Biodegradable HEMA-based hydrogels with enhanced mechanical properties.

Hydrogels are widely used in the biomedical field. Their main purposes are either to deliver biological active agents or to temporarily fill a defect until they degrade and are followed by new host tissue formation. However, for this latter application, biodegradable hydrogels are usually not capable to sustain any significant load. The development of biodegradable hydrogels presenting load-bearing capabilities would open new possibilities to utilize this class of material in the biomedical field. In this work, an original formulation of biodegradable photo-crosslinked hydrogels based on hydroxyethyl methacrylate (HEMA) is presented. The hydrogels consist of short-length poly(2-hydroxyethyl methacrylate) (PHEMA) chains in a star shape structure, obtained by introducing a tetra-functional chain transfer agent in the backbone of the hydrogels. They are cross-linked with a biodegradable N,O-dimethacryloyl hydroxylamine (DMHA) molecule sensitive to hydrolytic cleavage. We characterized the degradation properties of these hydrogels submitted to mechanical loadings. We showed that the developed hydrogels undergo long-term degradation and specially meet the two essential requirements of a biodegradable hydrogel suitable for load bearing applications: enhanced mechanical properties and low molecular weight degradation products. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1161-1169, 2016.

Improving hydrogels' toughness by increasing the dissipative properties of their network.

The weak mechanical performance and fragility of hydrogels limit their application as biomaterials for load bearing applications. The origin of this weakness has been explained by the low resistance to chains breakage composing the hydrogel and to the cracks propagation in the hydrogel submitted to loading conditions. These low resistance and crack propagation were in turn related to an insufficient energy dissipation mechanism in the hydrogel structure. The goal of this study is to evaluate the dissipation mechanism in covalently bonded hydrogels so that tougher hydrogels can be developed while keeping for the hydrogel a relatively high mechanical stiffness. By varying parameters such as cross-linker type or concentration as well as water ratio, the dissipative properties of HEMA-based hydrogels were investigated at large deformations. Different mechanisms such as special friction-like phenomena, nanoporosity, and hydrophobicity were proposed to explain the dissipative behavior of the tested hydrogels. Based on this analysis, it was possible to develop hydrogels with increased toughness properties.

Impact of synovial fluid flow on temperature regulation in knee cartilage.

Several studies have reported an increase of temperature in cartilage submitted to cyclic sinusoidal loading. The temperature increase is in part due to the viscous behavior of this tissue, which partially dissipates the input mechanical energy into heat. While the synovial fluid flow within the intra-articular gap and inside the porous cartilage is supposed to play an important role in the regulation of the cartilage temperature, no specific study has evaluated this aspect. In the present numerical study, a poroelastic model of the knee cartilage is developed to evaluate first the temperature increase in the cartilage due to dissipation and second the impact of the synovial fluid flow in the cartilage heat transfer phenomenon. Our results showed that, the local temperature is effectively increased in knee cartilage due to its viscous behavior. The synovial fluid flow cannot significantly preventing this phenomenon. We explain this result by the low permeability of cartilage and the moderate fluid exchange at the surface of cartilage under deformation.

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.

Intrinsic viscoelasticity increases temperature in knee cartilage under physiological loading.

Metabolism of proteoglycans and hyaluronic acid has been shown to be temperature-dependent in cartilage explants, with optimal anabolic effects between 36°C and 38°C. At rest, the temperature of human knee has a value of around 33°C. We aim to show in this study that viscoelastic properties of healthy human cartilage allow its temperature to reach those optimal temperatures during physiological mechanical loadings. We developed a model allowing to determine the temperature increase in cartilage due to viscous dissipation. The model had three parameters, which were determined experimentally. The first parameter was the energy dissipated by cartilage samples submitted to cyclic stimulation. It was obtained with standard in vitro mechanical testing. The second parameter was the cartilage heat capacity and was measured in vitro with differential scanning calorimetry. Finally, the third parameter was the time constant of cartilage heat transfer and was obtained with in vivo magnetic resonance thermometry performed on four volunteers. With these experimentally determined parameters, the model predicted that cartilage dissipation is sufficient to raise the temperature in healthy knee cartilage from 33°C to 36.7°C after a 1h walking. These results showed that intrinsic viscoelastic properties of the cartilage could induce a temperature increase optimal for the production of proteoglycans and hyaluronic acid. Interestingly, degenerated cartilage did not present high enough viscoelastic properties to significantly induce a temperature increase. Taken together, these data suggest an association between cartilage dissipation and its homeostasis.