A synthetic biomaterials approach to the prevention of postsurgical adhesions in neurosurgery

In the treatment of spinal stenosis and disc herniation, the lamina and ligamentum flavum are resected to access the spinal canal. When a fibrous scar replaces the surgical defect, the dura or spinal nerves can become tethered to the surrounding tissues. Kuslich et al. and Smyth and Wright demonstrated that light mechanical stimulation of injured spinal nerves induced intraoperative or postoperative sciatic pain similar to the patients’ preoperative state [1, 2]. Therefore, adhesive peridural fibrosis contributes to the recurrence of back pain following neurosurgery. In this dissertation, biomaterial membranes are evaluated for the prevention of scar progression to the dura and spinal nerves. Cell-impermeable, biodegradable tyrosine-derived polycarbonate membranes were fabricated by electrospinning. A degradable surfactant, trans-4-hyroxy-L-proline butyl ester HCl, enabled electrospinning from a low toxicity solvent (acetic acid). Anti-adhesion membranes with a 1:1 composition of glassy and rubbery polymers were fabricated by a dual-spinneret technique, where the composite membrane’s suture retention strength, delamination strength, and toughness were greater than conventional electrospun fabrics. Controlled delivery of an antifibrotic, cis-4-hydroxy-L-proline, was achieved through synthesis of drug precursors. Hexyl- and octyl-ester precursors enabled diffusion-controlled release of the antifibrotic over 1 or more weeks, while cis-4-hydroxy-L-proline diffused from poly(DTE carbonate) films within 24 hours. Composite membranes with and without antifibrotic were compared against polymer films and Integra LifeSciences’ DuraGen PLUS® in a rat laminectomy model. The extent of adhesions was evaluated at 4 and 8 weeks. The fracture of polymeric films permitted scar progression to the dura by 8 weeks, despite inhibition at 4 weeks. The composite membranes did not fracture and reduced the extent of adhesion from 84% (control) to 36%. All adhesions in the composite membrane group formed at the caudal tuck, suggesting that performance could be improved by device fixation. Any effect of cis-4-hydroxy-L-proline was obscured by caudal instability. DuraGen PLUS® limited the extent of adhesion to 11%, and the adhesions present were comparatively light. In this dissertation, a synthetic degradable membrane was compared against polymeric films and DuraGen PLUS® in peridural adhesion prevention. The membrane possessed inherent barrier properties, superior mechanical properties, and the ability to deliver an antifibrotic. However, the device did not achieve anti-adheisve performance comparable to Integra LifeSciences’ DuraGen PLUS® in a rat laminectomy model due to the electrospun anti-adhesion membrane’s instability within the implantation site.Ph.D.Includes bibliographical referencesIncludes vitaby Charles A. Flore

Characterization of Organics Consistent with b-Chitin Preserved in the Late Eocene Cuttlefish Mississaepia mississippiensis.

Background: Preservation of original organic components in fossils across geological time is controversial, but the potential such molecules have for elucidating evolutionary processes and phylogenetic relationships is invaluable. Chitin is one such molecule. Ancient chitin has been recovered from both terrestrial and marine arthropods, but prior to this study had not been recovered from fossil marine mollusks. Methodology/Principal Findings: Organics consistent with b-chitin are recovered in cuttlebones of Mississaepia mississippiensis from the Late Eocene (34.36 million years ago) marine clays of Hinds County, Mississippi, USA. These organics were determined and characterized through comparisons with extant taxa using Scanning Electron Microscopy/Energy Dispersive Spectrometry (SEM/EDS), Field Emission Scanning Electron Microscopy (Hyperprobe), Fourier Transmission Infrared Spectroscopy (FTIR) and Immunohistochemistry (IHC). Conclusions/Significance: Our study presents the first evidence for organics consistent with chitin from an ancient marine mollusk and discusses how these organics have been degraded over time. As mechanisms for their preservation, we propose that the inorganic/organic lamination of the cuttlebone, combined with a suboxic depositional environment with available free Fe2+ ions, inhibited microbial or enzymatic degradation.shell morphology and ultrastructure as a key to coleoid cephalopod phylogen