Highly porous polycaprolactone microspheres for skeletal repair promote a mature bone cell phenotype in vitro

Paterson, Thomas E.; Owen, Robert; Sherborne, Colin; Bahmaee, Hossein; Harding, Amy L.; Green, Nicola H.; Reilly, Gwendolen C.; Claeyssens, Frederik

Abstract

Improving our ability to treat skeletal defects is a critical medical challenge that necessitates the development of new biomaterials. One promising approach involves the use of degradable polymer microparticles with an interconnected internal porosity. Here, we employed a double emulsion to generate such round microparticles (also known as microspheres) from a polycaprolactone-based polymerised high internal phase emulsion (polyHIPE). These microspheres effectively supported the growth of mesenchymal progenitors over a 30-day period, and when maintained in osteogenic media, cells deposited a bone-like extracellular matrix, as determined by histological staining for calcium and collagen. Interestingly, cells with an osteocyte-like morphology were observed within the core of the microspheres indicating the role of a physical environment comparable to native bone for this phenotype to occur. At later timepoints, these cultures had significantly increased mRNA expression of the osteocyte-specific markers dentin matrix phosphoprotein-1 (Dmp-1) and sclerostin, with sclerostin also observed at the protein level. Cells pre-cultured on porous microspheres exhibited enhanced survival rates compared to those pre-cultured on non-porous counterparts when injected. Cells precultured on both porous and non-porous microspheres promoted angiogenesis in a chorioallantoic membrane (CAM) assay. In summary, the polycaprolactone polyHIPE microspheres developed in this study exhibit significant promise as an alternative to traditional synthetic bone graft substitutes, offering a conducive environment for cell growth and differentiation, with the potential for better clinical outcomes in bone repair and regeneration.

Citation

Paterson, T. E., Owen, R., Sherborne, C., Bahmaee, H., Harding, A. L., Green, N. H., Reilly, G. C., & Claeyssens, F. (2024). Highly porous polycaprolactone microspheres for skeletal repair promote a mature bone cell phenotype in vitro. Journal of Materials Chemistry B, 12(45), 11746-11758. https://doi.org/10.1039/d4tb01532k

• Journal Article Type: Article
• Acceptance Date: Oct 7, 2024
• Online Publication Date: Oct 17, 2024
• Publication Date: Dec 7, 2024
• Deposit Date: Oct 17, 2024
• Publicly Available Date: Oct 17, 2024
• Journal: Journal of Materials Chemistry B
• Print ISSN: 2050-750X
• Electronic ISSN: 2050-7518
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 45
• Pages: 11746-11758
• DOI: https://doi.org/10.1039/d4tb01532k
• Public URL: https://nottingham-repository.worktribe.com/output/40586059
• Publisher URL: https://pubs.rsc.org/en/content/articlelanding/2024/tb/d4tb01532k