title: Injectable laminin-functionalized hydrogel for nucleus pulposus regeneration.
abstract: Cell delivery to the pathological intervertebral disc (IVD) has significant therapeutic potential for enhancing IVD regeneration. The development of injectable biomaterials that retain delivered cells, promote cell survival, and maintain or promote an NP cell phenotype in vivo remains a significant challenge. Previous studies have demonstrated NP cell - laminin interactions in the nucleus pulposus (NP) region of the IVD that promote cell attachment and biosynthesis. These findings suggest that incorporating laminin ligands into carriers for cell delivery may be beneficial for promoting NP cell survival and phenotype. Here, an injectable, laminin-111 functionalized poly(ethylene glycol) (PEG-LM111) hydrogel was developed as a biomaterial carrier for cell delivery to the IVD. We evaluated the mechanical properties of the PEG-LM111 hydrogel, and its ability to retain delivered cells in the IVD space. Gelation occurred in approximately 20 min without an initiator, with dynamic shear moduli in the range of 0.9-1.4 kPa. Primary NP cell retention in cultured IVD explants was significantly higher over 14 days when cells were delivered within a PEG-LM111 carrier, as compared to cells in liquid suspension. Together, these results suggest this injectable laminin-functionalized biomaterial may be an easy to use carrier for delivering cells to the IVD.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Aubrey T
authors.initials: AT
authors.lastname: Francisco
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mancino
authors.forename: Robby D
authors.initials: RD
authors.lastname: Bowles
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Brunger
authors.forename: David M
authors.initials: DM
authors.lastname: Tainter
authors.forename: Yi-Te
authors.initials: YT
authors.lastname: Chen
authors.forename: William J
authors.initials: WJ
authors.lastname: Richardson
authors.forename: Farshid
authors.initials: F
authors.lastname: Guilak
authors.forename: Lori A
authors.initials: LA
authors.lastname: Setton
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007267:Injections; D007403:Intervertebral Disc / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000637:transplantation; D007797:Laminin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D055595:Mechanical Phenomena / Q000187:drug effects; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects*; D012212:Rheology / Q000187:drug effects; D034421:Sus scrofa
chemical_list: D001672:Biocompatible Materials; D007797:Laminin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D008156:Luciferases
keywords: Injectable; Intervertebral disc; Laminin; Nucleus pulposus; Organ culture; Polyethylene glycol