Kim Hae-Won, Knowles Jonathan C, Kim Hyoun-Ee
School of Materials Science and Engineering, Seoul National University, Seoul, 151-742, Korea.
J Biomed Mater Res B Appl Biomater. 2005 Aug;74(2):686-98. doi: 10.1002/jbm.b.30236.
Gelatin-hydroxyapatite (HA) nanocomposite porous scaffolds were fabricated biomimetically, and their feasibility as a drug-delivery carrier for tissue-regeneration and wound-healing treatments was addressed. The composite sols were prepared by the precipitation of HA up to 30 wt % within a gelatin solution with the use of calcium and phosphate precursors, and the porous scaffold was obtained by casting the sols and further freeze drying. The obtained bodies were crosslinked with carbodiimide derivatives to retain chemical and thermal integrity. The apatite precipitates were observed to be a poorly crystallized carbonate-substituted HA. The nanocomposite scaffolds had porosities of approximately 89-92% and exhibited a bimodal pore distribution, that is, the macropores (approximately 300-500 microm) of the framework structure, and micropores (approximately 0.5-1 microm) formed on the framework surface. Transmission electron microscopy (TEM) observation revealed the precipitation of highly elongated HA nanocrystals on the gelatin network. The well-developed porous structure and organized nanocomposite configurations were in marked contrast to the directly mixed gelatin-HA powder conventional composites. For drug-release tests, tetracycline, an antibiotic drug, was entrapped within the scaffold, and the drug-release profile was examined with processing parameters, such as HA amount in gelatin, crosslinking degree, and initial drug addition. The drug entrapment decreased with increasing HA amount, but increased with increasing crosslinking degree and initial drug addition. The crosslinking of the gelatin was the prerequisite to sustaining and controlling the drug releases. Compared to pure gelatin, the gelatin-HA nanocomposites had lower drug releases, because of their lower water uptake and degradation. All the nanocomposite scaffolds released drugs in proportion to the initial drug addition, suggesting their capacity to deliver drugs in a controlled manner. Based on the findings of the well-developed morphological feature and controlled drug-release profile, the gelatin-HA nanocomposite porous scaffolds are suggested to be potentially useful for hard-tissue regeneration.
采用仿生法制备了明胶 - 羟基磷灰石（HA）纳米复合多孔支架，并探讨了其作为组织再生和伤口愈合治疗药物递送载体的可行性。通过使用钙和磷酸盐前驱体在明胶溶液中沉淀高达30 wt%的HA来制备复合溶胶，通过浇铸溶胶并进一步冷冻干燥获得多孔支架。所得物体用碳二亚胺衍生物交联以保持化学和热稳定性。观察到磷灰石沉淀为结晶不良的碳酸盐取代HA。纳米复合支架的孔隙率约为89 - 92%，呈现双峰孔隙分布，即骨架结构的大孔（约300 - 500微米）和在骨架表面形成的微孔（约0.5 - 1微米）。透射电子显微镜（TEM）观察显示在明胶网络上沉淀出高度细长的HA纳米晶体。发达的多孔结构和有序的纳米复合结构与直接混合的明胶 - HA粉末传统复合材料形成鲜明对比。对于药物释放测试，将抗生素药物四环素包封在支架内，并通过加工参数（如明胶中HA的量、交联度和初始药物添加量）检查药物释放曲线。药物包封率随HA量的增加而降低，但随交联度和初始药物添加量的增加而增加。明胶的交联是维持和控制药物释放的前提条件。与纯明胶相比，明胶 - HA纳米复合材料的药物释放较低，因为它们的吸水率和降解率较低。所有纳米复合支架的药物释放量与初始药物添加量成比例，表明它们具有以可控方式递送药物的能力。基于发达的形态特征和可控的药物释放曲线的研究结果，表明明胶 - HA纳米复合多孔支架可能对硬组织再生有用。
