Genipin-Crosslinked Fibrin Hydrogels Modified With Collagen or Fibronectin as an Annulus Fibrosus Sealant

Low back pain (LBP) affects 80% of all adults at some point in their lives [1], and is often associated with intervertebral disc (IVD) degeneration, therefore, restorative solutions are of high importance. The IVD is composed of an outer ring of annulus fibrosus (AF) containing the pressurized nucleus pulposus (NP) center. NP replacement approaches and IVD procedures such as discectomy or discography involve rupture of the AF tissue for diagnosis or repair purposes. Even small defects to the outer AF can accelerate IVD degeneration [2]. Current closure techniques are limited to sutures and offer little in the way of tissue replacement or mechanical restoration of the AF [3]. A genipin crosslinked fibrin hydrogel offers some promise as an adhesive AF sealant [4]. Fibrin is FDA approved and genipin is a plant based chemical crosslinker with low cytotoxicity used with a variety of materials including fibrin for articular cartilage engineering [5]. Genipin crosslinked fibrin is a tunable material with comparable mechanical properties to native AF tissue and although cells remained viable on the gel, the relatively slow proliferation and presence of abnormal cells with rounded morphology motivated further optimization. To improve cytomorphology, key extracellular matrix proteins, collagen and fibronectin, were added to the formulation. It was hypothesized that the addition of these proteins would maintain the mechanical properties of this gel while improving cell morphology and viability. Several additional analyses were included to further characterize this gel including push-out strength, degradation and contraction tests.