Degoricija Lovorka, Bansal Prashant N, Söntjens Serge H M, Joshi Neel S, Takahashi Masaya, Snyder Brian, Grinstaff Mark W
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
Biomacromolecules. 2008 Oct;9(10):2863-72. doi: 10.1021/bm800658x. Epub 2008 Sep 19.
First generation, photocrosslinkable dendrimers consisting of natural metabolites (i.e., succinic acid, glycerol, and beta-alanine) and nonimmunogenic poly(ethylene glycol) (PEG) were synthesized divergently in high yields using ester and carbamate forming reactions. Aqueous solutions of these dendrimers were photocrosslinked with an eosin-based photoinitiator to afford hydrogels. The hydrogels displayed a range of mechanical properties based on their structure, generation size, and concentration in solution. All of the hydrogels showed minimal swelling characteristics. The dendrimer solutions were then photocrosslinked in situ in an ex vivo rabbit osteochondral defect (3 mm diameter and 10 mm depth), and the resulting hydrogels were subjected to physiologically relevant dynamic loads. Magnetic resonance imaging (MRI) showed the hydrogels to be fixated in the defect site after the repetitive loading regimen. The ([G1]-PGLBA-MA) 2-PEG hydrogel was chosen for the 6 month pilot in vivo rabbit study because this hydrogel scaffold could be prepared at low polymer weight (10 wt %) and possessed the largest compressive modulus of the 10% formulations, a low swelling ratio, and contained carbamate linkages, which are more hydrolytically stable than the ester linkages. The hydrogel-treated osteochondral defects showed good attachment in the defect site and histological analysis showed the presence of collagen II and glycosaminoglycans (GAGs) in the treated defects. By contrast, the contralateral unfilled defects showed poor healing and negligible GAG or collagen II production. Good mechanical properties, low swelling, good attachment to the defect site, and positive in vivo results illustrate the potential of these dendrimer-based hydrogels as scaffolds for osteochondral defect repair.
第一代由天然代谢产物（即琥珀酸、甘油和β-丙氨酸）和非免疫原性聚乙二醇（PEG）组成的可光交联树枝状大分子，通过酯和氨基甲酸酯形成反应以高收率发散合成。这些树枝状大分子的水溶液与基于曙红的光引发剂进行光交联，得到水凝胶。基于其结构、代数大小和溶液浓度，水凝胶表现出一系列机械性能。所有水凝胶均显示出最小的溶胀特性。然后将树枝状大分子溶液在体外兔骨软骨缺损（直径3mm，深度10mm）中原位光交联，并对所得水凝胶施加生理相关的动态载荷。磁共振成像（MRI）显示，在重复加载方案后，水凝胶固定在缺损部位。（[G1]-PGLBA-MA）2-PEG水凝胶被选用于为期6个月的兔体内初步研究，因为这种水凝胶支架可以在低聚合物重量（10 wt%）下制备，并且在10%配方中具有最大的压缩模量、低溶胀率，并且含有比酯键更耐水解的氨基甲酸酯键。水凝胶处理的骨软骨缺损在缺损部位显示出良好的附着，组织学分析显示在处理过的缺损中存在II型胶原蛋白和糖胺聚糖（GAGs）。相比之下，对侧未填充的缺损愈合不良，GAG或II型胶原蛋白的产生可忽略不计。良好的机械性能、低溶胀、对缺损部位的良好附着以及积极的体内结果说明了这些基于树枝状大分子的水凝胶作为骨软骨缺损修复支架的潜力。
