Incorporation of a silicon-based polymer to PEG-DA templated hydrogel scaffolds for bioactivity and osteoinductivity

Abstract

A scaffold that is inherently bioactive, osteoinductive and osteoconductive may guide mesenchymal stem cells (MSCs) to regenerate bone tissue in the absence of exogenous growth factors. Previously, we established that hydrogel scaffolds formed by crosslinking methacrylated star poly(dimethylsiloxane) (PDMS_star-MA) with diacrylated poly(ethylene glycol) (PEG-DA) promote bone bonding by induction of hydroxyapatite formation ("bioactive") and promote MSC lineage progression toward osteoblast-like fate ("osteoinductive"). Herein, we have combined solvent induced phase separation (SIPS) with a fused salt template to create PDMS_star-PEG hydrogel scaffolds with controlled PDMS_star-MA distribution as well as interconnected macropores of a tunable size to allow for subsequent cell seeding and neotissue infiltration ("osteoconductive"). Scaffolds were prepared with PDMS_star-MA of two number average molecular weights (M_ns) (2k and 7k) with varying PDMS_star-MA:PEG-DA ratios and template salt sizes. The distribution of PDMS_star-MA within the hydrogels was examined as well as pore size, percent interconnectivity, dynamic and static moduli, hydration, degradation and in vitro bioactivity (i.e. mineralization when exposed to simulated body fluid, SBF). Finally, cell culture with seeded human bone marrow-derived MSCs (hBMSCs) was used to confirm non-cytotoxicity and characterize osteoinductivity. Tunable, interconnected macropores were achieved by utilization of a fused salt template of a specified salt size during fabrication. Distribution of PDMS_star-MA within the PEG-DA matrix improved for the lower M_n and contributed to differences in specific material properties (e.g. local modulus) and cellular response. However, all templated SIPS PDMS_star-PEG hydrogels were confirmed to be bioactive, non-cytotoxic and displayed PDMS_star-MA dose-dependent osteogenesis. STATEMENT OF SIGNIFICANCE: A tissue engineering scaffold that can inherently guide mesenchymal stem cells (MSCs) to regenerate bone tissue without growth factors would be a more cost-effective and safe strategy for bone repair. Typically, glass/ceramic fillers are utilized to achieve this through their ability to induce hydroxyapatite formation ("bioactive") and promote MSC differentiation to an osteoblast-like fate ("osteoinductive"). Herein, we have fabricated an interconnected, macroporous PEG-DA hydrogel scaffold that utilizes PDMS_star-MA as a bioactive and osteoinductive scaffold component. We were able to show that these PDMS_star-PEG hydrogels maintain several key material characteristics for bone repair. Further, bioactivity and osteoinductivity were simultaneously achieved in human bone marrow-derived MSC culture, representing a notable achievement for an exclusively material-based strategy.

Keywords: Poly(dimethylsiloxane); Poly(ethylene glycol); Salt templating; Scaffold; Tissue engineering.