Cell-Seeded Adhesive Biomaterial for Repair of Annulus Fibrosus Defects in Intervertebral Discs

Abstract

Defects in the annulus fibrosus (AF) of intervertebral discs allow nucleus pulposus tissue to herniate causing painful disability. Microdiscectomy procedures remove herniated tissue fragments, but unrepaired defects remain allowing reherniation or progressive degeneration. Cell therapies show promise to enhance repair, but methods are undeveloped and carriers are required to prevent cell leakage. To address this challenge, this study developed and evaluated genipin-crosslinked fibrin (FibGen) as an adhesive cell carrier optimized for AF repair that can deliver cells, match AF material properties, and have low risk of extrusion during loading. Part 1 determined that feasibility of bovine AF cells encapsulated in high concentration FibGen (F140G6: 140 mg/mL fibrinogen; 6 mg/mL genipin) for 7 weeks could maintain high viability, but had little proliferation or matrix deposition. Part 2 screened tissue mechanics and in situ failure testing of nine FibGen formulations (fibrin: 35-140 mg/mL; genipin: 1-6 mg/mL). F140G6 formulation matched AF shear and compressive properties and significantly improved failure strength in situ. Formulations with reduced genipin also exhibited satisfactory material properties and failure behaviors warranting further biological screening. Part 3 screened AF cells encapsulated in four FibGen formulations for 1 week and found that reduced genipin concentrations increased cell viability and glycosaminoglycan production. F70G1 (70 mg/mL fibrinogen; 1 mg/mL genipin) demonstrated balanced biological and biomechanical performance warranting further testing. We conclude that FibGen has potential to serve as an adhesive cell carrier to repair AF defects with formulations that can be tuned to enhance biomechanical and biological performance; future studies are required to develop strategies to enhance matrix production.

Discogenic Back Pain: Literature Review of Definition, Diagnosis, and Treatment

“…Chondrocyte transplantation studies showed some positive results in a small number of participants; further studies are needed to show efficacy . Experimental studies demonstrated cell leakage following injection with ectopic calcifications as a potential complication, thus motivating the need for a cell carrier to help enhance cell injections …”

“…Although an FDA panel confirmed its efficacy in preventing reherniations following discectomy, the presence of lytic endplate lesions and device subsidence raised safety concerns . AF repair and NP replacement biomaterials and devices remain an emergent area of research as described in multiple excellent recent studies and reviews . These biomaterials must show efficacy for improved spinal healing or pain reduction, while also avoiding reherniation and/or adjacent tissue damage.…”

“…(130)(131)(132) Experimental studies demonstrated cell leakage following injection with ectopic calcifications as a potential complication, thus motivating the need for a cell carrier to help enhance cell injections. (133,134) IVD repair techniques or implant biomaterials for annulus closures and NP replacement have the potential to repair the IVD, yet also create a risk for reherniation, which can cause nerve compression and the possibility of a recurrent painful condition or worsening of a condition. As a result, especially after discectomy, IVD repair/closure techniques have been developed to prevent reherniation and consequent progression of IVD degeneration.…”

“…(137) AF repair and NP replacement biomaterials and devices remain an emergent area of research as described in multiple excellent recent studies and reviews. (132,134,(138)(139)(140)(141) These biomaterials must show efficacy for improved spinal healing or pain reduction, while also avoiding reherniation and/ or adjacent tissue damage.…”

Biomaterials for intervertebral disc regeneration: Current status and looming challenges

“…For example, poly (trimethylene carbonate) scaffold seeded with mesenchymal stem cells and covered with poly (ester‐urethane) membrane was tested in a bovine organ culture annulotomy model for AF rupture repair (Pirvu, Blanquer, Benneker, et al, ) and showed the ability to prevent herniation of NP tissue and stabilise the DH. Genipin/fibrin composite has demonstrated an excellent biomechanical and biological performance in vitro, as an adhesive cell carrier for AF regeneration or AF defects sealer (Cruz, Hom, Tyler, et al, ; Likhitpanichkul, Dreischarf, Illien‐Junger, et al, ). Additionally, a nanocomposite hydrogel consisting of gellan gum and cellulose nanocrystals was recently fabricated to meet the mechanical property of AF tissue in vitro (Pereira, Oliveira, Reis, et al, ).…”