title: Photocrosslinkable laminin-functionalized polyethylene glycol hydrogel for intervertebral disc regeneration.
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 (<1kPa) 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.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Aubrey T
authors.initials: AT
authors.lastname: Francisco
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Priscilla Y
authors.initials: PY
authors.lastname: Hwang
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Claire G
authors.initials: CG
authors.lastname: Jeong
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Liufang
authors.initials: L
authors.lastname: Jing
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA; Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA. Electronic address: lori.setton@duke.edu.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Setton
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007797:Laminin / Q000494:pharmacology*; D008027:Light; D055595:Mechanical Phenomena; D010641:Phenotype; D011092:Polyethylene Glycols / Q000494:pharmacology*; D012038:Regeneration / Q000187:drug effects*; D034421:Sus scrofa
chemical_list: D007797:Laminin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols
keywords: Intervertebral disc; Laminin; Nucleus pulposus; Photocrosslinking; Polyethylene glycol