Synthetic Matrices for Vascularization of Engineered Tissues

描述（由申请人提供）： 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受伤的自体活组织。目前的临床方法对于转移这种类型的组织是有效的。然而，由于缺乏适当的专门组织，这些方法受到极大限制。组织工程已显示出重建复杂的身体损伤的希望。可以被工程化的组织的体积受到可以被刺激以在植入材料内形成稳定血管的程度的限制。本研究的目标是优化PEG水凝胶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。这些目标是由以下假设驱动的：1）大孔水凝胶中内皮细胞迁移和侵袭的速度高于仅通过细胞蛋白水解降解的水凝胶，2）在血管侵入后降解和释放生长因子的材料中，血管稳定性增加，和3）在抵靠骨膜植入的腔室中增加血管形成将增加骨生成的体积和深度。这些假设将通过完成以下目标来解决：具体目标1：确定允许快速细胞和血管侵入的最佳PEG条件。具体目标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的影响。具体目标3：在引导组织制造的动物模型中量化水凝胶刺激快速、稳定的新血管形成以促进血管化骨形成的能力，并确定向水凝胶中添加成骨因子是否进一步增强骨形成。 这些研究的完成将导致工程化大体积组织的治疗方法的改进，复杂的伤口造成的战场创伤，平民创伤和肿瘤切除。 公共卫生相关性： 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。组织工程已经显示出对这些复杂伤口的重建的希望。可以被工程化的组织的体积受到可以被刺激以在植入材料内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，刺激血管形成。这些材料有可能改善从伊拉克和阿富汗目前冲突中返回的退伍军人所受身体伤害的重建和替代。

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.