Modulating immune response inside biomaterial-based nerve conduits to stimulate endogenous peripheral nerve regeneration

dc.contributor.advisor Bellamkonda, Ravi V.
dc.contributor.author Mokarram-Dorri, Nassir
dc.contributor.committeeMember Botchwey, Edward A.
dc.contributor.committeeMember English, Arthur W.
dc.contributor.committeeMember García, Andrés J.
dc.contributor.committeeMember Milam, Valeria
dc.contributor.department Materials Science and Engineering
dc.date.accessioned 2016-05-27T13:09:42Z
dc.date.available 2016-05-27T13:09:42Z
dc.date.created 2015-05
dc.date.issued 2015-01-26
dc.date.submitted May 2015
dc.date.updated 2016-05-27T13:09:42Z
dc.description.abstract Injuries to the peripheral nervous system (PNS) are major and common source of disability, impairing the ability to move muscles and/or feel normal sensations, or resulting in painful neuropathies. Annually traumatic nerve injuries resulting from collisions, gunshot wounds, fractures, motor vehicle accidents, lacerations, and other forms of penetrating trauma, affected more than 250,000 patients just in the U.S. The clinical gold standard to bridge long non-healing nerve gaps is to use a nerve autograft- typically the patient’s own sural nerve. However, autografts are not ideal because of the need for secondary surgery to ‘source’ the nerve, loss of function at the donor site, lack of appropriate source nerve in diabetic patients, neuroma formation, and the need for multiple graft segments. Despite our best efforts, finding alternative ‘nerve bridges’ for peripheral nerve repair remains challenging – of the four nerve ‘tubes’ FDA approved for use in the clinic, none is typically used to bridge gaps longer than 10 mm due to poor outcomes. Hence, there is a compelling need to design alternatives that match or exceed the performance of autografts across critically sized nerve gaps. Here we demonstrate that early modulation of innate immune response at the site of peripheral nerve injury inside biomaterials-based conduit can favorably bias the endogenous regenerative potential after injury that obviates the need for the downstream modulation of multiple factors and has significant implications for the treatment of long peripheral nerve gaps. Moreover, our study strongly suggests that more than the extent of macrophage presence, their specific phenotype at the site of injury influence the regenerative outcomes. This research will advance our knowledge regarding peripheral nerve regeneration, and help developing technologies that are likely to improve clinical outcomes after peripheral nerve injury. The significant results presented here are complementary to a growing body of evidence showing the direct correlation between macrophage phenotype and the regeneration outcome of injured tissues.
dc.description.degree Ph.D.
dc.format.mimetype application/pdf
dc.identifier.uri http://hdl.handle.net/1853/54860
dc.language.iso en_US
dc.publisher Georgia Institute of Technology
dc.subject Nerve repair
dc.subject Immunomodulation
dc.subject Macrophage
dc.title Modulating immune response inside biomaterial-based nerve conduits to stimulate endogenous peripheral nerve regeneration
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Bellamkonda, Ravi V.
local.contributor.corporatename School of Materials Science and Engineering
local.contributor.corporatename College of Engineering
relation.isAdvisorOfPublication f1573a22-1a64-4505-8ce5-3491adf90ce5
relation.isOrgUnitOfPublication 21b5a45b-0b8a-4b69-a36b-6556f8426a35
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
thesis.degree.level Doctoral
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
3.97 MB
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
3.87 KB
Plain Text