Regenerative Healing Using ECM Based Scaffolds

描述(申请人提供)：有越来越多的证据表明，成年哺乳动物受损器官的愈合过程可以被修改，以产生部分或全部再生的器官。大多数证据最初来自于对皮肤再生、周围神经再生和结膜再生的研究。最近，几个实验室在研究其他器官的再生方面取得了进展，包括心脏瓣膜、泌尿系统器官、骨骼和脊髓。在这项拟议的研究中，将研究周围神经系统再生的诱导机制。最近获得的证据表明，在大鼠坐骨神经横断愈合过程中，收缩成纤维细胞在再生神经周围形成一个包膜。数据表明，这些可收缩的成纤维细胞压迫再生的神经，限制了直径接近正常的发育。这一数据进一步表明，使用导致囊膜变薄的支架有望减弱收缩力量，提高再生质量。在修复大鼠周围神经的过程中，阻断收缩过程的研究将主要使用破坏收缩细胞的支架来阻止它们的组织。阻断α-平滑肌肌动蛋白合成的药理制剂也将被使用。再生神经的结构将部分通过新的方法进行研究，这种方法将适应受损的周围神经系统：双光子显微镜和二次谐波产生。我们将试图阐明受损神经愈合过程中收缩阻断的机制，并找出与诱导再生的联系。在修复大鼠周围神经的过程中，阻断收缩过程的研究将主要使用破坏收缩细胞的支架来阻止它们的组织。阻断α-平滑肌作用合成的药理制剂也将被使用。再生神经的结构将部分通过新的方法进行研究，这种方法将适应受损的周围神经系统：双光子显微镜和二次谐波产生。我们将试图阐明受损神经愈合过程中收缩阻断的机制，并找出与诱导再生的联系。

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.