title: Molecular sequelae of topographically guided peripheral nerve repair.
abstract: Peripheral nerve injuries cause severe disability with decreased nerve function often followed by neuropathic pain that impacts the quality of life. Even though use of autografts is the current gold standard, nerve conduits fabricated from electrospun nanofibers have shown promise to successfully bridge critical length nerve gaps. However, in depth analysis of the role of topographical cues in the context of spatio-temporal progression of the regenerative sequence has not been elucidated. Here, we explored the influence of topographical cues (aligned, random, and smooth films) on the regenerative sequence and potential to successfully support nerve regeneration in critical size gaps. A number of key findings emerged at the cellular, cytokine and molecular levels from the study. Higher quantities of IL-1α and TNF-α were detected in aligned fiber based scaffolds. Differential gene expression of BDNF, NGFR, ErbB2, and ErbB3 were observed suggesting a role for these genes in influencing Schwann cell migration, myelination, etc. that impact the regeneration in various topographies. Fibrin matrix stabilization and arrest of nerve-innervated muscle atrophy was also evident. Taken together, our data shed light on the cascade of events that favor regeneration in aligned topography and should stimulate research to further refine the strategy of nerve regeneration using topographical cues.
authors.affiliation: Neurological Biomaterials and Cancer Therapeutics Laboratory, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University School of Medicine, UA Whitaker Building, 313 Ferst Drive, Atlanta, GA, 30332-0535, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Mukhatyar
authors.forename: Balakrishna
authors.initials: B
authors.lastname: Pai
authors.forename: Isaac
authors.initials: I
authors.lastname: Clements
authors.forename: Akhil
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Richard
authors.initials: R
authors.lastname: Huber
authors.forename: Akash
authors.initials: A
authors.lastname: Mehta
authors.forename: Shoumit
authors.initials: S
authors.lastname: Mukhopadaya
authors.forename: Soumon
authors.initials: S
authors.lastname: Rudra
authors.forename: Gaurangkumar
authors.initials: G
authors.lastname: Patel
authors.forename: Lohitash
authors.initials: L
authors.lastname: Karumbaiah
authors.forename: Ravi
authors.initials: R
authors.lastname: Bellamkonda
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D048091:Guided Tissue Regeneration / Q000379:methods*; D008297:Male; D057139:Nanofibers / Q000737:chemistry*; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D009419:Nerve Tissue Proteins