Recovering Osteoblast Functionality on TiO2 Nanotube Surfaces Under Diabetic Conditions

Abstract

Introduction: Titanium (Ti) and its alloys (eg, Ti6 Al4V) are exceptional treatments for replacing or repairing bones and damaged surrounding tissues. Although Ti-based implants exhibit excellent osteoconductive performance under healthy conditions, the effec-tiveness and successful clinical achievements are negatively altered in diabetic patients. Concernedly, diabetes mellitus (DM) contributes to osteoblastic dysfunctionality, altering efficient osseointegration. This work investigates the beneficial osteogenic activity conducted by nanostructured TiO2 under detrimental microenvironment conditions, simulated by human diabetic serum. Methods: We evaluated the bone-forming functional properties of osteoblasts on synthesized TiO2 nanotubes (NTs) by anodization and Ti6Al4V non-modified alloy surfaces under detrimental diabetic conditions. To simulate the detrimental environment, MC3T3E-1 preosteoblasts were cultured under human diabetic serum (DS) of two diagnosed and metabolically controlled patients. Normal human serum (HS) was used to mimic health conditions and fetal bovine serum (FBS) as the control culture environment. We characterized the matrix mineralization under the detrimental conditions on the control alloy and the NTs. Moreover, we applied immunofluores-cence of osteoblasts differentiation markers on the NTs to understand the bone-expression stimulated by the biochemical medium conditions. Results: The diabetic conditions depressed the initial osteoblast growth ability, as evidenced by altered early cell adhesion and reduced proliferation. Nonetheless, after three days, the diabetic damage was suppressed by the NTs, enhancing the osteoblast activity. Therefore, the osteogenic markers of bone formation and the differentiation of osteoblasts were reactivated by the nanoconfigured surfaces. Far more importantly, collagen secretion and bone-matrix mineralization were stimulated and conducted to levels similar to those of the control of FBS conditions, in comparison to the control alloy, which was not able to reach similar levels of bone functionality than the NTs. Conclusion: Our study brings knowledge for the potential application of nanostructured biomaterials to work as an integrative platform under the detrimental metabolic status present in diabetic conditions.