Biodegradable gelatin microparticles as delivery systems for the controlled release of bone morphogenetic protein-2
Biodegradable gelatin microparticles as delivery systems for the controlled release of bone morphogenetic protein-2
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DOI：
10.1016/j.actbio.2008.04.002
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发表时间：
2008-09-01
影响因子：
9.7
通讯作者：
Mikos, Antonios G.
中科院分区：
文献类型：
--
作者：
Patel, Zarana S.;Yamamoto, Masaya;Mikos, Antonios G.
本工作评价了明胶微粒和可生物降解的复合支架在体内外对骨形态发生蛋白-2(BMP-2)的控制释放。研究了明胶交联剂(10和40 mM戊二醛)、BMP-2剂量(每mg干微粒6和60 ng BMP-2)、缓冲液类型(磷酸盐缓冲盐水和含胶原酶的PBS)和明胶类型(酸性和碱性)对BMP-2释放的影响。使用不同相对分子质量(8300和57500)的聚乳酸-乙醇酸(PLGA)微粒也观察了释放情况。用放射性标记的BMP-2进行了体外和体内研究，该体系的放射性碘标记首选氯胺-T法。BMP-2在PLGA微球中的释放呈现中等程度的突释，随后是最小的累积释放，而BMP-2在明胶微球中的体外释放表现为最小的突释和线性释放动力学。生长因子剂量对其归一化释放动力学的影响较小，可能是由于明胶结合和非结合BMP-2之间的平衡所致。酸性和碱性明胶微粒释放的差异可能是由于明胶合成所用的不同前处理条件造成的。明胶微粒单独和复合支架内的体外释放动力学在很大程度上取决于明胶的交联度；不同的缓冲液类型证实了控制释放依赖于明胶的酶降解来实现控制释放。最后，复合支架的体内研究显示，最小的破裂和线性释放长达28天。综上所述，剂量效应对BMP-2的释放影响很小，而不同的明胶类型和释放介质可以改变释放动力学。这些结果表明，通过改变碱性明胶的交联度，可以系统地控制BMP-2从明胶微粒中的传递。(C)2008 Acta Materialia Inc.由爱思唯尔有限公司出版。版权所有。
This work evaluated gelatin microparticles and biodegradable composite scaffolds for the controlled release of bone morphogenetic protein-2 (BMP-2) in vitro and in vivo. Gelatin crosslinking (10 and 40 mM glutaraldehyde), BMP-2 dose (6 and 60 ng BMP-2 per mg dry microparticles), buffer type (phosphate buffered saline (PBS) and collagenase-containing PBS), and gelatin type (acidic and basic) were investigated for their effects on BMP-2 release. Release profiles were also observed using poly(lactic-co-glycolic acid) (PLGA) microparticles with varying molecular weights (8300 and 57,500). In vitro and in vivo studies were conducted using radiolabeled BMP-2; the chloramine-T method was preferred over Bolton-Hunter reagent for radioiodination with this system. BMP-2 release from PLGA microparticles resulted in a moderate burst release followed by minimal cumulative release, while BMP-2 release from gelatin microparticles exhibited minimal burst release followed by linear release kinetics in vitro. Growth factor dose had a small effect on its normalized release kinetics probably because of an equilibrium between gelatin-bound and unbound BMP-2. Differences in release from acidic and basic gelatin microparticles may result from the different pretreatment conditions used for gelatin synthesis. The in vitro release kinetics for both gelatin microparticles alone and within composite scaffolds were dependent largely on the extent of gelatin crosslinking; varying buffer type served to confirm that controlled release relies on enzymatic degradation of the gelatin for controlled release. Finally, in vivo studies with composite scaffolds exhibited minimal burst and linear release up to 28 days. In summary, dose effects on BMP-2 release were found to be minimal while varying gelatin type and release medium can alter release kinetics. These results demonstrate that it systematic control of BMP-2 delivery from gelatin microparticles can be achieved by altering the extent of basic gelatin crosslinking. (C) 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.