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用于骨组织工程的多功能 P(3HB)/45S5 生物玻璃基复合支架

Multi-functional P(3HB) microsphere/45S5 Bioglass-based composite scaffolds for bone tissue engineering.

机构信息

Department of Molecular and Applied Biosciences, University of Westminster, London, UK.

出版信息

Acta Biomater. 2010 Jul;6(7):2773-86. doi: 10.1016/j.actbio.2009.12.054. Epub 2010 Jan 4.

DOI:10.1016/j.actbio.2009.12.054
PMID:20056174
Abstract

Novel multi-functional P(3HB) microsphere/45S5 Bioglass-based composite scaffolds exhibiting potential for drug delivery were developed for bone tissue engineering. 45S5 Bioglass-based glass-ceramic scaffolds of high interconnected porosity produced using the foam-replication technique were coated with biodegradable microspheres (size<2 microm) made from poly(3-hydroxybutyrate), P(3HB), produced using Bacillus cereus SPV. A solid-in-oil-in-water emulsion solvent extraction/evaporation technique was used to produce these P(3HB) microspheres. A simple slurry-dipping method, using a 1 wt.% suspension of P(3HB) microspheres in water, dispersed by an ultrasonic bath, was used to coat the scaffold, producing a uniform microsphere coating throughout the three-dimensional scaffold structure. Compressive strength tests confirmed that the microsphere coating slightly enhanced the scaffold mechanical strength. It was also confirmed that the microsphere coating did not inhibit the bioactivity of the scaffold when immersed in simulated body fluid (SBF) for up to 4 weeks. The hydroxyapatite (HA) growth rate on P(3HB) microsphere-coated 45S5 Bioglass composite scaffolds was very similar to that on the uncoated control sample, qualitatively indicating similar bioactivity. However, the surface topography of the HA surface layer was affected as shown by results obtained from white light interferometry. The roughness of the surface was much higher for the P(3HB) microsphere-coated scaffolds than for the uncoated samples, after 7 days in SBF. This feature would facilitate cell attachment and proliferation. Finally, gentamycin was successfully encapsulated into the P(3HB) microspheres to demonstrate the drug delivery capability of the scaffolds. Gentamycin release kinetics was determined using liquid chromatography-mass spectrometry. The release of the drug from the coated composite scaffolds was slow and controlled when compared to the observed fast and relatively uncontrolled drug release from the bone scaffold (without microsphere coating). Thus, this unique multifunctional bioactive composite scaffold has the potential to enhance cell attachment and to provide controlled delivery of relevant drugs for bone tissue engineering.

摘要

新型多功能 P(3HB)/45S5 生物玻璃基复合支架具有药物输送潜力,可用于骨组织工程。使用泡沫复制技术制备的高连通多孔 45S5 生物玻璃陶瓷支架用可生物降解的微球(<2 微米)进行涂覆,微球由 Bacillus cereus SPV 生产的聚(3-羟基丁酸酯),P(3HB)制成。采用固-油-水乳液溶剂萃取/蒸发技术制备这些 P(3HB)微球。使用简单的浆液浸渍法,将 P(3HB)微球在水中的 1wt%悬浮液(通过超声浴分散)涂覆在支架上,在三维支架结构中形成均匀的微球涂层。压缩强度测试证实,微球涂层略微提高了支架的机械强度。还证实,当支架在模拟体液(SBF)中浸泡长达 4 周时,微球涂层不会抑制支架的生物活性。在 P(3HB)微球涂覆的 45S5 生物玻璃复合支架上,羟基磷灰石(HA)的生长速度与未涂覆的对照样品非常相似,定性表明具有相似的生物活性。然而,如白光干涉测量结果所示,HA 表面层的表面形貌受到影响。在 SBF 中浸泡 7 天后,P(3HB)微球涂覆的支架的表面粗糙度比未涂覆的样品高得多。这一特性将有利于细胞附着和增殖。最后,成功地将庆大霉素包封在 P(3HB)微球中,以证明支架的药物输送能力。使用液相色谱-质谱法测定庆大霉素的释放动力学。与没有微球涂层的骨支架(bone scaffold)观察到的快速且相对不受控制的药物释放相比,药物从涂覆的复合支架中的释放是缓慢且受控的。因此,这种独特的多功能生物活性复合支架具有增强细胞附着和提供相关药物的控释的潜力,可用于骨组织工程。

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