Genipin-crosslinked fibrin hydrogels as a potential adhesive to augment intervertebral disc annulus repair

Abstract

Treatment of damaged intervertebral discs is a signifi cant clinical problem and, despite advances in the repair and replacement of the nucleus pulposus, there are few effective strategies to restore defects in the annulus fi brosus. An annular repair material should meet three specifi cations: have a modulus similar to the native annulus tissue, support the growth of disc cells, and maintain adhesion to tissue under physiological strain levels. We hypothesized that a genipin crosslinked fi brin gel could meet these requirements. Our mechanical results showed that genipin crosslinked fi brin gels could be created with a modulus in the range of native annular tissue. We also demonstrated that this material is compatible with the in vitro growth of human disc cells, when genipin:fi brin ratios were 0.25:1 or less, although cell proliferation was slower and cell morphology more rounded than for fi brin alone. Finally, lap tests were performed to evaluate adhesion between fi brin gels and pieces of annular tissue. Specimens created without genipin had poor handling properties and readily delaminated, while genipin crosslinked fi brin gels remained adhered to the tissue pieces at strains exceeding physiological levels and failed at 15-30%. This study demonstrated that genipin crosslinked fi brin gels show promise as a gap-fi lling adhesive biomaterial with tunable material properties, yet the slow cell proliferation suggests this biomaterial may be best suited as a sealant for small annulus fi brosus defects or as an adhesive to augment large annulus repairs. Future studies will evaluate degradation rate, fatigue behaviors, and long-term biocompatibility.

Enhancing cell migration in shape-memory alginate–collagen composite scaffolds: In vitro and ex vivo assessment for intervertebral disc repair

“…(11) For this reason, extensive research involving injectablebiomaterial candidates for NP regeneration have been explored, but surprisingly a limited number of similar systems have been targeted for annulus fibrosus tissue to date. (12)(13)(14)(15)(16) High-density injectable collagen gels have been investigated to fill punctured AF tissue in a rat tail model. Although no further sign of disc degeneration was observed in terms of hydration, as evaluated using MRI and disc height measurements post-implantation, incomplete AF tissue regeneration was observed in the inner region of the newly formed tissue, combined with a fibrous capsule in the outer part with dissimilarity in terms of extracellular matrix (ECM) composition compared to native AF tissue.…”

Biomaterials for intervertebral disc regeneration: past performance and possible future strategies

“…Cloyd et al, 2007;Gruber et al, 2006;Gupta et al, 2014;Hunt and Grover, 2010;Lazebnik et al, 2011;Nerurkar et al, 2010;Tilwani et al, 2012;Zhang et al, 2012 Fibrin Human plasma Surgical sealant Used as a singular or hybrid scaffold for NP and AF in vitro and in vivo testing. Acosta et al, 2011;Ahmed et al, 2008;Colombini et al, 2014;Diederichs et al, 2012;Eyrich et al, 2007;Hegewald et al, 2010;Ho et al, 2010;Likhitpanichkul et al, 2014;Ma et al, 2012;Park et al, 2011b;Pirvu et al, 2015;Schek et al, 2011;Stern et al, 2000;Stern et al, 2004;Sung et al, 1999;…”

“…In a bovine ex vivo AF defect model, fibrin/genipin hydrogels prevented disc height loss and remained integrated after more than 10,000 cycles of loading (Likhitpanichkul et al, 2014). Furthermore, it was demonstrated that AF cells remained viable and migrated into fibrin/genipin hydrogels (Likhitpanichkul et al, 2014;Schek et al, 2011). Fibrin hydrogels functionalised with TGF-β stimulated human MSCs (hMSC) to undergo chondrogenesis, although soluble TGF-β resulted in a more profound induction of regeneration (Diederichs et al, 2012).…”

The challenge and advancement of annulus fibrosus tissue engineering

“…The mechanical tests revealed that POM has an excellent deformability: the compressive stress, young's modulus, and tensile strength markedly increased as the polymerization time increased. There was no permanent deformation after 500 press-loading and release cycles with Poly-D-L-lactide/Bioglass [90,91] Silk [92,93] Genipin crosslinked fibrin [94] Single unit with fiber orientation Aligned alginate/chitosan [88] Polycarbonate polyurethane linked with dihydroxyl oligomer [95,96] Polycaprolactone [97,98] Poly-L-Lactide [99] Silk fibers/chondroitin sulphate [100] Collagen fibrils [101] Biphasic scaffold Poly (polycaprolactone triol malate)/DBM [102] Composite scaffold Poly-L-Lactide as AF and hyaluronic acid hydrogel as NP [24] Polyglycolic Acid/poly-l-lactic as AF and alginate hydrogel as NP [103] Silk scaffold as AF and silicon as NP or hyaluronic acid as NP [104,105] 30 % maximum strain. When implanted into mice back subcutaneous pocket, there were no inflammation responses were found [89].…”

“…The authors showed that mechanical modulus of genipin crosslinked fibrin gels can be created similar to native annular tissue. These gels can be used for small AF defects or as an adhesive to augment large annulus repair [94].…”