Microsphere-based drug releasing scaffolds for inducing osteogenesis of human mesenchymal stem cells in vitro.
In this study, in vitro osteogenesis was successfully achieved in human mesenchymal stem cells (hMSCs) by controlled release of the osteogenesis-inducing drugs dexamethasone, ascorbic acid (AA) and beta-glycerophosphate (GP) from poly(lactic-co-glycolic acid) (PLGA) sintered microsphere scaffolds (SMS). We investigated the osteogenesis of human MSCs (hMSCs) on dexamethasone laden PLGA-SMS (PLGA-Dex-SMS), and dexamethasone, AA and GP laden PLGA-SMS (PLGA-Com-SMS). hMSCs cultured on the microsphere systems, which act as drug release vehicles and also promote cell growth/tissue formation-displayed a strong osteogenic commitment locally. The osteogenic commitment of hMSCs on the scaffolds were verified by alkaline phosphatase (ALP) activity assay, calcium secretion assay, real-time PCR and immunohistochemistry analysis. The results indicated hMSCs cultured on PLGA-Com-SMS exhibited superior osteogenic differentiation owing to significantly high phenotypic expression of typical osteogenic genes-osteocalcin (OC), type I collagen, alkaline phosphatase (ALP), and Runx-2/Cbfa-1, and protein secretion of bone-relevant markers such as osteoclast and type I collagen when compared with PLGA-Dex-SMS. In conclusion, by promoting osteogenic development of hMSCs in vitro, this newly designed controlled release system opens a new door to bone reparation and regeneration.
Shi
Xuetao
X
School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, China.
Wang
Yingjun
Y
Varshney
Rohan R
RR
Ren
Li
L
Gong
Yihong
Y
Wang
Dong-An
DA
D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis*; D005994:Glycerophosphates / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D008863:Microspheres; D010012:Osteogenesis / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005994:Glycerophosphates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone; D001205:Ascorbic Acid; C031463:beta-glycerophosphoric acid