Synthetic Matrices for Vascularization of Engineered Tissues

描述(由申请人提供)： 项目概述战场创伤造成的身体伤害是重建工作面临的一些最大挑战。这些伤口的最佳替代物是未损伤的自体活体组织。目前的临床方法对于转移这种类型的组织是有效的。然而，由于缺乏合适的特殊组织，这些方法受到极大的限制。组织工程学在重建复杂的物理损伤方面显示出了良好的前景。可被工程化的组织的体积受到植入材料内刺激形成稳定血管的程度的限制。本研究的目标是优化聚乙二醇水凝胶的条件，以刺激体内广泛和稳定的血管形成，并使用这些水凝胶来增加可用于重建复杂骨骼缺损的血管化骨的体积。这些目标是由下述假设驱动的：1)内皮细胞在大孔水凝胶中的迁移和侵袭速度比仅通过细胞蛋白分解降解的水凝胶更快；2)血管稳定性在血管侵入后降解和释放生长因子的材料中增加，以及3)增加针对骨膜植入的腔室中的血管形成将增加成骨的体积和深度。这些假设将通过完成以下目标来解决：具体目标1：确定允许细胞和血管快速侵入的最佳聚乙二醇组分条件。特定目标2：确定材料降解和生长因子释放动力学对植入水凝胶中血管持久性和成熟度的影响。具体目标3：在引导组织构建的动物模型中，量化水凝胶刺激快速、稳定的新生血管促进血管化骨形成的能力，并确定在水凝胶中添加成骨因子是否进一步促进骨形成。这些研究的完成将带来大容量组织工程的改进方法，用于治疗战场创伤、平民创伤和肿瘤切除造成的复杂伤口。 公共卫生相关性： 项目叙述相关性战场创伤造成的身体伤害是重建工作面临的一些最大挑战。组织工程学在这些复杂伤口的重建方面显示出了希望。可被工程化的组织的体积受到植入材料内刺激形成稳定血管的程度的限制。这项研究的目标是设计新的生物材料来刺激血管形成。这些材料有可能改善伊拉克和阿富汗目前冲突归来的退伍军人遭受的身体伤害的重建和替换工作。

DESCRIPTION (provided by applicant): Project Summary Physical injuries resulting from battlefield trauma present some of the greatest challenges for reconstruction. The best replacement for these wounds is uninjured autologous living tissue. Current clinical methods are effective for transferring this type of tissue. However, the methods are extremely limited by a lack of appropriate specialized tissue. Tissue engineering has shown promise for the reconstruction of complex physical injuries. The volume of tissue that can be engineered is limited by the extent to which stable blood vessels can be stimulated to form within the implanted material. The goals of this research are to optimize PEG hydrogel conditions to stimulate extensive and stable vessel formation in vivo and to use these hydrogels to increase the volume of vascularized bone that can be engineered for reconstruction of complex skeletal defects These goals are driven by the hypotheses that 1) the speed of endothelial cell migration and invasion is higher within macroporous hydrogels than hydrogels degraded only by cell proteolysis, 2) vessel stability is increased in materials that degrade and release growth factors after vessel invasion, and 3) increasing vascularization in chambers implanted against the periosteum will increase the volume and depth of osteogenesis. These hypotheses will be addressed by completing the following objectives: Specific Objective 1: Identify optimal PEG conditions that permit rapid cell and blood vessel invasion. Specific Objective 2: Identify the effects of material degradation and growth factor release kinetics on vessel persistence and maturation in implanted hydrogels. Specific Objective 3: Quantify the ability of hydrogels that stimulate rapid, stable neovascularization to promote vascularized bone formation in an animal model of guided tissue fabrication and determine whether addition of an osteogenic factor to the hydrogels further enhances bone formation. Completion of theses studies will lead to improved methods for engineering large volume tissues for the treatment of complex wounds resulting from battlefield trauma, civilian trauma, and tumor resection. PUBLIC HEALTH RELEVANCE: Project Narrative Relevance Physical injuries resulting from battlefield trauma present some of the greatest challenges for reconstruction. Tissue engineering has shown promise for the reconstruction of these complex wounds. The volume of tissue that can be engineered is limited by the extent to which stable blood vessels can be stimulated to form within the implanted material. The goal of this research is to design new biomaterials that stimulate blood vessel formation. These materials have the potential to improve the reconstruction and replacement of physical injuries suffered by veterans returning from current conflicts in Iraq and Afghanistan.