Structural and Chemical Modification to Improve Adhesive and Material Properties of Fibrin-Genipin for Repair of Annulus Fibrosus Defects in Intervertebral Disks

Michelle A. Cruz, Steven McAnany, Nikita Gupta, Rose G. Long, Philip Nasser, David Eglin, Andrew C. Hecht, Svenja Illien-Junger, James C. Iatridis

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Annulus fibrosus (AF) defects from intervertebral disk (IVD) herniation and degeneration are commonly associated with back pain. Genipin-crosslinked fibrin hydrogel (FibGen) is an injectable, space-filling AF sealant that was optimized to match AF shear properties and partially restored IVD biomechanics. This study aimed to enhance mechanical behaviors of FibGen to more closely match AF compressive, tensile, and shear properties by adjusting genipin crosslink density and by creating a composite formulation by adding Poly(D,L-lactide-co-glycolide) (PDLGA). This study also evaluated effects of thrombin concentration and injection technique on gelation kinetics and adhesive strength. Increasing FibGen genipin concentration from 1 to 36 mg/mL significantly increased adhesive strength (-1/45 to 35 kPa), shear moduli (-1/410 to 110 kPa), and compressive moduli (-1/425 to 150 kPa) with concentration-dependent effects, and spanning native AF properties. Adding PDLGA to FibGen altered the material microstructure on electron microscopy and nearly tripled adhesive strength, but did not increase tensile moduli, which remained nearly 5× below native AF, and had a small increase in shear moduli and significantly decreased compressive moduli. Increased thrombin concentration decreased gelation rate to < 5 min and injection methods providing a structural FibGen cap increased pushout strength by -1/440%. We conclude that FibGen is highly modifiable with tunable mechanical properties that can be formulated to be compatible with human AF compressive and shear properties and gelation kinetics and injection techniques compatible with clinical discectomy procedures. However, further innovations, perhaps with more efficient fiber reinforcement, will be required to enable FibGen to match AF tensile properties.

Original languageEnglish
Article number084501
JournalJournal of Biomechanical Engineering
Volume139
Issue number8
DOIs
StatePublished - Aug 1 2017

Bibliographical note

Funding Information:
This study was supported by NIAMS Grant No. R01 AR057397. MAC was supported by NIH Grant No. R25 GM064118. Microscopy was performed in the Microscopy CORE at the Icahn School of Medicine at Mount Sinai, supported by NIH Shared Instrumentation Grant No. S10RR026639-01.

Publisher Copyright:
© 2017 by ASME.

Keywords

  • Annulus fibrosus repair
  • adhesive biomaterial
  • genipin
  • intervertebral disk herniation
  • tissue engineering

ASJC Scopus subject areas

  • Biomedical Engineering
  • Physiology (medical)

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