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注射到空心镁螺钉中的可生物降解骨形态发生蛋白-2水凝胶的成骨作用

Osteogenic Effect of a Biodegradable BMP-2 Hydrogel Injected into a Cannulated Mg Screw.

作者信息

Kim Seo-Young, Kim Yu-Kyoung, Chong Seong-Woo, Lee Kwang-Bok, Lee Min-Ho

机构信息

Department of Dental Biomaterials and Institute of Biodegradable Material, Institute of Oral Bioscience and BK21 Plus Project, School of Dentistry, Jeonbuk National University, 567, Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Republic of Korea.

Department of Orthopedic Surgery, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University Medical School, Gungiro 20, Deokjin-Gu, Jeonju-si, Jeollabuk-do 561-180, Republic of Korea.

出版信息

ACS Biomater Sci Eng. 2020 Nov 9;6(11):6173-6185. doi: 10.1021/acsbiomaterials.0c00709. Epub 2020 Oct 16.

DOI:10.1021/acsbiomaterials.0c00709
PMID:33449641
Abstract

Cannulated screws, containing an internal hole for inserting a guide pin, are commonly used in the management of bone fractures. Cannulated Mg screws can be biodegraded easily because their increased surface area including that of the inner hole rapidly reacts with body fluids. To delay biodegradation of cannulated Mg screws and improve bone regeneration, we developed a specific type of screw by injecting it with gelatin hydrogels [10 wt % gelatin with 0.09 v/v % glutaraldehyde (cross-linker)] containing different concentrations (5, 10, or 25 μg/mL) of bone morphogenic proteins (BMPs). We analyzed the properties and biocompatibility of the screws with and without BMP-2 and found that the release rate of BMP-2 in the hydrogel changed proportionately with the degradation rate of the cross-linked hydrogel. Loading BMP-2 in the hydrogel resulted in sustained release of BMP-2 for 25 to 40 days or more. The degradation rate of BMP-2 hydrogels was inversely proportional to the concentration of BMP-2. The injection of the hydrogels in the cannulated screw delayed biodegradation inside of the screw by simulated body fluid. It also induced uniform corrosion and the precipitation of bioactive compounds onto the surface of the screw. In addition, osteoblast proliferation was very active near the BMP-2 hydrogels, depending on the BMP-2 concentration. The BMP-2 in the hydrogel improved cell differentiation. The cannulated screw injected with 10 μL/mL BMP-2 hydrogel prevented implant biodegradation and enhanced osteoconduction and osteointegration inside and outside the screw. In addition, the properties of BMP-2-loaded hydrogels can be changed by controlling the amount of the cross-linker and protein, which could be useful for tissue regeneration in other fields.

摘要

空心螺钉带有用于插入导针的内孔,常用于骨折治疗。空心镁螺钉易于生物降解,因为其增加的表面积(包括内孔表面积)会迅速与体液发生反应。为了延缓空心镁螺钉的生物降解并促进骨再生,我们通过向其中注入含有不同浓度(5、10或25μg/mL)骨形态发生蛋白(BMPs)的明胶水凝胶[10wt%明胶与0.09v/v%戊二醛(交联剂)]开发了一种特殊类型的螺钉。我们分析了含BMP-2和不含BMP-2的螺钉的性能和生物相容性,发现水凝胶中BMP-2的释放速率与交联水凝胶的降解速率成比例变化。在水凝胶中加载BMP-2导致BMP-2持续释放25至40天或更长时间。BMP-2水凝胶的降解速率与BMP-2的浓度成反比。将水凝胶注入空心螺钉可延缓模拟体液对螺钉内部的生物降解。它还诱导了均匀腐蚀以及生物活性化合物在螺钉表面的沉淀。此外,根据BMP-2浓度,成骨细胞在BMP-2水凝胶附近增殖非常活跃。水凝胶中的BMP-2改善了细胞分化。注入10μL/mL BMP-2水凝胶的空心螺钉可防止植入物生物降解,并增强螺钉内外的骨传导和骨整合。此外,通过控制交联剂和蛋白质的量可以改变加载BMP-2的水凝胶的性能,这可能对其他领域的组织再生有用。

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