title: Mechanical restoration and failure analyses of a hydrogel and scaffold composite strategy for annulus fibrosus repair.
abstract: Unrepaired defects in the annulus fibrosus of intervertebral disks are associated with degeneration and persistent back pain. A clinical need exists for a disk repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of herniation. Multiple annulus repair strategies were developed using poly(trimethylene carbonate) scaffolds optimized for cell delivery, polyurethane membranes designed to prevent herniation, and fibrin-genipin adhesive tuned to annulus fibrosus shear properties. This three-part study evaluated repair strategies for biomechanical restoration, herniation risk and failure mode in torsion, bending and compression at physiological and hyper-physiological loads using a bovine injury model. Fibrin-genipin hydrogel restored some torsional stiffness, bending ROM and disk height loss, with negligible herniation risk and failure was observed histologically at the fibrin-genipin mid-substance following rigorous loading. Scaffold-based repairs partially restored biomechanics, but had high herniation risk even when stabilized with sutured membranes and failure was observed histologically at the interface between scaffold and fibrin-genipin adhesive. Fibrin-genipin was the simplest annulus fibrosus repair solution evaluated that involved an easily deliverable adhesive that filled irregularly-shaped annular defects and partially restored disk biomechanics with low herniation risk, suggesting further evaluation for disk repair may be warranted.
  
  
  CONCLUSIONS
  Lower back pain is the leading cause of global disability and commonly caused by defects and failure of intervertebral disk tissues resulting in herniation and compression of adjacent nerves. Annulus fibrosus repair materials and techniques have not been successful due to the challenging mechanical and chemical microenvironment and the needs to restore biomechanical behaviors and promote healing with negligible herniation risk while being delivered during surgical procedures. This work addressed this challenging biomaterial and clinical problem using novel materials including an adhesive hydrogel, a scaffold capable of cell delivery, and a membrane to prevent herniation. Composite repair strategies were evaluated and optimized in quantitative three-part study that rigorously evaluated disk repair and provided a framework for evaluating alternate repair techniques.
authors.affiliation: Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Collaborative Research Partner Annulus Fibrosus Rupture Program of AO Foundation, Davos, Switzerland.
authors.forename: Rose G
authors.initials: RG
authors.lastname: Long
authors.affiliation: Institute for Surgical Technology & Biomechanics, University of Bern, Bern, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bürki
authors.affiliation: Institute for Surgical Technology & Biomechanics, University of Bern, Bern, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Zysset
authors.affiliation: AO Research Institute Davos, Davos, Switzerland; Collaborative Research Partner Annulus Fibrosus Rupture Program of AO Foundation, Davos, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Eglin
authors.affiliation: Collaborative Research Partner Annulus Fibrosus Rupture Program of AO Foundation, Davos, Switzerland; University of Twente, Department of Biomaterials Science and Technology, PO Box 217, 7500 AE Enschede, The Netherlands; University of Groningen, University Medical Centre Groningen, Department of Biomedical Engineering, PO Box 196, 9700 AD Groningen, The Netherlands.
authors.forename: Dirk W
authors.initials: DW
authors.lastname: Grijpma
authors.affiliation: Collaborative Research Partner Annulus Fibrosus Rupture Program of AO Foundation, Davos, Switzerland; University of Twente, Department of Biomaterials Science and Technology, PO Box 217, 7500 AE Enschede, The Netherlands.
authors.forename: Sebastien B G
authors.initials: SBG
authors.lastname: Blanquer
authors.affiliation: Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Hecht
authors.affiliation: Leni & Peter W. May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Collaborative Research Partner Annulus Fibrosus Rupture Program of AO Foundation, Davos, Switzerland. Electronic address: james.iatridis@mssm.edu.
authors.forename: James C
authors.initials: JC
authors.lastname: Iatridis
mesh_terms: D000818:Animals; D002417:Cattle; D019544:Equipment Failure Analysis; D015718:Fibrin Tissue Adhesive / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D020007:Implants, Experimental; D007403:Intervertebral Disc; D055959:Intervertebral Disc Degeneration / Q000601:surgery; D011475:Prosthesis Failure; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D015718:Fibrin Tissue Adhesive; D020100:Hydrogels
keywords: Annular closure; Annulus fibrosus repair; Intervertebral disk degeneration; Intervertebral disk herniation; Spine biomechanics