The connective tissue response to Ti, NiCr and AgPd alloys

The aim of the study was to compare the connective tissue response of Lewis rats to Ti, NiCr and AgPd alloys. It was found that implants were covered by collagen-rich, well vascularized capsules. Titanium was covered by the thinnest capsule (57 ± 20 μm) and AgPd alloy was covered by the thickest capsule (239 ± 50 μm). The PCNA+ cell prevalence in the capsules was lower for titanium than for AgPd and NiCr. Mast cells formed a gradient to a depth of 1200 μm only for titanium implants. Cells with brown to black silver granules in the cytoplasm were observed close to AgPd implants. The results suggest that titanium implants induce a weaker connective tissue response than implants made from NiCr and AgPd alloys.     

Ultrastructural differences of the interface zone between bone and Ti 6Al 4V or commercially pure titanium

Commercially pure (CP) titanium and Ti 6Al 4V alloy were sputtered onto polycarbonate plastic implants to analyse hard tissue reactions to the two metals. The implants were inserted in the tibial methaphyses of five rabbits. Three months later they were removed and processed for light microscopy (LM) and transmission electron microscopy (TEM) investigations. At the LM level, disordered woven bone was seen in the interface zone of Ti 6Al 4V, whereas organized bone was observed in direct contact with the CP titanium implants. TEM examination of Ti 6Al 4V sections revealed a 500–1000 Å thick collagen-free proeoglycan layer compared to 200–400 Å for CP titanium. A surface analysis test was performed to compare the magnetron sputtered film with bulk Ti 6Al 4V alloy. This test revealed no major differences between the experimental implant and the bulk alloy. More natural-like tissue reactions were observed to CP titanium than to Ti 6Al 4V alloy.     

Reverse engineering of mandible and prosthetic framework: Effect of titanium implants in conjunction with titanium milled full arch bridge prostheses on the biomechanics of the mandible

This study aimed at investigating the effects of titanium implants and different configurations of full-arch prostheses on the biomechanics of edentulous mandibles. Reverse engineered, composite, anisotropic, edentulous mandibles made of a poly(methylmethacrylate) core and a glass fibre reinforced outer shell were rapid prototyped and instrumented with strain gauges. Brånemark implants RP platforms in conjunction with titanium Procera one-piece or two-piece bridges were used to simulate oral rehabilitations. A lateral load through the gonion regions was used to test the biomechanical effects of the rehabilitations. In addition, strains due to misfit of the one-piece titanium bridge were compared to those produced by one-piece cast gold bridges. Milled titanium bridges had a better fit than cast gold bridges. The stress distribution in mandibular bone rehabilitated with a one-piece bridge was more perturbed than that observed with a two-piece bridge. In particular the former induced a stress concentration and stress shielding in the molar and symphysis regions, while for the latter design these stresses were strongly reduced. In conclusion, prosthetic frameworks changed the biomechanics of the mandible as a result of both their design and manufacturing technology.     

Acute effects of reducing vertical displacement and step frequency on running economy

This work studies the immediate effects of altering the vertical displacement of the center of mass (VD) and step frequency (SF) on the metabolic cost of level treadmill running at 16 km · h(-1) on 16 male runners. Alterations of VD, SF, and the product VD × SF was induced using a novel feedback system, which presents target and current values to the runner by visual or auditory display. Target values were set to 5 and 10% reductions from individual baseline values. The results were expressed as relative changes from baseline values. Alterations led to an increase in metabolic cost in most cases, measured as V(O2) uptake per minute and kilogram of body mass. Correlations were weak. Still, linear multiple regression revealed a positive coefficient (0.28) for the relationship between VD × SF and V(O2). Separate rank correlation tests showed negative correlation (τ = -0.19) between SF and V(O2) and positive correlation (τ = 0.16) between VD and V(O2). There is a coupling between VD and SF caused by the mechanics of running; hence, isolated reduction of either factor was hard to achieve. The linear model also showed a negative coefficient for the relationship between the height of the center of mass above the ground (CoMh) and V(O2). The effect size was small (multiple R(2) 0.07 and 0.12). Still the results indicate that reducing VD × SF by reducing the vertical displacement can have a positive effect on running economy, but a concurrent reduction in CoMh may diminish the positive effect. Midterm and long-term effects of altering the technique should also be studied.     

