Porous gelatin/tricalcium phosphate/genipin composites containing lumbrokinase for bone repair.
Bone cell activities are very important in bone remodeling. This study investigates the effects of lumbrokinase on bone cell activities in cultures. Moreover, a biodegradable composite (GGT) containing genipin-crosslinked gelatin and β-tricalcium phosphate was prepared to carry lumbrokinase (GGTLK). Rat calvarial bone defects were filled with GGT and GGTLK composites. Bone healing was monitored in vivo by bioluminescence imaging and micro-CT. Lumbrokinase was found to have a dose-dependent effect on bone cell activities. Low concentrations (<1μg/ml) of lumbrokinase increased the viability, total alkaline phosphatase activity and mobility of osteoblasts, the number of total calcified nodules and the expression of osteopontin and osteocalcin; however, they considerably reduced the total tartrate-resistant acid phosphatase activity of osteoclasts. IVIS images revealed a stronger fluorescent signal in GGTLK-treated animals than in GGT-treated animals. Micro-CT analysis revealed that GGTLK induced more new bone formation than did GGT. These observations suggest that lumbrokinase released from GGTLK composite can enhance bone tissue regeneration.
School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan; Department of Chinese Medicine, Taichung Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, Taichung 40427, Taiwan.
Yuan-Tsung
YT
Fu
School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan; School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Integrated Chinese and Western Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
Shi-Yuan
SY
Sheu
School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan; Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 40402, Taiwan.
Yueh-Sheng
YS
Chen
Department of Chemical and Materials Engineering, National Yunlin University of Science and Technology, Yunlin 64002, Taiwan. Electronic address: chenkuo@yuntech.edu.tw.
Kuo-Yu
KY
Chen
School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan; Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 40402, Taiwan; Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan. Electronic address: chyao@mail.cmu.edu.tw.
Chun-Hsu
CH
Yao
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001861:Bone Regeneration; D018786:Bone Substitutes / Q000008:administration & dosage*; D002130:Calcium Phosphates / Q000737:chemistry*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D010450:Endopeptidases / Q000008:administration & dosage*; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D039823:Iridoids / Q000737:chemistry*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D016062:Porosity; D000067996:RAW 264.7 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000187:drug effects; D014945:Wound Healing; D055114:X-Ray Microtomography
D001672:Biocompatible Materials; D018786:Bone Substitutes; D002130:Calcium Phosphates; D004337:Drug Carriers; D039823:Iridoids; C485817:beta-tricalcium phosphate; D005780:Gelatin; C007834:genipin; D010450:Endopeptidases; C083421:lumbrokinase
Bone tissue regeneration; Gelatin; Genipin; Lumbrokinase; Tricalcium phosphate