Journal Article

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

Shineh, Ghazal, Shao, Jiayan, Xia, Yiyun, Janghour, Leila Mamizadeh, Gulati, Karan, Akhavan, Behnam, Yeo, Giselle C.

2025

Overview

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. [Display omitted] •A critical and mechanistically focused review of biomolecule-functionalized dental implants, with specific emphasis on strategies to enhance soft tissue integration and epithelial sealing.•Systematically evaluates both physical and covalent biomolecule immobilization techniques, comparing their stability, scalability, and biological effectiveness for clinical translation.•Bridges biomaterials science and biology by dissecting the molecular mechanisms by which immobilized biomolecules modulate cell adhesion, immune responses, and inflammation resolution at the implant–tissue interface.•Identifies current limitations and overlooked challenges in long-term coating performance, biomolecule stability, and reproducibility of functionalization techniques under physiological conditions.•Outlines a roadmap for the development of next-generation bioactive dental implants with enhanced soft tissue integration, highlighting opportunities for multi-agent loading, stimuli-responsive surfaces, and scalable plasma-enabled fabrication strategies.

• Publisher: Elsevier B.V,KeAi Publishing Communications Ltd,KeAi Communications Co., Ltd
• Subject: Adsorption / Bioengineering / Biofunctionalization / Biomolecule-implant interactions / Biomolecules / Collagen / Dental implants / Dental prosthetics / Design / Extracellular matrix / Fibroblasts / Growth factors / Immune response / Inflammation / Kinases / Lymphocytes / Microorganisms / Osseointegration / Pathogens / Peptides / Porosity / Proteins / Soft tissue integration / Soft tissues / Success / Surface bioengineering / Surface chemistry