Biomolecule-functionalized dental implant surfaces: Towards augmenting soft tissue integration.

Dental implants are the primary solution for tooth replacement, providing both aesthetic and functional restoration. Their long-term success depends not only on osseointegration but also on robust peri-implant soft tissue integration (PSTI), particularly in the transmucosal region, where a stable epithelial seal is critical to preventing microbial infiltration and peri-implant inflammation. While surface topography modifications such as roughness, morphology, and porosity influence gingival cell behavior, passive surface modifications alone are often insufficient to promote rapid PSTI. This raises a fundamental question in dental implant design: How can implant surfaces be bioengineered to actively promote PSTI rather than passively relying on cellular responses? This review examines how biofunctionalization has emerged as a transformative strategy in implant surface engineering and critically analyses the latest biofunctionalization strategies for dental implants, with a particular focus on the underlying mechanisms that regulate biomolecule-implant interactions. It evaluates biomolecule incorporation via physical and covalent attachment, highlighting their distinct advantages in stability, efficiency, and scalability. We discuss approaches for functionalizing dental implant surfaces with bioactive molecules, such as proteins and peptides, and cells to replicate natural biological interactions, regulate immune responses, and enhance antimicrobial defense mechanisms. By addressing how bioengineered surfaces can be designed to actively engage with biological systems, this review provides a framework for developing next-generation implant technologies that achieve more effective and predictable PSTI, with strong potential for clinical translation.