title: Preparation of porous bioceramics using reverse thermo-responsive hydrogels in combination with rhBMP-2 carriers: in vitro and in vivo evaluation.
abstract: Porous biphasic calcium phosphates (BCP) were fabricated using reverse thermo-responsive hydrogels with hydroxyapatite (HAp) and β-tricalcium (β-TCP) powder and planetary centrifugal mixer. This hydrogel mixture slurry will shrink and compress the HAp powder during the sintering process. The porous bioceramics are expected to have good mechanical properties after sintering at 1200°C. Reverse thermo-responsive hydrogels of poly[(N-isopropylacrylamide)-co-(methacrylic acid)] p(NiPAAm-MAA) were synthesized by free-radical cross-linking copolymerization, and their chemical properties were evaluated by nuclear magnetic resonance spectroscopy, infrared spectroscopy, and electrospray-ionization mass spectrometry. The lower critical solution temperature (LCST) of the hydrogel was determined using turbidity measurements. A thermogravimetric analysis was used to examine the thermal properties. The porous bioceramic properties were analyzed by X-ray diffraction, scanning electron microscopy, bulk density, compressive strength testing and cytotoxicity. The compressive strength and average porosity of the porous bioceramics were examined at approximately 6.8MPa and 66% under 10wt% p(NiPAAm-MAA)=99:1 condition. The ratio of HAp/β-TCP can adjust two different compositional behaviors during the 1200°C sintering process without resulting in cell toxicity. The (rhBMP-2)-HAp-PLGA carriers were fabricated as in our previous study of the double emulsion and drop-coating technique. Results of animal study included histological micrographs of the 1-mm defect in the femurs, with the rhBMP-2 carrier group, the bioceramic spacer group and the bioceramic spacer with rhBMP-2 carriers group showing better callus formation around the femur defect site than the control group. The optimal dual effects of the bone growth factors from osteoconductive bioceramics and osteoinductive rhBMP-2 carriers produced better bone formation.
authors.affiliation: Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Orthopaedics, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yin-Chih
authors.initials: YC
authors.lastname: Fu
authors.forename: Chung-Hwan
authors.initials: CH
authors.lastname: Chen
authors.forename: Chau-Zen
authors.initials: CZ
authors.lastname: Wang
authors.forename: Yan-Hsiung
authors.initials: YH
authors.lastname: Wang
authors.forename: Je-Ken
authors.initials: JK
authors.lastname: Chang
authors.forename: Gwo-Jaw
authors.initials: GJ
authors.lastname: Wang
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Ho
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Wang
mesh_terms: D016475:3T3 Cells; D000178:Acrylamides / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D002516:Ceramics / Q000737:chemistry*; D005269:Femur / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D055595:Mechanical Phenomena; D051379:Mice; D011109:Polymethacrylic Acids / Q000737:chemistry; D016062:Porosity; D013696:Temperature; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000178:Acrylamides; C525718:BMP2 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D020100:Hydrogels; D011109:Polymethacrylic Acids; C085085:poly(N-isopropylacrylamide-co-methacrylic acid)
keywords: Bioceramics; Biphasic calcium phosphates; Non-union defect; Reverse thermo-responsive; RhBMP-2 carriers