Guided Tissue Engineering of 3D Vascularized Tissues

3D 血管化组织的引导组织工程

• 批准号: 8814103
• 负责人: ERIC M BREY
• 金额: --
• 依托单位: EDWARD HINES JR VA HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8814103
• 关键词: Address; Animal Model; Animals; Area; Autologous; Biocompatible Materials; Biological; Blast Injuries; Blood Vessels; Clinic; Clinical; Complex; Conflict (Psychology); Craniofacial Abnormalities; Defect; Development; Devices; Engineering; Ethylene Glycols; Evaluation; Freedom; Generations; Goals; Grant; Growth Factor; Head and neck structure; Histocompatibility Testing; Hydrogels; Imaging Techniques; In Vitro; Incidence; Institutes; Investigation; Lead; Life; Medicine; Methods; Modeling; Movement; Operative Surgical Procedures; Osteogenesis; Patients; Periosteum; Polymers; Population; Pre-Clinical Model; Procedures; Research; Shapes; Solutions; Source; Staging; Structure; Surgeon; System; Techniques; Tissue Engineering; Tissues; Translating; Translations; Trauma; Vascular blood supply; Vascularization; Veterans; World War II; arm; base; bone; bone engineering; bone geometry; clinical application; craniofacial; design; engineering design; ethylene glycol; head/neck injury; implantation; improved; in vivo; meetings; operation; porous hydrogel; public health relevance; reconstruction; regenerative; response; scaffold; skeletal; success

The successful translation of tissue engineering therapies into clinical application that will benefit veterans requires overcoming a number of technical, biological and surgical challenges. The volume of tissue that can be engineered is limited by the extent to which stable blood vessels can be stimulated to form. An extensive, stable blood supply is required to meet mass transport demands in the new tissues and most methods are optimized for engineering tissues in small volume pre-clinical models. We have shown that implantation of a chamber containing model tissue engineering therapies against the periosteum can lead to the generation of three-dimensional vascularized bone of clinically appropriate shape and volume.4 This technique has been translated into clinical application but required an autologous source of bone for the chamber components. Broad application of this approach requires the identification of alternative, non- autologous tissue sources. Tissue engineering has the potential to provide alternative sources for chamber components. In our previous MERIT grant we investigated and optimized the design of porous hydrogel scaffolds for vascularized tissue formation. In the previous cycle we developed techniques for polymer synthesis and design, evaluated vascularization and cellular response to these biomaterial scaffolds in vitro, in vivo, and in silico, and investigated new imaging techniques for the evaluation of tissue engineering strategies. These studies illustrate our ability to promote and influence vascular ingrowth into engineered tissues. Challenges remain in regards to achieving vascular ingrowth sufficient for engineering large volumes of bone, coordinating vascularization and bone formation and engineering complex structures suitable for clinical application. The broad goals of this proposal are to 1) investigate and optimize the design of biosignal-embedded poly(ethylene glycol)-based hydrogels for engineering vascularized bone and 2) apply these materials for engineering vascularized bone for reconstruction of large, complex craniofacial defects. In order to achieve our goals we will complete the following specific aims: Objective 1: Investigate and optimize the generation of gradients scaffolds for stimulating vascularized tissue invasion into porous hydrogels. Objective 2: Investigate porous hydrogel systems for coordination of vascularization and bone formation in porous hydrogels in vitro and in vivo. Objective 3: Develop topological optimization methods for applying the clinically-translatable large animal model to engineer vascularized bone of appropriate volume and structure for clinical application. This is an ambitious proposal focused on the optimization of techniques that will bring new reconstructive techniques closer to the clinic.

组织工程疗法成功转化为临床应用将受益 退伍军人需要克服许多技术、生物和外科挑战。组织体积 可以改造的范围受到刺激形成稳定血管的程度的限制。一个 需要广泛、稳定的血液供应来满足新组织和大多数组织中的物质运输需求 方法针对小体积临床前模型中的工程组织进行了优化。我们已经证明 植入含有针对骨膜的组织工程疗法模型的腔室可以导致 生成临床上合适形状和体积的三维血管化骨。4 该技术已转化为临床应用，但需要自体骨源 室组件。这种方法的广泛应用需要确定替代的、非 自体组织来源。组织工程有潜力为腔室提供替代来源 成分。 在我们之前的 MERIT 资助中，我们研究并优化了多孔水凝胶支架的设计 血管化组织形成。在上一个周期中，我们开发了聚合物合成技术和 在体外、体内和体内设计、评估这些生物材料支架的血管化和细胞反应 silico，并研究了用于评估组织工程策略的新成像技术。这些 研究表明我们有能力促进和影响血管向工程组织内生长。挑战 仍然致力于实现足以工程化大量骨骼的血管向内生长，协调 血管化和骨形成以及适合临床应用的工程复杂结构。这 该提案的主要目标是 1) 研究和优化生物信号嵌入聚乙烯的设计 用于工程血管化骨的基于乙二醇）的水凝胶，2）将这些材料应用于工程 用于重建大型复杂颅面缺损的血管化骨。为了实现我们的目标，我们 将完成以下具体目标： 目标 1：研究并优化用于刺激血管化组织的梯度支架的生成 侵入多孔水凝胶。 目标 2：研究协调血管化和骨形成的多孔水凝胶系统 体外和体内多孔水凝胶。 目标3：开发应用于临床可移植大型动物的拓扑优化方法 模型来设计适当体积和结构的血管化骨以供临床应用。 这是一个雄心勃勃的提案，重点是技术优化，将带来新的 更接近临床的重建技术。