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A potential treatment modality for joint pain due to cartilage degradation is electromagnetic fields (EMF) that can be delivered, noninvasively, to chondrocytes buried within cartilage. A pulsed EMF in clinical use for recalcitrant bone fracture healing has been modified to be delivered as a pulsed electric field (PEF) through capacitive coupling. It was the objective of this study to determine whether the PEF signal could have a direct effect on chondrocytes in vitro. This study shows that a 30-min PEF treatment can increase DNA content of chondrocyte monolayer by approximately 150% at 72 h poststimulus. Studies intended to explore the biological mechanism showed this PEF signal increased nitric oxide measured in culture medium and cGMP measured in cell extract within the 30-min exposure period. Increasing calcium in the culture media or adding the calcium ionophore A23187, without PEF treatment, also significantly increased short-term nitric oxide production. The inhibitor W7, which blocks calcium/calmodulin, prevented the PEF-stimulated increase in both nitric oxide and cGMP. The inhibitor L-NAME, which blocks nitric oxide synthase, prevented the PEF-stimulated increase in nitric oxide, cGMP, and DNA content. An inhibitor of guanylate cyclase (LY83583) blocked the PEF-stimulated increase in cGMP and DNA content. A nitric oxide donor, when present for only 30 min, increased DNA content 72 h later. Taken together, these results suggest the transduction pathway for PEF-stimulated chondrocyte proliferation involves nitric oxide and the production of nitric oxide may be the result of a cascade that involves calcium, calmodulin, and cGMP production.

This investigation tested the hypothesis that delivering mesenchymal stem cell-seeded implants to a tendon gap model results in significantly improved repair biomechanics. Cultured, autologous, marrow-derived mesenchymal stem cells were suspended in a collagen gel delivery vehicle; the cell-gel composite was subsequently contracted onto a pretensioned suture. The resulting tissue prosthesis was then implanted into a 1-cm-long gap defect in the rabbit Achilles tendon. Identical procedures were performed on the contralateral tendon, but only the suture material was implanted. The tendon-implant constructs were evaluated 4, 8, and 12 weeks later by biomechanical and histological criteria. Significantly greater load-related structural and material properties were seen at all time intervals in the mesenchymal stem cell-treated tendons than in the contralateral, treated control repairs (p < 0.05), which contained suture alone with natural cell recruitment. The values were typically twice those for the control tissues at each time interval. Load-related material properties for the treated tissues also increased significantly over time (p < 0.05). The treated tissues had a significantly larger cross-sectional area (p < 0.05), and their collagen fibers appeared to be better aligned than those in the matched controls. The results indicate that delivering mesenchymal stem cell-contracted, organized collagen implants to large tendon defects can significantly improve the biomechanics, structure, and probably the function of the tendon after injury.