Guided Tissue Engineering of 3D Vascularized Tissues

3D 血管化组织的引导组织工程

• 批准号: 8634262
• 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/8634262
• 关键词: Address; Animal Model; Animals; Area; Autologous; Biocompatible Materials; Biological; Blast Injuries; Blood Vessels; Clinic; Clinical; Complex; Conflict (Psychology); 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; craniofacial complex; 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.

组织工程疗法的成功转化为临床应用， 退伍军人需要克服一些技术、生物和外科挑战。的组织的体积 但这受限于稳定血管的刺激形成程度。一个 需要广泛、稳定的血液供应来满足新组织中的大量运输需求， 优化方法以在小体积临床前模型中工程化组织。我们已经证明 将包含模型组织工程疗法的腔室植入骨膜可导致 生成具有临床适当形状和体积的三维血管化骨。4这 该技术已被转化为临床应用，但需要自体骨源， 腔室组件。要广泛采用这一办法，就需要确定替代性的、非- 自体组织来源。组织工程有可能提供替代来源的室 件. 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， 设计，评价血管化和细胞反应，这些生物材料支架在体外，体内， silico，并研究了新的成像技术，用于评估组织工程策略。这些 研究表明我们有能力促进和影响血管长入工程组织。挑战 在实现血管向内生长方面，仍然足以制造大量骨， 血管化和骨形成以及工程化适合于临床应用的复杂结构。的 本研究的主要目标是：1）研究和优化生物信号包埋聚乙烯的设计 乙二醇）基水凝胶用于工程化血管化骨和2）将这些材料应用于工程化 血管化骨重建大型复杂颅面缺损。为了实现我们的目标，我们 将完成以下具体目标： 目的1：研究和优化梯度支架的制备，以刺激血管化组织 侵入多孔水凝胶。 目的2：研究多孔水凝胶系统在血管化和骨形成中的协调作用。 多孔水凝胶的体外和体内研究。 目标3：为临床可平移大型动物的拓扑优化研究提供理论依据 模型，以工程血管化骨适当的体积和结构的临床应用。 这是一个雄心勃勃的建议，重点是优化技术，将带来新的 更接近诊所的重建技术