Chen Faming, Wu Zhifen, Wang Qintao, Wu Hong, Zhang Yongjie, Nie Xin, Jin Yan
Center Laboratory for Tissue Engineering, College of Stomatology, Fourth Military Medical University, Xi'an, China.
Pharmacology. 2005 Nov;75(3):133-44. doi: 10.1159/000088212. Epub 2005 Sep 9.
Hydrogels are based on hydrophilic polymers which are cross-linked to prevent dissolution in water. Because hydrogels can contain large amounts of water, they are interesting devices for the delivery of protein drugs. In this contribution, biodegradable dextran-co-gelatin hydrogel microspheres (DG-MPs) are described which are based on physical interactions and are particularly suitable for the controlled delivery of pharmaceutically active proteins. The unique feature of this preparation system is that the hydrogel microsphere formation takes place in an all-aqueous solution, by which the use of organic solvents is avoided. We investigated the preparation and biological activities of recombinant human bone morphogenetic protein-2 (rhBMP2)-loaded dextran-co-gelatin hydrogel microspheres (rhBMP2-DG-MPs), which aimed to keep rhBMP2's biological activity and to achieve a long-term sustained release of rhBMP2. The microspheres' average diameter was about 20-40 microm and rhBMP2 release in vitro could be maintained for >10 days. Cytology studies showed that using rhBMP2-DG-MPs could promote the proliferation and osteoblastic differentiation of periodontal ligament cells better than using rhBMP2 aqueous solution. By a freeze-drying method, rhBMP2-DG-MPs could be adhered in chitosan membranes for guided tissue regeneration use, namely functionalized membranes. To evaluate bone regeneration induced by rhBMP2-DG-MPs, an animal experiment with canine class III furcation defects was adopted and the results indicated that using rhBMP2-DG-MPs incorporating scaffolds and functionalized membranes could gain more periodontal tissue regeneration than using scaffolds and general membranes soaked with concentrated rhBMP2 aqueous solution. Therefore, those studies demonstrate the potential of DG-MPs in the sustained delivery of low dosages of rhBMP2 to periodontal defects.
水凝胶是基于亲水性聚合物，这些聚合物通过交联以防止在水中溶解。由于水凝胶可以包含大量的水，它们是用于蛋白质药物递送的有趣装置。在本论文中，描述了基于物理相互作用的可生物降解的葡聚糖 - 共 - 明胶水凝胶微球（DG - MPs），其特别适用于药物活性蛋白质的控释。该制备系统的独特之处在于水凝胶微球的形成发生在全水溶液中，从而避免了有机溶剂的使用。我们研究了负载重组人骨形态发生蛋白 - 2（rhBMP2）的葡聚糖 - 共 - 明胶水凝胶微球（rhBMP2 - DG - MPs）的制备和生物学活性，旨在保持rhBMP2的生物学活性并实现rhBMP2的长期持续释放。微球的平均直径约为20 - 40微米，rhBMP2在体外的释放可以维持超过10天。细胞学研究表明，使用rhBMP2 - DG - MPs比使用rhBMP2水溶液能更好地促进牙周膜细胞的增殖和成骨细胞分化。通过冷冻干燥法，rhBMP2 - DG - MPs可以粘附在壳聚糖膜上用于引导组织再生，即功能化膜。为了评估rhBMP2 - DG - MPs诱导的骨再生，采用了犬III类根分叉缺损的动物实验，结果表明，使用包含支架和功能化膜的rhBMP2 - DG - MPs比使用浸泡有浓缩rhBMP2水溶液的支架和普通膜能获得更多的牙周组织再生。因此，这些研究证明了DG - MPs在向牙周缺损部位持续递送低剂量rhBMP2方面的潜力。
