Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model
- 640 Downloads
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.
Materials and 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.
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.
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.
KeywordsDisc degeneration Nucleotomy Porcine animal model Ultraviolet light polymerization Hyaluronic acid hydrogel matrix
We thank Bernhard Pieta for helping with animal acquisition and surgical assistance.
Conflict of interest
- 7.Omlor GW, Bertram H, Kleinschmidt K, Fischer J, Brohm K, Guehring T, Anton M, Richter W (2010) Methods to monitor distribution and metabolic activity of mesenchymal stem cells following in vivo injection into nucleotomized porcine intervertebral discs. Eur Spine J 19(4):601–612PubMedCrossRefGoogle Scholar
- 13.Abbushi A, Endres M, Cabraja M, Kroppenstedt SN, Thomale UW, Sittinger M, Hegewald AA, Morawietz L, Lemke AJ, Bansemer VG, Kaps C, Woiciechowsky C (2008) Regeneration of intervertebral disc tissue by resorbable cell-free polyglycolic acid-based implants in a rabbit model of disc degeneration. Spine 33:1527–1532PubMedCrossRefGoogle Scholar
- 14.Endres M, Abbushi A, Thomale UW, Cabraja M, Kroppenstedt SN, Morawietz L, Casalis PA, Zenclussen ML, Lemke AJ, Horn P, Kaps C, Woiciechowsky C (2010) Intervertebral disc regeneration after implantation of a cell-free bioresorbable implant in a rabbit disc degeneration model. Biomaterials 31:5836–5841PubMedCrossRefGoogle Scholar
- 15.Nakashima S, Matsuyama Y, Takahashi K, Satoh T, Koie H, Kanayama K, Tsuji T, Maruyama K, Imagama S, Sakai Y, Ishiguro N (2009) Regeneration of intervertebral disc by the intradiscal application of cross-linked hyaluronate hydrogel and cross-linked chondroitin sulfate hydrogel in a rabbit model of intervertebral disc injury. Biomed Mater Eng 19:421–429PubMedGoogle Scholar
- 17.Chou AI, Nicoll SB (2008) Characterization of photocrosslinked alginate hydrogels for nucleus pulposus cell encapsulation. J Biomed Mater Res A 91(1):187–194Google Scholar
- 20.Omlor GW, Nerlich AG, Wilke HJ, Pfeiffer M, Lorenz H, Schaaf-Keim M, Bertram H, Richter W, Carstens C, Guehring T (2009) A new porcine in vivo animal model of disc degeneration—response of annulus fibrosus cells, chondrocyte-like nucleus pulposus cells and notochordal nucleus pulposus cells to partial nucleotomy. Spine 34(25):2730–2739PubMedCrossRefGoogle Scholar
- 22.Weiler C, Lopez-Ramos M, Mayer HM, Korge A, Siepe CJ, Wuertz K, Weiler V, Boos N, Nerlich AG (2011) Histological analysis of surgical lumbar intervertebral disc tissue provides evidence for an association between disc degeneration and increased body mass index. BMC Res Notes 4:497PubMedCrossRefGoogle Scholar
- 32.Key JA, Ford LT (1948) Experimental intervertebral-disc lesions. J Bone Joint Surg Am 30:621–630Google Scholar