Rational Surface Engineering Reduces Advanced Glycation End-Product Adsorption and Improves Implant Integration

Advanced glycation end-products (AGEs) accumulate in metabolic diseases such as diabetes and are closely associated with poor outcomes following implantation. However, how these molecules influence events at the biomaterial interface has remained largely unknown. Here, we identify AGEs as critical biointerfacial modifiers that adsorb onto implant surfaces, reprogram immune responses, promote fibrotic encapsulation, impair angiogenesis, and compromise osseointegration. This suggests a potential mechanism by which metabolic disease disrupts biomaterial-tissue integration. By engineering titanium surfaces enriched with amine or carboxyl functionalities, we create AGE-resistant biointerfaces that effectively suppress pro-inflammatory M1 macrophage polarization, promote an anti-inflammatory M2 macrophage phenotype, reduce fibrotic encapsulation, enhance angiogenesis, and improve osseointegration across ex vivo, in vitro, and in vivo diabetic models. These findings establish disease-informed surface chemistry as a design paradigm for next-generation implants intended for metabolically compromised and other high-risk patient populations.