Phosphonate-chitosan functionalization of a multi-channel hydroxyapatite scaffold for interfacial implant-bone tissue integration

Abstract

Nonunion associated with long bone defects continues to be highly researched both experimentally and clinically. A porous hydroxyapatite (HAp) scaffold has been recognized as a bone repair and substitute material clinically, but its use in segmental bone defects has been limited by poor integration and stability, as a consequence of scaffold strength unmatched with the native bone. Herein, we designed a multi-channel HAp-based scaffold for application in segmental bone defects, with a specific geometry and design. It possesses the required porosity for bone tissue regeneration with sufficient mechanical properties. We also developed a surface functionalization/modification method with the goal of early scaffold integration and stability. Initial functionalization with poly(vinyl phosphonic acid), PVPA, allowed simple attachment of a chitosan polymeric layer. The modification improved the biocompatibility of the scaffold and attachment of rat bone marrow-derived mesenchymal stem cells (rBMSC) in vitro. The modification also served as a buffer between the implant scaffold and bone tissue. Significant improvement in the integration behavior with better interlocking of the scaffold to bone tissue was observed for the modified scaffolds implanted in rabbit tibiae. The modified HAp scaffolds exhibited early interfacial implant-bone tissue integration with enhanced new bone formation and high potential for use in segmental bone defects.