Chih-Wei Chiang1,2, Chih-Hwa Chen3,4,5,6, Yankuba B Manga4, Shao-Chan Huang4, Kun-Mao Chao1,7, Pei-Ru Jheng4, Pei-Chun Wong4, Batzaya Nyambat4, Mantosh Kumar Satapathy4, Er-Yuan Chuang4,8. 1. Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, 10617, Taiwan. 2. Department of Orthopedics, Taipei Medical University Hospital, Taipei, 11031, Taiwan. 3. Department of Orthopedics, Taipei Medical University-Shuang Ho Hospital, New Taipei City, 23561, Taiwan. 4. Graduate Institute of Biomedical Materials and Tissue Engineering, International PhD Program in Biomedical Engineering, School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, 11031, Taiwan. 5. School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan. 6. Research Center of Biomedical Device, Taipei Medical University, Taipei, 11031, Taiwan. 7. Department of Computer Science and Information Engineering, National Taiwan University, Taipei, 10617, Taiwan. 8. Cell Physiology and Molecular Image Research Center, Taipei Medical University-Wan Fang Hospital, Taipei, 116, Taiwan.
Abstract
BACKGROUND AND PURPOSE: Strontium ranelate (SrR) is an oral pharmaceutical agent for osteoporosis. In recent years, numerous unwanted side effects of oral SrR have been revealed. Therefore, its clinical administration and applications are limited. Hereby, this study aims to develop, formulate, and characterize an effective SrR carrier system for spinal bone regeneration. METHODS: Herein, glycol chitosan with hyaluronic acid (HA)-based nanoformulation was used to encapsulate SrR nanoparticles (SrRNPs) through electrostatic interaction. Afterward, the poly(ethylene glycol) diacrylate (PEGDA)-based hydrogels were used to encapsulate pre-synthesized SrRNPs (SrRNPs-H). The scanning electron microscope (SEM), TEM, rheometer, Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were used to characterize prepared formulations. The rabbit osteoblast and a rat spinal decortication models were used to evaluate and assess the developed formulation biocompatibility and therapeutic efficacy. RESULTS: In vitro and in vivo studies for cytotoxicity and bone regeneration were conducted. The cell viability test showed that SrRNPs exerted no cytotoxic effects in osteoblast in vitro. Furthermore, in vivo analysis for new bone regeneration mechanism was carried out on rat decortication models. Radiographical and histological analysis suggested a higher level of bone regeneration in the SrRNPs-H-implanted groups than in the other experimental groups. CONCLUSION: Local administration of the newly developed formulated SrR could be a promising alternative therapy to enhance bone regeneration in bone-defect sites in future clinical applications.
BACKGROUND AND PURPOSE: Strontium ranelate (SrR) is an oral pharmaceutical agent for osteoporosis. In recent years, numerous unwanted side effects of oral SrR have been revealed. Therefore, its clinical administration and applications are limited. Hereby, this study aims to develop, formulate, and characterize an effective SrR carrier system for spinal bone regeneration. METHODS: Herein, glycol chitosan with hyaluronic acid (HA)-based nanoformulation was used to encapsulate SrR nanoparticles (SrRNPs) through electrostatic interaction. Afterward, the poly(ethylene glycol) diacrylate (PEGDA)-based hydrogels were used to encapsulate pre-synthesized SrRNPs (SrRNPs-H). The scanning electron microscope (SEM), TEM, rheometer, Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were used to characterize prepared formulations. The rabbit osteoblast and a rat spinal decortication models were used to evaluate and assess the developed formulation biocompatibility and therapeutic efficacy. RESULTS: In vitro and in vivo studies for cytotoxicity and bone regeneration were conducted. The cell viability test showed that SrRNPs exerted no cytotoxic effects in osteoblast in vitro. Furthermore, in vivo analysis for new bone regeneration mechanism was carried out on rat decortication models. Radiographical and histological analysis suggested a higher level of bone regeneration in the SrRNPs-H-implanted groups than in the other experimental groups. CONCLUSION: Local administration of the newly developed formulated SrR could be a promising alternative therapy to enhance bone regeneration in bone-defect sites in future clinical applications.
Authors: V Nardone; R Zonefrati; C Mavilia; C Romagnoli; S Ciuffi; S Fabbri; G Palmini; G Galli; A Tanini; M L Brandi Journal: Stem Cells Int Date: 2015-07-09 Impact factor: 5.443