Karami, P. | Search bioRxiv

bioRxiv2022

Wet Adhesive Hydrogels to Correct Malacic Trachea (Tracheomalacia): A Proof of Concept

Tracheomalacia (TM) is a condition in which the anterior part of the trachea consisting of cartilage and/or the posterior part consisting muscle are too soft to ensure its mechanical support. This situation may result in an excessive and potentially lethal collapse of the airway in the newborns. Current treatment techniques include tracheal reconstruction, tracheoplasty, endo- and extraluminal stents, but are all facing important limitations. To reduce the shortcomings of actual TM treatments, this work proposes a new strategy by wrapping an adhesive hydrogel patch extraluminally around a malacic trachea. To validate this approach, first a numerical model revealed that a hydrogel patch with sufficient mechanical and adhesion strength can potentially preserve the tracheas physiological shape. Accordingly, a new hydrogel formulation was synthesized employing the hydroxyethyl acrylamide (HEAam) and polyethylene glycol methacrylate (PEGDMA) as main polymer network and crosslinker, respectively. These hydrogels provide excellent adhesion on wet tracheal surfaces, thanks to a two-step photo-polymerization approach. Ex vivo experiments revealed that the developed adhesive hydrogel patches can restrain the collapsing of malacic trachea under applied negative pressure. This study, to be confirmed by in vivo studies, is open to the possibility of a new treatment in the difficult clinical situation of tracheomalacia in newborns.

bioengineering↗

bioRxiv2021

Temperature Evolution Following Joint Loading Promotes Chondrogenesis by Synergistic Cues via Calcium Signaling

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 synergy 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, a synergetic effect was observed for upregulation of Sox9 by application of the physiological thermo-mechanical stimulus. Multimodal 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 cells 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.

bioengineering↗