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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS051320-03
Application #
7384991
Study Section
Special Emphasis Panel (ZRG1-MDCN-K (54))
Program Officer
Kleitman, Naomi
Project Start
2006-04-15
Project End
2010-02-28
Budget Start
2008-03-01
Budget End
2009-02-28
Support Year
3
Fiscal Year
2008
Total Cost
$382,451
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Wadduwage, Dushan N; Kay, Jennifer; Singh, Vijay Raj et al. (2018) Automated fluorescence intensity and gradient analysis enables detection of rare fluorescent mutant cells deep within the tissue of RaDR mice. Sci Rep 8:12108
Yannas, Ioannis V; Tzeranis, Dimitrios S; So, Peter T C (2018) Regeneration mechanism for skin and peripheral nerves clarified at the organ and molecular scales. Curr Opin Biomed Eng 6:1-7
Hosseini, Poorya; Jin, Di; Yaqoob, Zahid et al. (2018) Single-shot dual-wavelength interferometric microscopy. Methods 136:35-39
Wadduwage, Dushan N; Singh, Vijay Raj; Choi, Heejin et al. (2017) Near-common-path interferometer for imaging Fourier-transform spectroscopy in wide-field microscopy. Optica 4:546-556
Yannas, Ioannis V; Tzeranis, Dimitrios S; So, Peter T C (2017) Regeneration of injured skin and peripheral nerves requires control of wound contraction, not scar formation. Wound Repair Regen 25:177-191
Hosseini, Poorya; Abidi, Sabia Z; Du, E et al. (2016) Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease. Proc Natl Acad Sci U S A 113:9527-32
Tzeranis, Dimitrios S; Soller, Eric C; Buydash, Melissa C et al. (2016) In Situ Quantification of Surface Chemistry in Porous Collagen Biomaterials. Ann Biomed Eng 44:803-15
Kang, Jeon Woong; So, Peter T C; Dasari, Ramachandra R et al. (2015) High resolution live cell Raman imaging using subcellular organelle-targeting SERS-sensitive gold nanoparticles with highly narrow intra-nanogap. Nano Lett 15:1766-72
Cha, Jae Won; Yew, Elijah Y S; Kim, Daekeun et al. (2015) Non-descanned multifocal multiphoton microscopy with a multianode photomultiplier tube. AIP Adv 5:084802
Hosseini, Poorya; Sung, Yongjin; Choi, Youngwoon et al. (2015) Scanning color optical tomography (SCOT). Opt Express 23:19752-62

Showing the most recent 10 out of 22 publications