Template‐Enabled Biofabrication of Thick 3D Tissues with Patterned Perfusable Macrochannels

Abstract

Interconnected pathways in 3D bioartificial organs are essential to retaining cell activity in thick functional 3D tissues. 3D bioprinting methods have been widely explored in biofabrication of functionally patterned tissues; however, these methods are costly and confined to thin tissue layers due to poor control of low-viscosity bioinks. Here, cell-laden hydrogels that could be precisely patterned via water-soluble gelatin templates are constructed by economical extrusion 3D printed plastic templates. Tortuous co-continuous plastic networks, designed based on triply periodic minimal surfaces (TPMS), serve as a sacrificial pattern to shape the secondary sacrificial gelatin templates. These templates are eventually used to form cell-encapsulated gelatin methacryloyl (GelMA) hydrogel scaffolds patterned with the complex interconnected pathways. The proposed fabrication process is compatible with photo-crosslinkable hydrogels wherein prepolymer casting enables incorporation of high cell populations with high viability. The cell-laden hydrogel constructs are characterized by robust mechanical behavior. In vivo studies demonstrate a superior cell ingrowth into the highly permeable constructs compared to the bulk hydrogels. Perfusable complex interconnected networks within cell-encapsulated hydrogels may assist in engineering thick and functional tissue constructs through the permeable internal channels for efficient cellular activities in vivo.

A Cohesive Shear-Thinning Biomaterial for Catheter-Based Minimally Invasive Therapeutics

“…Hydrogels with multifunctional macroscopic functionalities have enabled a broad spectrum of advanced medical therapeutics. − The physical properties of hydrogels such as injectability and mechanical robustness are regulated by the molecular interactions among their building blocks, such as polymer chains and nanoparticles via noncovalent and/or covalent binding within a three-dimensional (3D) network. − For example, covalent bonds impart mechanical resilience to elastic hydrogel biomaterials, whereas noncovalent interactions, such as ionic binding, often enable energy dissipation to withstand cyclic deformations and minimize mechanical mismatch at soft tissue interfaces. , …”

The 3D Bioprinted Scaffolds for Wound Healing

“…They are essential structural components of living systems, providing support in and around cells, and they are important for tissue functions [152]. The skin, for instance, has a challenging, complex structure to bioprint, consisting of two major compartments: epidermis, dermis, and a third region known as the subcutaneous tissue [153,154]. Because of this, tissue-engineered skin remains elusive despite extensive research, due to the skin's multi-stratified anisotropic structure.…”

Vascularization in Bioartificial Parenchymal Tissue: Bioink and Bioprinting Strategies

“…Gelatin [ 14 , 22 , 27 , 39 , 47 , 63 , 83 ], alginate [ 87 , 102 , 103 ], Pluronic ® F127 [ 68 , 85 , 86 , 104 , 105 , 106 , 107 ], agarose [ 108 ], poly(vinyl alcohol) [ 109 ], and carbohydrate mixtures [ 43 , 88 ] can serve as sacrificial inks. In a next step, sacrificial templates are embedded in low-viscosity bioinks containing effector cells, which then can be adequately cured [ 110 ]. After sufficient crosslinking, the sacrificial materials are removed [ 110 ].…”

“…In a next step, sacrificial templates are embedded in low-viscosity bioinks containing effector cells, which then can be adequately cured [ 110 ]. After sufficient crosslinking, the sacrificial materials are removed [ 110 ]. Removal can be accomplished by dissolution with a solvent [ 14 , 47 , 85 , 86 , 103 , 106 , 110 , 111 ], temperature regulation [ 14 , 27 , 46 , 83 , 104 , 105 , 106 , 110 ], or pH regulation [ 58 , 85 ], leaving a microfluidic network of patterned microchannels or even vascular tree-like channels in the construct [ 22 , 47 , 83 , 87 , 110 ].…”

“…After sufficient crosslinking, the sacrificial materials are removed [ 110 ]. Removal can be accomplished by dissolution with a solvent [ 14 , 47 , 85 , 86 , 103 , 106 , 110 , 111 ], temperature regulation [ 14 , 27 , 46 , 83 , 104 , 105 , 106 , 110 ], or pH regulation [ 58 , 85 ], leaving a microfluidic network of patterned microchannels or even vascular tree-like channels in the construct [ 22 , 47 , 83 , 87 , 110 ]. Perfusion of such a network with ECs and their subsequent partial adherence has the potential to result in coating of the inner wall [ 27 , 47 , 63 , 83 , 87 , 105 , 111 ] ( Figure 3 a).…”