Martine LaBerge

Phospholipid composition of articular cartilage boundary lubricant.

The mechanism of lubrication in normal human joints depends on loading and velocity conditions. Boundary lubrication, a mechanism in which layers of molecules separate opposing surfaces, occurs under severe loading. This study was aimed at characterizing the phospholipid composition of the adsorbed molecular layer on the surface of normal cartilage that performs as a boundary lubricant. The different types of phospholipid adsorbed onto the surface of cartilage were isolated by extraction and identified by chromatography on silica gel paper and mass spectroscopy. The main phospholipid classes identified were quantified by a phosphate assay. Gas chromatography and electrospray ionization mass spectrometry were used to further characterize the fatty acyl chains in each major phospholipid component and to identify the molecular species present. Phosphatidylcholine (41%), phosphatidylethanolamine (27%) and sphingomyelin (32%) were the major components of the lipid layer on the normal cartilage surface. For each lipid type, a mixture of fatty acids was detected, with a higher percentage of unsaturated species compared to saturated species. The most abundant fatty acid observed with all three lipid types was oleic acid (C18:1). Additional work to further quantify the molecular species using electrospray ionization mass spectrometry is recommended.

Frictional properties of poly(MPC-co-BMA) phospholipid polymer for catheter applications.

A fundamental understanding of surface properties of the biomaterials at a nanometer scale should be generated in order to understand cellular responses of the tissue to biomaterials thereby minimizing or eliminating tissue trauma at a macrometer scale. In this study poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) ([poly(MPC-co-BMA]) was evaluated as a potential coating material for vascular applications to provide smooth catheterization using atomic force microscopy (AFM) techniques.A uniform coating of [poly(MPC-co-BMA] equivalent to a thickness of 2.5 microm on a polyurethane (PU) catheter material was provided using dip casting technique. Using a contact mode AFM, no significant difference in surface roughness (R(a)) and frictional force (f) between uncoated (R(a)=10.2+/-1.9 nm, f=0.907+/-0.02) and coated (R(a)=11.7+/-1.8 nm, f=0.930+/-0.06) surfaces was observed under dry conditions. However, under wet conditions the R(a) of the coated surface (3.4+/-1.0 nm) was significantly lower than uncoated PU surface (9.0+/-1.8 nm). The coating on PU substrate offered the least frictional resistance (f=0.004+/-0.001) illustrating enhanced boundary lubrication capability due to hydration of phosphorylcholine polymer as compared to a significantly higher f for uncoated PU (0.017+/-0.007) surfaces. These tribological and chemical characteristics of the [poly(MPC-co-BMA)] coating could increase the overall efficacy of PU for clinical applications.

Comparison of polyethylene tibial insert damage from in vivo function and in vitro wear simulation.

Function and wear of total knee arthroplasties were compared by analysis of damage patterns on polyethylene tibial inserts retrieved from patients (Group R) with inserts obtained after in vitro force‐controlled knee joint wear simulation. Two simulator input profiles were evaluated, including standard walking (Group W), and combined walking and stair descent (Group W + S), simulating varied activities and a more severe physiological environment. Damage regions on all inserts were quantitatively assessed. On average, inserts in all groups had internally rotated damage patterns and the greatest articular deformation in the lateral compartment. These patterns were more pronounced in Group W + S compared to Group W. Deformation rates of simulated inserts were analogous to about six years of physiologic function. However, both groups of simulated inserts generally underestimated the magnitude of damage area and extent observed on retrieved inserts, consistent with differences in the simulators tibiofemoral contact mechanics and those known to occur in patients during functional activities. Modification of simulator inputs, such as the increased anteroposterior excursion and more severe loading conditions in Group W + S, can generate greater wear volume, larger damage areas, and increased surface deformation rates compared to standard inputs.

Effect of stair descent loading on ultra-high molecular weight polyethylene wear in a force-controlled knee simulator

