title: Riboflavin crosslinked high-density collagen gel for the repair of annular defects in intervertebral discs: An in vivo study.
abstract: Open annular defects compromise the ability of the annulus fibrosus to contain nuclear tissue in the disc space, and therefore lead to disc herniation with subsequent degenerative changes to the entire intervertebral disc. This study reports the use of riboflavin crosslinked high-density collagen gel for the repair of annular defects in a needle-punctured rat-tail model. High-density collagen has increased stiffness and greater hydraulic permeability than conventional low-density gels; riboflavin crosslinking further increases these properties. This study found that treating annular defects with crosslinked high-density collagen inhibited the progression of disc degeneration over 18 weeks compared to untreated control discs. Histological sections of FITC-labeled collagen gel revealed an early tight attachment to host annular tissue. The gel was subsequently infiltrated by host fibroblasts which remodeled it into a fibrous cap that bridged the outer disrupted annular fibers and partially repaired the defect. This repair tissue enhanced retention of nucleus pulposus tissue, maintained physiological disc hydration, and preserved hydraulic permeability, according to MRI, histological, and mechanical assessments. Degenerative changes were partially reversed in treated discs, as indicated by an increase in nucleus pulposus size and hydration between weeks 5 and 18. The collagen gel appeared to work as an instant sealant and by enhancing the intrinsic healing capabilities of the host tissue.
authors.affiliation: Weill Cornell Brain and Spine Center, Department of Neurological Surgery, Weill Cornell Medical College, New York, NY, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Grunert
authors.affiliation: Department of Biomedical Engineering, Cornell University, United States.
authors.forename: Brandon H
authors.initials: BH
authors.lastname: Borde
authors.affiliation: Weill Cornell Brain and Spine Center, Department of Neurological Surgery, Weill Cornell Medical College, New York, NY, United States.
authors.forename: Sara B
authors.initials: SB
authors.lastname: Towne
authors.affiliation: Weill Cornell Brain and Spine Center, Department of Neurological Surgery, Weill Cornell Medical College, New York, NY, United States.
authors.forename: Yu
authors.initials: Y
authors.lastname: Moriguchi
authors.affiliation: Department of Biomedical Engineering, Cornell University, United States.
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Hudson
authors.affiliation: Department of Biomedical Engineering, Cornell University, United States; Sibley School of Mechanical and Aerospace Engineering, Cornell University, United States.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Bonassar
authors.affiliation: Weill Cornell Brain and Spine Center, Department of Neurological Surgery, Weill Cornell Medical College, New York, NY, United States. Electronic address: roger@hartlmd.net.
authors.forename: Roger
authors.initials: R
authors.lastname: Härtl
mesh_terms: D000818:Animals; D003094:Collagen / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005782:Gels / Q000737:chemistry; D048091:Guided Tissue Regeneration / Q000295:instrumentation* / Q000379:methods; D007405:Intervertebral Disc Displacement / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008422:Materials Testing; D051381:Rats; D011923:Rats, Nude; D012256:Riboflavin / Q000737:chemistry*; D054457:Tissue Scaffolds; D059145:Total Disc Replacement / Q000295:instrumentation*; D016896:Treatment Outcome
chemical_list: D003432:Cross-Linking Reagents; D005782:Gels; D003094:Collagen; D012256:Riboflavin
keywords: Annulus fibrosus repair; Disc degeneration; Disc herniation; High density collagen gel; Rat tail model; Riboflavin crosslinking