SOX9 gene plus heparinized TGF-β 3 coated dexamethasone loaded PLGA microspheres for inducement of chondrogenesis of hMSCs

Biomaterials. 2012 Oct;33(29):7151-63. doi: 10.1016/j.biomaterials.2012.06.023. Epub 2012 Jul 11.

Abstract

Microparticulated types of scaffolds have been widely applied in stem cell therapy and the tissue engineering field for the regeneration of wound tissues. During application of simple genes or growth factors and cell delivery vehicles, we designed a method that employs dexamethsone loaded PLGA microspheres consisting of polyplexed SOX9 genes plus heparinized TGF-β 3 on the surface of polymeric microspheres prepared using a layer-by-layer (LbL) method. The fabrication of the polyplexed SOX9 genes plus heparinized TGF-β 3 and their subsequent coating onto dexamethsone loaded PLGA microspheres represents a method for functionalization of the polymeric matrix. The use of SOX9 gene plus heparinized TGF-β 3 coated dexamethsone loaded PLGA microspheres was evaluated to determine their potential as both gene carriers and cell delivery vehicle. By adhesion of hMSCs onto SOX9 gene plus heparinized TGF-β 3 coated dexamethsone loaded PLGA microspheres, the chondrogenesis-related specific genes of collagen type II were increased 30 times comparing to control. Also, the specific extracellular matrix of glycosaminoglycan (GAG) production of hMSCs adhered onto SOX9 gene plus heparinized TGF-β 3 coated dexamethasone loaded PLGA microspheres increased more 2.5 times than control group. Not only in vitro culture but in vivo results, the specific genes of COMP, aggrecan, collagen type II, and SOX9 showed much more gene expressions such as 20, 15, 10, 8 times.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Survival
  • Chondrocytes / cytology*
  • Dexamethasone / chemistry*
  • Female
  • Gene Expression Regulation
  • Glycosaminoglycans / chemistry
  • Heparin / chemistry
  • Humans
  • Lactic Acid / chemistry*
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microspheres*
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / chemistry
  • SOX9 Transcription Factor / genetics*
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology
  • Time Factors
  • Transforming Growth Factor beta3 / metabolism*

Substances

  • Glycosaminoglycans
  • Polymers
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Tetrazolium Salts
  • Thiazoles
  • Transforming Growth Factor beta3
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Dexamethasone
  • Heparin
  • thiazolyl blue