Composite material consisting of microporous beta-TCP ceramic and alginate-dialdehyde-gelatin for controlled dual release of clindamycin and bone morphogenetic protein 2

Abstract

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

Dual release of daptomycin and BMP-2 from a composite of β-TCP ceramic and ADA gelatin

“…The CaCl 2 solutions also contained the same concentration of daptomycin and/or BMP-2 as in the gel. The distribution of the gel in the ceramic has already been measured in a previous work [30,38] using fluorescein and fluorescence microscopy. Therefore, we have not done so here.…”

“…The characterization procedures closely mirrored those detailed in prior publications [30,38]. The structural and pore size analyses were conducted using Environmental Scanning Electron Microscopy (ESEM) (FEI Quanta 250 FEG, Hillsboro, USA), Micro-computed Tomography (µCT) (Scanco Micro-CT 50, Brüttisellen, Switzerland), and porosimetry (Porotec Pascal 140/440, Hofheim, Germany).…”

“…Gelatin and alginate were sterilized by using low temperature hydrogen peroxide gas plasma sterilization (pressure 63.3 Pa; temperature 50 °C; diffusion time 8 min; plasma time 4 min; H 2 O 2 concentration 6 wt%; peroxyacetic acid 1 wt%) [39]. The fabrication of alginate di-aldehyde (ADA) was carried out as already described by us elsewhere [38]. Daptomycin hydrochloride (Cubicin 500 mg Daptomycin i.v.…”

“…Samples from release days 1, 2, 3, 6, 9, 14, 21, and 28 of daptomycin BMP-2 release were tested. The exact procedure is already described elsewhere [30,38]. Defined dilutions of each concentration (original concentration as well as 4 above and 4 below the MIC) were prepared which were then tested for MIC in a microtiter experiment with S. aureus (ATCC 29213).…”

Advancing 3D Dental Implant Finite Element Analysis: Incorporating Biomimetic Trabecular Bone with Varied Pore Sizes in Voronoi Lattices

“…Similar to composite materials, bone has directional dependency under external loads [23][24][25][26][27][28], which makes it crucial yet challenging to accurately simulate using traditional computer-aided design (CAD) models [29][30][31]. These conventional models, which frequently assume isotropic or orthotropic features, considerably simplify the complex behavior of human cancellous bone.…”