3D Printing of Micropatterned Scaffolds for Orientated Tissue Regeneration
Many tissues in the body, such as arteries, muscles, tendons, nerves, possess a distinctive spatial organization of cells, which is essential for their specific mechanical and biological functions. The ability to regenerate tissues in a way that mirrors such spatial organization is essential for reinstating their unique functional characteristics. However, current scaffold designs often struggle with accurately controlling the spatial organization of cells and tissues, especially in scenarios that require the coordination of multiple cell types. Surface topography can provide potent guidance on the organization and function at both cellular and tissue levels, known as contact guidance. Nonetheless, fabrication of surface microtopography, especially at the single-cell scale, on three-dimensional (3D) objects with curved surfaces, such as 3D scaffolds, remains an enormous challenge. To tackle this challenge, our lab developed a unique 3D printing technology, named micro continuous liquid interface production (μCLIP), to produce scaffolds with well-defined topographical patterns. The surface micropatterns on 3D-printed scaffolds would guide the spatial organization of cells and tissues, holding great promise for the functional regeneration of orientated tissues.
3D Bioprinting of Strong Living Scaffolds for Load-Bearing Tissue Regeneration
The concurrent restoration of mechanical properties and biological functions is critical for the regeneration of load-bearing tissues, such as knee meniscus. However, it remains a significant challenge due to a lack of mechanically robust and biocompatible materials. Biomaterials, such as tough polymers, that can fabricate mechanically strong scaffolds are often not compatible with concurrent fabrication of cells. Conversely, biomaterials, such as hydrogels, that can encapsulate cells are mechanically weak (elastic modulus of most hydrogels E < 0.1 MPa). Therefore, an effective fabrication method to create mechanically robust and biologically functional scaffolds is warranted. To address this issue, we leverage the customized 3D printing technique and the innovative development of a two-phase emulsion bioink to enable the encapsulation of living cells and other biologics into tough polymers or elastomers. The key innovation of this work lies in the establishment of a new strategy to unify two dissimilar materials into a 3D bioprinting platform, enabling the fabrication of a strong living scaffold with built-in mechanical robustness and encapsulated living biologics for optimal regeneration of loading-bearing tissues.
Biofabrication of Mechano-Accurate Tissue Models
The development of in vitro disease models has aroused great interest as a viable alternative to animal models for the study of pathophysiology and drug discovery. Nevertheless, existing in vitro models fall short in their ability to replicate crucial local environmental factors, such as stiffness, which plays an important role in developing numerous diseases. For instance, the local matrix stiffening is a critical hallmark of atherosclerosis, which refers to the development of atheromatous plaques in the inner lining of the arteries and stands as a leading cause of global mortality and the loss of productive life years. Nonetheless, controlling local stiffness in 3D structures remains challenging with conventional biofabrication techniques. To address this issue, we have pioneered a new 3D printing paradigm, known as gray-scale digital light processing (gDLP). For the first time, we have achieved spatial control over local stiffness within complex 3D structures. We will use the gDLP-based technique to produce in vitro tissue models that faithfully replicate mechanical microenvironments, including local stiffening, within 3D structures. The produced mechano-accurate tissue models will provide a more reliable platform for investigating pathophysiology and assessing therapeutic responses compared to existing in vitro models.