Browsing by Author "Bowles, Robby D"

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    In Vivo luminescent imaging of NF-κB activity and serum cytokine levels predict pain sensitivities in a rodent model of osteoarthritis.
    (Arthritis Rheum, 2013-11-18) Bowles, Robby D; Mata, Brian A; Bell, Richard D; Mwangi, Timothy K; Huebner, Janet L; Kraus, Virginia B; Setton, Lori A
    Objective: To investigate the relationship between NF-κB activity, cytokine levels, and pain sensitivities in a rodent model of osteoarthritis (OA). Method: OA was induced in transgenic NF-κB luciferase reporter mice via mono-iodoacetate (MIA) intra-articular injection. Using luminescent imaging we evaluated the temporal kinetics of NF-κB activity and its relationship to the development of pain sensitivities and serum cytokine levels in this model. Results: MIA induced a transient increase in joint-related NF-кB activity at early time points (day 3 post-injection) and an associated biphasic pain (mechanical allodynia) response. NF-кB activity, serum IL-6, IL-1β, and IL-10 accounted for ~75% of the variability in pain-related mechanical sensitivities in this model. Specifically, NF-кB activity was strongly correlated to mechanical allodynia and serum IL-6 levels in the inflammatory pain phase of this model (day 3), while serum IL-1β was strongly correlated to pain sensitivities in the chronic pain phase of the model (day 28). Conclusion: Our findings suggest that NF-кB activity, IL-6 and IL-1β may be playing distinct roles in pain sensitivity development in this model of arthritis and may act to distinguish the acute from chronic pain phases of this model. This work establishes luminescent imaging of NF-кB activity as a novel imaging biomarker of pain sensitivities in this model of OA. © 2013 American College of Rheumatology.
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    Injectable laminin-functionalized hydrogel for nucleus pulposus regeneration.
    (Biomaterials, 2013-10) Francisco, Aubrey T; Mancino, Robert J; Bowles, Robby D; Brunger, Jonathan M; Tainter, David M; Chen, Yi-Te; Richardson, William J; Guilak, Farshid; Setton, Lori A
    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.