ECM stiffness enhances chondrocyte differentiation by priming cells for a potent response to TGFβ. ECM stiffness modifies the TGFβ pathway at multiple levels, including stiffness-sensitive induction of TGFβ1 expression, Smad3 phosphorylation, and synergistic activation of chondrocyte differentiation, by combining TGFβ and an inductive ECM stiffness.

Summary Objective This study investigated a novel approach to induce chondrogenic differentiation of human mesenchymal stem cells (hMSC). We hypothesized that a structured three-dimensional co-culture using hMSC and chondrocytes would provide chondroinductive cues to hMSC without inducing hypertrophy. Method In an effort to promote optimal chondrogenic differentiation of hMSC, we created bilaminar cell pellets (BCPs), which consist of a spherical population of hMSC encased within a layer of juvenile chondrocytes (JC). In addition to histologic analyses, we examined proteoglycan content and expression of chondrogenic and hypertrophic genes in BCPs, JC pellets, and hMSC pellets grown in the presence or absence of TGFβ following 21 days of culture in either growth or chondrogenic media. Results In either growth or chondrogenic media, we observed that BCPs and JC pellets produced more proteoglycan than hMSC pellets treated with TGFβ. BCPs and JC pellets also exhibited higher expression of the chondrogenic genes Sox9, aggrecan, and collagen 2A1, and lower expression of the hypertrophic genes matrix metalloproteinase-13, Runx2, collagen 1A1, and collagen 10A1 than hMSC pellets. Histologic analyses suggest that juvenile chondrocytes promote chondrogenic differentiation of cells in BCPs without hypertrophy. Furthermore, when cultured in hypoxic and inflammatory conditions intended to mimic the injured joint microenvironment, BCPs produced significantly more proteoglycan than either JC pellets or hMSC pellets. Conclusion The BCP co-culture promotes a chondrogenic phenotype without hypertrophy and, relative to pellet cultures of hMSCs or JCs alone, is more resistant to the adverse conditions anticipated at the site of articular cartilage repair.

Radiographic Union Score for Tibia (RUST) and modified RUST (mRUST) are radiographic tools for quantitatively evaluating fracture healing using a cortical scoring system. This tool has high intra-class correlation coefficients (ICCs); however, little evidence has evaluated the scores against the physical properties of bone healing. Closed, stabilized fractures were made in the femora of C3H/HeJ male mice (8-12 week-old) of two dietary groups: A control and a phosphate restricted diet group. Micro-computed tomography (µCT) and torsion testing were carried out at post-operative days (POD) 14, 21, 35, and 42 (n = 10-16) per group time-point. Anteroposterior and lateral radiographic views were constructed from the µCT scans and scored by five raters. The raters also indicated if the fracture were healed. ICCs were 0.71 (mRUST) and 0.63 (RUST). Both RUST scores were positively correlated with callus bone mineral density (BMD) (r = 0.85 and 0.80, p < 0.001) and bone volume fraction (BV/TV) (r = 0.86 and 0.80, p < 0.001). Both RUST scores positively correlated with callus strength (r = 0.35 and 0.26, p < 0.012) and rigidity (r = 0.50 and 0.39, p < 0.001). Radiographically healed calluses had a mRUST ≥13 and a RUST ≥10 and had excellent relationship to structural and biomechanical metrics. Effect of delayed healing due to phosphate dietary restrictions was found at later time points with all mechanical properties (p < 0.011), however no differences found in the RUST scores (p > 0.318). Clinical relevance of this study is both RUST scores showed high correlation to physical properties of healing and generally distinguished healed vs. non-healed fractures. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:945-953, 2018.

Objective: To determine whether a continuous femoral nerve block after open reduction internal fixation of tibial plateau fractures would diminish Visual Analog Scale (VAS) scores and/or systemic narcotic intake. Design: Randomized controlled trial. Setting: Level 1 academic trauma center. Patients: Forty-two consecutive patients with operatively treated tibial plateau fractures. Intervention: Continuous femoral nerve catheter for postoperative pain management was performed in the experimental group. Main Outcome Measures: Both the VAS scores for pain and narcotic intake were assessed at 4, 8, 12, 24, 36, 48, and 72 hours postoperatively. Results: Forty-two patients were enrolled in this study. There were 21 women and 21 men 21-70 years of age (avg 49) with operatively treated tibial plateau fractures. Twenty-one patients were randomized to receive a femoral nerve block with 5 crossovers for technical reasons. Accordingly, we analyzed 16 patients with femoral nerve blocks and 26 with standard care. There were no significant differences between the study groups regarding age, sex, or fracture type. There was no significant difference in VAS scores between the control and experimental group at any time point. The total systemic morphine equivalent for the femoral nerve block group and the control group was 375 and 397 respectively (P = 0.76). Across groups, patients with bicondylar fractures tended to have higher VAS than those with unicondylar fractures and to use more narcotics, although neither was statistically significant. Conclusion: Femoral nerve blocks for postoperative pain management in tibial plateau fractures did not demonstrate an improvement in pain relief or narcotic use. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.