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载有庆大霉素的复合磷酸钙骨水泥修饰乳化明胶微球的力学性能、药物释放、生物相容性及抗菌活性的体外研究

Mechanical Properties, Drug Release, Biocompatibility, and Antibacterial Activities of Modified Emulsified Gelatin Microsphere Loaded with Gentamicin Composite Calcium Phosphate Bone Cement In Vitro.

作者信息

Hu Ming-Hsien, Shih Bo-Sin, Liu Shih-Ming, Huang Ssu-Meng, Ko Chia-Ling, Chen Wen-Cheng

机构信息

Orthopedic Department, Show Chwan Memorial Hospital, Changhua 500, Taiwan.

Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung City 402, Taiwan.

出版信息

Materials (Basel). 2024 Jul 19;17(14):3578. doi: 10.3390/ma17143578.

DOI:10.3390/ma17143578
PMID:39063872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11279002/
Abstract

Bone defects are commonly addressed with bone graft substitutes; however, surgical procedures, particularly for open and complex fractures, may pose a risk of infection. As such, a course of antibiotics combined with a drug carrier is often administered to mitigate potential exacerbations. This study involved the preparation and modification of emulsified (Em) crosslinking-gelatin (gel) microspheres (m-Em) to reduce their toxicity. The antibiotic gentamicin was impregnated into gel microspheres (m-EmG), which were incorporated into calcium phosphate bone cement (CPC). The study investigated the effects of m-EmG@CPC on antibacterial activity, mechanical properties, biocompatibility, and proliferation and mineralization of mouse progenitor osteoblasts (D1 cells). The average size of the gel microspheres ranged from 22.5 to 16.1 μm, with no significant difference between the groups ( > 0.05). Most of the oil content within the microspheres was transferred through modification, resulting in reduced cytotoxicity. Furthermore, antibiotic-impregnated m-EmG did not compromise the intrinsic properties of the microspheres and exhibited remarkably antibacterial effects. After combining with CPC (m-EmG@CPC), the microspheres did not significantly hinder the CPC reaction and produced the main product, hydroxyapatite (HA). However, the compressive strength of the largest microsphere content of 0.5 wt.% m-EmG in CPC decreased significantly from 59.8 MPa of CPC alone to 38.7 MPa of 0.5m-EmG@CPC ( < 0.05). The 0.5m-EmG@CPC composite was effective against () and () in drug release and antibacterial tests. Compared with m-EmG alone, the 0.5m-EmG@CPC composite showed no toxicity to mouse fibroblast cells (L929). Additionally, the proliferation and mineralization of mouse osteoblastic osteoprogenitor cells (D1 cells) did not have a negative impact on the 0.5m-EmG@CPC composite over time in culture compared with CPC alone. Results suggest that the newly developed antibacterial 0.5m-EmG@CPC composite bone cement did not negatively affect the performance of osteoprogenitor cells and could be a new option for bone graft replacement in surgeries.

摘要

骨缺损通常采用骨移植替代物来处理;然而,外科手术,尤其是开放性和复杂性骨折的手术,可能会带来感染风险。因此,通常会使用一个疗程的抗生素并结合药物载体来减轻潜在的病情加重。本研究涉及乳化(Em)交联明胶(gel)微球(m-Em)的制备和改性,以降低其毒性。将抗生素庆大霉素浸渍到明胶微球(m-EmG)中,然后将其掺入磷酸钙骨水泥(CPC)中。该研究调查了m-EmG@CPC对小鼠祖成骨细胞(D1细胞)的抗菌活性、力学性能、生物相容性以及增殖和矿化的影响。明胶微球的平均尺寸在22.5至16.1μm之间,各组之间无显著差异(>0.05)。通过改性,微球内的大部分油含量被转移,从而降低了细胞毒性。此外,浸渍抗生素的m-EmG没有损害微球的固有特性,并表现出显著的抗菌效果。与CPC结合(m-EmG@CPC)后,微球没有显著阻碍CPC反应,并产生了主要产物羟基磷灰石(HA)。然而,CPC中最大微球含量为0.5 wt.%的m-EmG时,其抗压强度从单独CPC的59.8 MPa显著降低至0.5m-EmG@CPC的38.7 MPa(<0.05)。在药物释放和抗菌测试中,0.5m-EmG@CPC复合材料对()和()有效。与单独的m-EmG相比,0.5m-EmG@CPC复合材料对小鼠成纤维细胞(L929)没有毒性。此外,与单独的CPC相比,在培养过程中,小鼠成骨祖细胞(D1细胞)的增殖和矿化对0.5m-EmG@CPC复合材料没有负面影响。结果表明,新开发的抗菌0.5m-EmG@CPC复合骨水泥对祖成骨细胞的性能没有负面影响,可能是手术中骨移植替代的一种新选择。

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