UNRAVELLING TISSUE REMODELLING PROCESSES AT THE BONE-IMPLANT INTERFACE OF BIODEGRADABLE MEDICAL-GRADE POLYCAPROLACTONE SCAFFOLDS

Scaffold-guided bone regeneration (SGBR) requires a comprehensive understanding of the tissue remodeling processes at the bone-implant interface to establish and maintain osseointegration. Eight distinct configurations of the bone-implant interface have been identified for solid metal implants, which consist of mineralized, partially mineralized, and unmineralized regions. However, these classifications do not address biodegradable materials, such as medical-grade polycaprolactone β-tricalcium phosphate calcium phosphate (mPCL-TCP-CaP) scaffolds. These scaffolds are bioresorbable and porous, which promotes SGBR. Unlike the static interface observed with non-degradable solid materials, mPCL-TCP-CaP scaffolds actively facilitate cellular attachment, growth, differentiation, and proliferation. This process allows for scaffold degradation and the gradual development of new tissue over time. Our 12-month studies on large (3cm) segmental tibial bone defects in sheep, which utilized histological, immunohistochemical, and scanning electron microscopy analyses, demonstrated that contact osteogenesis—a prerequisite for metal implant osseointegration—occurs at the bone-implant interface of these bioresorbable scaffolds. The porous architecture and the degradable nature of the mPCL-TCP-CaP scaffolds influence the process of contact osteogenesis, resulting in a unique integration mechanism. Specifically, bone formation occurs directly on the scaffold surface, with the newly formed bone extracellular matrix (ECM) gradually extending inward towards the scaffold. As the scaffold degrades, the bone ECM progressively occupies the spaces previously occupied by the scaffold struts. The osteogenic potential of these scaffolds stems from their bioactive properties, particularly the β-TCP and CaP components, which enhance bone cell adhesion and proliferation. These components promote the differentiation of osteoprogenitor cells into osteoblasts and osteoclasts, facilitating a coupled remodeling process mediated by osteopontin integrin-dependent adhesion, with osteocalcin preferentially accumulating at the bone-implant interface. Additionally, the space created during scaffold degradation is crucial for ECM remodeling and maintaining fluid flow and metabolite transport. This process is further supported by the activity of macrophages and foreign body giant cells at the scaffold-bone interface. This scaffold-guided bone ECM formation ensures structural integrity and effective osseointegration of mPCL-TCP-CaP scaffolds, which is essential for the long-term success of bone repair strategies. This research addresses significant challenges in the integration of orthopedic implants with tissue, which is critical for the success of bone reconstructive surgeries. Poor implant integration remains a major issue, often leading to mechanical failure, prolonged recovery times, revision surgeries, and increased healthcare costs.