Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Tissue Eng Part A. 2011 Mar;17(5-6):691-701. doi: 10.1089/ten.TEA.2010.0123. Epub 2010 Dec 18.
We used the tarsus of an adult Xenopus laevis frog as an in vivo load-bearing model to study the regeneration of critical-size defects (CSD) in long bones. We found the CSD for this bone to be about 35% of the tarsus length. To promote regeneration, we implanted biocompatible 1,6 hexanediol diacrylate scaffolds soaked with bone morphogenetic proteins-4 and vascular endothelial growth factors. In contrast to studies that use scaffolds as templates for bone formation, we used scaffolds as a growth factor delivery vehicle to promote cartilage-to-bone regeneration. Defects in control frogs were filled with scaffolds lacking growth factors. The limbs were harvested at a series of time points ranging from 3 weeks to 6 months after implantation and evaluated using micro-computed tomography and histology. In frogs treated with growth factor-loaded scaffolds, we observed a cartilage-to-bone regeneration in the skeletal defect. Five out of eight defects were completely filled with cartilage by 6 weeks. Blood vessels had invaded the cartilage, and bone was beginning to form in ossifying centers. By 3 months, these processes were well advanced, and extensive ossification was observed in 6-month samples. In contrast, the defects in control frogs showed only formation of fibrous scar tissue. This study demonstrates the utility of a Xenopus model system for tissue engineering research and that the normal in vivo mechanism of endochondral bone development and fracture repair can be mimicked in the repair of CSD with scaffolds used as growth factor delivery mechanisms.
我们使用成年非洲爪蟾的跗骨作为活体承重模型，研究长骨临界尺寸缺陷（CSD）的再生。我们发现这种骨骼的 CSD 约为跗骨长度的 35%。为了促进再生，我们植入了生物相容性的 1,6 己二醇二丙烯酸酯支架，支架中浸泡有骨形态发生蛋白-4 和血管内皮生长因子。与使用支架作为骨形成模板的研究不同，我们使用支架作为生长因子的输送载体来促进软骨到骨的再生。在对照青蛙的缺陷中，植入了缺乏生长因子的支架。在植入后的 3 周到 6 个月的一系列时间点采集肢体，并使用微计算机断层扫描和组织学进行评估。在接受负载生长因子支架治疗的青蛙中，我们观察到在骨骼缺陷处发生了软骨到骨的再生。在 6 周时，有 5 个缺陷中有 8 个完全被软骨填充。血管已经侵入软骨，并且在成骨中心开始形成骨。在 3 个月时，这些过程进展良好，在 6 个月的样本中观察到广泛的骨化。相比之下，对照青蛙的缺陷仅显示出纤维状瘢痕组织的形成。这项研究证明了非洲爪蟾模型系统在组织工程研究中的实用性，并且正常的体内软骨内骨发育和骨折修复机制可以通过使用支架作为生长因子输送机制来模拟 CSD 的修复。
