Proteomics of regenerated tissue in response to a titanium implant with a bioactive surface in a rat tibial defect model

Raluca M Boteanu,Felicia Antohe,Emanuel Dragan,Valentina Grumezescu,Luminita Ivan,Sorin M Croitoru,Gabriel Socol,Florentina Safciuc,Viorel I Suica,Constantin Vlagioiu,Marioara Chiritoiu,Livia E Sima,Elena Uyy

doi:10.1038/s41598-020-75527-2

Abstract

Due to their excellent mechanical and biocompatibility properties, titanium-based implants are successfully used as biomedical devices. However, when new bone formation fails for different reasons, impaired fracture healing becomes a clinical problem and affects the patient's quality of life. We aimed to design a new bioactive surface of titanium implants with a synergetic PEG biopolymer-based composition for gradual delivery of growth factors (FGF2, VEGF, and BMP4) during bone healing. The optimal architecture of non-cytotoxic polymeric coatings deposited by dip coating under controlled parameters was assessed both in cultured cells and in a rat tibial defect model (100% viability). Notably, the titanium adsorbed polymer matrix induced an improved healing process when compared with the individual action of each biomolecules. High-performance mass spectrometry analysis demonstrated that recovery after a traumatic event is governed by specific differentially regulated proteins, acting in a coordinated response to the external stimulus. Predicted protein interactions shown by STRING analysis were well organized in hub-based networks related with response to chemical, wound healing and response to stress pathways. The proposed functional polymer coatings of the titanium implants demonstrated the significant improvement of bone healing process after injury.

Highlights

Due to their excellent mechanical and biocompatibility properties, titanium-based implants are successfully used as biomedical devices
In this study, using biochemical and proteomics analyses, we developed and evaluated an implant of titanium coated with a Poly, (PEG) matrix containing fibroblast growth factor-2 (FGF2), vascular endothelial growth factor (VEGF) and Poly (3-hydroxybutyrate-co3-hydroxyvalerate), (PHBV) microspheres embedded with BMP4 in a rat diaphyseal in vivo tibial defect model
We showed that a coated titanium implant with FGF2, VEGF and BMP4 incorporated into PEG speeded up the healing process in a rat tibial defect model

Summary

Introduction

Due to their excellent mechanical and biocompatibility properties, titanium-based implants are successfully used as biomedical devices. We aimed to design a new bioactive surface of titanium implants with a synergetic PEG biopolymerbased composition for gradual delivery of growth factors (FGF2, VEGF, and BMP4) during bone healing. Besides controlling endothelial cell activities, VEGF is a direct modulator of bone development[17] by stimulating differentiation of periosteal progenitor cells to osteoblasts[18] and regulating osteoclastic differentiation and migration[19] Despite of all this knowledge related to bone regeneration assisted by titanium implant, detailed mechanisms driving proper bone healing are insufficiently understood, requesting further in-depth studies. In this study, using biochemical and proteomics analyses, we developed and evaluated an implant of titanium coated with a Poly (ethylene glycol), (PEG) matrix containing FGF2, VEGF and Poly (3-hydroxybutyrate-co3-hydroxyvalerate), (PHBV) microspheres embedded with BMP4 in a rat diaphyseal in vivo tibial defect model. The new research uncovered by mass spectrometry provides an extended list of proteins that may open up better bone wound treatment strategies in the future

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Conclusion