Regenerative Healing Using ECM Based Scaffolds

使用基于 ECM 的支架进行再生治疗

• 批准号: 7220056
• 负责人: IOANNIS V YANNAS
• 金额: $ 37.94万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7220056
• 关键词: Actins; Adhesions; Adult; Agonist; Animals; Antibodies; Axon; Biological Assay; Blocking Antibodies; Caliber; Cell-Matrix Junction; Cells; Cicatrix; Class; Collagen Fiber; Condition; Confocal Microscopy; Cultured Cells; Data; Development; Disorientation; Disruption; Extracellular Matrix; Fibroblasts; Focal Adhesion Kinase 1; Generations; Healed; Heart Valves; Histology; Image; In Vitro; 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; Photons; 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; Week; base; bone; capsule; conjunctiva; day; density; dosage; expectation; healing; improved; inhibitor/antagonist; injured; instrument; migration; prevent; programs; relating to nervous system; response; rho; scaffold; sciatic nerve; second harmonic; two-photon; urologic

DESCRIPTION (provided by applicant): 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: 2-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: 2-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.

描述（由申请人提供）：有积累的证据表明，可以修改成人哺乳动物中受伤器官的愈合过程，以产生部分或全乙烯的器官。大多数证据最初来自对皮肤再生，周围神经再生和结膜再生的研究。 最近，在几个实验室中，在其他器官的再生研究中，包括心脏瓣膜，泌尿科器官，骨骼和脊髓的进展。在拟议的研究中，将在周围神经系统中研究诱导再生的机制。最近获得的证据表明，在横向大鼠坐骨神经的愈合过程中，收缩的成纤维细胞在围绕着再生神经的胶囊中组织起来。数据表明，这些收缩成纤维细胞会压缩再生神经，从而限制了直径接近正常的发展。该数据进一步表明，使用诱导该胶囊稀疏的脚手架有望削弱收缩力，从而提高再生的质量。将主要使用混乱的收缩细胞，阻止其组织的脚手架来研究大鼠愈合外周神经的收缩过程。 还将采用阻断合成A平滑肌肌动蛋白合成的药理剂。再生神经的结构将部分通过新方法研究，该方法将适应受伤的周围神经系统：2光子显微镜和第二次谐波生成。将尝试在受伤的神经治愈过程中阐明收缩阻塞的机制，并发现与诱导的再生相关（如果有的话）。将主要使用混乱的收缩细胞，阻止其组织的脚手架来研究大鼠愈合外周神经的收缩过程。还将采用阻断A-Smooth肌肉作用合成的药理剂。再生神经的结构将部分通过新方法研究，该方法将适应受伤的周围神经系统：2光子显微镜和第二次谐波生成。将尝试在受伤的神经治愈过程中阐明收缩阻塞的机制，并发现与诱导的再生相关（如果有的话）。