Sustained Release of Catechin from Gelatin and Its Effect on Bone Formation in Critical Sized Defects in Rat Calvaria
Sustained Release of Catechin from Gelatin and Its Effect on Bone Formation in Critical Sized Defects in Rat Calvaria
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DOI：
10.2485/jhtb.29.77
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发表时间：
2020-01-01
影响因子：
0.4
通讯作者：
Umeda, Makoto
中科院分区：
文献类型：
--
作者：
Honda, Yoshitomo;Huan, Anqi;Umeda, Makoto
由于难以维持其在受影响部位的稳定性，植物源多酚在骨组织工程中的潜力尚未完全实现。儿茶素，例如表没食子儿茶素没食子酸酯（EGCG），在骨再生医学中并未得到充分利用。在这里，我们证明了用 EGCG 对明胶进行化学和非化学修饰，可以在大鼠颅骨的临界尺寸骨缺损（9 毫米）中产生明显的骨形成能力。我们制备了两种含有 EGCG 的明胶海绵：EGCG 化学改性真空加热明胶海绵 (AC-vhEGCG-GS) 和 EGCG 真空加热明胶海绵（无化学改性；NC-vhEGCG-GS）。使用扫描电子显微镜、降解性和 EGCG 保留测试对这两种海绵进行了表征。使用微型计算机断层扫描和苏木精-伊红染色评估海绵的骨形成能力；使用天狼星红染色和偏光显微镜测定新形成骨的质量（胶原成熟）。两种海绵均具有海绵状且柔软的质地，大孔尺寸为50-150μm，可降解性的差异可以忽略不计。 NC-vhEGCG-GSs 在 1 小时内释放所有 EGCG 含量，而 AC-vhEGCG-GSs 保留 75% 的 EGCG 长达 24 小时。此外，植入后 4 周，AC-vhEGCG-GS 的骨形成明显高于 NC-vhEGCG-GS，而胶原成熟的差异可以忽略不计。这些结果表明，用 EGCG 对明胶进行化学改性可能是一种有前途的策略，可以充分利用 EGCG 的药理作用来制备天然聚合物海绵。此外，明胶中EGCG的释放速率可能是影响EGCG体内功能的筛选参数。
The potential of plant-derived polyphenols in bone tissue engineering has not been fully realized owing to difficulties in maintaining their stability in affected parts. Catechins, such as epigallocatechin gallate (EGCG), are not fully utilized in bone regenerative medicine. Here, we demonstrated that chemical and non-chemical modifications of gelatin with EGCG resulted in distinct bone-forming abilities in critical-sized bone defects (9 mm) in rat calvaria. We prepared two EGCG-containing gelatin sponges: vacuum-heated gelatin sponges modified chemically with EGCG (AC-vhEGCG-GS) and vacuum-heated gelatin sponges with EGCG (no chemical modification; NC-vhEGCG-GS). Both sponges were characterized using scanning electron microscopy and degradability and EGCG-retention tests. The bone-forming ability of the sponges were estimated using micro-computed tomography and hematoxylin-eosin staining; the quality of newly formed bone (collagen maturation) was determined using picrosirius red staining and polarized microscopy. Both sponges had a spongy and soft texture with macropores ranging 50-150 mu m with negligible differences in degradability. The NC-vhEGCG-GSs released all their EGCG content within 1 h, whereas AC-vhEGCG-GSs retained 75% of the EGCG for up to 24 h. In addition, AC-vhEGCG-GSs resulted in a significantly greater bone formation than NC-vhEGCG-GSs 4 w after implantation, with negligible differences in collagen maturation. These results suggest that the chemical modification of gelatin with EGCG might be a promising strategy to fully utilize the pharmacological effects of EGCG for natural polymer-based sponges. Moreover, the release rate of EGCG from gelatin is possibly a screening parameter affecting the function of EGCG in vivo.