Roles of vascularization and innervation in regenerative medicine

血管化和神经支配在再生医学中的作用

基本信息

  • 批准号:
    9190519
  • 负责人:
  • 金额:
    $ 5.77万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-06-02 至 2019-05-31
  • 项目状态:
    已结题

项目摘要

ROLES OF VASCULARIZATION AND INNERVATION IN REGENERATIVE MEDICINE Skeletal muscle defects, such as those presented from traumatic injuries such as severe car crashes, cancer resections, or battlefield injuries, represent a significant healthcare problem. These large scale injuries overwhelm the innate repair mechanisms present in skeletal muscle and result in the clinical pathology termed volumetric muscle loss (VML). The current standard of care for VML repair is an autologous graft, which has a reduced functional outcome and is limited by re-innervation and re-vascularization, which may ultimately result in graft failure via tissue necrosis. There are several tissue engineered strategies designed to treat VML defects; however, none of these strategies simultaneously target vascularization and innervation. Tissue regeneration includes a complex set of coordinated events involving the growth, re-vascularization, and re-innervation of new tissue. Often, the success of tissue engineered constructs is limited by their ability to integrate with host vascular and neuronal tissue. The extent to which these systems communicate to support regeneration remains poorly understood. We hypothesize that vascularization and innervation are critical processes that are required to direct and sustain cell migration and differentiation in tissue regeneration. Further, we hypothesize that the signaling between vascularization and innervation are complementary to instruct regeneration. We will investigate the temporal nature of these signaling mechanisms to determine if vascularization precedes innervation, or vice versa, in mammalian regeneration by designing a biomaterial system where the distance between the two cell types and the availability of extracellular matrix molecules will be systematically varied to assess vascular and neuronal network formation (Aim 1). Concurrently, we will assess the ability of soluble factors within biomimetic constructs to model vascularization and innervation by determining the maturity and functionality of these tissue structures in a controlled in vitro environment (Aim 2). Finally, to address the clinical need of craniofacial VML injuries, we will develop a vascularized and innervated skeletal muscle model to understand how these processes affect and instruct skeletal muscle tissue formation by measuring force production of tissue constructs (Aim 3). The overall goal of this proposal is to generate an in vitro culture system to understand the interactions between vascularization and innervation processes, to elucidate signaling mechanisms involved, and ultimately to identify strategies to enhance tissue regeneration.
血管化和神经支配在再生医学中的作用 骨骼肌缺陷,如严重车祸等创伤性损伤, 癌症切除术或战场损伤代表了重要的健康护理问题。这些大规模的伤害 压倒了骨骼肌中存在的先天修复机制,并导致称为 肌肉体积损失(VML)。VML修复的当前护理标准是自体移植物,其具有 功能结果降低,并受到神经支配和血管重建的限制,这可能最终导致 组织坏死导致移植物衰竭有几种组织工程策略设计用于治疗VML 缺陷;然而,这些策略中没有一个同时靶向血管化和神经支配。 组织再生包括一组复杂的协调事件,涉及生长,血管再生, 和新组织的神经再生通常,组织工程构建物的成功受限于它们的能力, 与宿主血管和神经组织整合。这些系统进行通信以支持 再生仍然知之甚少。我们假设血管化和神经支配是关键 在组织再生中,这些过程是指导和维持细胞迁移和分化所需的。 此外,我们假设血管化和神经支配之间的信号是互补的, 指示再生。我们将研究这些信号机制的时间性质,以确定是否 通过设计一种生物材料, 系统,其中两种细胞类型之间的距离和细胞外基质分子的可用性将 系统地改变以评估血管和神经元网络的形成(目的1)。同时,我们将 评估仿生结构内的可溶性因子模拟血管化和神经支配的能力, 确定这些组织结构在受控的体外环境中的成熟度和功能性(目标2)。 最后,为了解决颅面VML损伤的临床需求,我们将开发一种血管化和神经支配的 骨骼肌模型,以了解这些过程如何影响和指导骨骼肌组织的形成 通过测量组织构建体的力产生(目标3)。本提案的总体目标是, 体外培养系统,以了解血管化和神经支配过程之间的相互作用, 阐明相关的信号机制,并最终确定增强组织再生的策略。

项目成果

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Jonathan M. Grasman其他文献

Jonathan M. Grasman的其他文献

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{{ truncateString('Jonathan M. Grasman', 18)}}的其他基金

Acellular composite hydrogel scaffolds for volumetric muscle regeneration
用于体积肌肉再生的脱细胞复合水凝胶支架
  • 批准号:
    10372733
  • 财政年份:
    2022
  • 资助金额:
    $ 5.77万
  • 项目类别:
Acellular composite hydrogel scaffolds for volumetric muscle regeneration
用于体积肌肉再生的脱细胞复合水凝胶支架
  • 批准号:
    10835331
  • 财政年份:
    2022
  • 资助金额:
    $ 5.77万
  • 项目类别:
Acellular composite hydrogel scaffolds for volumetric muscle regeneration
用于体积肌肉再生的脱细胞复合水凝胶支架
  • 批准号:
    10555267
  • 财政年份:
    2022
  • 资助金额:
    $ 5.77万
  • 项目类别:
Designing Fibrin Microthread Scaffolds for Skeletal Muscle Regeneration
设计用于骨骼肌再生的纤维蛋白微丝支架
  • 批准号:
    8524360
  • 财政年份:
    2013
  • 资助金额:
    $ 5.77万
  • 项目类别:
Designing Fibrin Microthread Scaffolds for Skeletal Muscle Regeneration
设计用于骨骼肌再生的纤维蛋白微丝支架
  • 批准号:
    8669728
  • 财政年份:
    2013
  • 资助金额:
    $ 5.77万
  • 项目类别:

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