Pathology-Adaptive Biomaterial Interfaces Selectively Modulate AGE-Modified Protein Corona To Restore Osteogenesis

Abstract

Advanced glycation end products (AGEs) accumulate in the serum of people with diabetes, some chronic conditions, and aging and impair osseointegration by reshaping the protein corona and activating oxidative stress pathways at the biomaterial interface. Here, we introduce a pathology-adaptive surface engineering strategy in which plasma polymer coatings with defined functional chemistries are designed to selectively modulate AGE adsorption while preserving physiological protein interactions. Titanium was functionalized with carboxyl (–COOH), amine (–NH2), or hydrocarbon (–CH3) plasma polymers to precisely modulate interfacial chemistry. Carboxyl- and amine-functionalized surfaces significantly reduced AGE adsorption compared to hydrophobic controls while maintaining total serum protein adsorption, indicating selective exclusion of glycated species. This modulation of the AGE-modified protein corona attenuated the generation of reactive oxygen species, suppressed apoptosis, and restored osteogenic gene expression in bone marrow mesenchymal stem cells following exposure to AGEs. Functionalized coatings supported sustained proliferation and enhanced mineralization, demonstrating the recovery of regenerative capacity in a metabolically compromised environment. The AGE–RAGE axis was identified as a key driver of macrophage inflammatory activation. These findings establish pathology-adaptive surface chemistry as a materials strategy to selectively regulate disease-associated protein adsorption and restore regenerative performance under glycation stress.