{"title":"An MSC Chemotactic and Bone-Replaceable PLGA Material Involving Chemokine Loading OCP for Orthopedic Bone Defect Repair.","authors":"Yasuaki Kuriyama, Ryo Hamai, Yu Mori, Ryuichi Kanabuchi, Kazuyoshi Baba, Kaori Tsuchiya, Toshimi Aizawa, Osamu Suzuki","doi":"10.1021/acsabm.5c00549","DOIUrl":null,"url":null,"abstract":"<p><p>This study investigated whether a composite consisting of octacalcium phosphate (OCP) and porous poly(lactide-<i>co</i>-glycolide) (PLGA) involving recombinant stromal-derived factor-1 (SDF-1) can be used to repair severe orthopedic bone defects. Four experiments were conducted: 1) analysis of loading and release of a model protein for SDF-1, cytochrome c for OCP/PLGA; 2) observation of the effect of SDF-1 on migration of mesenchymal stem cells (MSCs) in the presence of OCP/PLGA in vitro; 3) histomorphometry and immunohistochemistry of bone regeneration of OCP/PLGA/SDF-1 by its implantation into a 3 mm diameter rat femoral transcortical defect for 4 weeks; and 4) micro-CT analysis of the tissue and Fourier transform infrared (FTIR) spectroscopy using undecalcified specimens. The binding effects of cytochrome c and SDF-1 on 40 wt % OCP/PLGA were compared using OCP/PLGA with SDF-1 or cytochrome c prepared under saturated (S) and supersaturated (SS) conditions, containing low or high calcium and phosphate ion concentrations. The loading rates were higher in OCP/PLGA regardless of SS conditions than in PLGA, while the release rate was higher in OCP/PLGA loaded under SS conditions throughout the time, up to 168 h. MSC migration was most enhanced in the OCP/PLGA and loaded under SS conditions for up to 48 h. Bone regeneration was enhanced in OCP/PLGA loaded under SS conditions followed by S conditions and no SDF-1 loading of the OCP/PLGA for up to 4 weeks. Micro-CT and FTIR analyses suggested the material's biodegradation and new bone replacement, which was consistent with the histomorphometry. Osteocalcin-positive cells, tartrate-resistant acid phosphatase-positive cells, and C-X-C motif chemokine receptor type 4 positive cells were localized around the OCP/PLGA under SS conditions, corresponding to higher resorption of the OCP granules. The results suggest that OCP/PLGA involving SDF-1 may repair severe orthopedic bone defects.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1021/acsabm.5c00549","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
This study investigated whether a composite consisting of octacalcium phosphate (OCP) and porous poly(lactide-co-glycolide) (PLGA) involving recombinant stromal-derived factor-1 (SDF-1) can be used to repair severe orthopedic bone defects. Four experiments were conducted: 1) analysis of loading and release of a model protein for SDF-1, cytochrome c for OCP/PLGA; 2) observation of the effect of SDF-1 on migration of mesenchymal stem cells (MSCs) in the presence of OCP/PLGA in vitro; 3) histomorphometry and immunohistochemistry of bone regeneration of OCP/PLGA/SDF-1 by its implantation into a 3 mm diameter rat femoral transcortical defect for 4 weeks; and 4) micro-CT analysis of the tissue and Fourier transform infrared (FTIR) spectroscopy using undecalcified specimens. The binding effects of cytochrome c and SDF-1 on 40 wt % OCP/PLGA were compared using OCP/PLGA with SDF-1 or cytochrome c prepared under saturated (S) and supersaturated (SS) conditions, containing low or high calcium and phosphate ion concentrations. The loading rates were higher in OCP/PLGA regardless of SS conditions than in PLGA, while the release rate was higher in OCP/PLGA loaded under SS conditions throughout the time, up to 168 h. MSC migration was most enhanced in the OCP/PLGA and loaded under SS conditions for up to 48 h. Bone regeneration was enhanced in OCP/PLGA loaded under SS conditions followed by S conditions and no SDF-1 loading of the OCP/PLGA for up to 4 weeks. Micro-CT and FTIR analyses suggested the material's biodegradation and new bone replacement, which was consistent with the histomorphometry. Osteocalcin-positive cells, tartrate-resistant acid phosphatase-positive cells, and C-X-C motif chemokine receptor type 4 positive cells were localized around the OCP/PLGA under SS conditions, corresponding to higher resorption of the OCP granules. The results suggest that OCP/PLGA involving SDF-1 may repair severe orthopedic bone defects.
期刊介绍：
ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications.
The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.
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