title: 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.
abstract: 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.
authors.affiliation: Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: S-H
authors.initials: SH
authors.lastname: Chen
authors.forename: X-L
authors.initials: XL
authors.lastname: Wang
authors.forename: X-H
authors.initials: XH
authors.lastname: Xie
authors.forename: L-Z
authors.initials: LZ
authors.lastname: Zheng
authors.forename: D
authors.initials: D
authors.lastname: Yao
authors.forename: D-P
authors.initials: DP
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Leng
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Qin
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism* / Q000494:pharmacology; D002113:Calcification, Physiologic / Q000187:drug effects / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002130:Calcium Phosphates / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005419:Flavonoids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D005419:Flavonoids; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000469:Alkaline Phosphatase; C018392:tricalcium phosphate; D002118:Calcium; C499403:icaritin