Photocrosslinkable laminin-functionalized polyethylene glycol hydrogel for intervertebral disc regeneration

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2014-03-01

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Abstract

Intervertebral disc (IVD) disorders and age-related degeneration are believed to contribute to lower back pain. There is significant interest in cell-based strategies for regenerating the nucleus pulposus (NP) region of the disc; however, few scaffolds have been evaluated for their ability to promote or maintain an immature NP cell phenotype. Previous studies have shown that NP cell-laminin interactions promote cell adhesion and biosynthesis, which suggests a laminin-functionalized biomaterial may be useful for promoting or maintaining the NP cell phenotype. Here, a photocrosslinkable poly(ethylene glycol)-laminin 111 (PEG-LM111) hydrogel was developed. The mechanical properties of PEG-LM111 hydrogel could be tuned within the range of dynamic shear moduli values previously reported for human NP. When primary immature porcine NP cells were seeded onto PEG-LM111 hydrogels of varying stiffnesses, LM111-presenting hydrogels were found to promote cell clustering and increased levels of sGAG production as compared to stiffer LM111-presenting and PEG-only gels. When cells were encapsulated in 3-D gels, hydrogel formulation was found to influence NP cell metabolism and expression of proposed NP phenotypic markers, with higher expression of N-cadherin and cytokeratin 8 observed for cells cultured in softer (<1 kPa) PEG-LM111 hydrogels. Overall, these findings suggest that soft, LM111-functionalized hydrogels may promote or maintain the expression of specific markers characteristic of an immature NP cell phenotype. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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10.1016/j.actbio.2013.11.013

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Francisco, Aubrey T, Priscilla Y Hwang, Claire G Jeong, Liufang Jing, Jun Chen and Lori A Setton (2014). Photocrosslinkable laminin-functionalized polyethylene glycol hydrogel for intervertebral disc regeneration. Acta Biomaterialia, 10(3). pp. 1102–1111. 10.1016/j.actbio.2013.11.013 Retrieved from https://hdl.handle.net/10161/8876.

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Setton

Lori A. Setton

Adjunct Professor of Biomedical Engineering

Research in Setton's laboratory is focused on the role of mechanical factors in the degeneration and repair of soft tissues of the musculoskeletal system, including the intervertebral disc, articular cartilage and meniscus. Work in the Laboratory is focused on engineering and evaluating materials for tissue regeneration and drug delivery. Studies combining engineering and biology are also used to determine the role of mechanical factors to promote and control healing of cartilaginous tissues. Research in the Laboratory is funded by The National Institutes of Health, The Coulter Foundation and The North Carolina Biotechnology Center.


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