title: Biofabrication of a PLGA-TCP-based porous bioactive bone substitute with sustained release of icaritin.
abstract: A phytomolecule, icaritin, has been identified and shown to be osteopromotive for the prevention of osteoporosis and osteonecrosis. This study aimed to produce a bioactive poly (l-lactide-co-glycolide)-tricalcium phosphate (PLGA-TCP)-based porous scaffold incorporating the osteopromotive phytomolecule icaritin, using a fine spinning technology. Both the structure and the composition of icaritin-releasing PLGA-TCP-based scaffolds were evaluated by scanning electron microscopy (SEM). The porosity was quantified by both water absorption and micro-computed tomography (micro-CT). The mechanical properties were evaluated using a compression test. In vitro release of icaritin from the PLGA-TCP scaffold was quantified by high-performance liquid chromatography (HPLC). The attachment, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the composite scaffold were evaluated. Both an in vitro cytotoxicity test and an in vivo test via muscular implantation were conducted to confirm the scaffold's biocompatibility. The results showed that the PLGA-TCP-icaritin composite scaffold was porous, with interconnected macro- (about 480 µm) and micropores (2-15 µm). The mechanical properties of the PLGA-TCP-icaritin scaffold were comparable with those of the pure PLGA-TCP scaffold, yet was spinning direction-dependent. Icaritin content was detected in the medium and increased with time. The PLGA-TCP-icaritin scaffold facilitated the attachment, proliferation and osteogenic differentiation of BMSCs. In vitro cytotoxicity test and in vivo intramuscular implantation showed that the composite scaffold had no toxicity with good biocompatibility. In conclusion, an osteopromotive phytomolecule, icaritin, was successfully incorporated into PLGA-TCP to form an innovative porous composite scaffold with sustained release of osteopromotive icaritin, and this scaffold had good biocompatibility and osteopromotion, suggesting its potential for orthopaedic applications.
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, People's Republic of China.|Department of Orthopaedics, First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Xin-Hui
authors.initials: XH
authors.lastname: Xie
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, People's Republic of China.|Translational Medicine Research and Development Centre, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China.
authors.forename: Xin-Luan
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, People's Republic of China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, People's Republic of China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: He
authors.affiliation: Department of Mechanical Engineering, Hong Kong University of Science and Technology, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Leng
authors.affiliation: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Tang
authors.affiliation: Department of Orthopaedics, Shenzhen People's Hospital, Second Clinical Medical College, Ji'nan University, Shenzhen, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, People's Republic of China.|Translational Medicine Research and Development Centre, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
mesh_terms: D000469:Alkaline Phosphatase / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001854:Bone Marrow Cells / Q000166:cytology; D018786:Bone Substitutes / Q000737:chemistry*; D001842:Bone and Bones / Q000473:pathology; D002130:Calcium Phosphates / Q000737:chemistry*; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D005419:Flavonoids / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D011817:Rabbits; D013314:Stress, Mechanical; D013499:Surface Properties; D023822:Tissue Engineering / Q000379:methods*; D014867:Water / Q000737:chemistry; D055114:X-Ray Microtomography
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D005419:Flavonoids; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000469:Alkaline Phosphatase; C018392:tricalcium phosphate; C499403:icaritin