Regenerative Engineering of Complex Musculoskeletal Tissues and Joints

复杂肌肉骨骼组织和关节的再生工程

基本信息

批准号：
9130099
负责人：
CATO T. LAURENCIN
金额：
$ 79.75万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-18 至 2019-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Over the past 20 years, the P.I. has performed substantial work in the development of engineered systems for the regeneration of musculoskeletal tissues. Systems inspired by his work in the area of bone and soft tissue have now been implanted in man. Now I will use the collective expertise and insight I have obtained to test a bold, new hypothesis that complex tissues and joints can be created and similarly find their way to clinical use in man. For this I will use principles of Regenerative Engineering, concepts recently published in Science, Translational Medicine that refer to the use of new advances in materials science, stem cell science and the understanding of cues from developmental biology in heuristic approaches toward complex tissue regeneration. I will explore integrating the individual component tissues developed via the regenerative engineering approach using expertise in developing matrix and cell-matrix constructs for engineering tissues. As the next step we will develop what I term integrated graft systems (IGS) such as osteochondral, osteoligamentous, muscle/tendon and vascularized tissues. Subsequent steps will examine the integration of peripheral nerve into the tissue systems and to develop additional component tissues. Cues are important. I will use experience in drug delivery and investigate the use of biological effector molecules such as the bone morphogenetic proteins as cues for differentiation. We have recently described a group of molecules we term inducerons-small molecule inducers of differentiation that may be particularly suited for musculoskeletal regeneration. Working with our collaborator, we will utilize cues from developmental biology, particularly limb regeneration as an important part of our work. Finally, we have gained substantial expertise in electrical/biomechanical cues for tissue regeneration. I believe we can utilize these cues for the generation of new functional joint tissues as well as integrate

描述（由申请人提供）：在过去的20年中，P.I。在为肌肉骨骼组织再生的工程系统的开发中开发了大量工作。受他在骨骼和软组织领域的工作启发的系统现已植入人。现在，我将使用我获得的集体专业知识和洞察力来检验一个大胆的新假设，即可以创建复杂的组织和关节，并类似地找到他们在人类中的临床使用方式。为此，我将使用重生工程的原理，最近发表在科学上的概念，转化医学，指的是在材料科学，干细胞科学中使用新进步，以及对发展生物学的提示在启发式生物学方法中的理解。我将探索通过使用再生工程方法开发的单个组件组织，利用为工程组织开发矩阵和细胞矩阵构建体的专业知识。作为下一步，我们将开发我所说的整合移植系统（Ig），例如骨软骨，骨骨质，肌肉/肌腱和血管化组织。随后的步骤将检查周围神经与组织系统的整合并开发其他组成组织。提示很重要。我将利用药物递送的经验，并研究生物学效应分子（例如骨形态发生蛋白）作为分化的提示。我们最近描述了一组分子，我们将诱导剂诱导剂分化的分子定为分子，这可能特别适合肌肉骨骼再生。与我们的合作者合作，我们将利用发展生物学的线索，尤其是肢体再生作为我们工作的重要组成部分。最后，我们在组织再生的电/生物力学线索方面获得了丰富的专业知识。我相信我们可以利用这些提示来生成新的功能联合组织并整合