Apparent transverse compressive material properties of the digital flexor tendons and the median nerve in the carpal tunnel

Carpal tunnel syndrome is a frequently encountered peripheral nerve disorder caused by mechanical insult to the median nerve, which may in part be a result of impingement by the adjacent digital flexor tendons. Realistic finite element (FE) analysis to determine contact stresses between the flexor tendons and median nerve depends upon the use of physiologically accurate material properties. To assess the transverse compressive properties of the digital flexor tendons and median nerve, these tissues from ten cadaveric forearm specimens were compressed transversely while under axial load. The experimental compression data were used in conjunction with an FE-based optimization routine to determine apparent hyperelastic coefficients (μ and α) for a first-order Ogden material property definition. The mean coefficient pairs were μ=35.3 kPa, α=8.5 for the superficial tendons, μ=39.4 kPa, α=9.2 for the deep tendons, μ=24.9 kPa, α=10.9 for the flexor pollicis longus (FPL) tendon, and μ=12.9 kPa, α=6.5 for the median nerve. These mean Ogden coefficients indicate that the FPL tendon was more compliant at low strains than either the deep or superficial flexor tendons, and that there was no significant difference between superficial and deep flexor tendon compressive behavior. The median nerve was significantly more compliant than any of the flexor tendons. The material properties determined in this study can be used to better understand the functional mechanics of the carpal tunnel soft tissues and possible mechanisms of median nerve compressive insult, which may lead to the onset of carpal tunnel syndrome.     

Fresh-frozen human bone allograft in vertical ridge augmentation: clinical and tomographic evaluation of bone formation and resorption

The aim of the current study is to evaluate fresh-frozen human bone allografts (FHBAs) used in vertical ridge augmentation clinically and by computed tomography, and to analyze the resulting bone formation and graft resorption. Sixteen FHBAs were grafted in the maxillae and mandibles of 9 patients. The FHBAs, which were provided by the Musculoskeletal Tissue Bank of Marilia Hospital (Unioss), were frozen at -80°C. After 7?months, dental implants were placed and bone parameters were evaluated. Vertical bone formation was measured by computerized tomography before (T0) and at 7?months (T1) after the surgical procedure. Bone graft resorption was measured clinically from a landmark screw head using a periodontal probe. The results were analyzed by Student's t-test. Significant differences existed in the bone formation values at T0 and T1, with an average change of 4.03?±?1.69?mm. Bone graft resorption values were 1.0?±?0.82?mm (20%). Implants were placed with varying insertion torque values (35-45?Ncm), and achieved primary stability. This study demonstrates that FHBAs promote satisfactory vertical bone formation with a low resorption rates, good density, and primary implant stability.     

p38 MAPK-dependent small HSP27 and αB-crystallin phosphorylation in regulation of myocardial function following cardioplegic arrest

