Incorporating 4D into Bioprinting: Real‐Time Magnetically Directed Collagen Fiber Alignment for Generating Complex Multilayered Tissues

Abstract

In vitro multilayered tissues with mimetic architectures resembling native tissues are valuable tools for application in medical research. In this study, an advanced bioprinting strategy is presented for aligning collagen fibers contained in functional bioinks. Streptavidin-coated iron nanoparticles are embedded in printable bioinks with varying concentrations of low gelling temperature agarose and type I collagen. By applying a straightforward magnetic-based mechanism in hydrogels during bioprinting, it is possible to align collagen fibers in less concentrated hydrogel blends with a maximum agarose concentration of 0.5 w/v%. Conversely, more elevated concentrations of agarose in printable blends show random collagen fiber distribution. Interestingly, hydrogel blends with unidirectionally aligned collagen fibers show significantly higher compression moduli compared to hydrogel blends including random fibers. Considering its application in the field of cartilage tissue engineering, bioprinted constructs with alternating layers of aligned and random fibers are fabricated. After 21 days of culture, cell-loaded constructs with alternating layers of aligned and random fibers express markedly more collagen II in comparison to solely randomly oriented fiber constructs. These encouraging results translate the importance of the structure and architecture of bioinks used in bioprinting in light of their use for tissue engineering and personalized medical applications.

3D Bioprinting: from Benches to Translational Applications

“…Although their approach does not yet include cells in the process, the shape control of bioprinted constructs via magnetic stimulation offers a novel and highly promising method for 4D bioprinting. A similar approach of magnetic field stimulation was demonstrated by Betsch et al, who used a magnetic field to align collagen fibers within a bioprinted tissue . They incorporated streptavidin‐coated iron nanoparticles in a bioink of agarose and type I collagen.…”

Transformer Hydrogels: A Review

“…Several researchers have demonstrated the versatility and adaptability of stimuli‐responsive hydrogels coupled with 4D biofabrication methods for the fabrication of vascular constructs, biomimetic tissue and in vitro cancer models . One can classify the applications of stimuli‐responsive hydrogels in tissue engineering into three main groups based on the dimensional changes of the structures: 2D, 2D‐to‐3D, and 3D …”

“…Betsch et al used a 3D bioprinter that incorporated an electromagnetic microvalve. They developed 3D‐printable biocompatible magnetic hydrogels by combining iron nanoparticles, agarose, and collagen . They were able to change the directional properties of the collagen fibers during 3D‐printing by magnetically activating the iron particles to mimic the microstructural features of native tissues.…”

Advanced Bottom‐Up Engineering of Living Architectures

“…Adding to this, magnetic iron nanoparticles were exploited to recapitulate the anisotropy of human cartilage in bottom‐up engineered 3D constructs . Such nanomaterials have been used to direct collagen alignment during bioprinting, thus enabling the fabrication of multilayered chondrocyte‐laden constructs with intercalating layers of aligned/random collagen fibers.…”