Regenerative Healing Using ECM Based Scaffolds

使用基于 ECM 的支架进行再生治疗

• 批准号: 7384991
• 负责人: IOANNIS V YANNAS
• 金额: $ 38.25万
• 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/7384991
• 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; 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

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.

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为 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。近日，有进展报道称 多个实验室研究其他器官的再生，包括心脏瓣膜、泌尿器官、骨骼和 脊髓。 在拟议的研究中，将研究周围神经系统再生诱导的机制。 最近获得的证据表明，在横断的大鼠坐骨神经愈合过程中，收缩性成纤维细胞组织 在围绕再生神经的胶囊中。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。该数据进一步表明支架的使用 导致该胶囊变薄预计会削弱收缩力，从而提高再生质量。 将主要使用支架来研究阻断大鼠周围神经愈合过程中的收缩过程 扰乱收缩细胞，阻止其组织。阻断a-smooth合成的药物 还将使用肌肉肌动蛋白。再生神经的结构将通过新方法进行部分研究 它将适应受伤的周围神经系统：双光子显微镜和二次谐波发生。 将尝试阐明受伤神经愈合过程中收缩阻断的机制，并 找出与诱导再生的关联（如果有的话）。 将主要使用支架来研究阻断大鼠周围神经愈合过程中的收缩过程 扰乱收缩细胞，阻止其组织。阻断a-smooth合成的药物 还将使用肌肉动作。新的研究人员将部分研究再生神经的结构 将适应受伤的周围神经系统的方法：双光子显微镜和第二 谐波的产生。将尝试阐明愈合过程中收缩阻断的机制。 受伤的神经，并找出与诱导再生的关联（如果有的话）。