International Journal of Nanomedicine (Nov 2022)

Recovering Osteoblast Functionality on TiO2 Nanotube Surfaces Under Diabetic Conditions

  • Valdez-Salas B,
  • Castillo-Uribe S,
  • Beltran-Partida E,
  • Curiel-Alvarez M,
  • Perez-Landeros O,
  • Guerra-Balcazar M,
  • Cheng N,
  • Gonzalez-Mendoza D,
  • Flores-Peñaloza O

Journal volume & issue
Vol. Volume 17
pp. 5469 – 5488

Abstract

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Benjamin Valdez-Salas,1 Sandra Castillo-Uribe,1 Ernesto Beltran-Partida,1 Mario Curiel-Alvarez,1 Oscar Perez-Landeros,1 Minerva Guerra-Balcazar,2 Nelson Cheng,3 Daniel Gonzalez-Mendoza,4 Olivia Flores-Peñaloza1 1Laboratorio de Biología Molecular y Cáncer, Instituto de Ingeniería, Universidad Autónoma de Baja California, Mexicali, Baja California, México; 2Facultad de Ingeniería, División de Investigación y Posgrado, Universidad Autónoma de Querétaro, Querétaro, México; 3Magna International Pte Ltd, Singapore; 4Instituto de Ciencias Agrícolas, Universidad Autónoma de Baja California, Mexicali, Baja California, MéxicoCorrespondence: Ernesto Beltran-Partida, Laboratorio de Biología Molecular y Cáncer, Instituto de Ingeniería, Universidad Autónoma de Baja California, Blvd. Benito Juárez y Calle de la Normal, Mexicali, Baja California, C.P. 21280, México, Email [email protected]: Titanium (Ti) and its alloys (eg, Ti6Al4V) are exceptional treatments for replacing or repairing bones and damaged surrounding tissues. Although Ti-based implants exhibit excellent osteoconductive performance under healthy conditions, the effectiveness 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 immunofluorescence 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.Graphical Abstract: Keywords: osteoblast regeneration, bone surface interactions, cellular nanomodulation

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