BIOMECHANICS 1022 www.spinejournal.com June 2011 SPINE Volume 36, Number 13, pp 1022–1029 ©2011, Lippincott Williams & Wilkins Copyright © 2011 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. A Novel Thiol-Modified Hyaluronan and Elastin- Like Polypetide Composite Material for Tissue Engineering of the Nucleus Pulposus of the Intervertebral Disc Isaac L. Moss, MDCM, MASc,*† Lyle Gordon, BSc,† Kimberly A. Woodhouse, PhD,†‡ Cari M. Whyne, PhD,*† and Albert J.M. Yee, MD, MSc,*† 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 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. 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 T here are limited treatment options available for patients with symptomatic intervertebral disc (IVD) degeneration. Current surgical management of degenerative disc disease (DDD) is primarily directed toward end-stage disease; however, there has been considerable enthusiasm in tissue-engineered and cell-based strategies that hold future promise in treating early disease. In early degeneration, damage is predominantly in the nucleus pulposus (NP) of the IVD, resulting in loss of aggrecan and key extracellular matrix (ECM) components. 1 The glycos- aminoglycan hyaluronan (HA) is considered an essential ECM component of the IVD and forms large proteoglycan aggregates through interaction with aggrecan, link protein, and other ECM molecules. These interactions are mechanically important for the load-bearing function of NP tissue and the IVD. HA has been explored as a possible treatment of IVD de- generation. Stern et al 2 observed that porcine NP cells cul- tured in fibrin/HA matrix expressed higher levels of proteo- glycans when compared with alginate cell cultures. Injection of high-molecular weight HA into a primate DDD model demonstrated improved gross, histologic, and radiographic outcomes. 3 Several other investigators have observed HA- based scaffolds to be a hospitable environment for NP cells. 4–8 Despite these positive observations, formulations of HA com- mercially available, and those previously investigated behave as viscous liquids and material extravasation from the IVD From the *Department of Surgery, University of Toronto, Toronto, Ontario, Canada; †Advanced Regenerative Tissue Engineering Centre (ARTEC)/Ortho- paedics Biomechanics Laboratory (OBL), Sunnybrook Research Institute, Sun- nybrook Health Sciences Centre, Toronto, Ontario, Canada; and ‡Faculty of Applied Science, Queen’s University, Kingston, Ontario, Canada. Acknowledgment date: March 9, 2010. Revision date: April 27, 2010. Acceptance date: May 10, 2010. The manuscript submitted does not contain information about medical device(s)/drug(s). Funding for this work was provided by the Ontario Centres of Excellence and Elastin Specialties. One or more of the author(s) has/have received or will receive benefits for personal or professional use from a commercial party related directly or indi- rectly to the subject of this manuscript. Address correspondence and reprint requests to Albert J.M. Yee, MD, Sunny- brook Health Sciences Centre, 2075 Bayview Ave, Room MG371B, Toronto, Ontario, Canada; E-mail: Albert.Yee@sunnybrook.ca 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. Key words: intervertebral disc, elastin, hyaluronan, hydrogel, tissue engineering, biomechanics. Spine 2011;36:1022–1029 DOI: 10.1097/BRS.0b013e3181e7b705