Tabata Y, Ikada Y
Institute for Frontier Medical Sciences, Kyoto University, Research Center for Biomedical Engineering, Japan.
Biomaterials. 1999 Nov;20(22):2169-75. doi: 10.1016/s0142-9612(99)00121-0.
Biodegradable gelatin hydrogels were prepared through the glutaraldehyde crosslinking of acidic gelatin with an isoelectric point (IEP) of 5.0 and the basic gelatin with an IEP of 9.0. The hydrogel water content was changed by the concentration of both gelatin and glutaraldehyde, used for hydrogel preparation. An aqueous solution of basic fibroblast growth factor (bFGF) was sorbed into the gelatin hydrogel freeze-dried to obtain a bFGF-incorporating gelatin hydrogel. Irrespective of the hydrogel water content, approximately 30% of the incorporated bFGF was released from the bFGF-incorporating acidic gelatin hydrogel, within the first day into phosphate-buffered saline solution at 37 degrees C, followed by no substantial release. Probably, the basic bFGF complexed with the acidic gelatin through poly-ion complexation would not be released under the in vitro non-degradation condition of gelatin. On the contrary, almost 100% of the incorporated bFGF was initially released from all types of basic gelatin hydrogels. This is due to the simple diffusion of bFGF because of no complexation between bFGF and the basic gelatin. When implanted subcutaneously into the mouse back, bFGF-incorporating acidic and basic gelatin hydrogels with higher water contents were degraded with time faster than those with lower water contents. Significant neovascularization was induced around the implanted site of the bFGF-incorporating acidic gelatin hydrogel. The induction period prolonged with the decrease in hydrogel water content. On the other hand, such a prolonged vascularization effect was not achieved by the bFGF-incorporating basic gelatin hydrogel and the hydrogel initially exhibited less enhanced effect, irrespective of the water content. These findings indicate that the controlled release of biologically active bFGF is caused by biodegradation of the acidic gelatin hydrogel, resulting in induction of vascularization effect dependent on the water content. It is possible that only the transient vascularization by the basic gelatin hydrogel is due to the initial large burst in bFGF release, probably because of the down regulation of bFGF receptor.
通过戊二醛交联等电点（IEP）为5.0的酸性明胶和IEP为9.0的碱性明胶制备了可生物降解的明胶水凝胶。用于水凝胶制备的明胶和戊二醛的浓度改变了水凝胶的含水量。将碱性成纤维细胞生长因子（bFGF）的水溶液吸附到冻干的明胶水凝胶中，以获得含bFGF的明胶水凝胶。无论水凝胶含水量如何，在第一天内，约30%的掺入bFGF从含bFGF的酸性明胶水凝胶中释放到37℃的磷酸盐缓冲盐溶液中，随后无大量释放。可能是通过聚离子络合与酸性明胶络合的碱性bFGF在明胶的体外非降解条件下不会释放。相反，几乎100%的掺入bFGF最初从所有类型的碱性明胶水凝胶中释放。这是由于bFGF与碱性明胶之间没有络合，bFGF简单扩散所致。当皮下植入小鼠背部时，含水量较高的含bFGF的酸性和碱性明胶水凝胶随时间降解的速度比含水量较低的水凝胶快。在含bFGF的酸性明胶水凝胶植入部位周围诱导出显著的新血管形成。诱导期随水凝胶含水量的降低而延长。另一方面，含bFGF的碱性明胶水凝胶未实现这种延长的血管生成作用，且无论含水量如何，该水凝胶最初表现出的增强作用较小。这些发现表明，生物活性bFGF的控释是由酸性明胶水凝胶的生物降解引起的，导致血管生成作用的诱导取决于含水量。碱性明胶水凝胶仅引起短暂的血管生成，可能是由于bFGF受体的下调导致bFGF最初大量释放。
