Designing Topographically Textured Microparticles For Induction and Modulation of Osteogenesis in Mesenchymal Stem Cell Engineering

Amer, M. H.; Alvarez-Paino, M.; McLaren, J.; Pappalardo, F.; Trujillo, S.; Wong, J. Q.; Shrestha, S.; Abdelrazig, S.; Lee, J. B.; Stevens, L.; Kim, D. H.; Gonzalez-Garcia, C.; Needham, D.; Salmeron-Sanchez, M.; Shakesheff, K. M.; Alexander, M. R.; Alexander, C.; Rose, F. R.

doi:10.1101/2020.03.22.002279

bioRxiv · 10.1101/2020.03.22.002279

Designing Topographically Textured Microparticles For Induction and Modulation of Osteogenesis in Mesenchymal Stem Cell Engineering

Amer, M. H.·Alvarez-Paino, M.·McLaren, J.·Pappalardo, F.·Trujillo, S.·Wong, J. Q.·Shrestha, S.·Abdelrazig, S.·Lee, J. B.·Stevens, L.·Kim, D. H.·Gonzalez-Garcia, C.·Needham, D.·Salmeron-Sanchez, M.·Shakesheff, K. M.·Alexander, M. R.·Alexander, C.·Rose, F. R.

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Abstract

Mesenchymal stem cells have been the focus of intense research in bone development and regeneration. We demonstrate the potential of microparticles as modulating moieties of osteogenic response by utilizing their architectural features. Topographically textured microparticles of varying microscale features were produced by exploiting phase-separation of a readily-soluble sacrificial component from polylactic acid. The influence of varying topographical features on primary human mesenchymal stem cell attachment, proliferation and markers of osteogenesis was investigated. In the absence of osteoinductive supplements, cells cultured on textured microparticles exhibited notably increased expression of osteogenic markers relative to conventional smooth microparticles. They also exhibited varying morphological, attachment and proliferation responses. Significantly altered gene expression and metabolic profiles were observed, with varying histological characteristics in vivo. This study highlights how tailoring topographical design offers cell-instructive 3D microenvironments which allow manipulation of stem cell fate by eliciting the desired downstream response without use of exogenous osteoinductive factors.

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Amer, M. H., Alvarez-Paino, M., McLaren, J., Pappalardo, F., Trujillo, S., Wong, J. Q., Shrestha, S., Abdelrazig, S., Lee, J. B., Stevens, L., Kim, D. H., Gonzalez-Garcia, C., Needham, D., Salmeron-Sanchez, M., Shakesheff, K. M., Alexander, M. R., Alexander, C., Rose, F. R.. 2020-03-24. Designing Topographically Textured Microparticles For Induction and Modulation of Osteogenesis in Mesenchymal Stem Cell Engineering. https://doi.org/10.1101/2020.03.22.002279

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