Bioprinted Vascularized Tissue Constructs

生物打印血管化组织结构

• 批准号: 9313171
• 负责人: Jonathan Talbot Butcher
• 金额: $ 18.25万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9313171
• 关键词: 3D Print; Acute; Address; Adipose tissue; Adult; Affect; American; Anastomosis - action; Anatomy; Architecture; Area; Autologous; Beds; Biological; Blood Vessels; Blood capillaries; Burn Trauma; Caliber; Cell Density; Cell Differentiation process; Cells; Cessation of life; Chronic; Chronic Disease; Clinical; Complex; Convection; Data; Dermal; Development; Diabetes Mellitus; Dimensions; Elements; Endothelial Cells; Engineering; Engraftment; Environment; Geometry; Human; Hydrogels; In Vitro; Infection; Injury; Legal patent; Location; Mechanics; Mesenchymal; Mesenchymal Stem Cells; Modeling; Morbidity - disease rate; Nude Rats; Operative Surgical Procedures; Patients; Pattern; Perfusion; Pericytes; Phenotype; Physiological; Printing; Reconstructive Surgical Procedures; Regenerative Medicine; Rodent; Role; Site; Skin; Skin graft; Structure; Surface; Surgical Flaps; Technology; Testing; Thick; Thinness; Tissue Engineering; Tissue Grafts; Tissue Harvesting; Tissues; Translations; Vascular blood supply; Vascular resistance; Vascularization; Veins; Work; angiogenesis; biofabrication; bioprinting; blood perfusion; capillary; cell behavior; cell motility; clinically translatable; cost; density; design; efficacy testing; femoral artery; fluid flow; hemodynamics; in vivo; innovation; interest; irradiation; novel; open wound; preconditioning; reconstruction; response; scale up; shear stress; vascular tissue engineering; vasculogenesis; wound

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.

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 伤口可能会造成永久性损伤、毁容，甚至可能导致死亡。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。无论是全层皮肤移植还是仅真皮层移植，这些表面皮肤移植 无法满足重建手术的大量需求。当应用于患者时，这些 由于无法在这些困难的伤口床中血管化，移植物常常失败。血流动力学效率高、 开放的血管网络是控制植入和长期存活的最重要因素 任何替代组织。目前将血管网络纳入工程体积的方法 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。这些网络具有有限的血流动力学控制、高血管阻力和 如果扩大规模，它们可能不会蓬勃发展。我们率先使用组织生物制造 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。该提案将测试如何规定宏观尺度 血管网络几何形状控制局部微血管血管生成反应和整体组织 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 3D打印血管通道内的局部流动模式影响内皮细胞的保留和 血管生成发芽。第二个目标测试是否嵌入大量间充质干细胞 增强内皮细胞在特定血流动力学环境中的保留和发芽。第三个目标 应用先前目标的结果并测试合理设计的活体3D打印的功效 体内血管化组织等同物。开发了一种创新的啮齿动物吻合模型 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 有关内皮细胞和间充质细胞对血管反应的相互作用的信息 体外和体内的几何形状和流体流动。