Regenerative Healing Using ECM Based Scaffolds

描述（由申请人提供）：有越来越多的证据表明，成年哺乳动物中受损器官的愈合过程可以改变，以产生部分或全部再生的器官。大多数证据最初来自皮肤再生、周围神经再生和结膜再生的研究。 最近，几个实验室报告了其他器官再生研究的进展，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，在愈合的横断大鼠坐骨神经，收缩成纤维细胞组织在一个胶囊，周围的再生神经。这些数据表明，这些收缩性成纤维细胞压缩再生神经，限制了接近正常直径的发育。该数据进一步表明，使用诱导该囊变薄的支架预计会减弱收缩力，提高再生质量。在大鼠周围神经愈合过程中阻断收缩过程将主要使用扰乱收缩细胞的支架进行研究，防止其组织化。 还将使用阻断α-平滑肌肌动蛋白合成的药理学试剂。再生神经的结构将通过新的方法进行部分研究，该方法将适用于受损的外周神经系统：双光子显微镜和二次谐波发生。将试图阐明在损伤神经愈合过程中收缩阻滞的机制，并找出与诱导再生的关联（如果有的话）。在大鼠周围神经愈合过程中阻断收缩过程将主要使用扰乱收缩细胞的支架进行研究，防止其组织化。还将使用阻断α-平滑肌作用的合成的药理学试剂。再生神经的结构将通过新的方法进行部分研究，该方法将适用于受损的外周神经系统：双光子显微镜和二次谐波发生。将试图阐明在损伤神经愈合过程中收缩阻滞的机制，并找出与诱导再生的关联（如果有的话）。

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.