Enhanced Osteoinduction and Angioinduction via Polymer/CaO2 Bone Tissue Engineeri

描述（由申请人提供）：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，BMP）使其具有临床活性。虽然有希望，但生长因子具有显著的缺点，包括其有限的溶解度、不稳定性、免疫原性和高成本。此外，已显示负载BMP的支架在支架表面上诱导大多数骨形成，而细胞渗透到支架本体中有限。为了缓解这一问题，一些研究人员已经递送BMP和血管诱导生长因子（例如VEGF）以促进整个支架的骨发育。虽然含有两种类型的生长因子的构建体已经显示出前景，但使用生长因子的缺点仍然存在。由于这些限制，存在开发用于骨再生疗法的新策略的需要。来自PI研究小组的初步数据提供了证据，证明过氧化氢和氢氧化钙可以诱导脂肪来源的干细胞分别产生它们自己的VEGF和BMP- 2。过氧化钙是FDA批准的食品添加剂，以渐进和受控的方式分解为过氧化氢和钙离子。它是高度稳定和廉价的，使其成为临床上可行的替代使用生长因子。本研究的目的是：1）评价过氧化钙在兔间充质干细胞中的血管诱导和骨诱导潜力，2）将这些作用与外源性递送生长因子VEGF和BMP-2进行比较，3）创建复合聚（丙交酯-共-glyoclide）/过氧化钙烧结微球支架并评估其促进骨再生的能力。将使用兔尺骨临界尺寸缺损模型确定支架的生物学性能。我们假设过氧化钙的生物活性将显着改善骨组织再生在体内生长因子加载聚（丙交酯-共-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.