title: Fibrin glue as a stabilization strategy in peripheral nerve repair when using porous nerve guidance conduits.
abstract: Porous conduits provide a protected pathway for nerve regeneration, while still allowing exchange of nutrients and wastes. However, pore sizes >30 µm may permit fibrous tissue infiltration into the conduit, which may impede axonal regeneration. Coating the conduit with Fibrin Glue (FG) is one option for controlling the conduit's porosity. FG is extensively used in clinical peripheral nerve repair, as a tissue sealant, filler and drug-delivery matrix. Here, we compared the performance of FG to an alternative, hyaluronic acid (HA) as a coating for porous conduits, using uncoated porous conduits and reverse autografts as control groups. The uncoated conduit walls had pores with a diameter of 60 to 70 µm that were uniformly covered by either FG or HA coatings. In vitro, FG coatings degraded twice as fast as HA coatings. In vivo studies in a 1 cm rat sciatic nerve model showed FG coating resulted in poor axonal density (993 ± 854 #/mm2), negligible fascicular area (0.03 ± 0.04 mm2), minimal percent wet muscle mass recovery (16 ± 1 in gastrocnemius and 15 ± 5 in tibialis anterior) and G-ratio (0.73 ± 0.01). Histology of FG-coated conduits showed excessive fibrous tissue infiltration inside the lumen, and fibrin capsule formation around the conduit. Although FG has been shown to promote nerve regeneration in non-porous conduits, we found that as a coating for porous conduits in vivo, FG encourages scar tissue infiltration that impedes nerve regeneration. This is a significant finding considering the widespread use of FG in peripheral nerve repair.
authors.affiliation: New Jersey Center for Biomaterials, Rutgers-The State University of New Jersey, 145 Bevier Road, Piscataway, NJ, 08854, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Bhatnagar
authors.affiliation: New Jersey Center for Biomaterials, Rutgers-The State University of New Jersey, 145 Bevier Road, Piscataway, NJ, 08854, USA.|School of Pharmacy, University of Wyoming, 1000 E University Ave Dept. 3375, Laramie, WY, 82071, USA.
authors.forename: Jared S
authors.initials: JS
authors.lastname: Bushman
authors.affiliation: New Jersey Center for Biomaterials, Rutgers-The State University of New Jersey, 145 Bevier Road, Piscataway, NJ, 08854, USA.
authors.forename: N Sanjeeva
authors.initials: NS
authors.lastname: Murthy
authors.affiliation: New Jersey Center for Biomaterials, Rutgers-The State University of New Jersey, 145 Bevier Road, Piscataway, NJ, 08854, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Merolli
authors.affiliation: New Jersey Center for Biomaterials, Rutgers-The State University of New Jersey, 145 Bevier Road, Piscataway, NJ, 08854, USA.
authors.forename: Hilton M
authors.initials: HM
authors.lastname: Kaplan
authors.affiliation: New Jersey Center for Biomaterials, Rutgers-The State University of New Jersey, 145 Bevier Road, Piscataway, NJ, 08854, USA. kohn@rutgers.edu.
authors.forename: Joachim
authors.identifier: http://orcid.org/0000-0002-5834-6536
authors.initials: J
authors.lastname: Kohn
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D019245:Compressive Strength; D003432:Cross-Linking Reagents / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D018482:Muscle, Skeletal / Q000378:metabolism; D009416:Nerve Regeneration; D011108:Polymers / Q000737:chemistry; D016062:Porosity; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D015718:Fibrin Tissue Adhesive; D020100:Hydrogels; D011108:Polymers; D006820:Hyaluronic Acid