Sustained release of melatonin from poly (lactic-co-glycolic acid) (PLGA) microspheres to induce osteogenesis of human mesenchymal stem cells in vitro.
Melatonin promotes bone formation and prevents bone degradation via receptor-dependent or receptor-independent actions. The aim of this study is to encapsulate melatonin into poly (lactic-co-glycolic acid) (PLGA) microspheres (PLGA-MEL-MS) and create a melatonin sustained release system, then to evaluate its effect on the osteogenesis of human mesenchymal stem cells (hMSCs) in vitro. PLGA-MEL-MS were prepared by single emulsion solvent evaporation technique. Scanning electron microscopy demonstrated the incorporation of melatonin did not disturb the conventional generation of PLGA microspheres in size and morphology. In vitro drug release assay showed that PLGA-MEL-MS exhibited a biphasic drug release pattern: a low initial burst release effect with approximately 40% drug release at the first 3 days and a relatively retarded and continuous release with about 85% drug release over the 25 days. Cell proliferation assay demonstrated that PLGA-MEL-MS had no apparent effect on proliferation of human MSCs. In an osteogenesis assay, PLGA-MEL-MS obviously enhanced alkaline phosphatase (ALP) mRNA expression and increased ALP activity compared to that in the control group. Meanwhile, several markers of osteoblast differentiation were also significantly upregulated, including runx2, osteopontin, and osteocalcin. Furthermore, quantificational alizarin red-based assay demonstrated that PLGA-MEL-MS significantly enhanced calcium deposit of hMSCs compared to the controls. Therefore, this simple melatonin sustained release system can control released melatonin to generate a microenvironment with a relatively stable concentration of melatonin for a period of time to support osteogenic differentiation of hMSCs in vitro. This suggests that this system may be used as bone growth stimulator in bone healing in vivo.
Department of Orthopedics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China School of Life Science, Sun Yat-Sen University, Guangzhou, China School of Materials Science and Engineering, South China University of Technology, Guangzhou, China Department of Orthopedics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Liangming
L
Zhang
Jinling
J
Zhang
You
Y
Ling
Changhua
C
Chen
Anjing
A
Liang
Yan
Y
Peng
Hong
H
Chang
Peiqiang
P
Su
Dongsheng
D
Huang
D000469:Alkaline Phosphatase / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage; D008550:Melatonin / Q000008:administration & dosage*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D008863:Microspheres; D010012:Osteogenesis / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000008:administration & dosage; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D055815:Young Adult
D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000469:Alkaline Phosphatase; D008550:Melatonin