Bioprinting of hybrid tissue constructs with tailorable mechanical properties

Abstract

Tissue/organ printing aims to recapitulate the intrinsic complexity of native tissues. For a number of tissues, in particular those of musculoskeletal origin, adequate mechanical characteristics are an important prerequisite for their initial handling and stability, as well as long-lasting functioning. Hence, organized implants, possessing mechanical characteristics similar to the native tissue, may result in improved clinical outcomes of regenerative approaches. Using a bioprinter, grafts were constructed by alternate deposition of thermoplastic fibers and (cell-laden) hydrogels. Constructs of different shapes and sizes were manufactured and mechanical properties, as well as cell viability, were assessed. This approach yields novel organized viable hybrid constructs, which possess favorable mechanical characteristics, within the same range as those of native tissues. Moreover, the approach allows the use of multiple hydrogels and can thus produce constructs containing multiple cell types or bioactive factors. Furthermore, since the hydrogel is supported by the thermoplastic material, a broader range of hydrogel types can be used compared to bioprinting of hydrogels alone. In conclusion, we present an innovative and versatile approach for bioprinting, yielding constructs of which the mechanical stiffness provided by thermoplastic polymers can potentially be tailored, and combined specific cell placement patterns of multiple cell types embedded in a wide range of hydrogels.

Reinforcement of hydrogels using three-dimensionally printed microfibres

“…In addition, in absolute terms, the stiffness of the biodegradable composites was comparable to the stiffness of articular cartilage, which has been reported to range from 400 to 800 kPa (refs 43-45). On the other hand, the stiffness of scaffolds fabricated with traditional 3D-printing was one order of magnitude larger than that of the articular cartilage, which is consistent with previous reports 30,33 . The porosity of these scaffolds ranged between 72 and 89%, whereas the porosities reported in the literature range from 28.9 and 91.2% (refs 39,46,47).…”

“…The mechanical properties of hydrogels in such composites are less demanding; therefore, they can be processed with a low crosslink density, which is beneficial for cell migration and the formation of neo-tissue 2,3 . Recent composite systems include nonwoven scaffolds manufactured via solution-electrospinning techniques 9,[24][25][26][27] and scaffolds fabricated via 3D-printing [28][29][30][31][32][33] . Owing to the small fibre diameters that can be obtained, electrospun meshes have the potential to mimic native tissue extracellular matrix structures, including its mechanical properties.…”

3D‐Bioprinted Osteoblast‐Laden Nanocomposite Hydrogel Constructs with Induced Microenvironments Promote Cell Viability, Differentiation, and Osteogenesis both In Vitro and In Vivo

“…Aqueous 20% HA is similar in viscosity to the 20%PEG–7%Clay prehydrogel solution (Figure 2A) and was suitable for the 3D‐bioprinting of cells. The choice of concentration is important, not only for printability but also the primary hydrogel structure should not be impacted by the addition of the second material 10. Moreover, when the HA concentration exceeds 20%, the printing pressure needed for successful printing would surpass 100 kPa, which would negatively impact on the viability of the printed cells 8, 11.…”

Advances in bioprinted cell-laden hydrogels for skin tissue engineering

“…A major challenge in skin bioprinting, is designing suitable bioinks to produce 3D cellular constructs with intricate geometries, shape fidelity, and high resolution in the placement of cells. In the biofabrication field, traditional approaches to generate such constructs often involve (1) the sequential printing of cell-laden hydrogels or melt extruded thermoplastic fibres, (2) the formulation of viscous bioinks by adding high molecular weight polymers (e.g., hyaluronic acid, HA), or (3) the use of increased polymer concentrations and crosslinking densities [152,173,174,193]. The combination of hydrogel bioprinting with melt extrusion has been successfully explored to design well-defined 3D constructs with improved mechanical properties, which is of special interest for load bearing tissues [80], but of limited application in soft tissues.…”