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Regenerative Healing Using ECM Based Scaffolds

使用基于 ECM 的支架进行再生治疗

基本信息

批准号：
7563988
负责人：
IOANNIS V YANNAS
金额：
$ 39.56万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-04-15 至 2012-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7563988
关键词：
Actins Adhesions Adult Agonist Animals Antibodies Axon Biological Assay Blocking Antibodies Caliber Cell Culture Techniques Cell-Matrix Junction Cells Cicatrix Collagen Fiber Confocal Microscopy Data Development Disorientation Extracellular Matrix Fibroblasts Focal Adhesion Kinase 1 Generations Healed Heart Valves Histology Image Integrins Laboratories Lead Length Longitudinal Studies Mammals Measurable Measurement Mechanics Methodology Methods Microscopy Modeling Monitor Morphology Myofibroblast Myosin ATPase Natural regeneration Nerve Nerve Regeneration Operative Surgical Procedures Optical Biopsy Optics Organ Pathway interactions Peripheral Nerves Peripheral Nervous System Phosphorylation Process Property Radial Rattus Reporting Research Research Personnel Rho-associated kinase Skin Smooth Muscle Smooth Muscle Actin Staining Method Solutions Spectrum Analysis Spinal Cord Staining method Stains Structure Surface Techniques Testing Thick Tissues Traction Trichrome stain base bone capsule conjunctiva density dosage expectation healing improved in vitro testing inhibitor/antagonist injured instrument migration prevent programs regenerative relating to nervous system response rho scaffold sciatic nerve second harmonic skin regeneration two-photon urologic

项目摘要

There is accumulating evidence that the healing process of an injured organ in the adult mammal can be modified to yield a partly or wholly regenerated organ. The majority of the evidence has originally come from studies of skin regeneration, peripheral nerve regeneration and conjunctiva regeneration. Recently, progress has been reported in several laboratories in studies of regeneration of other organs, including heart valves, urological organs, bone and the spinal cord. In the proposed study the mechanism of induction of regeneration will be studied in the peripheral nervous system. Recently obtained evidence shows that during healing of the transected rat sciatic nerve, contractile fibroblasts organize in a capsule that surrounds the regenerating nerve. The data suggest that these contractile fibroblasts compress the regenerating nerve, limiting development of a near normal diameter. This data further suggests that use of scaffolds that induces thinning of this capsule is expected to weaken contractile forces, enhancing the quality of regeneration. Blocking of the contraction process in healing peripheral nerves in rats will be studied primarily using scaffolds that disorganize contractile cells, preventing their organization. Pharmacological agents that block synthesis of a-smooth muscle actin will also be employed. The structure of the regenerating nerve will be studied in part by new methodology that will be adapted to the injured peripheral nervous system: two-photon microscopy and second harmonic generation. An attempt will be made to elucidate the mechanism of contraction blocking during healing of injured nerves, and to find out an association, if any, with induced regeneration. Blocking of the contraction process in healing peripheral nerves in rats will be studied primarily using scaffolds that disorganize contractile cells, preventing their organization. Pharmacological agents that block synthesis of a-smooth muscle action will also be employed. The structure of the regenerating nerve will be studied in part by new methodology that will be adapted to the injured peripheral nervous system: two-photon microscopy and second harmonic generation. An attempt will be made to elucidate the mechanism of contraction blocking during healing of injured nerves, and to find out an association, if any, with induced regeneration.

有越来越多的证据表明，成年哺乳动物受伤器官的愈合过程可以被修改，产生部分或全部再生的器官。大多数证据最初来自皮肤研究再生、周围神经再生和结膜再生。最近，据报道，几个实验室在研究其他器官的再生，包括心脏瓣膜，泌尿器官，骨骼和脊髓在拟定研究中，将在周围神经系统中研究再生诱导机制。最近获得的证据表明，在大鼠坐骨神经横断愈合过程中，收缩性成纤维细胞组织在一个包围着再生神经的囊里。这些数据表明，这些收缩性成纤维细胞压缩再生神经，限制接近正常直径的发育。该数据进一步表明，诱导这种胶囊变薄，预计将削弱收缩力，提高再生质量。将主要使用支架来研究大鼠周围神经愈合中收缩过程的阻断，破坏收缩细胞阻止它们的组织阻断α-平滑肌合成的药物也将使用肌肉肌动蛋白。再生神经的结构将通过新的方法学进行部分研究这将适用于受伤的周围神经系统：双光子显微镜和二次谐波产生。本文试图阐明损伤神经愈合过程中收缩阻滞的机制，找出与诱导再生之间的联系，如果有的话。将主要使用支架来研究大鼠周围神经愈合中收缩过程的阻断，破坏收缩细胞阻止它们的组织阻断α-平滑肌合成的药物还将使用肌肉动作。再生神经的结构将部分由新的方法，将适用于受伤的周围神经系统：双光子显微镜和第二次谐波发生本文将试图阐明创伤愈合过程中收缩阻滞的机制。损伤的神经，并找出一个协会，如果有的话，与诱导再生。