Comparative study of osteogenic potential of a composite scaffold incorporating either endogenous bone morphogenetic protein-2 or exogenous phytomolecule icaritin: An in vitro efficacy study

• Published in: Acta biomaterialia 2012-08, Vol.8 (8), p.3128-3137
• Main Authors: Chen, S.-H., Wang, X.-L., Xie, X.-H., Zheng, L.-Z., Yao, D., Wang, D.-P., Leng, Y., Zhang, G., Qin, L.
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - metabolism; Animals; bioactive properties; Bioactivity preservation; Biochemistry; Biocompatibility; bioengineering; Biomedical materials; BMP-2; bone formation; bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Bone Morphogenetic Protein 2 - metabolism; Bone Morphogenetic Protein 2 - pharmacology; Bones; Calcification, Physiologic - drug effects; Calcification, Physiologic - genetics; calcium; Calcium - metabolism; Calcium Phosphates - chemistry; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cells, Cultured; cultured cells; Degradation; Flavonoids - pharmacology; gene expression; gene expression regulation; Gene Expression Regulation - drug effects; genes; Humans; Hydrogen-Ion Concentration - drug effects; Icaritin; In vitro testing; Kinetics; Lactic Acid - chemistry; Male; Materials Testing; messenger RNA; Microscopy, Electron, Scanning; mineralization; Molecular Weight; orthopedics; Osteogenesis - drug effects; Osteogenesis - genetics; Osteogenic potential; PLGA/TCP; Polyglycolic Acid - chemistry; Porosity - drug effects; Rabbits; Recombinant Proteins - pharmacology; Scaffolds; stem cells; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism; TCP (protocol); Tissue Scaffolds - chemistry; Transforming Growth Factor beta - pharmacology; tricalcium phosphate
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2012.04.030

A local delivery system with sustained and efficient release of therapeutic agents from an appropriate carrier is desirable for orthopedic applications. Novel composite scaffolds made of poly (lactic-co-glycolic acid) with tricalcium phosphate (PLGA/TCP) were fabricated by an advanced low-temperature rapid prototyping technique, which incorporated either endogenous bone morphogenetic protein-2 (BMP-2) (PLGA/TCP/BMP-2) or phytomolecule icaritin (ICT) (PLGA/TCP/ICT) at low, middle and high doses. PLGA/TCP served as control. In vitro degradation, osteogenesis and release tests showed statistical differences among PLGA/TCP/ICT, PLGA/TCP and PLGA/TCP/BMP-2 groups, where PLGA/TCP/ICT had the desired slow release of bioactive icaritin in a dose-dependent manner, whereas there was almost no BMP-2 release from the PLGA/TCP/BMP-2 scaffolds. PLGA/TCP/ICT significantly increased more ALP activity, upregulated mRNA expression of osteogenic genes and enhanced calcium deposition and mineralization in rabbit bone marrow stem cells cultured on scaffolds compared with the other two groups. These results indicate the desired degradation rate, osteogenic capability and release property in PLGA/TCP/ICT composite scaffold, as icaritin preserved its bioactivity and structure after incorporation, while PLGA/TCP/BMP-2 did not show an initially expected osteogenic potential, owing to loss of the original bioactivity of BMP-2 during its incorporation and fabrication procedure. The results suggest that PLGA/TCP composite scaffolds incorporating osteogenic ICT might be a promising approach for bone tissue bioengineering and regeneration.