Holt Ginger E, Halpern Jennifer L, Lynch Conor C, Devin Clinton J, Schwartz Herbert S
Department of Orthopaedics and Rehabilitation, Vanderbilt University School of Medicine, Nashville, TN 37232-8774, USA.
Clin Orthop Relat Res. 2008 Aug;466(8):1890-6. doi: 10.1007/s11999-008-0295-3. Epub 2008 May 28.
The in vivo bioreactor is a hermetically sealed, acellular hydroxyapatite scaffold coated with growth factors that has a pulsating vascular pedicle leash threaded through its center. Tissue-engineered bone is created in weeks while the bioreactor remains embedded under the skin of an animal. The bioreactor also provides a model to study osteogenesis and pathologic scenarios such as tumor progression and metastasis by creating a controlled microenvironment that makes skeletogenesis amenable to genetic and physical manipulation. Animal euthanasia is required to quantitate bioreactor osteogenesis through histomorphometry. Nondestructive measures of new bone growth within the bioreactor are critical to future applications and are the primary questions posed in this study. We compared microcomputed tomography and micro-MRI assessments of bioreactor osteogenesis with conventional histomorphometric measurements in 24 bioreactors and asked if new bone formation could be calculated while the animal was alive. Microcomputed tomography visually, but not numerically, differentiated engineered new bone on its coral scaffold. Dynamic contrast-enhanced micro-MRI demonstrated augmented vascular flow through the bioreactor. Three-dimensional imaging can nondestructively detect tissue-engineered osteogenesis within the implanted bioreactor in vivo, furthering the usefulness of this unique model system.
体内生物反应器是一种密封的、涂有生长因子的无细胞羟基磷灰石支架,其中心有一根脉动的血管蒂穿过。在生物反应器仍埋置于动物皮下的数周内即可生成组织工程骨。该生物反应器还提供了一个模型,通过创建一个可控的微环境来研究骨生成以及肿瘤进展和转移等病理情况,使骨骼生成易于进行基因和物理操作。需要对动物实施安乐死,以便通过组织形态计量学对生物反应器骨生成进行定量分析。生物反应器内新骨生长的无损测量对于未来的应用至关重要,也是本研究提出的主要问题。我们在24个生物反应器中,将生物反应器骨生成的微型计算机断层扫描和微型磁共振成像评估与传统组织形态计量学测量进行了比较,并探讨了能否在动物存活时计算出新骨形成情况。微型计算机断层扫描能直观地而非通过数值区分珊瑚支架上的工程化新骨。动态对比增强微型磁共振成像显示通过生物反应器的血管流量增加。三维成像能够在体内无损检测植入生物反应器内的组织工程骨生成情况,从而提高这个独特模型系统的实用性。