Defining Osseointegration for Biodegradable Scaffolds based on Histological, Immunohistochemical and Ultrastructural Analysis

Osseointegration of metal implants refers to the formation of a direct, intimate, and stable interface between bone and the implant surface under physiological loads, without intervening fibrous tissue. This concept is largely based on the long-term fixation of non-degradable implants, where bone remodeling occurs around a permanent material. However, there is no equivalent framework defining de biological integration of biodegradable scaffolds used for scaffold-guided bone regeneration (SGBR), whose architecture, mechanical properties, and surface chemistry are intentionally desined to change over time. Consequently, definitions developed for permanent mettalic are frequently applied to biodegradable scaffolds, leading to uncertainty regarding whether these scaffolds truly "osseointegrate". We argue that the biological processes at biodegradable scaffold-bone interfaces fundamentally differs from that of metallic implants, and should be distinguished. Rather than classical "bone anchorage", biodegradable scaffolds support a dynamic, immunologically active, and mechanically evolving bone-scaffold interface in which fibrous encapsulation and bone formation compete. This paper aims to clarify these issues not by redefining osseointegration in general, but by adapting it specifically to osteoconductive biodegradable scaffolds in SGBR. Using evidence from a series of studies in well-characterised large-animal models of segmental bone defects, we propose a new framework that captures the temporal, cellular, and structural complexities of osseointegration of biodegradable scaffolds in living organisms. STATEMENT OF SIGNIFICANCE: Biodegradable scaffolds are intended to facilitate bone regeneration and gradually degrade as new tissue develops. Nevertheless, there is limited knowledge about how these materials interact with bone over extended periods. This research examines the bone-scaffold interface over 36-months using histology, immunohistochemistry, scanning electron microscopy, and Raman spectroscopy. Results indicate that biodegradable scaffolds do not form the permanent bonds commonly defined as osseointegration in metallic implants. Instead, they establish a dynamic interface that evolves as the organ bone, composed of mineralised tissue, blood vessels, and extracellular matrix, remodels around the degrading scaffold. These insights improve our understanding of scaffold-guided bone regeneration and will guide the development of next-generation biodegradable scaffolds that shorten the timeframe and better support long-term bone growth.