4.8 Article

In situ pocket-type microcarrier (PMc) as a therapeutic composite: Regeneration of cartilage with stem cells, genes, and drugs

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 332, Issue -, Pages 337-345

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2020.08.057

Keywords

Pocket-type microcarrier; Gold nanoparticle; SOX9; Stem cells; Water-in-oil-in-water (W; O; W) emulsion

Funding

  1. Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2019R1A6A1A03032888, NRF-2020R1A2C3009783, NRF-2017M3A9C6061360]

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By controlling the size of the pockets in pocket-type micro-carriers, cell adhesion can be facilitated and adapted to cells of different sizes. A 1:1 ratio of F-127 to DOPA-bPEI, with F-127 concentration at 10 mg/ml, is suitable for adhering 20-30μm stem cells. The use of gold nanoparticles complex and dexamethasone in PMcs promotes cartilage differentiation.
We prepared pocket-type micro-carriers (PMc) with pores larger than 30 ?m for use in cell delivery by adding 40 mg pluronic F-127 copolymers (F-127) to biodegradable PLGA dissolved in dichloromethane solution. The controlling the size of the pockets in this way facilitates the adhesion of cells by regulating the size of the pockets according to the cells having various sizes. The size of PMc pores could be controlled within a range of 2 to 30 ?m by varying the F-127 content. The ratio of F-127 to DOPA-bPEI was most appropriate at 1: 1, and the pocket size at 10 mg/ml of F-127 was appropriate for adhering 20?30 ?m stem cells. F-127 containing SOX9 pDNA, in combination with DOPA-polyethylene?coated gold nanoparticles and dexamethasone loaded in PMcs, promoted cartilage differentiation. Gold nanoparticles complex and dexamethasone (DEX) loaded in PMcs were identified by micro-CT imaging and fluorescence imaging, respectively. By captured in pore generated on/in microspheres, the stem cells were safe and stable for use in delivery, both in vitro and in an animal model. Thus, microsphere pores can safely capture stem cells, and at the same time provide a microenvironment in which the captured stem cells can differentiate into chondrocytes.

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