Of balls, inks and cages: Hybrid biofabrication of 3D tissue analogs

Abstract

The overarching principle of three-dimensional (3D) bioprinting is the placing of cells or cell clusters in the 3D space to generate a cohesive tissue microarchitecture that comes close to in vivo characteristics. To achieve this goal, several technical solutions are available, generating considerable combinatorial bandwidth: (i) Support structures are generated first, and cells are seeded subsequently; (ii) alternatively, cells are delivered in a printing medium, so-called “bioink,” that contains them during the printing process and ensures shape fidelity of the generated structure; and (iii) a “scaffold-free” version of bioprinting, where only cells are used and the extracellular matrix is produced by the cells themselves, also recently entered a phase of accelerated development and successful applications. However, the scaffold-free approaches may still benefit from secondary incorporation of scaffolding materials, thus expanding their versatility. Reversibly, the bioink-based bioprinting could also be improved by adopting some of the principles and practices of scaffold-free biofabrication. Collectively, we anticipate that combinations of these complementary methods in a “hybrid” approach, rather than their development in separate technological niches, will largely increase their efficiency and applicability in tissue engineering.

Hybrid Bioprinting of Chondrogenically Induced Human Mesenchymal Stem Cell Spheroids

“…Hydrogels have been widely used as 3D matrices for cell application. They are used as a medium for the retention of cells after injection in the cartilage defect site or as a carrier for cells or spheroids during bio-ink based extrusion printing to ensure shape fidelity of the construct (Moldovan et al, 2018;Li et al, 2019). Common biomaterials used in cartilage engineering are collagen, alginate, hyaluronic acid, etc., because of their FIGURE 11 | Evaluation of cartilaginous phenotype of microtissues post printing.…”

“…As an alternative to injecting or assembling spheroids at random, 3D printing technologies can be used to assemble the cellular building blocks in a directed manner with high spatial control in a complex predesigned configuration. In bio-ink based extrusion bioprinting, biomaterials can be used as viscous carriers for the deposition of cells or spheroids, to restrain them and to ensure shape fidelity of the printed construct (Moldovan et al, 2018). Moreover, hydrogels are widely used in cell-based cartilage regeneration as a pro-chondrogenic environment as they can mimic the biological and physical properties of the native ECM (Vega et al, 2017).…”

Strategies for Articular Cartilage Repair and Regeneration

“…Therefore, investigations were directed into developing scaffold-free strategies. Three dimensional (3D) bioprinting is the placing of cells in a 3D space to generate a cohesive tissue microarchitecture akin to the in vivo characteristics (Moldovan et al, 2019). Hydrogels are fast becoming a common printing media which are then jetted with cells, an approach referred to as bio-ink based hybrid bioprinting (Laternser et al, 2018;Moldovan et al, 2019).…”

“…Three dimensional (3D) bioprinting is the placing of cells in a 3D space to generate a cohesive tissue microarchitecture akin to the in vivo characteristics (Moldovan et al, 2019). Hydrogels are fast becoming a common printing media which are then jetted with cells, an approach referred to as bio-ink based hybrid bioprinting (Laternser et al, 2018;Moldovan et al, 2019). Hydrogels can differ in their physical properties including viscosity and rigidity, which has implications for the mechanical environment, and the amount of natural cell binding motifs.…”

Tuning the Phenotype of Cartilage Tissue Mimics by Varying Spheroid Maturation and Methacrylamide‐Modified Gelatin Hydrogel Characteristics

“…Using bioink‐based extrusion bioprinting, cells or spheroids are deposited in a viscous hydrogel precursor solution to restrain them and to provide structural support of the printed tissue. [ 16 ] Besides a cell‐ or spheroid‐carrier function, hydrogels can be utilized as smart biomaterials to mimic the native tissue and to deliver the appropriate biophysical signals to directly regulate and tune cell differentiation by varying hydrogel composition, biopolymer concentration, and elasticity. [ 17 ] Since hydrogels are water swollen polymer networks, they already resemble the native fibro‐ and hyaline‐cartilage where water is the most abundant component.…”