We previously demonstrated that myocardial p38 mitogen-activated protein kinase (MAPK) and heat shock protein 27 (HSP27) are phosphorylated following cardioplegic arrest in patients undergoing cardiac surgery and correlate with reduced cardiac function. The following studies were performed to determine whether inhibition of p38 MAPK and/or overexpression of nonphosphorylatable HSP27 improves cardiac function following cardioplegic arrest. Langendorff-perfused isolated rat hearts were subjected to 2 h of intermittent cold cardioplegia followed by 30 min of reperfusion. Hearts were treated with (CP+SB) or without (CP) the p38 MAPK inhibitor SB-203580 (5 μM) supplied in the cardioplegia. Sham-treated hearts served as controls. In separate experiments, isolated rat ventricular myocytes infected with either green fluorescent protein (GFP) or a nonphosphorylatable HSP27 mutant (3A-HSP27) were subjected to 3 h of cold hypoxic cardioplegia and simulated reperfusion (CP) followed by video microscopy and length change measurements. Baseline parameters of cardiac function were similar between groups [left ventricular developed pressure (LVDP), 119 ± 4.9 mmHg; positive and negative first derivatives of LV pressure (± dP/dt), 3,139 ± 245 and 2, 314 ± 110 mmHg/s]. CP resulted in reduced cardiac function (LVDP, 72.2 ± 5.8 mmHg; ± dP/dt, 2,076 ± 231 and -1,317 ± 156 mmHg/s) compared with baseline. Treatment with 5 μM SB-203580 significantly improved CP-induced cardiac function (LVDP, 101.9 ± 0 mmHg; ± dP/dt, 2,836 ± 163 and -2,108 ± 120 mmHg/s; P = 0.03, 0.01, and 0.04, CP+SB vs. CP). Inhibition of p38 MAPK significantly lowered CP-induced p38 MAPK, HSP27, and αB-crystallin (cryAB) phosphorylation. In vitro CP decreased myocyte length changes from 10.3 ± 1.5% (GFP) to 5.7 ± 0.8% (GFP+CP). Infection with 3A-HSP27 completely rescued CP-induced decreased myocyte contraction (11.1 ± 1.0%). However, infection with 3A-HSP27 did not block the endogenous HSP27 response. We conclude that inhibition of p38 MAPK and subsequent HSP27 and cryAB phosphorylation and/or overexpression of nonphosphorylatable HSP27 significantly improves cardiac performance following cardioplegic arrest. Modulation of HSP27 phosphorylation may improve myocardial stunning following cardiac surgery.     

Locally measured shear moduli of pulmonary tissue and global lung mechanics in mechanically ventilated rats

This study was aimed at measuring shear moduli in vivo in mechanically ventilated rats and comparing them to global lung mechanics. Wistar rats (n = 28) were anesthetized, tracheally intubated, and mechanically ventilated in supine position. The animals were randomly assigned to the healthy control or the lung injury group where lung injury was induced by bronchoalveolar lavage. The respiratory system elastance E(rs) was analyzed based on the single compartment resistance/elastance lung model using multiple linear regression analysis. The shear modulus (G) of alveolar parenchyma was studied using a newly developed endoscopic system with adjustable pressure at the tip that was designed to induce local mechanostimulation. The data analysis was then carried out with an inverse finite element method. G was determined at continuous positive airway pressure (CPAP) levels of 15, 17, 20, and 30 mbar. The resulting shear moduli of lungs in healthy animals increased from 3.3 ± 1.4 kPa at 15 mbar CPAP to 5.8 ± 2.4 kPa at 30 mbar CPAP (P = 0.012), whereas G was ~2.5 kPa at all CPAP levels for the lung-injured animals. Regression analysis showed a negative correlation between G and relative E(rs) in the control group (r = -0.73, P = 0.008 at CPAP = 20 mbar) and no significant correlation in the lung injury group. These results suggest that the locally measured G were inversely associated with the elastance of the respiratory system. Rejecting the study hypothesis the researchers concluded that low global respiratory system elastance is related to high local resistance against tissue deformation.     

Spatial relationships between shearing stresses and pressure on the plantar skin surface during gait

Based on the hypothesis that diabetic foot lesions have a mechanical etiology, extensive efforts have sought to establish a relationship between ulcer occurrence and plantar pressure distribution. However, these factors are still not fully understood. The purpose of this study was to simultaneously record shear and pressure distributions in the heel and forefoot and to answer whether: (i) peak pressure and peak shear for anterior-posterior (AP) and medio-lateral (ML) occur at different locations, and if (ii) peak pressure is always centrally located between sites of maximum AP and ML shear stresses. A custom built system was used to collect shear and pressure data simultaneously on 11 subjects using the 2-step method. The peak pressure was found to be 362 kPa ± 106 in the heel and 527 kPa ± 123 in the forefoot. In addition, the average peak shear values were higher in the forefoot than in the heel. The greatest shear on the plantar surface of the forefoot occurred in the anterior direction (mean and std. dev.: 37.7 ± 7.6 kPa), whereas for the heel, peak shear the foot was in the posterior direction (21.2 ± 5 kPa). The results of this study suggest that the interactions of the shear forces caused greater "spreading" in the forefoot and greater tissue "dragging" in the heel. The results also showed that peak shear stresses do not occur at the same site or time as peak pressure. This may be an important factor in locating where skin breakdown occurs in patients at high-risk for ulceration.     

