Degradable Segmented Polyurethane Elastomers for Bone Tissue Engineering: Effect of Polycaprolactone Content

Abstract

Segmented polyurethanes (PURs), consisting of degradable poly(a-hydroxy ester) soft segments and aminoacid-derived chain extenders, are biocompatible elastomers with tunable mechanical and degradative properties suitable for a variety of tissue-engineering applications. In this study, a family of linear PURs synthesized from poly(ϵ-caprolactone) (PCL) diol, 1,4-diisocyanobutane and tyramine with theoretical PCL contents of 65–80 wt% were processed into porous foam scaffolds and evaluated for their ability to support osteoblastic differentiation in vitro. Differential scanning calorimetry and mechanical testing of the foams indicated increasing polymer crystallinity and compressive modulus with increasing PCL content. Next, bone marrow stromal cells (BMSCs) were seeded into PUR scaffolds, as well as poly(lactic-co-glycolic acid) (PLGA) scaffolds, and maintained under osteogenic conditions for 14 and 21 days. Analysis of cell number indicated a systematic decrease in cell density with increasing PUR stiffness at both 14 and 21 days in culture. However, at these same time points the relative mRNA expression for the bone-specific proteins osteocalcin and the growth factors bone morphogenetic protein-2 and vascular endothelial growth factor gene expression were similar among the PURs. Finally, prostaglandin E2 production, alkaline phosphatase activity and osteopontin mRNA expression were highly elevated on the most-crystalline PUR scaffold as compared to the PLGA and PUR scaffolds. These results suggest that both the modulus and crystallinity of the PUR scaffolds influence cell proliferation and the expression of osteoblastic proteins.

Keywords:

• Polyurethane
• modulus
• polycaprolactone
• crystallinity
• mesenchymal stem cell
• osteoblastic differentiation

Acknowledgements

The authors would like to thank Stephen McCartney and John McIntosh for their assistance and expertise with the SEM. In addition, the authors would like to thank Sha Yang from the Department of Chemistry and Dr. Garth Wilkes from the Department of Chemical Engineering at Virginia Tech for their assistance with the DSC measurements and analysis. This project was funded by the National Institutes of Health (R21-AR015945).

Notes

aTheoretical PCL content data were taken from Kavlock et al. [21].

bPLGA data were taken from Goldstein et al. [27].