Inducing Mechanical Stimuli to Tissues Grown on a Magnetic Gel Allows Deconvoluting the Forces Leading to Traumatic Brain Injury.

Traumatic brain injury (TBI), which is characterized by damage to the brain resulting from a sudden traumatic event, is a major cause of death and disability worldwide. It has short- and long-term effects, including neuroinflammation, cognitive deficits, and depression. TBI consists of multiple steps that may sometimes have opposing effects or mechanisms, making it challenging to investigate and translate new knowledge into effective therapies. In order to better understand and address the underlying mechanisms of TBI, we have developed an in vitro platform that allows dynamic simulation of TBI conditions by applying external magnetic forces to induce acceleration and deceleration injury, which is often observed in human TBI. Endothelial and neuron-like cells were successfully grown on magnetic gels and applied to the platform. Both cell types showed an instant response to the TBI model, but the endothelial cells were able to recover quickly-in contrast to the neuron-like cells. In conclusion, the presented in vitro model mimics the mechanical processes of acceleration/deceleration injury involved in TBI and will be a valuable resource for further research on brain injury.

A Platform for Assessing Cellular Contractile Function Based on Magnetic Manipulation of Magnetoresponsive Hydrogel Films.

Despite significant advancements in in vitro cardiac modeling approaches, researchers still lack the capacity to obtain in vitro measurements of a key indicator of cardiac function: contractility, or stroke volume under specific loading conditions-defined as the pressures to which the heart is subjected prior to and during contraction. This work puts forward a platform that creates this capability, by providing a means of dynamically controlling loading conditions in vitro. This dynamic tissue loading platform consists of a thin magnetoresponsive hydrogel cantilever on which 2D engineered myocardial tissue is cultured. Exposing the cantilever to an external magnetic field-generated by positioning magnets at a controlled distance from the cantilever-causes the hydrogel film to stretch, creating tissue load. Next, cell contraction is induced through electrical stimulation, and the force of the contraction is recorded, by measuring the cantilever's deflection. Force-length-based measurements of contractility are then derived, comparable to clinical measurements. In an illustrative application, the platform is used to measure contractility both in untreated myocardial tissue and in tissue exposed to an inotropic agent. Clear differences are observed between conditions, suggesting that the proposed platform has significant potential to provide clinically relevant measurements of contractility.