Cell and organ printing 2: Fusion of cell aggregates in three‐dimensional gels

Abstract

We recently developed a cell printer (Wilson and Boland, 2003) that enables us to place cells in positions that mimic their respective positions in organs. However, this technology was limited to the printing of two-dimensional (2D) tissue constructs. Here we describe the use of thermosensitive gels to generate sequential layers for cell printing. The ability to drop cells on previously printed successive layers provides a real opportunity for the realization of three-dimensional (3D) organ printing. Organ printing will allow us to print complex 3D organs with computer-controlled, exact placing of different cell types, by a process that can be completed in several minutes. To demonstrate the feasibility of this novel technology, we showed that cell aggregates can be placed in the sequential layers of 3D gels close enough for fusion to occur. We estimated the optimum minimal thickness of the gel that can be reproducibly generated by dropping the liquid at room temperature onto a heated substrate. Then we generated cell aggregates with the corresponding (to the minimal thickness of the gel) size to ensure a direct contact between printed cell aggregates during sequential printing cycles. Finally, we demonstrated that these closely-placed cell aggregates could fuse in two types of thermosensitive 3D gels. Taken together, these data strongly support the feasibility of the proposed novel organ-printing technology. Anat Rec Part A 272A: 497-502, 2003.

Prospectus of cultured meat—advancing meat alternatives

“…Currently there are two detailed proposals based on emerging field of tissue engineering (Boland et al 2003;Zandonella 2003) for using cell culture for producing in vitro meat. Both these proposals are similar in nature and neither of the two has been tested.…”

Engineering biological structures of prescribed shape using self-assembling multicellular systems

“…In addition, rapid prototyping technology has successfully been applied for computer-aided deposition of cells in gels to create 3D tissue constructs (13,14). We suggest that cell aggregates may be used as drops of ''bio-ink,'' which, upon implantation or ''printing'' into a scaffold (''bio-paper''), have the ability to fuse into 3D organ structures (15)(16)(17).…”

Advances in bioprinted cell-laden hydrogels for skin tissue engineering

“…In order to adapt a material for bioprinting technologies, it is important to take into account whether the technical characteristics of the printing device afford the design of biologically relevant constructs for a given application. By placing suitable cell types in appropriate positions, the tissue construct may then mature into a tissue/organ and late achieve functionality either inside a bioreactor or in vivo [22]. The ideal properties of hydrogels for bioprinting include stability, sterilization, biodegradability, adequate mechanical properties and swelling characteristics, but it is also required that both hydrogel chemistry and crosslinking mechanisms promote cell function [126].…”