Influence of the structure of the support surface under the sole on vertical posture during standing with different body weight distributions between legs

The vertical posture was studied during standing with fееt on the support surfaces of different structures. The movements of the center of pressure (CP) of each leg and the common CP (CCP) were recorded while the subject stood with a support on a smooth floor and with the support of one foot on a spike mat (SM) with different load distributions between the legs. When the body weight was transferred to one leg during standing under ordinary conditions on a smooth floor, the CP of the loaded leg moved more than the CP of the unloaded leg; i.e., the posture sway was compensated mainly due to the activity of the loaded leg, which created a larger torque. When the subject stood with one foot on the SM, the CP movement of this leg did not depend on the leg load and was about 60% of the CP movement of the leg on the smooth floor. Apparently, the CP displacement of the unloaded leg on smooth support was larger than the CP displacement of the loaded leg creating the torque necessary for compensating the body sway. Thus, maintaining the vertical posture was carried out mainly by the leg standing on the smooth support. It is assumed that additional stimulation of different surface and deep receptors of the foot caused by foot support on the SM hampered the perception of its CP position, and the vertical posture was maintained mainly by the leg afferent signals from which more precisely reflected the CP position.     

Accessory muscle activation during the superimposed burst technique

Quadriceps muscle activation is assessed using the superimposed burst technique. This technique involves percutaneous muscle stimulation superimposed during maximal isometric volitional knee extension. It is unknown whether accessory muscle activation during maximal knee extension influences estimates of quadriceps muscle activation. Our aim was to compare accessory muscle activation while performing the superimposed burst technique using investigator delivered verbal instruction to constrain the system (CS) and a participant preferred (PP) technique. Twenty five healthy, active individuals (13M/12F, age=23.8 ± 3.35, height=72.73 ± 14.51 cm, and weight=175.29 ± 9.59 kg) were recruited for this study. All participants performed superimposed burst testing with (CS) and without (PP) verbal instruction to encourage isolated quadriceps activation during maximal isometric knee extension. The main outcome variables measured were knee extension torque, quadriceps central activation ratio and mean EMG of vastus lateralis, biceps femoris, and lumbar paraspinal muscles. There were significant differences in knee extension torque (CS=2.87 ± 0.93 Nm/kg, PP=3.40 ± 1.12 Nm/kg, p<0.001), superimposed burst torque (CS=3.40 ±0.98 Nm/kg, PP=3.75 ± 1.11 Nm/kg, p=0.002) and quadriceps CAR (CS=84.1 ± 12.0%, PP=90.2 ± 9.9%, p<0.001) between the techniques. There was also a significant difference in lumbar paraspinal EMG (CS=6.40 ± 8.52%, PP=11.86 ± 14.89%, p=0.043) between the techniques however vastus lateralis EMG was not significantly different. Patient instruction via verbal instruction to constrain proximal structures may help patient minimize confounders to knee extension torque generation while maximizing quadriceps activation.     

Stress analysis and failure prediction in the proximal femur before and after total hip replacement

An investigation was performed to determine the effects of the presence of two lengths of proximal Müller prosthesis on predicted failure loads, as compared to those for an intact femur. Three-dimensional stresses in a bone/cement/prosthesis system were determined using finite element methods, with both isotropic and transversely isotropic material properties used for the diaphyseal cortex. Significant increases in prosthesis stem stresses were found when the transversely isotropic material properties were employed in the diaphyseal cortex. This leads to the conclusion that accurate anisotropic material properties for bone are essential for precise stress determination and optimum design in prosthetic implants. Failure loads were also predicted for vertical compression and axial torque, similar to available experimental conditions, and were within the range of the experimental failure data found in the literature. The technique developed herein can be used to systematically assess existing as well as future implant designs, taking into account the complex three-dimensional interaction effects of the overall bone/cement/prosthesis system.     

