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.

Microfluidic Chip for Odontoblasts in Vitro.

Odontoblast processes, which grow inside dentin tubules, are critical parts of odontoblasts, and they play an important role in dentin hypersensitivity. However, modeling the growth of odontoblast processes in vitro is difficult, which hinders the study of dentin hypersensitivity and other dental diseases. To our knowledge, no technique has yet been developed to induce the growth of odontoblast processes from a cell body in vitro. In the current study, we fabricated a microfluidic chip via soft lithography. The microchannels on the chip can mimic the microstructures of dentin tubules, and the microchambers that connect to the microchannels can be used for odontoblast culture. We successfully induced the growth of odontoblast processes from cell bodies by using this chip. In addition, we designed chips with different microchannel sizes (i.e., 2, 4, 6, and 8 µm) to investigate the relationship between the growth of odontoblast processes and the geometric constraint imposed by microchannels. Experimental results show that the growth of odontoblast processes can be successfully induced by 2 µm channels. However, odontoblasts will migrate in the 4, 6, and 8 µm channels. This finding indicates that 2 µm is the appropriate size for inducing the growth of odontoblast processes in vitro. This value is consistent with the size of dentin tubules in vivo. The fabricated microfluidic chip can serve as a powerful tool for investigating the physiology and pathology of odontoblast processes in the future and developing treatment solutions for dental diseases, such as dentin hypersensitivity.

Bioprinting-Based PDLSC-ECM Screening for in Vivo Repair of Alveolar Bone Defect Using Cell-Laden, Injectable and Photocrosslinkable Hydrogels.

Periodontitis is an inflammatory disease worldwide that may result in periodontal defect (especially alveolar bone defect) and even tooth loss. Stem-cell-based approach combined with injectable hydrogels has been proposed as a promising strategy in periodontal treatments. Stem cells fate closely depends on their extracellular matrix (ECM) characteristics. Hence, it is necessary to engineer an appropriate injectable hydrogel to deliver stem cells into the defect while serving as the ECM during healing. Therefore, stem cell-ECM interaction should be studied for better stem cell transplantation. In this study, we developed a bioprinting-based strategy to study stem cell-ECM interaction and thus screen an appropriate ECM for in vivo repair of alveolar bone defect. Periodontal ligament stem cells (PDLSCs) were encapsulated in injectable, photocrosslinkable composite hydrogels composed of gelatin methacrylate (GelMA) and poly(ethylene glycol) dimethacrylate (PEGDA). PDLSC-laden GelMA/PEGDA hydrogels with varying composition were efficiently fabricated via a 3D bioprinting platform by controlling the volume ratio of GelMA-to-PEGDA. PDLSC behavior and fate were found to be closely related to the engineered ECM composition. The 4/1 GelMA/PEGDA composite hydrogel was selected since the best performance in osteogenic differentiation in vitro. Finally, in vivo study indicated a maximal and robust new bone formation in the defects treated with the PDLSC-laden hydrogel with optimized composition as compared to the hydrogel alone and the saline ones. The developed approach would be useful for studying cell-ECM interaction in 3D and paving the way for regeneration of functional tissue.

4D Bioprinting for Biomedical Applications.

3D bioprinting has been developed to effectively and rapidly pattern living cells and biomaterials, aiming to create complex bioconstructs. However, placing biocompatible materials or cells into direct contact via bioprinting is necessary but insufficient for creating these constructs. Therefore, '4D bioprinting' has emerged recently, where 'time' is integrated with 3D bioprinting as the fourth dimension, and the printed objects can change their shapes or functionalities when an external stimulus is imposed or when cell fusion or postprinting self-assembly occurs. In this review, we highlight recent developments in 4D bioprinting technology. Additionally, we review the uses of 4D bioprinting in tissue engineering and drug delivery. Finally, we discuss the major roadblocks to this approach, together with possible solutions, to provide future perspectives on this technology.

Fabrication of Microscale Hydrogels with Tailored Microstructures based on Liquid Bridge Phenomenon.

Microscale hydrogels (microgels) find widespread applications in various fields, such as drug delivery, tissue engineering, and biosensing. The shape of the microgels is a critical parameter that can significantly influence their function in these applications. Although various methods have been developed (e.g., micromolding, photolithography, microfluidics, and mechanical deformation method), it is still technically challenging to fabricate microgels with tailored microstructures. In this study, we have developed a simple and versatile method for preparing microgels by stretching hydrogel precursor droplets between two substrates to form a liquid bridge. Microgels with tailored microstructures (e.g., barrel-like, dumbbell-like, or funnel-like shapes) have been achieved through adjusting the distance between and the hydrophobicity of the two substrates. The developed method holds great potential to impact multiple fields, such as drug delivery, tissue engineering, and biosensing.