Nguyen Anh H, McKinney Jay, Miller Tobias, Bongiorno Tom, McDevitt Todd C
The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332-0535, USA.
The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332-0535, USA; The Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0535, USA.
Acta Biomater. 2015 Feb;13:101-10. doi: 10.1016/j.actbio.2014.11.028. Epub 2014 Nov 20.
Gelatin has been commonly used as a delivery vehicle for various biomolecules for tissue engineering and regenerative medicine applications due to its simple fabrication methods, inherent electrostatic binding properties, and proteolytic degradability. Compared to traditional chemical cross-linking methods, such as the use of glutaraldehyde (GA), methacrylate modification of gelatin offers an alternative method to better control the extent of hydrogel cross-linking. Here we examined the physical properties and growth factor delivery of gelatin methacrylate (GMA) microparticles (MPs) formulated with a wide range of different cross-linking densities (15-90%). Less methacrylated MPs had decreased elastic moduli and larger mesh sizes compared to GA MPs, with increasing methacrylation correlating to greater moduli and smaller mesh sizes. As expected, an inverse correlation between microparticle cross-linking density and degradation was observed, with the lowest cross-linked GMA MPs degrading at the fastest rate, comparable to GA MPs. Interestingly, GMA MPs at lower cross-linking densities could be loaded with up to a 10-fold higher relative amount of growth factor than conventional GA cross-linked MPs, despite the GA MPs having an order of magnitude greater gelatin content. Moreover, a reduced GMA cross-linking density resulted in more complete release of bone morphogenic protein 4 and basic fibroblast growth factor and accelerated release rate with collagenase treatment. These studies demonstrate that GMA MPs provide a more flexible platform for growth factor delivery by enhancing the relative binding capacity and permitting proteolytic degradation tunability, thereby offering a more potent controlled release system for growth factor delivery.
由于明胶具有简单的制备方法、固有的静电结合特性和蛋白水解降解性，它已被广泛用作各种生物分子的递送载体，用于组织工程和再生医学应用。与传统的化学交联方法（如使用戊二醛（GA））相比，明胶的甲基丙烯酸酯改性提供了一种更好地控制水凝胶交联程度的替代方法。在这里，我们研究了用不同交联密度（15-90%）配制的甲基丙烯酸明胶（GMA）微粒（MPs）的物理性质和生长因子递送情况。与GA MPs相比，甲基丙烯酰化程度较低的MPs弹性模量降低，孔径增大，甲基丙烯酰化程度增加与模量增大和孔径减小相关。正如预期的那样，观察到微粒交联密度与降解之间呈负相关，交联程度最低的GMA MPs降解速度最快，与GA MPs相当。有趣的是，尽管GA MPs的明胶含量高一个数量级，但交联密度较低的GMA MPs负载的生长因子相对量可比传统GA交联MPs高10倍。此外，GMA交联密度降低导致骨形态发生蛋白4和碱性成纤维细胞生长因子的释放更完全，并且胶原酶处理后释放速率加快。这些研究表明，GMA MPs通过增强相对结合能力和允许蛋白水解降解可调性，为生长因子递送提供了一个更灵活的平台，从而为生长因子递送提供了一个更有效的控释系统。
