatite composite hydrogel promotes tendon-bone healing in rabbits after anterior cruciate ligament reconstruction.

Abstract

Accumulating evidence supports the role of cartilage tissue engineering in cartilage defect repair, but the biological function has yet to be fully explained. In this work, kartogenin (KGN), an emerging chondroinductive nonprotein small molecule, was incorporated into a composite hydrogel of polyvinyl alcohol/nano-hydroxyapatite (PVA/n-HA) to fabricate an appropriate microenvironment for tendon-bone healing after anterior cruciate ligament (ACL) reconstruction. KGN/PVA/n-HA composite hydrogel scaffolds were prepared by in situ synthesis and physical adsorption, followed by characterization under a scanning electron microscope. The scaffolds were transplanted into healthy New Zealand White (NZW) rabbits. It was confirmed that KGN/PVA/n-HA scaffolds were successfully prepared and exhibited good supporting properties and excellent biocompatibility. Unilateral ACL reconstruction was constructed with tendon autograft in NZW rabbits, and the morphology and diameter of collagen fiber were analyzed. The scaffolds were shown to promote ACL growth and collagen fiber formation. Furthermore, microcomputerized tomography analysis and bone formation histology were performed to detect new bone formation. KGN/PVA/n-HA scaffolds effectively alleviated cartilage damage and prevented the occurrence of osteoarthritis. Meanwhile, ligament-bone healing and bone formation were observed in the presence of KGN/PVA/n-HA scaffolds. In conclusion, these results suggest that the KGN/PVA/n-HA scaffolds can facilitate tendon-bone healing after ACL reconstruction and might be considered novel hydrogel biomaterials in cartilage tissue engineering.