The pediatric upper limb motion index and a temporal-spatial logistic regression: quantitative analysis of upper limb movement disorders during the Reach & Grasp Cycle

This study describes a novel pediatric upper limb motion index (PULMI) for children with cerebral palsy (CP). The PULMI is based on three-dimensional kinematics and provides quantitative information about upper limb motion during the Reach & Grasp Cycle. We also report key temporal-spatial parameters for children with spastic, dyskinetic, and ataxic CP. Participants included 30 typically-developing (TD) children (age=10.9±4.1 years) and 25 children with CP and upper limb involvement (age=12.3±3.7 years), Manual Ability Classification System (MACS) levels I-IV. The PULMI is calculated from the root-mean-square difference for eight kinematic variables between each child with CP and the average TD values, and scaled such that the TD PULMI is 100±10. The PULMI was significantly lower among children with CP compared to TD children (Wilcoxon Z=-5.06, p<.0001). PULMI scores were significantly lower among children with dyskinetic CP compared to spastic CP (Z=-2.47, p<.0135). There was a strong negative correlation between PULMI and MACS among children with CP (Spearman's rho=-.78, p<.0001). Temporal-spatial values were significantly different between CP and TD children: movement time (Z=4.06, p<.0001), index of curvature during reach (Z=3.68, p=.0002), number of movement units (Z=3.72, p=.0002), angular velocity of elbow extension during reach (Z=-3.96, p<.0001), and transport(1):reach peak velocities (Z=-2.48, p=.0129). A logistic regression of four temporal-spatial parameters, the Pediatric Upper Limb Temporal-Spatial Equation (PULTSE), correctly predicted 19/22 movement disorder subtypes (spastic versus dyskinetic CP). The PULMI, PULTSE, and key temporal-spatial parameters of the Reach & Grasp Cycle offer a quantitative approach to analyzing upper limb function in children with CP.     

Numerical investigation of bone remodelling around immediately loaded dental implants using sika deer (Cervus nippon) antlers as implant bed

This study combines finite element method and animal studies, aiming to investigate tissue remodelling processes around dental implants inserted into sika deer antler and to develop an alternative animal consuming model for studying bone remodelling around implants. Implants were inserted in the antlers and loaded immediately via a self-developed loading device. After 3, 4, 5 and 6 weeks, implants and surrounding tissue were taken out. Specimens were scanned by μCT scanner and finite element models were generated. Immediate loading and osseointegration conditions were simulated at the implant-tissue interface. A vertical force of 10 N was applied on the implant. During the healing time, density and Young’s modulus of antler tissue around the implant increased significantly. For each time point, the values of displacement, stresses and strains in the osseointegration model were lower than those of the immediate loading model. As the healing time increased, the displacement of implants was reduced. The 3-week immediate loading model (9878 ± 1965 μstrain) illustrated the highest strains in the antler tissue. Antler tissue showed similar biomechanical properties as human bone in investigating the bone remodelling around implants, therefore the use of sika deer antler model is a promising alternative in implant biomechanical studies.     

A new single work bout test to estimate critical power and anaerobic work capacity

