A novel thiol-modified hyaluronan and elastin-like polypetide composite material for tissue engineering of the nucleus pulposus of the intervertebral disc.

摘要

STUDY DESIGN: 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. OBJECTIVE: 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. SUMMARY OF BACKGROUND DATA: 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. METHODS: TM-HA and ELP were combined in various concentrations and cross-linked using poly (ethylene glycol) diacrylate. Resulting materials were evaluated biomechanically using confined compression 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. RESULTS: 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. CONCLUSIONS: 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.