Multifunctional periosteum-mimetic biomaterials for guided bone-healing
Gulistan Kocer (TNW-MNF), Aurora M. Serrano (TNW-MNF), Francisco Conceição (TNW-AST), Dodo Wasserberg (TNW-MNF), Nathalie Bravenboer (Amsterdam UMC), Jenneke Klein-Nulend (ACTA, VU Amsterdam), Peter Nolte (ACTA, VU Amsterdam), Liliana Moreira Teixeira (TNW-AST), Pascal Jonkheijm (TNW-MNF)
Abstract
Non-union bone fractures, defects that show no healing potential, present a severe clinical problem and significantly decreases the quality of life. While surgical interventions are a common approach, a long-term sustainable strategy is required to tackle this problem. This can be achieved by taking inspiration from a native tissue with very high bone-healing capacity: the periosteum membrane that line the bone surfaces. Since the natural resources of periosteum are limited, advanced biomaterials-based strategies are needed to achieve mechanically robust, periosteum-mimetic bone-lining grafts for defect closure. To this end, we proposed to develop novel periosteum-mimetic cell-instructive biomaterials from fully-synthetic, clinically applied, mechanically robust, but biologically inert polyethylene terephthalate (PET) woven membrane meshes. These meshes can allow selective localization of bone cells, similar to native periosteum, and can be biofunctionalized in a chemically controlled way. We optimized and verified the biofunctionalization of membrane meshes with cell-adhesive peptides and were able to incorporate the membranes into a 3D near-physiological model (bone-on-chip microfluidic devices), which enables to study non-union defects with human-derived tissue fragments, in an unprecedented way. The focus of this project is to investigate the behavior of human derived bone (progenitor) cells on PET membrane biomaterials that are functionalized with specific peptide ligands for cell adhesion and a peptide that can bind and physiologically present bone morphogenetic growth factor-2 (BMP-2, induces bone differentiation). The membrane biomaterial resulting in the highest degree of bone differentiation and cell proliferation will be implemented bone-on-chip studies, a critical step towards validation of clinically-relevant bone-inducing periosteum-like biomaterials.