Abstract A loading protocol approximating forces, torques and motions at the knee during stair descent was developed from previously published data for input into a force-controlled knee simulator. A set of total knee replacements (TKRs) was subjected to standard walking cycles and stair descent cycles at a ratio of 70:1 for 5 million cycles. Another set of implants with similar articular geometry and the same ultra-high molecular weight polyethylene (UHMWPE) resin (GUR 415), sterilization and packaging was tested with standard walking cycles only. Implant kinematics, gravimetric wear and surface roughness of the UHMWPE inserts were analysed for both sets of implants. Contact stresses were calculated for both loading protocols using a Hertzian line contact model. Significantly greater weight loss (p < 0.05) and more severe surface damage of UHMWPE inserts resulted with the walking + stair descent loading protocol compared to walking cycles only. Anterior-posterior (AP) tibiofemoral contact point displacements were lower during stair descent than walking, but not significantly different (p = 0.05). Contact stresses were significantly higher during stair descent than walking, owing to higher axial loads and the smaller radius of curvature of the femoral components at higher flexion angles. High contact stresses on UHMWPE components are likely to accelerate the fatigue of the material, resulting in more severe wear, similar to what is observed in retrieved implants. Thus the inclusion of loading protocols for activities of daily living in addition to walking is warranted for more realistic in vitro testing of TKRs.

Potential Improvements in Shock-Mitigation Efficacy of a Polyurea-Augmented Advanced Combat Helmet

The design of the currently used Advanced Combat Helmet (ACH) has been optimized to attain maximum protection against ballistic impacts (fragments, shrapnel, etc.) and hard-surface collisions. However, the ability of the ACH to protect soldiers against blast loading appears not to be as effective. Polyurea, a micro-segregated elastomeric copolymer has shown superior shock-mitigation capabilities. In the present work, a combined Eulerian/Lagrangian transient non-linear dynamics computational fluid/solid interaction analysis is used to investigate potential shock-mitigation benefits which may result from different polyurea-based design augmentations of the ACH. Specific augmentations include replacement of the currently used suspension-pad material with polyurea and the introduction of a thin polyurea internal lining/external coating to the ACH shell. Effectiveness of different ACH designs was quantified by: (a) establishing the main forms of mild traumatic brain injury (mTBI); (b) identifying the key mechanical causes for these injuries; and (c) quantifying the extents of reductions in the magnitude of these mechanical causes. The results obtained show that while the ACH with a 2-mm-thick polyurea internal lining displays the best blast mitigation performance, it does not provide sufficient protection against mTBI.

A study of the blast‐induced brain white‐matter damage and the associated diffuse axonal injury

Purpose – Blast‐induced traumatic brain injury (TBI) is a signature injury of the current military conflicts. Among the different types of TBI, diffuse axonal injury (DAI) plays an important role since it can lead to devastating effects in the inflicted military personnel. To better understand the potential causes associated with DAI, this paper aims to investigate a transient non‐linear dynamics finite element simulation of the response of the brain white matter to shock loading.Design/methodology/approach – Brain white matter is considered to be a heterogeneous material consisting of fiber‐like axons and a structure‐less extracellular matrix (ECM). The brain white matter microstructure in the investigated corpus callosum region of the brain is idealized using a regular hexagonal arrangement of aligned equal‐size axons. Deviatoric stress response of the axon and the ECM is modeled using a linear isotropic viscoelastic formulation while the hydrostatic stress response is modeled using a shock‐type equatio...

Hydroxyapatite composites designed for antibiotic drug delivery and bone reconstruction: a caprine model.

The purpose of this study was to investigate the feasibility of fabricating a drug delivery system that serves a dual function, to eradicate infection as well as to provide a scaffold for osseous integration. Two porous composite systems were fabricated using hydroxyapatite (HA) as the carrier for gentamicin sulfate (GS), an aminoglycoside antibiotic. Structural and mechanical properties of porous HA-GS composites were characterized and the in vitro release behavior of GS from fabricated composites was monitored and compared with the well-known polymethylmethacrylate (PMMA)-GS delivery system. Scanning electron microscopy revealed a macropore range of 150 to 200 microm and 100 to 190 microm for the sintered and unsintered HA-GS composites, respectively. The effect of GS inclusion on bone apposition and ingrowth was assessed using a caprine model. Plugs 10 mm x 6 mm of cylindrical tricalcium phosphate, sintered HA, and sintered HA-GS were implanted in the femoral diaphysis for a period of 6 weeks. Data collected during the in vitro study showed that GS can successfully be incorporated into HA and used as a drug delivery system to eradicate Staphylococcus aureus. In vivo data confirmed that the inclusion of GS within a ceramic matrix did not stimulate or inhibit osteointegration or bone apposition. In conclusion, the fabricated sintered HA-GS composite may be beneficial in the treatment of infected osseous sites as a drug delivery system.

