Bioprinted Vascularized Tissue Constructs

项目概要 烧伤、外伤和糖尿病引起的急性和慢性损伤通常会导致无法闭合的开口 wounds subject to permanent damage, disfigurement, and potentially death.这是一个特别 具有挑战性的问题，这种侮辱跨越了相对较大的区域，留下了很少的潜在地点 自体组织收获。因此，替代大块组织等效物的开发是一个 主要兴趣是组织工程和再生医学领域。市售 产品仅针对皮肤。 Whether full-thickness or dermal layer-only, these surface skin grafts 无法满足重建手术的大量需求。当应用于患者时，这些 grafts often fail due to inability to vascularize in these difficult wound beds.血流动力学效率高、 patent vascular network is the most important factor governing the engraftment and long-term survival 任何替代组织。 Current approaches to incorporate a vascular network in engineered bulk 组织仅成功地产生了微尺度（<1 cm3）的均匀毛细血管丛 组织成分。 These networks possess limited hemodynamic control, high vascular resistance, and likely will not thrive if they could be scaled up. We have pioneered the use of tissue biofabrication 开发具有不同大小管腔的可灌注血管化组织等同物的策略， 它模仿天然的微血管结构。 This proposal will test how prescribed macro-scale vascular network geometries control local microvascular angiogenic response and overall tissue 灌注和植入。该提案有三个目标。第一个目标是确定具体如何 local flow patterns within 3D printed vascular channels influence endothelial cell retention and 血管生成发芽。 The second aim tests whether embedded bulk mesenchymal stem cells augments endothelial retention and sprouting in defined hemodynamic environments.第三个目标 applies the results of the previous aims and tests the efficacy of rationally designed living 3D printed 体内血管化组织等同物。 An innovative rodent anastomosis model is developed to 回答这些问题。该提案将建立并验证一种新的临床可转化方法 血管网络移植物制造技术。研究结果也将贡献重要的新成果 information about the interplays between endothelial and mesenchymal in response to vessel 体外和体内的几何形状和流体流动。

Project Summary Acute and chronic injuries resulting from burns, trauma, and diabetes often result in uncloseable open wounds subject to permanent damage, disfigurement, and potentially death. This is an especially challenging problem where such insults span a relatively large area leaving few sites for potential autologous tissue harvest. The development of replacement bulk tissue equivalents is therefore a major interest in the fields of tissue engineering and regenerative medicine. Commercially available products only address the skin. Whether full-thickness or dermal layer-only, these surface skin grafts cannot fulfill the substantial volume needs of reconstructive surgery. When applied to patients, these grafts often fail due to inability to vascularize in these difficult wound beds. A hemodynamically efficient, patent vascular network is the most important factor governing the engraftment and long-term survival of any replacement tissue. Current approaches to incorporate a vascular network in engineered bulk tissues have succeeded only in generating homogeneous capillary plexuses in microscale (<1 cm3) tissue elements. These networks possess limited hemodynamic control, high vascular resistance, and likely will not thrive if they could be scaled up. We have pioneered the use of tissue biofabrication strategies to develop perfusable vascularized tissue equivalents with heterogeneously sized lumens, which mimics the native microvascular architecture. This proposal will test how prescribed macro-scale vascular network geometries control local microvascular angiogenic response and overall tissue perfusion and engraftment. This proposal has three aims. The first aim is to determine how specific local flow patterns within 3D printed vascular channels influence endothelial cell retention and angiogenic sprouting. The second aim tests whether embedded bulk mesenchymal stem cells augments endothelial retention and sprouting in defined hemodynamic environments. The third aim applies the results of the previous aims and tests the efficacy of rationally designed living 3D printed vascularized tissue equivalents in vivo. An innovative rodent anastomosis model is developed to answer these questions. This proposal will establish and validate a new clinically translatable technology for vascular network graft fabrication. The results will also contribute significant new information about the interplays between endothelial and mesenchymal in response to vessel geometries and fluid flows in vitro and in vivo.