Modulate stress distribution with bio-inspired irregular architected materials towards optimal tissue support.

Natural materials typically exhibit irregular and non-periodic architectures, endowing them with compelling functionalities such as body protection, camouflage, and mechanical stress modulation. Among these functionalities, mechanical stress modulation is crucial for homeostasis regulation and tissue remodeling. Here, we uncover the relationship between stress modulation functionality and the irregularity of bio-inspired architected materials by a generative computational framework. This framework optimizes the spatial distribution of a limited set of basic building blocks and uses these blocks to assemble irregular materials with heterogeneous, disordered microstructures. Despite being irregular and non-periodic, the assembled materials display spatially varying properties that precisely modulate stress distribution towards target values in various control regions and load cases, echoing the robust stress modulation capability of natural materials. The performance of the generated irregular architected materials is experimentally validated with 3D printed physical samples - a good agreement with target stress distribution is observed. Owing to its capability to redirect loads while keeping a proper amount of stress to stimulate bone repair, we demonstrate the potential application of the stress-programmable architected materials as support in orthopedic femur restoration.

Metabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines.

As key mediators of cellular communication, extracellular vesicles (EVs) have been actively explored for diagnostic and therapeutic applications. However, effective methods to functionalize EVs and modulate the interaction between EVs and recipient cells are still lacking. Here we report a facile and universal metabolic tagging technology that can install unique chemical tags (e.g., azido groups) onto EVs. The surface chemical tags enable conjugation of molecules via efficient click chemistry, for the tracking and targeted modulation of EVs. In the context of tumor EV vaccines, we show that the conjugation of toll-like receptor 9 agonists onto EVs enables timely activation of dendritic cells and generation of superior antitumor CD8+ T cell response. These lead to 80% tumor-free survival against E.G7 lymphoma and 33% tumor-free survival against B16F10 melanoma. Our study yields a universal technology to generate chemically tagged EVs from parent cells, modulate EV-cell interactions, and develop potent EV vaccines.

Algorithmic encoding of adaptive responses in temperature-sensing multimaterial architectures.

We envision programmable matters that can alter their physical properties in desirable manners based on user input or autonomous sensing. This vision motivates the pursuit of mechanical metamaterials that interact with the environment in a programmable fashion. However, this has not been systematically achieved for soft metamaterials because of the highly nonlinear deformation and underdevelopment of rational design strategies. Here, we use computational morphogenesis and multimaterial polymer 3D printing to systematically create soft metamaterials with arbitrarily programmable temperature-switchable nonlinear mechanical responses under large deformations. This is made possible by harnessing the distinct glass transition temperatures of different polymers, which, when optimally synthesized, produce local and giant stiffness changes in a controllable manner. Featuring complex geometries, the generated structures and metamaterials exhibit fundamentally different yet programmable nonlinear force-displacement relations and deformation patterns as temperature varies. The rational design and fabrication establish an objective-oriented synthesis of metamaterials with freely tunable thermally adaptive behaviors. This imbues structures and materials with environment-aware intelligence.

Digital synthesis of free-form multimaterial structures for realization of arbitrary programmed mechanical responses.

SignificanceCreating structures to realize function-oriented mechanical responses is desired for many applications. Yet, the use of a single material phase and heuristics-based designs may fail to attain specific target behaviors. Here, through a deterministic algorithmic procedure, multiple materials with dissimilar properties are intelligently synthesized into composite structures to achieve arbitrary prescribed responses. Created structures possess unconventional geometry and seamless integration of multiple materials. Despite geometric complexity and varied material phases, these structures are fabricated by multimaterial manufacturing, and tested to demonstrate that wide-ranging nonlinear responses are physically and accurately realized. Upon heteroassembly, resulting structures provide architectures that exhibit highly complex yet navigable responses. The proposed strategy can benefit the design of function-oriented nonlinear mechanical devices, such as actuators and energy absorbers.