Development and initial characterization of a chemically stabilized elastin-glycosaminoglycan-collagen composite shape-memory hydrogel for nucleus pulposus regeneration

Nucleus pulposus (NP) is a resilient and hydrophilic tissue which plays a significant role in the biomechanical function of the intervertebral disc (IVD). Destruction of the NP extracellular matrix (ECM) is observed during the early stages of IVD degeneration. Herein, we describe the development and initial characterization of a novel biomaterial which attempts to recreate the resilient and hydrophilic nature of the NP via the construction of a chemically stabilized elastin-glycosaminoglycan-collagen (EGC) composite hydrogel. Results demonstrated that a resilient, hydrophilic hydrogel which displays a unique "shape-memory" sponge characteristic could be formed from a blend of soluble elastin aggregates, chondroitin-6-sulfate, hyaluronic acid and collagen following freeze-drying, stabilization with a carbodiimide and penta-galloyl glucose-based fixative, and subsequent partial degradation with glycosaminoglycan degrading enzymes. The resultant material exhibited the ability to restore its original dimensions and water content following multi-cycle mechanical compression and illustrated resistance to accelerated enzymatic degradation. Preliminary in vitro studies utilizing human adipose derived stem cells (hADSCs) demonstrated that the material was cytocompatible and supported differentiation towards an NP cell-like phenotype. In vivo biocompatibility studies illustrated host cell infiltration and evidence of active remodeling following 4 weeks of implantation. Feasibility studies demonstrated that the EGC hydrogel could be delivered via minimally invasive methods.