Progressive and symptomatic intervertebral disc (IVD) degeneration is a multi-factor process which places significant physical, social, and economic burden on the global society. It has been recognized that the degenerative process first manifests within the nucleus pulposus (NP) region of the IVD. Therefore it has been theorized that replacement of this tissue with a suitable surrogate may slow or halt progression of degeneration. With this information in mind, the primary focus of this research was to develop and characterize novel biomimetic hydrogels to be used for regenerating the NP with the long-term goal of creating a living engineered tissue replacement.;Two approaches to biomimetic hydrogel development were utilized in this research. The first approach involved the complete decellularization of porcine NP tissue which resulted in a material (termed the "APNP" hydrogel) devoid of host cell remnants that exhibited maintenance of much of the native NP extracellular matrix including collagen type II and aggrecan. The APNP hydrogel exhibited slightly reduced mechanical, osmotic swelling and biochemical characteristics by comparison to native human NP. Furthermore, considering the long term goal of introducing autologous cells into the hydrogels prior to implantation into the IVD, this material has illustrated the ability to support human stem cell differentiation towards an NP cell-like phenotype and exhibits evidence of in vivo biocompatibility.;While the APNP hydrogel may be an obvious choice for NP scaffold development, difficulties encountered early-on during the decellularization development process led us to investigate an alternative hydrogel in parallel. Composed of defined quantities of purified soluble elastin, glycosaminoglycans, and type I collagen, a resilient and mechanically robust hydrogel exhibiting a shape-memory sponge characteristic has also been developed. Termed the "EGC" hydrogel, this material can withstand unconfined compressive loading during which it expels water, and upon unloading, the hydrogel immediately returns to its original conformation while concurrently reabsorbing its original water content. This hydrogel exhibited the ability to resist accelerated enzymatic degradation and supports stem cell viability and glycosaminoglycan production.;Overall, it is envisioned that this research may help illustrate the feasibility of using these hydrogel materials for regenerative medicine approaches to combat IVD degeneration.
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