Xeno-Hybrid Bone Graft Releasing Biomimetic Proteins Promotes Osteogenic Differentiation of hMSCs.

Hao Zhu,Eva Filová,Giuseppe Perale,Veronika Hefka Blahnová,Fabio Boniolo,Ståle Petter Lyngstadaas,Felice Betge,Håvard Jostein Haugen,Jun Xiao

doi:10.3389/fcell.2020.619111

Abstract

Bone defect is a noteworthy health problem and is the second most transplanted tissue after blood. Numerous bone grafts are designed and applied in clinics. Limitations, however, from different aspects still exist, including limited supply, mechanical strength, and bioactivity. In this study, two biomimetic peptides (P2 and P6) are incorporated into a composite bioactive xeno hybrid bone graft named SmartBonePep®, with the aim to increase the bioactivity of the bone graft. The results, which include cytotoxicity, proliferation rate, confocal microscopy, gene expression, and protein qualification, successfully prove that the SmartBonePep® has multi-modal biological effects on human mesenchymal stem cells from bone marrow. The effective physical entrapment of P6 into a composite xeno-hybrid bone graft, withstanding manufacturing processes including exposure to strong organic solvents and ethylene oxide sterilization, increases the osteogenic potential of the stem cells as well as cell attachment and proliferation. P2 and P6 both show a strong biological potential and may be future candidates for enhancing the clinical performance of bone grafts.

Highlights

Trauma, surgical resection, infections, degeneration, and a myriad of external and internal factors can alone or in combination lead to critical-size bone defects
This study aims to investigate the potential of biomimetic peptides, belonging to a group of proteins called “intrinsically disordered proteins” (IDPs), which are highly diverse in their effects and yet adaptable and specific, in their action
Variances of biomolecule stimuli, such as recombinant growth factors have been successfully embedded in other bone graft materials for promoting osteogenic differentiation or enhancing osseointegration, these biomolecules are associated with both high costs and lack of sufficient evidences of safety and efficacy (Fu et al, 2013; James et al, 2016), which impedes long-term clinical applications

Summary

Introduction

Surgical resection, infections, degeneration, and a myriad of external and internal factors can alone or in combination lead to critical-size bone defects. Such defects are severe public health issues and take impact on public healthcare and on the quality of life of the patients involved (Wang and Yeung, 2017). Skeletal tissues have certain capacity of self-healing, it remains limited in critical-size defects where callus formation is unable to bridge and stabilize the compromised bone. This situation often results in non-union fractures, the formation of pseudarthroses or skeletal deformation (Winkler et al, 2018). Bone grafts and bone graft substitutes play an important role in terms of mechanically

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