Arne Vogel

Controlled release from a mechanically-stimulated thermosensitive self-heating composite hydrogel

Temperature has been extensively explored as a trigger to control the delivery of a payload from environment-sensitive polymers. The need for an external heat source only allows limited spatiotemporal control over the delivery process. We propose a new approach by using the dissipative properties of a hydrogel matrix as an internal heat source when the material is mechanically loaded. The system is comprised of a highly dissipative hydrogel matrix and thermo-sensitive nanoparticles that shrink upon an increase in temperature. Exposing the hydrogel to a cyclic mechanical loading for a period of 5 min leads to an increase of temperature of the nanoparticles. The concomitant decrease in the volume of the nanoparticles increases the permeability of the hydrogel network facilitating the release of its payload. As a proof-of-concept, we showed that the payload of the hydrogel is released after 5-8 min following the initiation of the mechanical loading. This delivery method would be particularly suited for the release of growth factor as it has been shown that cell receptor to growth factor is activated 5-20 min following a mechanical loading.

Prediction of spatio-temporal bone formation in scaffold by diffusion equation

Developing a successful bone tissue engineering strategy entails translation of experimental findings to clinical needs. A major leap forward toward this goal is developing a quantitative tool to predict spatial and temporal bone formation in scaffold. We hypothesized that bone formation in scaffold follows diffusion phenomenon. Subsequently, we developed an analytical formulation for bone formation, which had only three unknown parameters: C, the final bone volume fraction, α, the so-called scaffold osteoconduction coefficient, and h, the so-called peri-scaffold osteoinduction coefficient. The three parameters were estimated by identifying the model within vivo data of polymeric scaffolds implanted in the femoral condyle of rats. In vivo data were obtained by longitudinal micro-CT scanning of the animals. Having identified the three parameters, we used the model to predict the course of bone formation in two previously published in vivo studies. We found the predicted values to be consistent with the experimental ones. Bone formation into a scaffold can then adequately be described through diffusion phenomenon. This model allowed us to spatially and temporally predict the outcome of tissue engineering scaffolds with only 3 physically relevant parameters.

Damping properties of the nucleus pulposus

BACKGROUND The nucleus pulposus is extremely deformable and it is not uncommon to observe strain amplitudes as large as 12.5% in physiological loading conditions. It has been shown that the nucleus pulposus contributes to the damping properties of the intervertebral disc. The quantification of the damping properties of the nucleus pulposus under physiological large deformations is then a key aspect for its mechanical characterization and for the design of nucleus replacement devices. METHODS A specific mechanical device has been developed to encapsulate nucleus pulposus tissues into a deformable and permeable device, while quantifying its water content. The specific damping capacity was defined by dividing the energy loss by the work input. With this device and definition, the specific damping capacity of the bovine coccygeal nucleus pulposus was quantified in large compressive deformations (12.5%) and for frequencies ranging between 10(-2) and 10(1)Hz. FINDINGS It is found that the specific damping capacity of the nucleus pulposus of the bovine coccygeal ranged between 18 and 36%. The lowest values of specific damping capacity are found for frequencies corresponding to the dynamics of loads in all day activities such as walking (0.1 to 1Hz). INTERPRETATION The nucleus pulposus contributes to dissipate energy under physiological large deformations. However, it seems that the nucleus pulposus is designed so that damping is minimal for frequencies corresponding to moderate daily activities.

Viscohyperelastic Strain Energy Function

In this chapter, we present a framework allowing to catch the viscoelastic behavior of soft tissues under large deformation. As illustration, we propose to follow the necessary steps to develop a novel dissipation potential that details the short-time component of viscoelastic response within the constitutive framework set forth by Pioletti and Rakotomanana (2000, Eur. J. Mech. A Solids, 19 (5), 749–759) for both short- and long-term memory effects in finite deformations. The proposed dissipation potential is capable of predicting various nonlinear viscoelastic behavior with just four descriptive material parameters whose introduction of which greatly simplifies the task in contrasting different strain-rate sensitive materials. Its theoretical development, material properties identification and numerical implementation are presented. This procedure is applied to uniaxial data of a biologic soft tissue, namely, the annulus fibrosus of a porcine intervertebral disc.

Dissipation Can Act as a Mechanobiological Signal in Cartilage Differentiation

Knee cartilage is a soft tissue having viscoelastic properties. Under cyclic loadings, viscoelastic materials dissipate mechanical loadings through heat generation. In knee cartilage, this heat might not be convected because of the tissue avascularity, resulting thus to a local temperature increase. As cells are sensitive to temperature, these thermo-mechanical phenomena of energy dissipation could influence their metabolism. The goal of this study is to evaluate the effect of thermogenesis on chondrogenic differentiation. First, we focused our work in quantifying the heat generated in cartilage as a result to deformation. On a cellular level, the effect of thermal alterations on cell metabolism was assessed looking at the gene expression of transcription factors involved in chondrogenesis. Hence, human chondro-progenitor cells were cultured at 33°C and 37°C for 48 h and 96 h. An up-regulation in mRNA expression levels of Sox9 and its co-activator PGC-1α has been observed. These results point to a thermal contribution to chondrogenic gene expression.Copyright

MULTI-MODELING DISSIPATIVE POTENTIAL FOR NONLINEAR VISCOELASTICITY: ANNULUS FIBROSUS APPLICATION

Computational joint biomechanics requires detailed constitutive modelling for biological materials and accurate description of the strain-rate response under fast loading. In this work we present a novel dissipation potential that details the short-time component of non-linear viscoelastic response within the constitutive framework set forth by [Pioletti, 2000] for both short and long-time memory effects in finite deformation. We used descriptive material parameters whose introduction greatly simplifies the task of describing and contrasting different strain-rate sensitive materials. The particular dissipation potential proposed automatically meet the second law of thermodynamics. The procedure is applied to the annulus fibrosus under uni-axial compression.