title: Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model.
abstract: BACKGROUND
  Disc degeneration and re-herniation after nucleotomy procedures are common problems. Simultaneous application of hyaluronic acid (HA)-based matrix has been proposed to limit disc degeneration. This, however, is hampered by loss of the substituted matrix out of the disc. Hence, in situ polymerization of the injected matrix with ultraviolet light (UVL) directly used after injection may be useful. Therefore, this study evaluates a new HA/collagen hydrogel matrix with in situ polymerization after implantation in an established porcine nucleotomy model.
  
  
  METHODS
  12 mature minipigs were used. A total of 60 lumbar discs were analyzed. 36 discs underwent partial nucleotomy with a 16G biopsy needle. Of those, 24 discs received matrix (porcine nucleus pulposus collagenous scaffold component and chemically modified HA) which was in situ polymerized using UVL immediately after transplantation. 12 nucleotomized discs and 24 non-nucleotomized discs served as controls. After 24 weeks, animals were killed. X-rays, MRIs, histology, and gene expression analysis were done.
  
  
  RESULTS
  Disc height was reduced equally after sole nucleotomy and nucleotomy with HA treatment and in MRIs signal intensity decreased. For both nucleotomy groups, the nucleus histo-degeneration score showed a significant increase compared to controls. In histology, HA treatment resulted in more scarring and inflammation in the annulus. Gene expression of catabolic MMPs was up-regulated, whereas IFN-gamma, IL-6, and IL-1b were unchanged.
  
  
  CONCLUSIONS
  Although nucleotomy and administration of the implant material did not cause generalized inflammation of the disc, localized annular damage with annulus inflammation and scarring resulted in detrimental degenerative disc changes. As a result, therapeutic strategies should strongly focus on the prevention of annular damage or techniques for annular repair to remain disc integrity.
authors.affiliation: Division of Experimental Orthopaedics, Department of Orthopedics, Trauma Surgery and Paraplegiology, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, 69118, Heidelberg, Germany. Georg.Omlor@med.uni-heidelberg.de
authors.forename: G W
authors.initials: GW
authors.lastname: Omlor
authors.forename: A G
authors.initials: AG
authors.lastname: Nerlich
authors.forename: H
authors.initials: H
authors.lastname: Lorenz
authors.forename: T
authors.initials: T
authors.lastname: Bruckner
authors.forename: W
authors.initials: W
authors.lastname: Richter
authors.forename: M
authors.initials: M
authors.lastname: Pfeiffer
authors.forename: T
authors.initials: T
authors.lastname: Gühring
mesh_terms: D000818:Animals; D003094:Collagen / Q000627:therapeutic use*; D004195:Disease Models, Animal; D017586:Diskectomy / Q000009:adverse effects; D006820:Hyaluronic Acid / Q000627:therapeutic use*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000627:therapeutic use*; D007150:Immunohistochemistry; D055959:Intervertebral Disc Degeneration / Q000601:surgery*; D008161:Lumbosacral Region; D008279:Magnetic Resonance Imaging; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D013556:Swine, Miniature
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid; D003094:Collagen