由微孔β-TCP 陶瓷和藻酸盐-戊二醛-明胶组成的复合材料,用于控制克林霉素和骨形态发生蛋白 2 的双重释放。
Composite material consisting of microporous beta-TCP ceramic and alginate-dialdehyde-gelatin for controlled dual release of clindamycin and bone morphogenetic protein 2.
机构信息
G.E.R.N. Tissue Replacement, Regeneration & Neogenesis, Department of Orthopedics and Trauma Surgery, Medical Center Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Engesserstraße 4, 79108, Freiburg, Germany.
Medical Center Albert-Ludwigs-University of Freiburg, Institute of Microbiology and Hygiene, Hermann-Herder-Straße 11, 79104, Freiburg, Germany.
出版信息
J Mater Sci Mater Med. 2023 Jul 27;34(8):39. doi: 10.1007/s10856-023-06743-1.
The aim of this study was to produce a composite of microporous β-TCP filled with alginate-gelatin crosslinked hydrogel, clindamycin and bone morphogenetic protein (BMP-2) to prolong the drug-release behaviour for up to 28 days. The most promising alginate-di-aldehyde(ADA)-gelatin gel for drug release from microcapsules was used to fill microporous β-TCP ceramics under directional flow in a special loading chamber. Dual release of clindamycin and BMP-2 was measured on days 1, 2, 3, 6, 9, 14, 21 and 28 by high performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA). After release, the microbial efficacy of the clindamycin was checked and the biocompatibility of the composite was tested in cell culture. Clindamycin and the model substance FITC-protein A were released from microcapsules over 28 days. The clindamycin burst release was 43 ± 1%. For the loaded ceramics, a clindamycin release above the minimal inhibitory concentration (MIC) until day 9 and a burst release of 90.56 ± 2.96% were detected. BMP-2 was released from the loaded ceramics in low concentrations over 28 days. The release of active substances from β-TCP and hydrogel have already been extensively studied. Directional flow loading is a special procedure in which the ceramic could act as a stabilizer in the bone and, as a biodegradable system, enables a single-stage surgical procedure. Whether ADA-gelatin gel is suitable for this procedure as a more biodegradable alternative to pure alginate or whether a dual release is possible in this composite has not yet been investigated.
本研究的目的是制备一种填充有藻酸盐-明胶交联水凝胶、克林霉素和骨形态发生蛋白(BMP-2)的微孔 β-TCP 复合材料,以延长药物释放行为长达 28 天。最有前途的用于从微胶囊中释放药物的藻酸盐-二醛(ADA)-明胶凝胶被用于在特殊加载室中的定向流中填充微孔 β-TCP 陶瓷。通过高效液相色谱(HPLC)和酶联免疫吸附测定(ELISA)在第 1、2、3、6、9、14、21 和 28 天测量克林霉素和 BMP-2 的双重释放。释放后,检查克林霉素的微生物功效,并在细胞培养中测试复合材料的生物相容性。克林霉素和模型物质 FITC-蛋白 A 从微胶囊中释放超过 28 天。克林霉素的突释为 43±1%。对于负载的陶瓷,在第 9 天之前检测到克林霉素释放量超过最低抑菌浓度(MIC),并且突释率为 90.56±2.96%。BMP-2 在 28 天内从负载的陶瓷中以低浓度释放。β-TCP 和水凝胶中活性物质的释放已经得到了广泛的研究。定向流加载是一种特殊的程序,其中陶瓷可以在骨骼中充当稳定剂,并且作为可生物降解的系统,能够实现单阶段手术。ADA-明胶凝胶是否适合作为纯藻酸盐的更可生物降解的替代品,或者是否可以在这种复合材料中实现双重释放,尚未得到研究。
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