Effect of acetabular cup abduction angle on wear of ultrahigh-molecular-weight polyethylene in hip simulator testing.

The effect of acetabular component positioning on the wear rates of metal-on-polyethylene articulations has not been extensively studied. Placement of acetabular cups at abduction angles of more than 40° has been noted as a possible reason for early failure caused by increased wear. We conducted a study to evaluate the effects of different acetabular cup abduction angles on polyethylene wear rate, wear area, contact pressure, and contact area. Our in vitro study used a hip joint simulator and finite element analysis to assess the effects of cup orientation at 4 angles (0°, 40°, 50°, 70°) on wear and contact properties. Polyethylene bearings with 28-mm cobalt-chrome femoral heads were cycled in an environment mimicking in vivo joint fluid to determine the volumetric wear rate after 10 million cycles. Contact pressure and contact area for each cup abduction angle were assessed using finite element analysis. Results were correlated with cup abduction angles to determine if there were any differences among the 4 groups. The inverse relationship between volumetric wear rate and acetabular cup inclination angle demonstrated less wear with steeper cup angles. The largest abduction angle (70°) had the lowest contact area, largest contact pressure, and smallest head coverage. Conversely, the smallest abduction angle (0°) had the most wear and most head coverage. Polyethylene wear after total hip arthroplasty is a major cause of osteolysis and aseptic loosening, which may lead to premature implant failure. Several studies have found that high wear rates for cups oriented at steep angles contributed to their failure. Our data demonstrated that larger cup abduction angles were associated with lower, not higher, wear. However, this potentially "protective" effect is likely counteracted by other complications of steep cup angles, including impingement, instability, and edge loading. These factors may be more relevant in explaining why implants fail at a higher rate if cups are oriented at more than 40° of abduction.

E-cadherin synergistically induces hepatospecific phenotype and maturation of embryonic stem cells in conjunction with hepatotrophic factors.

Since effective cell sourcing is a major challenge for the therapeutic management of liver disease and liver failure, embryonic stem (ES) cells are being widely investigated as a promising source of hepatic-like cells with their proliferative and pluripotent capacities. Cell-cell interactions are crucial in embryonic development modulating adhesive and signaling functions; specifically, the cell-cell adhesion ligand, cadherin is instrumental in gastrulation and hepatic morphogenesis. Inspired by the role of cadherins in development, we investigated the role of expression of E-cadherin in cultured murine ES cells on the induction of hepatospecific phenotype and maturation. The cadherin-expressing embryonic stem (CE-ES) cells intrinsically formed pronounced cell aggregates and cuboidal morphology whereas cadherin-deficient cadherin-expressing embryonic stem (CD-ES) cells remained more spread out and corded in morphology. Through controlled stimulation with single or combined forms of hepatotrophic growth factors; hepatocyte growth factor (HGF), dexamethasone (DEX) and oncostatin M (OSM), we investigated the progressive maturation of CE-ES cells, in relation to the control, CD-ES cells. Upon growth factor treatment, the CE-ES cells adopted a more compacted morphology, which exhibited a significant hepatocyte-like cuboidal appearance in the presence of DEX-OSM-HGF. In contrast, the CD-ES cells exhibited a mixed morphology and appeared to be more elongated in the presence of DEX-OSM-HGF. Reverse-transcriptase polymerase chain reaction was used to delineate the most differentiating condition in terms of early (alpha-fetoprotein (AFP)), mid (albumin), and late-hepatic (glucose-6-phosphatase) markers in relation to growth factor presentation for both CE-ES and CD-ES cells. We report that following the most differentiating condition of DEX-OSM-HGF stimulation, CE-ES cells expressed increased levels of albumin and glucose-6-phosphatase, whereas the CD-ES cells showed low levels of AFP and marginal levels of albumin and glucose-6-phosphatase. These trends suggest that the membrane expression of E-cadherin in ES cells can elicit a marked response to growth factor stimulation and lead to the induction of later stages of hepatocytic maturation. Thus, cadherin-engineered ES cells could be used to harness the cross-talk between the hepatotrophic and cadherin-based signaling pathways for controlled acceleration of ES hepatodifferentiation.

Engineering hepatocellular morphogenesis and function via ligand-presenting hydrogels with graded mechanical compliance.

In order to evaluate the sensitivity of hepatocellular cultures to variations in both substrate stiffness and bioactive ligand presentation, hepatocytes were cultured on differentially compliant polyacrylamide gel discs functionalized with varying amounts of the ECM ligand, fibronectin (FN). Subconfluent cell cultures were established in a multiwell plate format enabling the systematic evaluation of cellular response to both underlying substrate rigidity and substrate ligand concentration. Hepatocellular morphogenesis, regulated by a combination of both ligand density and substrate compliance, resulted in a broad spectrum of patterns of cellular reorganization and assembly ranging from highly two-dimensionally spread cells to highly compact, three-dimensional spheroids. Cell compaction was promoted by increasing levels of substrate mechanical compliance and generally inhibited by increasing concentrations of substrate-bound FN. We identified regimes of substrate compliance in which cells are highly responsive or relatively insensitive to the level of substrate-based ligands. For example, while FN presentation did not have a large impact on cell morphogenesis for cultures on highly compliant gels (G' = 1.9 kPa), hepatocytes on "firm" substrates of intermediate compliance (G' = 5.6 kPa) exhibited approximately a 2-fold increase in cell area between the highest and lowest FN concentrations used in this study. Further, we show that increasing substrate compliance at constant ligand concentration results in increased levels of liver-specific albumin secretion while increasing levels of FN at constant substrate rigidity yield reduced liver-specific functional activity. These substrate-elicited differences in cell function also coincided with analogous changes in the transcript levels of metabolic, growth-related, and liver-specific gene markers. Notably, these results also demonstrated that "firm" gel substrates elicit the most hepatocyte functional sensitivity to substrate-based FN presentation. Overall, our findings indicate that hepatocellular responsiveness to ligand concentration can be acutely regulated by gradation of substrate compliance, suggesting that concerted biochemical and biophysical design strategies may be critical toward the fabrication of hepatospecific biomaterials that effectively support desired levels of liver-specific function.