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.

Graphical Abstract

中文翻译：

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由微孔β-TCP陶瓷和藻酸盐-二醛-明胶组成的复合材料，用于克林霉素和骨形态发生蛋白2的受控双重释放

本研究的目的是生产一种微孔 β-TCP 填充海藻酸盐-明胶交联水凝胶、克林霉素和骨形态发生蛋白 (BMP-2) 的复合材料，以将药物释放行为延长长达 28 天。最有前途的用于微胶囊药物释放的海藻酸二醛（ADA）明胶凝胶被用于在特殊装载室中定向流动下填充微孔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，检查了克林霉素的微生物功效，并在细胞培养中测试了复合材料的生物相容性。克林霉素和模型物质 FITC-蛋白 A 在 28 天内从微胶囊中释放。克林霉素突释率为 43 ± 1%。对于装载的陶瓷，直到第 9 天检测到克林霉素释放高于最低抑制浓度 (MIC)，并且检测到突释为 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手术，其中陶瓷可以充当骨骼中的稳定剂，并且作为可生物降解的系统，可以实现单阶段外科手术。ADA-明胶凝胶是否适合该程序作为纯海藻酸盐的更可生物降解的替代品，或者该复合材料是否可以双重释放尚未进行研究。

图形概要