The purpose of this study was to develop a 3-minute, all-out test protocol using the Monark cycle ergometer for estimating the critical power (CP) and anaerobic work capacity (AWC) with the resistance based on body weight. Twelve moderately trained adults (mean age ± SD = 23.2 ± 3.5 years) performed an incremental cycle ergometer test to exhaustion. The CP and AWC were estimated from the original work limit (W(lim)) vs. time limit (T(lim)) relationship (CP(PT)) and a 3-minute all-out test (CP(3min)) against a fixed resistance and compared with the CP and AWC estimated from the new 3-minute tests on the Monark cycle ergometer (CP(3.5%) and CP(4.5%)). The resistance values for the CP(3.5%) and CP(4.5%) tests were set at 3.5 and 4.5% of the subject's body weight (kilograms). The results indicated that there were no significant differences (p > 0.05) among mean CP values for CP(PT) (178 ± 47 W), CP(3.5%) (173 ± 40 W), and CP(4.5%) (186 ± 44 W). The mean CP(3min) (193 ± 54 W), however, was significantly greater than CP(PT) and CP(3.5%). There were no significant differences in AWC for the CP(PT) (13,412 ± 6,247 J), CP(3min) (10,895 ± 2,923 J), and CP(4.5%) (9,842 ± 4,394 J). The AWC values for the CP(PT) and CP(3min), however, were significantly greater than CP(3.5%) (8,357 ± 2,946 J). The results of this study indicated that CP and AWC could be estimated from a single 3-minute work bout test on the Monark cycle ergometer with the resistance set at 4.5% of the body weight. A single work bout test with the resistance based on the individual's body weight provides a practical and accessible method to estimate CP and AWC.     

Hybrid titanium/biodegradable polymer implants with an hierarchical pore structure as a means to control selective cell movement

In order to improve implant success rate, it is important to enhance their responsiveness to the prevailing conditions following implantation. Uncontrolled movement of inflammatory cells and fibroblasts is one of these in vivo problems and the porosity properties of the implant have a strong effect on these. Here, we describe a hybrid system composed of a macroporous titanium structure filled with a microporous biodegradable polymer. This polymer matrix has a distinct porosity gradient to accommodate different cell types (fibroblasts and epithelial cells). The main clinical application of this system will be the prevention of restenosis due to excessive fibroblast migration and proliferation in the case of tracheal implants. METHODOLOGY/PRINCIPAL FINDINGS: A microbead-based titanium template was filled with a porous Poly (L-lactic acid) (PLLA) body by freeze-extraction method. A distinct porosity difference was obtained between the inner and outer surfaces of the implant as characterized by image analysis and Mercury porosimetry (9.8±2.2 μm vs. 36.7±11.4 μm, p≤0.05). On top, a thin PLLA film was added to optimize the growth of epithelial cells, which was confirmed by using human respiratory epithelial cells. To check the control of fibroblast movement, PKH26 labeled fibroblasts were seeded onto Titanium and Titanium/PLLA implants. The cell movement was quantified by confocal microscopy: in one week cells moved deeper in Ti samples compared to Ti/PLLA. CONCLUSIONS: In vitro experiments showed that this new implant is effective for guiding different kind of cells it will contact upon implantation. Overall, this system would enable spatial and temporal control over cell migration by a gradient ranging from macroporosity to nanoporosity within a tracheal implant. Moreover, mechanical properties will be dependent mainly on the titanium frame. This will make it possible to create a polymeric environment which is suitable for cells without the need to meet mechanical requirements with the polymeric structure.     

A dynamic warm-up model increases quadriceps strength and hamstring flexibility

Research suggests that static stretching can negatively influence muscle strength and power and may result in decreased functional performance. The dynamic warm-up (DWU) is a common alternative to static stretching before physical activity, but there is limited research investigating the effects of a DWU. The purpose of this study was to compare the acute effects of a DWU and static stretching warm-up (SWU) on muscle flexibility, strength, and vertical jump using a randomized controlled trial design. Forty-five volunteers were randomly assigned into a control (CON), SWU, or DWU group. All participants rode a stationary bicycle for 5 minutes and completed a 10-minute warm-up protocol. During this protocol, the DWU group performed dynamic stretching and running, the SWU group performed static stretching, and the CON group rested. Dependent variables were measured immediately before and after the warm-up protocol. A digital inclinometer measured flexibility (degrees) for the hamstrings, quadriceps, and hip flexor muscles. An isokinetic dynamometer measured concentric and eccentric peak torque (N·m/kg) for the hamstrings and quadriceps. A force plate was used to measure vertical jump height (meters) and power (watts). In the DWU group, there was a significant increase in hamstring flexibility (pretest: 26.4 ± 13.5°, posttest: 16.9 ± 9.4°; p < .0001) and eccentric quadriceps peak torque (pretest: 2.49 ± 0.83 N·m/kg, posttest: 2.78 ± 0.69 N·m/kg; p = 0.04). The CON and SWU did not significantly affect any flexibility, strength, or vertical jump measures (p > 0.05). The DWU significantly improved eccentric quadriceps strength and hamstrings flexibility, whereas the SWU did not facilitate any positive or negative changes in muscle flexibility, strength, power, or vertical jump. Therefore, the DWU may be a better preactivity warm-up choice than an SWU.     

