New Injection Repair Strategy Can Prevent Risk of Re-herniation, Reduce Disability and Pain

Elizabeth Hofheinz, M.P.H., M.Ed.

Noting that current tissue engineering practices used to seal annulus fibrosus (AF) defects are lacking, researchers from the Icahn School of Medicine at Mount Sinai in New York, along with researchers from The City College of New York, developed an injectable repair strategy to bond a biomaterial to native tissue.

The study, “Development of a two-part biomaterial adhesive strategy for annulus fibrosus repair and ex vivo evaluation of implant herniation risk,” appears in the November 2020 edition of Biomaterials.

Co-author James C. Iatridis, Ph.D. is Mount Sinai Professor and Vice Chair for Research in the Leni & Peter W. May Department of Orthopedics and Director of the Spine Research Program at the Icahn School of Medicine, Mount Sinai Health System.

Dr. Iatridis told OSN, “Our research has been focused on AF repair and the need to develop advanced biomaterials that resist herniation and can be injected in a minimally invasive manner. We are designing strategies that are amenable to repairing smaller disc defects that can prevent progressive disc disruption, and to larger defects that might enhance current discectomy procedures.”

According to the authors, “The two-part strategy for AF repair included: (1) an interpenetrating network (IPN) hydrogel comprising synthetic (poly (ethylene glycol) diacrylate/PEGDA) and natural (fibronectin-conjugated fibrin/FN-Fibrin) polymer networks, and (2) a dual-modified (oxidized and methacrylated) glycosamino- glycan (GAG) that covalently bonds this injectable hydrogel to extra-cellular matrix proteins in the IVD.”

The investigators set out: “(1) to optimize adhesive properties of the tissue-hydrogel interface by screening across sulfated and unsulfated GAGs and enhancing degrees of GAG methacrylation and oxidation, (2) to assess the cytocompatibility of the optimal dual-modified GAG product used to bond the void-filling hydrogel to AF tissue, and (3) to scale this method of AF repair to a large animal model of simulated discectomy ex vivo and determine the effect of hydrogel elasticity on implant herniation risk.”

“We show that dual-modified hyaluronic acid imparts greater adhesion to AF tissue than dual-modified chondroitin sulfate, where the degree of oxidation is more strongly correlated with adhesion strength than methacrylation,” wrote the authors. “We apply this strategy to an ex vivo bovine model of discectomy and demonstrate that PEGDA molecular weight tunes hydrogel mechanical properties and affects herniation risk, where IVDs repaired with low-modulus hydrogels composed of 20kDa PEGDA failed at levels at or exceeding discectomy, the clinical standard of care…”

Dr. Iatridis told OSN: “There were two major milestones in this work. The first was developing the dual modified glycosaminoglycan, or ‘priming’ agent that permits the hydrogel to covalently bond directly to the native tissue collagen. The second development was our finding that repairing the simulated intervertebral disc defect with a soft, and more compliant hydrogel demonstrated reduced herniation risk as compared to the hydrogel that matched the material properties of the native annulus fibrosus.”

“We’re currently advancing these studies using a large animal intervertebral disc injury model and hope those studies will inform future translation to human intervertebral discs.”