Combining adhesive and nonadhesive injectable hydrogels for intervertebral disc repair in an ovine discectomy model

Christopher J Panebianco; Caroline Constant; Andrea J Vernengo; Dirk Nehrbass; Dominic Gehweiler; Tyler J DiStefano; Jesse Martin; David J Alpert; Saad B Chaudhary; Andrew C Hecht; Alan C Seifert; Steven B Nicoll; Sibylle Grad; Stephan Zeiter; James C Iatridis

doi:10.1002/jsp2.1293

Combining adhesive and nonadhesive injectable hydrogels for intervertebral disc repair in an ovine discectomy model

JOR Spine. 2023 Dec 1;6(4):e1293. doi: 10.1002/jsp2.1293. eCollection 2023 Dec.

Authors

Christopher J Panebianco^{1

2}, Caroline Constant³, Andrea J Vernengo^{3

4}, Dirk Nehrbass³, Dominic Gehweiler³, Tyler J DiStefano¹, Jesse Martin⁵, David J Alpert⁵, Saad B Chaudhary¹, Andrew C Hecht¹, Alan C Seifert⁶, Steven B Nicoll⁵, Sibylle Grad³, Stephan Zeiter³, James C Iatridis¹

Affiliations

¹ Leni and Peter W. May Department of Orthopaedics Icahn School of Medicine at Mount Sinai New York New York USA.
² Department of Orthopaedic Surgery University of Pennsylvania Philadelphia Pennsylvania USA.
³ AO Research Institute Davos Davos Switzerland.
⁴ Department of Chemical Engineering Rowan University Glassboro NJ USA.
⁵ Department of Biomedical Engineering The City College of New York New York New York USA.
⁶ Biomedical Engineering and Imaging Institute Icahn School of Medicine at Mount Sinai New York New York USA.

Abstract

Background: Intervertebral disc (IVD) disorders (e.g., herniation) directly contribute to back pain, which is a leading cause of global disability. Next-generation treatments for IVD herniation need advanced preclinical testing to evaluate their ability to repair large defects, prevent reherniation, and limit progressive degeneration. This study tested whether experimental, injectable, and nonbioactive biomaterials could slow IVD degeneration in an ovine discectomy model.

Methods: Ten skeletally mature sheep (4-5.5 years) experienced partial discectomy injury with cruciate-style annulus fibrosus (AF) defects and 0.1 g nucleus pulposus (NP) removal in the L1-L2, L2-L3, and L3-L4 lumbar IVDs. L4-L5 IVDs were Intact controls. IVD injury levels received: (1) no treatment (Injury), (2) poly (ethylene glycol) diacrylate (PEGDA), (3) genipin-crosslinked fibrin (FibGen), (4) carboxymethylcellulose-methylcellulose (C-MC), or (5) C-MC and FibGen (FibGen + C-MC). Animals healed for 12 weeks, then IVDs were assessed using computed tomography (CT), magnetic resonance (MR) imaging, and histopathology.

Results: All repaired IVDs retained ~90% of their preoperative disc height and showed minor degenerative changes by Pfirrmann grading. All repairs had similar disc height loss and Pfirrmann grade as Injury IVDs. Adhesive AF sealants (i.e., PEGDA and FibGen) did not herniate, although repair caused local endplate (EP) changes and inflammation. NP repair biomaterials (i.e., C-MC) and combination repair (i.e., FibGen + C-MC) exhibited lower levels of degeneration, less EP damage, and less severe inflammation; however, C-MC showed signs of herniation via biomaterial expulsion.

Conclusions: All repair IVDs were noninferior to Injury IVDs by IVD height loss and Pfirrmann grade. C-MC and FibGen + C-MC IVDs had the best outcomes, and may be appropriate for enhancement with bioactive factors (e.g., cells, growth factors, and miRNAs). Such bioactive factors appear to be necessary to prevent injury-induced IVD degeneration. Application of AF sealants alone (i.e., PEGDA and FibGen) resulted in EP damage and inflammation, particularly for PEGDA IVDs, suggesting further material refinements are needed.

Keywords: annulus fibrosus repair; carboxymethylcellulose–methylcellulose; fibrin; hydrogels; injectable biomaterials; intervertebral disc; nucleus pulposus repair; ovine discectomy model; poly(ethylene glycol) diacrylate.

Abstract

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