Native Collagen Preservation Versus Exogenous Collagen Addition in Xenogeneic Bone Substitutes for Dental Regeneration: Effects of Processing on Crystallinity, Remodeling, and Graft Persistence

Xenogeneic bone substitutes are widely used in dental regeneration, yet materials commonly described as collagen-containing or collagenated may differ fundamentally in their composition and biological behavior. This narrative review examines xenografts from the perspective of their manufacturing process, focusing on the distinction between preservation of native bone collagen and exogenous collagen addition, which may follow chemical or thermal processing and may also coexist with retained donor collagen. Thermal processing progressively removes the native organic matrix and carbonate components and, particularly at higher temperatures, increases mineral crystallinity and promotes the transformation of bone into a more ceramic-like scaffold. Such materials are highly osteoconductive but may exhibit very slow resorption and long-term particle persistence. Exogenous collagen can subsequently be incorporated into the processed mineral scaffold to improve cohesion, handling, and adaptation and potentially influence biological responses, but does not restore the original hierarchical mineral–collagen architecture. Conversely, chemical or enzymatic processing may preserve native collagen together with a less extensively transformed mineral phase. Available preclinical and clinical evidence suggests that some donor-collagen-retaining xenografts show higher new-bone and lower residual-graft fractions than specific anorganic comparators, although differences in animal source, porosity, mineral structure, and manufacturing protocols preclude attributing these effects exclusively to collagen preservation. We therefore use native-collagen-preserving xenografts (NCP-XG) and exogenous-collagen-supplemented xenografts (ECS-XG) as overlapping descriptors, with conformation, architecture and mineral properties recorded separately. This descriptive framework may improve interpretation of collagen-containing xenografts, but tissue fractions do not directly quantify graft replacement and collagen origin alone does not establish clinical superiority.