Injectable laminin-functionalized hydrogel for nucleus pulposus regeneration

Abstract

Cell delivery to the pathological intervertebral disc (IVD) has significant therapeutic potential for enhancing IVD regeneration. The development of injectable biomaterials that retain delivered cells, promote cell survival, and maintain or promote an NP cell phenotype in vivo remains a significant challenge. Previous studies have demonstrated NP cell – laminin interactions in the nucleus pulposus (NP) region of the IVD that promote cell attachment and biosynthesis. These findings suggest that incorporating laminin ligands into carriers for cell delivery may be beneficial for promoting NP cell survival and phenotype. Here, an injectable, laminin-111 functionalized poly(ethylene glycol) (PEG-LM111) hydrogel was developed as a biomaterial carrier for cell delivery to the IVD. We evaluated the mechanical properties of the PEG-LM111 hydrogel, and its ability to retain delivered cells in the IVD space. Gelation occurred in approximately 20 minutes without an initiator, with dynamic shear moduli in the range of 0.9 – 1.4 kPa. Primary NP cell retention in cultured IVD explants was significantly higher over 14 days when cells were delivered within a PEG-LM111 carrier, as compared to cells in liquid suspension. Together, these results suggest this injectable laminin-functionalized biomaterial may be an easy to use carrier for delivering cells to the IVD.

Development of kartogenin-conjugated chitosan–hyaluronic acid hydrogel for nucleus pulposus regeneration

“…This also enables mechanical load transduction, which is important for the synthesis of the NP matrix. 27 Incorporating cells into the CS/HA hydrogel solution reduces clustering and poor distribution of transplanted cells. Moreover, after gelation, the hydrogel provides a temporary three-dimensional matrix to increase cell retention and survival.…”

Hypoxia promotes nucleus pulposus phenotype in 3D scaffolds in vitro and in vivo

“…4,5,15 However, hydrogel scaffolds lack structural integrity and are probably unsuitable as a tissue-engineering application when not combined with a more rigid structure. The scaffolds used in our present study were fabricated by using a phase-separation technique with a nanofibrous matrix and highly interconnected macropores.…”

Laminin Enriched Scaffolds for Tissue Engineering Applications

“…57 NP cells are known to cluster and produce more proteoglycan rich matrix when cultured on soft (<0.5kPa) LM rich substrates as compared to fibronectin or collagen. 57 Francisco et al 58 developed injectable, LM-111 functionalized PEG hydrogels by combining PEG-LM111 conjugates with PEG-octoacrylate and PEG-dithiol under physiological conditions. Bioluminescence studies showed that PEG-LM111 hydrogels significantly improved encapsulated NP cell survival and retention over a 14 day period in IVD explants.…”