Use of a centrifugal bioreactor for cartilaginous tissue formation from isolated chondrocytes

Although a centrifugal bioreactor (CCBR) supports high-density mammalian suspension cell cultures by balancing drag, buoyancy, and centrifugal forces, to date anchorage-dependent cultures have not been tried. Also, steady or intermittent hydrostatic pressures of 8 to 500 kPa, and shears of 0.02 to 1.4 N/m(2) can be simultaneously applied in the CCBR. This article demonstrates the use of a CCBR to stimulate chondrogenesis in a high-density culture. At 3 weeks, histological results show even distribution of glycosaminoglycan (GAG) and collagen, with 1,890 ± 270 cells/mm(2) cell densities that exceed those of 1,470 ± 270 in pellet cultures. Analysis of collagen content reveals similar levels for all treatment groups; 6.8 ± 3.5 and 5.0 ± 0.4 μg collagen/μg DNA for 0.07 and 0.26 MPa CCBR cultures, respectively, in contrast to 6.6 ± 1.9 values for control pellet cultures. GAG levels of 5.6 ± 1.5 and 4.1 ± 0.9 μg GAG /μg DNA are present for cultures stressed at 0.07 and 0.26 MPa, respectively, in comparison to control pellet cultures at the 8.4 ± 0.9 level. Although results to date have not revealed mechanical stress combinations that stimulate chondrogenesis over unstressed controls, system advantages include continuous culture at cell densities above those in the pellet, precise medium control, the ability to independently vary multiple mechanical stresses over a broad range, and the flexibility for integration of scaffold features for future chondrogenesis stimulation studies.     

Mapping elasticity moduli of atherosclerotic plaque in situ via atomic force microscopy

Several studies have suggested that evolving mechanical stresses and strains drive atherosclerotic plaque development and vulnerability. Especially, stress distribution in the plaque fibrous capsule is an important determinant for the risk of vulnerable plaque rupture. Knowledge of the stiffness of atherosclerotic plaque components is therefore of critical importance. In this work, force mapping experiments using atomic force microscopy (AFM) were conducted in apolipoprotein E-deficient (ApoE(-/-)) mouse, which represents the most widely used experimental model for studying mechanisms underlying the development of atherosclerotic lesions. To obtain the elastic material properties of fibrous caps and lipidic cores of atherosclerotic plaques, serial cross-sections of aortic arch lesions were probed at different sites. Atherosclerotic plaque sub-structures were subdivided into cellular fibrotic, hypocellular fibrotic and lipidic rich areas according to histological staining. Hertz's contact mechanics were used to determine elasticity (Young's) moduli that were related to the underlying histological plaque structure. Cellular fibrotic regions exhibit a mean Young modulus of 10.4±5.7kPa. Hypocellular fibrous caps were almost six-times stiffer, with average modulus value of 59.4±47.4kPa, locally rising up to ～250kPa. Lipid rich areas exhibit a rather large range of Young's moduli, with average value of 5.5±3.5kPa. Such precise quantification of plaque stiffness heterogeneity will allow investigators to have prospectively a better monitoring of atherosclerotic disease evolution, including arterial wall remodeling and plaque rupture, in response to mechanical constraints imposed by vascular shear stress and blood pressure.