During loading of viscoelastic tissues, part of the mechanical energy is transformed into heat that can locally increase the tissue temperature, a phenomenon known as self-heating. In the framework of mechanobiology, it has been accepted that cells react and adapt to mechanical stimuli. However, the cellular effect of temperature increase as a by-product of loading has been widely neglected. In this work, we focused on cartilage self-heating to present a ‘thermo-mechanobiological’ paradigm, and demonstrate how the coupling of a biomimetic temperature evolution and mechanical loading could influence cell behavior. We thereby developed a customized in vitro system allowing to recapitulate pertinent in vivo physical cues and determined the cells chondrogenic response to thermal and/or mechanical stimuli. Cellular mechanisms of action and potential signaling pathways of thermo-mechanotransduction process were also investigated. We found that co-existence of thermo-mechanical cues had a superior effect on chondrogenic gene expression compared to either signal alone. Specifically, the expression of Sox9 was significantly upregulated by application of the physiological thermo-mechanical stimulus. Multimodal transient receptor potential vanilloid 4 (TRPV4) channels were identified as key mediators of thermo-mechanotransduction process, which becomes ineffective without external calcium sources. We also observed that the isolated temperature evolution, as a by-product of loading, is a contributing factor to the cell response and this could be considered as important as the conventional mechanical loading. Providing an optimal thermo-mechanical environment by synergy of heat and loading portrays new opportunity for development of novel treatments for cartilage regeneration and can furthermore signal key elements for emerging cell-based therapies.
Development of mechanically durable and biologically inductive hydrogels is a major challenge for load-bearing applications such as engineered cartilage. Dissipative capacity of articular cartilage is central to its functional behavior when submitted to loading. While fluid frictional drag is playing a significant role in this phenomenon, the flow-dependent source of dissipation is mostly overlooked in the design of hydrogel scaffolds. Herein, we propose an original strategy based on the combination of fluidic and polymeric dissipation sources to simultaneously enhance hydrogel mechanical and mechanobiological performances. The nondestructive dissipation processes were carefully designed by hybrid cross-linking of the hydrogel network and low permeability of the porous structure. It was found that intrachain and pore water distribution in the porous hydrogels improves the mechanical properties in high water fractions. In contrast to widely reported tough hydrogels presenting limited load support capability at low strain values, we obtained stiff and dissipative hydrogels with unique fatigue behavior. We showed that the fatigue resistance capability is not a function of morphology, dissipation level, and stiffness of the viscoelastic hydrogels but rather depends on the origin of the dissipation. Moreover, the preserved dissipation source under mechanical stimulation maintained a mechanoinductive niche for enhancing chondrogenesis owing to fluid frictional drag contribution. The proposed strategy can be widely used to design functional scaffolds in high loading demands for enduring physiological stimuli and generating regulatory cues to cells.
Intrinsically adhesive hydrogels have various functions in biomedical areas particularly in minimally-invasive surgical treatments. [1,2] In these medical situations, bioadhesives have to present not only strong adhesion to wet tissues but specific ranges of injectability, degradability, swelling, biocompatibility, and mechanical match. [3,4] This is particularly challenging as the adhesive mechanism of the hydrogel should also allow proper material functionality in its bulk. The adhesion of hydrogels could be enhanced by strong bonds with the tissue as well as the material's capacity to dissipate energy. [5,6] Dissipative double-network hydrogels show high adhesion when either the tissue or the hydrogel substrate is chemically treated, so that the interfacial bonds can be created. However, it is difficult to use these adhesive systems in minimally-invasive biomedical situations, in which hydrogel must be injected and formed in situ and tissue treatment would impose serious limitations. In Attaching hydrogels to soft internal tissues is crucial for the development of various biomedical devices. Tough sticky hydrogel patches present high adhesion, yet with lack of injectability and the need for treatment of contacting surface. On the contrary, injectable and photo-curable hydrogels are highly attractive owing to their ease of use, flexibility of filling any shape, and their minimally invasive character, compared to their conventional preformed counterparts. Despite recent advances in material developments, a hydrogel that exhibits both proper injectability and sufficient intrinsic adhesion is yet to be demonstrated. Herein, a paradigm shift is proposed toward the design of intrinsically adhesive networks for injectable and photo-curable hydrogels. The bioinspired design strategy not only provides strong adhesive contact, but also results in a wide window of physicochemical properties. The adhesive networks are based on a family of polymeric backbones where chains are modified to be intrinsically adhesive to host tissue and simultaneously form a hydrogel network via a hybrid cross-linking mechanism. With this strategy, adhesion is achieved through a controlled synergy between the interfacial chemistry and bulk mechanical properties. The functionalities of the bioadhesives are demonstrated for various applications, such as tissue adhesives, surgical sealants, or injectable scaffolds.
The complex shear modulus of an electrorheological (ER) adaptive sandwich beam is optimally estimated to model the system for vibration control. In the composition of a three layered beam, the ER fluid layer is embedded between two constraining layers. Using finite element (FE) method, the governing equations of the composite viscoelastic beam are derived. The developed model is compared with the results found in the literature. In addition, for a fabricated ER sandwich beam, the ASTM E756 standard is employed to estimate the complex shear modulus of the viscoelastic layer in different electric fields. An optimization procedure is conducted based on particle swarm optimization (PSO). In this process, the rough estimation of complex shear modulus extracted by ASTM E756 is modified to correlate the results of the FE model and the experimental tests. The updated FE model is mapped into an appropriate form that can be used for control objectives. Finally, a semi-active sliding mode control is utilized to attenuate the vibration of the adaptive sandwich beam by tuning its electric field dependent characteristics.
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