Enhanced Osteoinduction and Angioinduction via Polymer/CaO2 Bone Tissue Engineeri

描述(申请人提供)：骨组织工程支架通常需要使用骨诱导生长因子(例如骨形态发生蛋白，BMPs)来使其在临床上可行。生长因子虽然前景看好，但存在着溶解性有限、不稳定、免疫原性和成本较高等问题。此外，BMP负载的支架已被证明在支架表面诱导大部分骨形成，但细胞对支架整体的渗透有限。为了缓解这一问题，一些研究人员提供了BMP和血管诱导生长因子(如血管内皮生长因子)，以促进整个支架的骨发育。虽然包含这两种类型的生长因子的构建已经显示出希望，但使用生长因子的缺点仍然存在。由于这些局限性，有必要开发骨再生治疗的新策略。来自PI团队的初步数据提供了证据，证明过氧化氢和氢氧化钙可以分别诱导脂肪干细胞产生自己的血管内皮生长因子和骨形态发生蛋白-2。过氧化钙是FDA批准的一种食品添加剂，以一种渐进和受控的方式分解为过氧化氢和钙离子。它高度稳定，价格低廉，使其成为临床上可行的使用生长因子的替代品。本研究计划的目标是1)评估过氧化钙在兔骨髓间充质干细胞中的血管诱导和骨诱导潜能，2)比较这些作用与外源性生长因子血管内皮生长因子和骨形态发生蛋白-2的作用，以及3)制备聚丙交酯-葡萄糖共聚物/过氧化钙复合烧结微球支架，并评估其促进骨再生的能力。支架的生物学性能将使用兔尺骨临界大小的缺损模型来确定。我们假设过氧化钙的生物活性将显著促进体内骨组织的再生，而不是生长因子负载的聚丙交酯-乙交酯支架。

DESCRIPTION (provided by applicant): Bone tissue engineering scaffolds often require the use of osteoinductive growth factors (e.g. bone morphogenetic proteins, BMPs) to make them clinically viable. While promising, growth factors have significant drawbacks including their limited solubility, instability, immunogenicity, and high cost. Also, BMP-loaded scaffolds have been shown to induce most bone formation on the surface of the scaffold with limited cellular penetration into the bulk of the scaffold. To alleviate this problem, some researchers have delivered both BMPs and angioinductive growth factors (e.g. VEGF) to facilitate bone development throughout the scaffold. While constructs containing both types of growth factors have shown promise, the disadvantages of using growth factors still exist. Due to these limitations, there exists a need to develop novel strategies for bone regeneration therapies. Preliminary data from the PI's group provides evidence that hydrogen peroxide and calcium hydroxide can induce adipose-derived stem cells to produce their own VEGF and BMP- 2, respectively. Calcium peroxide, a FDA-approved food additive, dissociates into hydrogen peroxide and calcium ions in a gradual and controlled fashion. It is highly stable and inexpensive making it a clinically viable alternative to using growth factors. The objectives of th present research proposal are 1) to evaluate the angioinductive and osteoinductive potential of calcium peroxide in rabbit mesenchymal stem cells, 2) to compare these effects to the exogenous delivery of the growth factors VEGF and BMP-2, and 3) to create composite poly(lactide-co-glyoclide) / calcium peroxide sintered microsphere scaffolds and assess their capacity to facilitate bone regeneration. The biological performance of the scaffolds will be determined using a rabbit ulnar critical size defect model. We hypothesize the bioactivity of calcium peroxide will significantly improve bone tissue regeneration in vivo over growth factor loaded poly(lactide-co-glycolide) scaffolds.