Screening the Degradation of Polymer Microparticles on a Chip
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ABSTRACT:
SUBMITTER: Davachi S
PROVIDER: S-EPMC9835179 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
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Project description:IntroductionPolymer materials used in medical devices and treatments invariably encounter cellular networks. For the device to succeed in tissue engineering applications, the polymer must promote cellular interactions through adhesion and proliferation. To predict how a polymer will behave in vitro, these material-cell interactions need to be well understood.MethodsTo study polymer structure-property relationships, microparticles of four chemically distinct tyrosol-derived poly(ester-arylate) polymers and a commercially available poly(lactic acid-co-glycolic acid) (PLGA) copolymer were prepared and their interactions with cells investigated. Cell loading concentration was optimized and cell adhesion and proliferation evaluated. Particles were also tested for their ability to adsorb bone morphogenetic protein-2 (BMP-2) and differentiate a myoblast cell line towards an osteoblast lineage through BMP-2 loading and release.ResultsWhile cell adhesion was observed on all particles after 24 h of incubation, the highest degree of cell adhesion occurred on polymers with smaller crystallites. At longer incubation times, cells proliferated on all particle formulations, regardless of the differences in polymer properties. High BMP-2 loading was achieved for all particle formulations and all formulations showed a burst release. Even with the burst release, cells cultured on all formulations showed an upregulation in alkaline phosphatase (ALP) activity, a measure of osteoblast differentiation.ConclusionsAs with cell adhesion, the polymer with the smaller crystallite showed the most ALP activity. We suggest that smaller crystallites serve as a proxy for topographical roughness to elicit the observed responses from cells. Furthermore, we have drawn a correlation between the polymer crystallite with the hydration potential using surface analysis techniques.Graphical abstractSupplementary informationThe online version contains supplementary material available at 10.1007/s12195-022-00729-9.
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Project description:As the prevalence of age-related fibrotic diseases continues to increase, novel antifibrotic therapies are emerging to address clinical needs. However, many novel therapeutics for managing chronic fibrosis are small-molecule drugs that require frequent dosing to attain effective concentrations. Although bolus parenteral administrations have become standard clinical practice, an extended delivery platform would achieve steady-state concentrations over a longer time period with fewer administrations. This study lays the foundation for the development of a sustained release platform for the delivery of (+)SW033291, a potent, small-molecule inhibitor of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) enzyme, which has previously demonstrated efficacy in a murine model of pulmonary fibrosis. Herein, we leverage fine-tuned cyclodextrin microparticles-specifically, β-CD microparticles (β-CD MPs)-to extend the delivery of the 15-PGDH inhibitor, (+)SW033291, to over one week.
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