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Biomechanical, in vitro, and initial in vivo evaluation of a thiol-modified hyaluronan (TM-HA) and elastin-like polypeptide (ELP) composite hydrogel for nucleus pulposus (NP) tissue engineering.To investigate the utility of a TM-HA and ELP composite material as a potential tissue-engineering scaffold to reconstitute the NP in early degenerative disc disease (DDD) on the basis of both biomechanical and biologic parameters.DDD is a common ailment with enormous medical, psychosocial, and economic ramifications. Only end-stage surgical therapies are currently widely available. A less invasive, early stage therapy may provide a clinically relevant treatment option.TM-HA and ELP were combined in various concentrations and cross-linked using poly (ethylene glycol) diacrylate. Resulting materials were evaluated biomechanically using confined com-pression to determine biphasic material properties. In vitro cell culture with human intervertebral disc (IVD) cells seeded within TM-HA/ELP scaffolds was analyzed for cell viability and phenotype. The hydrogels’ materials were evaluated in an established New Zealand White (NZW) rabbit model of DDD.The addition of ELP to TM-HA–based hydrogels resulted in a stiffer construct, which is less stiff than native NP but has time-dependant loading characteristics that may be desirable when injected into the IVD. In vitro experiments demonstrated 70% cell viability at 3 weeks with apparent maintenance of phenotype on the basis of morphologic and immunohistochemical data. The addition of ELP had a positive desirable biomechanical effect but did not have a significant positive or negative biologic effect on cell activity. The in vivo feasibility study demonstrated favorable material characteristics and biocompatibility for application as a minimally invasive injectable NP supplement.TM-HA–based hydrogels provide a hospitable environment for human IVD cells and have material characteristics, particularly when supplemented with ELPs that are attractive for potential application as an injectable NP supplement.