RESUMO
Hydrogels with embedded functional particulates are widely used to create soft materials with innovative functionalities. In order to advance these soft materials to functional devices and machines, critical technical challenges are the precise positioning of particulates within the hydrogels and the construction of the hydrogels into a complex geometry. Inkjet printing is a promising method for addressing these challenges and ultimately achieving hydrogels with voxelized functionalities, so-called digital hydrogels. However, the development of the inkjet printing process primarily relies on empirical optimization of its printing and curing protocol. In this study, a general scaling law is proposed to predict the transport of particulates within the hydrogel during inkjet printing. This scaling law is based on a hypothesis that water-matrix interaction during the curing of inkjet-printed particle-laden polymeric drops determines the intra-drop particle distribution. Based on the hypothesis, a dimensionless similarity parameter of the water-matrix interaction is proposed, determined by the hydrogel's water evaporation coefficient, particle size, and mechanical properties. The hypothesis was tested by correlating the intra-drop particle distribution to the similarity parameter. The results confirmed the scaling law capable of guiding ink formulation and printing and curing protocol.
RESUMO
Hydrogels with particulates, including proteins, drugs, nanoparticles, and cells, enable the development of new and innovative biomaterials. Precise control of the spatial distribution of these particulates is crucial to produce advanced biomaterials. Thus, there is a high demand for manufacturing methods for particle-laden hydrogels. In this context, 3D printing of hydrogels is emerging as a promising method to create numerous innovative biomaterials. Among the 3D printing methods, inkjet printing, so-called drop-on-demand (DOD) printing, stands out for its ability to construct biomaterials with superior spatial resolutions. However, its printing processes are still designed by trial and error due to a limited understanding of the ink behavior during the printing processes. This review discusses the current understanding of transport processes and hydrogel behaviors during inkjet printing for particulate-laden hydrogels. Specifically, we review the transport processes of water and particulates within hydrogel during ink formulation, jetting, and curing. Additionally, we examine current inkjet printing applications in fabricating engineered tissues, drug delivery devices, and advanced bioelectronics components. Finally, the challenges and opportunities for next-generation inkjet printing are also discussed.
RESUMO
Recent advances in biomaterials and 3D printing/culture methods enable various tissue-engineered tumor models. However, it is still challenging to achieve native tumor-like characteristics due to lower cell density than native tissues and prolonged culture duration for maturation. Here, we report a new method to create tumoroids with a mechanically active tumor-stroma interface at extremely high cell density. This method, named "inkjet-printed morphogenesis" (iPM) of the tumor-stroma interface, is based on a hypothesis that cellular contractile force can significantly remodel the cell-laden polymer matrix to form densely-packed tissue-like constructs. Thus, differential cell-derived compaction of tumor cells and cancer-associated fibroblasts (CAFs) can be used to build a mechanically active tumor-stroma interface. In this methods, two kinds of bioinks are prepared, in which tumor cells and CAFs are suspended respectively in the mixture of collagen and poly (N-isopropyl acrylamide-co-methyl methacrylate) solution. These two cellular inks are inkjet-printed in multi-line or multi-layer patterns. As a result of cell-derived compaction, the resulting structure forms tumoroids with mechanically active tumor-stroma interface at extremely high cell density. We further test our working hypothesis that the morphogenesis can be controlled by manipulating the force balance between cellular contractile force and matrix stiffness. Furthermore, this new concept of "morphogenetic printing" is demonstrated to create more complex structures beyond current 3D bioprinting techniques.