Strain imaging of the lateral collateral ligament using high frequency and conventional ultrasound imaging: An ex-vivo comparison.

Recent first attempts of in situ ultrasound strain imaging in collateral ligaments encountered a number of challenges and illustrated a clear need for additional studies and more thorough validation of the available strain imaging methods. Therefore, in this study we experimentally validated ultrasound strain measurements of ex vivo human lateral collateral ligaments in an axial loading condition. Moreover, the use of high frequency ultrasound (>20 MHz) for strain measurement was explored and its performance compared to conventional ultrasound. The ligaments were stretched up to 5% strain and ultrasound measurements were compared to surface strain measurements from optical digital image correlation (DIC) techniques. The results show good correlations between ultrasound based and DIC based strain measures with R2 values of 0.71 and 0.93 for high frequency and conventional ultrasound, subsequently. The performance of conventional ultrasound was significantly higher compared to high frequency ultrasound strain imaging, as the high frequency based method seemed more prone to errors. This study demonstrates that ultrasound strain imaging is feasible in ex vivo lateral collateral ligaments, which are relatively small structures. Additional studies should be designed for a more informed assessment of optimal in vivo strain measurements in collateral knee ligaments.

The influence of ligament modelling strategies on the predictive capability of finite element models of the human knee joint.

In finite element (FE) models knee ligaments can represented either by a group of one-dimensional springs, or by three-dimensional continuum elements based on segmentations. Continuum models closer approximate the anatomy, and facilitate ligament wrapping, while spring models are computationally less expensive. The mechanical properties of ligaments can be based on literature, or adjusted specifically for the subject. In the current study we investigated the effect of ligament modelling strategy on the predictive capability of FE models of the human knee joint. The effect of literature-based versus specimen-specific optimized material parameters was evaluated. Experiments were performed on three human cadaver knees, which were modelled in FE models with ligaments represented either using springs, or using continuum representations. In spring representation collateral ligaments were each modelled with three and cruciate ligaments with two single-element bundles. Stiffness parameters and pre-strains were optimized based on laxity tests for both approaches. Validation experiments were conducted to evaluate the outcomes of the FE models. Models (both spring and continuum) with subject-specific properties improved the predicted kinematics and contact outcome parameters. Models incorporating literature-based parameters, and particularly the spring models (with the representations implemented in this study), led to relatively high errors in kinematics and contact pressures. Using a continuum modelling approach resulted in more accurate contact outcome variables than the spring representation with two (cruciate ligaments) and three (collateral ligaments) single-element-bundle representations. However, when the prediction of joint kinematics is of main interest, spring ligament models provide a faster option with acceptable outcome.

Preparation, Characterization, and Optimization of Folic Acid-Chitosan-Methotrexate Core-Shell Nanoparticles by Box-Behnken Design for Tumor-Targeted Drug Delivery.

The objective of this study was to investigate the combined influence of independent variables in the preparation of folic acid-chitosan-methotrexate nanoparticles (FA-Chi-MTX NPs). These NPs were designed and prepared for targeted drug delivery in tumor. The NPs of each batch were prepared by coaxial electrospray atomization method and evaluated for particle size (PS) and particle size distribution (PSD). The independent variables were selected to be concentration of FA-chitosan, ratio of shell solution flow rate to core solution flow rate, and applied voltage. The process design of experiments (DOE) was obtained with three factors in three levels by Design expert software. Box-Behnken design was used to select 15 batches of experiments randomly. The chemical structure of FA-chitosan was examined by FTIR. The NPs of each batch were collected separately, and morphologies of NPs were investigated by field emission scanning electron microscope (FE-SEM). The captured pictures of all batches were analyzed by ImageJ software. Mean PS and PSD were calculated for each batch. Polynomial equation was produced for each response. The FE-SEM results showed the mean diameter of the core-shell NPs was around 304 nm, and nearly 30% of the produced NPs are in the desirable range. Optimum formulations were selected. The validation of DOE optimization results showed errors around 2.5 and 2.3% for PS and PSD, respectively. Moreover, the feasibility of using prepared NPs to target tumor extracellular pH was shown, as drug release was greater in the pH of endosome (acidic medium). Finally, our results proved that FA-Chi-MTX NPs were active against the human epithelial cervical cancer (HeLa) cells.

A comparison between dynamic implicit and explicit finite element simulations of the native knee joint.

The finite element (FE) method has been widely used to investigate knee biomechanics. Time integration algorithms for dynamic problems in finite element analysis can be classified as either implicit or explicit. Although previously both static/dynamic implicit and dynamic explicit method have been used, a comparative study on the outcomes of both methods is of high interest for the knee modeling community. The aim of this study is to compare static, dynamic implicit and dynamic explicit solutions in analyses of the knee joint to assess the prediction of dynamic effects, potential convergence problems, the accuracy and stability of the calculations, the difference in computational time, and the influence of mass-scaling in the explicit formulation. The heel-strike phase of fast, normal and slow gait was simulated for two different body masses in a model of the native knee. Our results indicate that ignoring the dynamic effect can alter joint motion. Explicit analyses are suitable to simulate dynamic loading of the knee joint in high-speed simulations, as this method offers a substantial reduction of the computational time with a similar prediction of cartilage stresses and meniscus strains. Although mass-scaling can provide even more gain in computational time, it is not recommended for high-speed activities, in which inertial forces play a significant role.