The Quantification of Physiologically Relevant Cross-Shear Wear Phenomena on Orthopaedic Bearing Materials Using the MAX-Shear Wear Testing System

Background: The occurrence of multi-directional sliding motion between total knee replacement bearing surfaces is theorized to be a primary wear and failure mechanism of ultra-high molecular weight poly(ethylene) (UHMWPE). To better quantify the tribologic mechanisms of this cross-shear wear, the MAX-Shear wear-testing system was developed to evaluate candidate biomaterials under controlled conditions of cross-shear wear. Method of approach: A computer controlled traveling x-y stage under a 3 degree-of-freedom statically loaded pin is used to implement the complex multi-directional motion pathways observed during TKR wear simulation. A MHz collection of dynamic x-y friction was available on all six environmentally controlled stations. The functionality of this testing platform was proven in a 100,000 cycle, 11.6 MPa, wear test using 15.0 mm diameter polished stainless steel spheres against flat GUR4150 UHMWPE. A five-pointed star wear pattern was used to incorporate the physiologically relevant cross-shear sliding conditions of stop/start, 50mm∕s entraining velocity and five crossing angles of 72°. Using normalized volumetric reconstruction of the resulting surface damage, a direct quantitative relationship between linear and cross-shear surface damage intensity was obtained. Results: Cross-shear surface damage volume loss was found to be 2.94 (±0.88) times that associated with linear sliding under identical tribologic conditions. SEM analysis of linear wear damage showed consistent fibril orientation along the direction of sliding while cross-shear wear damage showed multi-directional fibril orientations and increased surface roughness. Significant increases in discrete crossing-point friction coefficients were recorded throughout testing. Conclusions: This scientific approach to quantifying the tribologic effects of cross-shear provides fundamental wear mechanism data that are critical in evaluating potential biomaterials for use as in vivo bearings. Relevant multi-axis, cross-shear wear testing is necessary to provide quantifiable measures of complex biomaterials wear phenomena.

Fabrication and characterization of dipalmitoylphosphatidylcholine-attracting elastomeric material for joint replacements

Wear debris associated with the polyethylene components of total joint replacements has been shown to induce bone resorption which contributes to implant loosening. In an effort to promote lubrication and reduce wear in artificial hip joints, the use of the cushion bearing concept has been proposed previously; however, an elastomeric material tested as a cushion bearing has been shown to have poor tribological properties during initiation of motion from rest. The goal of this project was to fabricate and characterize an elastomer that has the ability to attract to its surface naturally occurring boundary lubricants from an aqueous solution. The test elastomer and appropriate controls were characterized using fluorescence, electron spin resonance and X-ray photoelectron spectroscopy. The test elastomer was found to have an enhanced ability to attract dipalmitoylphosphatidylcholine, a known physiological boundary lubricant. A cushion bearing that also encourages boundary lubrication represents a potential improvement over currently existing orthopaedic implant-bearing materials.

Role of cytoskeletal components in stress-relaxation behavior of adherent vascular smooth muscle cells.

A number of recent studies have demonstrated the effectiveness of atomic force microscopy (AFM) for characterization of cellular stress-relaxation behavior. However, this techniques recent development creates considerable need for exploration of appropriate mechanical models for analysis of the resultant data and of the roles of various cytoskeletal components responsible for governing stress-relaxation behavior. The viscoelastic properties of vascular smooth muscle cells (VSMCs) are of particular interest due to their role in the development of vascular diseases, including atherosclerosis and restenosis. Various cytoskeletal agents, including cytochalasin D, jasplakinolide, paclitaxel, and nocodazole, were used to alter the cytoskeletal architecture of the VSMCs. Stress-relaxation experiments were performed on the VSMCs using AFM. The quasilinear viscoelastic (QLV) reduced-relaxation function, as well as a simple power-law model, and the standard linear solid (SLS) model, were fitted to the resultant stress-relaxation data. Actin depolymerization via cytochalasin D resulted in significant increases in both rate of relaxation and percentage of relaxation; actin stabilization via jasplakinolide did not affect stress-relaxation behavior. Microtubule depolymerization via nocodazole resulted in nonsignificant increases in rate and percentage of relaxation, while microtubule stabilization via paclitaxel caused significant decreases in both rate and percentage of relaxation. Both the QLV reduced-relaxation function and the power-law model provided excellent fits to the data (R(2)=0.98), while the SLS model was less adequate (R(2)=0.91). Data from the current study indicate the important role of not only actin, but also microtubules, in governing VSMC viscoelastic behavior. Excellent fits to the data show potential for future use of both the QLV reduced-relaxation function and power-law models in conjunction with AFM stress-relaxation experiments.