Moxiao Li

Patterning Cellular Alignment through Stretching Hydrogels with Programmable Strain Gradients

The graded mechanical properties (e.g., stiffness and stress/strain) of excellular matrix play an important role in guiding cellular alignment, as vital in tissue reconstruction with proper functions. Though various methods have been developed to engineer a graded mechanical environment to study its effect on cellular behaviors, most of them failed to distinguish stiffness effect from stress/strain effect during mechanical loading. Here, we construct a mechanical environment with programmable strain gradients by using a hydrogel of a linear elastic property. When seeding cells on such hydrogels, we demonstrate that the pattern of cellular alignment can be rather precisely tailored by substrate strains. The experiment is in consistency with a theoritical prediction when assuming that focal adhesions (FAs) would drive a cell to reorient to the directions where they are most stable. A fundamental theory has also been developed and is excellent in agreement with the complete temporal alignment of cells. This work not only provides important insights into the cellular response to the local mechanical microenvironment but can also be utilized to engineer patterned cellular alignment that can be critical in tissue remodeling and regenerative medicine applications.

Capillary Origami Inspired Fabrication of Complex 3D Hydrogel Constructs

Hydrogels have found broad applications in various engineering and biomedical fields, where the shape and size of hydrogels can profoundly influence their functions. Although numerous methods have been developed to tailor 3D hydrogel structures, it is still challenging to fabricate complex 3D hydrogel constructs. Inspired by the capillary origami phenomenon where surface tension of a droplet on an elastic membrane can induce spontaneous folding of the membrane into 3D structures along with droplet evaporation, a facile strategy is established for the fabrication of complex 3D hydrogel constructs with programmable shapes and sizes by crosslinking hydrogels during the folding process. A mathematical model is further proposed to predict the temporal structure evolution of the folded 3D hydrogel constructs. Using this model, precise control is achieved over the 3D shapes (e.g., pyramid, pentahedron, and cube) and sizes (ranging from hundreds of micrometers to millimeters) through tuning membrane shape, dimensionless parameter of the process (elastocapillary number Ce ), and evaporation time. This work would be favorable to multiple areas, such as flexible electronics, tissue regeneration, and drug delivery.

An approach to quantifying 3D responses of cells to extreme strain

The tissues of hollow organs can routinely stretch up to 2.5 times their length. Although significant pathology can arise if relatively large stretches are sustained, the responses of cells are not known at these levels of sustained strain. A key challenge is presenting cells with a realistic and well-defined three-dimensional (3D) culture environment that can sustain such strains. Here, we describe an in vitro system called microscale, magnetically-actuated synthetic tissues (micro-MASTs) to quantify these responses for cells within a 3D hydrogel matrix. Cellular strain-threshold and saturation behaviors were observed in hydrogel matrix, including strain-dependent proliferation, spreading, polarization, and differentiation, and matrix adhesion retained at strains sufficient for apoptosis. More broadly, the system shows promise for defining and controlling the effects of mechanical environment upon a broad range of cells.

Magnetically Actuated Droplet Manipulation and Its Potential Biomedical Applications

Droplet manipulation has found broad applications in various engineering and biomedical fields, such as biochemistry, microfluidic systems, drug delivery, and tissue engineering. Many methods have been developed to enhance the ability for manipulating droplets, among which magnetically actuated droplet manipulation has attracted widespread interests due to its remote, noninvasive manipulation ability and biocompatibility. This review summarizes the approaches and their principles that enable actuating the droplet magnetically. The potential biomedical applications of such a technique in bioassay, cell assembly, and tissue engineering are given.

Biofriendly, Stretchable, and Reusable Hydrogel Electronics as Wearable Force Sensors

The ever-growing overlap between stretchable electronic devices and wearable healthcare applications is igniting the discovery of novel biocompatible and skin-like materials for human-friendly stretchable electronics fabrication. Amongst all potential candidates, hydrogels with excellent biocompatibility and mechanical features close to human tissues are constituting a promising troop for realizing healthcare-oriented electronic functionalities. In this work, based on biocompatible and stretchable hydrogels, a simple paradigm to prototype stretchable electronics with an embedded three-dimensional (3D) helical conductive layout is proposed. Thanks to the 3D helical structure, the hydrogel electronics present satisfactory mechanical and electrical robustness under stretch. In addition, reusability of stretchable electronics is realized with the proposed scenario benefiting from the swelling property of hydrogel. Although losing water would induce structure shrinkage of the hydrogel network and further undermine the function of hydrogel in various applications, the worn-out hydrogel electronics can be reused by simply casting it in water. Through such a rehydration procedure, the dehydrated hydrogel can absorb water from the surrounding and then the hydrogel electronics can achieve resilience in mechanical stretchability and electronic functionality. Also, the ability to reflect pressure and strain changes has revealed the hydrogel electronics to be promising for advanced wearable sensing applications.