Coculture of mesenchymal stem cells (MSCs) with articular chondrocytes (ACs) increases glycosaminoglycan (GAG) accumulation compared to monoculture. MSCs might (1) differentiate into ACs (progenitor role) and/or (2) stimulate AC matrix metabolism (trophic role). MSCs lose the ability to undergo chondrogenesis after extended passaging. We hypothesized that MSCs act predominantly as progenitors, and that late-passage MSCs without chondrogenic potential would be unable to increase GAG in coculture. Early-and late-passage human MSCs (hMSCs) were grown in pellet monoculture under chondrogenic conditions and in pellet coculture with bovine ACs. Chondrogenesis was assessed with GAG quantification, safranin-O staining, and quantitative PCR (qPCR). Contributions of human and bovine cells were assessed with species-specific qPCR and human-specific immunostaining. Latepassage hMSCs did not undergo chondrogenesis in monoculture with chondrogenic stimuli or in coculture with ACs. Early-passage hMSCs underwent chondrogenesis only in response to chondrogenic stimuli. Coculture pellets in both cases accumulated as much GAG/DNA as monoculture AC pellets. Aggrecan transcription was not increased in coculture. Late-passage hMSCs that do not undergo chondrogenesis are capable of stimulating GAG accumulation in coculture with ACs. This supports a trophic effect of hMSCs on ACs. hMSCs may have therapeutic utility even after prolonged passaging.

Keywords: preimplantation immersion anesthesia local anesthetic opioid pain total knee arthroplasty a b s t r a c t Background: Most patients experience moderate to severe pain after total knee arthroplasty (TKA). We hypothesized that intraoperative treatment of cut bone surfaces with local anesthetic (preimplantation immersion anesthesia, PIA) would lead to decreased postoperative pain and opioid consumption. Methods: Records of 76 patients who underwent unilateral, cemented TKA were retrospectively reviewed. For PIA patients, surgical wounds were immersed in local anesthetic solution immediately prior to component implantation. Both PIA (n ¼ 43) and control (n ¼ 33) groups received multimodal pain management, including intra-articular local anesthetic injections. Endpoints were opioid consumption and mean pain scores for postoperative day (POD) 0, 1, and 2. Demographic, medical, and social factors were included in multivariate analyses. Results: PIA patients reported significantly lower mean pain scores than controls on PODs 0 and 1 (both P < .005). Pain scores on POD 2 were similar. PIA patients used 45%-33% less opioids on PODs 0, 1, and 2 (all P < .005). POD 0 pain scores showed a significant interaction between PIA treatment and preoperative opioid use (P ¼ .013). On POD 1, PIA was the only factor associated with lower mean pain scores (P < .001). No factors were significant for POD 2. PIA was the only factor associated with lower postoperative opioid consumption on PODs 0 and 2 (both P < .005). For POD 1, PIA and increasing age (both P .005) were associated with lower postoperative opioid consumption. Conclusion: PIA was associated with significant reductions in opioid use and mean pain scores after TKA.Published by Elsevier Inc.

Surgical-site delivery of local anesthetics decreases pain and opioid consumption after total knee arthroplasty (TKA). The optimal route of administration is unknown. We compared local anesthetic delivery using periarticular soft-tissue infiltration to delivery using a combination of preimplantation immersion and intra-articular injection (combination treatment). The records of patients who underwent unilateral, cemented, primary TKA with spinal anesthesia and adductor canal blocks at a single Veterans Affairs Medical Center were retrospectively reviewed. Three subgroups were compared, including controls who did not receive additional local anesthetics, patients who received periarticular infiltration, and patients who received combination treatment. Mean daily pain scores and mean 24-hour opioid consumption on postoperative days (PODs) 0 and 1 were calculated, and analysis of variance was used to assess for significant differences. Factors that were associated with lower pain scores and opioid consumption were then identified using multivariate stepwise regression. There were 26 controls, 25 periarticular infiltration patients, and 39 combination patients. The periarticular infiltration cohort had significantly lower mean pain scores and opioid consumption than controls on POD 0, but not on POD 1. The combination cohort had significantly lower mean pain scores and opioid consumption than controls on PODs 0 and 1. There were no significant differences between the infiltration and combination groups on either day. Multivariate regression analysis showed that infiltration was associated with significantly decreased opioid consumption on both days and decreased pain on POD 0. Combination treatment was associated with significantly decreased pain and opioid consumption on both days. Both local anesthetic periarticular infiltration and combination treatment are associated with decreased pain and opioid consumption after TKA. The stronger effects of the combination treatment compared with periarticular infiltration on POD 1 suggests that combination delivery may have a longer duration of action.