Immunoinflammatory Mechanisms and Biocompatibility of Bioactive Dental Biomaterials: From Fundamental Insights to Clinical Translation.

Biomaterials are substances designed to interact with living systems for diagnostic, therapeutic, or regenerative purposes. Their clinical success is governed not only by their bulk physicochemical properties but more importantly, by their surface properties and interfacial characteristics, which regulate early protein adsorption and subsequently downstream cellular responses. Biocompatibility, therefore, extends far beyond the absence of toxicity, encompassing the ability of a material to modulate the foreign body response, promote tissue repair, and tissue integration. Understanding these mechanisms is essential for designing materials that minimize fibrous encapsulation while enhancing regeneration. This need becomes particularly evident in dental implantology, where biomaterials are indispensable for functional rehabilitation, yet biological complications continue to represent a major clinical challenge. In response to these limitations, recent advances in surface engineering and nanotechnology have facilitated the development of bioactive materials to enhance healing outcomes. Building upon these developments, the present review compiles and critically examines current evidence on interactions between a biomaterial surface and surrounding tissue, with a particular emphasis on host response, regulatory frameworks, and their translational implications. Furthermore, it discusses preclinical validation strategies in accordance with ISO guidelines and proposes a pragmatic roadmap for clinical translation, with special attention to the importance of regulatory alignment.