Osteogenic differentiation of hBMSCs on porous photo-crosslinked poly(trimethylene carbonate) and nano-hydroxyapatite composites

Mike A Geven,Anna Lapomarda,Olivier Guillaume,Christoph M Sprecher,David Eglin,Giovanni Vozzi,Dirk W Grijpma

doi:10.1016/j.eurpolymj.2021.110335

Mike A Geven, Anna Lapomarda + Show 5 more

Open Access

https://doi.org/10.1016/j.eurpolymj.2021.110335

Copy DOI

Abstract

Large bone defects are challenging to repair and novel implantable materials are needed to aid in their reconstruction. Research in the past years has proven the beneficial effect of porosity in an implant on osteogenesis in vivo. Building on this research we report here on porous composites based on photo-crosslinked poly(trimethylene carbonate) and nano-hydroxyapatite. These composites were prepared by a temperature induced phase separation of poly(trimethylene carbonate) macromers from solution in ethylene carbonate. By controlling the ethylene carbonate content in viscous dispersions of nano-hydroxyapatite in poly(trimethylene carbonate) macromer solutions, composites with 40 wt% nano-hydroxyapatite and 27 to 71% porosity were prepared. The surface structure of these porous composites was affected by their porosity and their topography became dominated by deep micro-pore channels with the majority of pore widths below 20 µm and rougher surfaces on the nano-scale. The stiffness and toughness of the composites decreased with increasing porosity from 67 to 3.5 MPa and 263 to 2.2 N/mm2, respectively. In cell culture experiments, human bone marrow mesenchymal stem cells proliferated well on the composites irrespective of their porosity. Furthermore, differentiation of the cells was demonstrated by determination of ALP activity and calcium production. The extent of differentiation was affected by the porosity of the films, offering a reduced mechanical incentive for osteogenic differentiation at higher porosities with topographies likely offering a reduced possibility for cells to aggregate and to elongate into morphologies favourable for osteogenic differentiation. This ultimately resulted in a 3-fold reduction of calcium production of the differentiated cells on composites with 71% porosity compared to those on composites with 27% porosity.

Highlights

In recent years in vitro and in vivo research in bone tissue engineering has increased the understanding of factors controlling the clinical outcome of reconstruction
General discussion In this work, we have demonstrated that using temperature-induced phase separation (TIPS) with varying amounts of a crystallisable solvent allows for the modification of microscale porosity of photo-crosslinked poly(trimethylene carbonate) (PTMC) and nHA composites
In this work we have shown that resins based on PTMC-MA, nHA and EC are suitable for the preparation of porous composites with varying porosity

Summary

Introduction

In recent years in vitro and in vivo research in bone tissue engineering has increased the understanding of factors controlling the clinical outcome of reconstruction It is known which size features are desired for the porosity of an implant[1,2,3,4,5,6], which surface micro- and nano structure is efficacious[7,8,9,10,11,12,13,14], and how the mechanical properties [15,16,17] affect the osteogenicity and –integration of an implant. More recent progress in the formation of porous implants has demonstrated that additive manufacturing tech niques allow for preparation of well-defined and interconnected poros ities[32,35] or that the combination of porogen leaching and additive manufacturing allows for formation of structures with porosity on different size scales[36,37]

Methods

Results

Conclusion