gms | German Medical Science

Objectives: Articular cartilage is not easy to recreate, since it is a highly organized tissue. An important focus in current tissue-engineering strategies is on the development of engineered tissues with design strategies that closely mimic the complex structure of native tissues. Innovative 3D-printing technology shows promise for creating complex composite tissue constructs. This study aims on bioprinting articular cartilage substitutes by using a magnetic-based fiber alignment mechanism.

Methods: A plastic adaptor was designed, which fitted a 2mT cylindrical magnet. This adaptor was mounted on a custom-built 3D printer. Streptavidin coated iron nanoparticles were embedded in printable bioinks with varying concentrations of agarose and type 1 collagen. Human chondrocytes were isolated using standardized protocols. Cell-loaded blends and cell-loaded magnetic blends were printed as one layer, while cell-loaded and magnetic blends were printed as two overlaying layers. Thereafter, printed samples were incubated for 21 days in chondrogenic medium. Type I collagen fibers were visualized by second-harmonic imaging using a two-photon microscope, and the mechanical strength was evaluated with a universal testing machine. Evaluation of chondrogenesis was based on histological stainings and GAG production.

Results and conclusion: Pure type I collagen hydrogels showed the most effective unidirectional collagen fiber alignment amongst studied samples. Hydrogel blends with the highest agarose content in the mixture exhibited a lack of fiber alignment, independently of the presence of a magnetic field. 0.5 % agarose-0.2 % collagen hydrogels appeared to have the highest tendency for unidirectional fiber alignment using a magnetic field (Fig.1). Interestingly, the incorporation of a magnetic field resulted in significantly increased compression moduli of up to 20 % (p<0.05). Histological stainings showed similar proteoglycan production in magnetic materials with aligned collagen fibers compared to controls. This was supported by similar GAG/DNA content.

This study demonstrated the feasibility of remodeling collagen fibers hydrogels whilst bioprinting. Higher concentrations of agarose in the blend limited the collagen fiber alignment. However, collagen fiber alignment was still feasible in lower agarose concentrations ranging from 0.3 to 0.5 w/v %. Even though there was no statistical difference among fiber alignment in this range of agarose-collagen blends, hydrogels of 0.5 w/v % agarose with 0.2 w/v % showed a slight tendency for better collagen fiber alignment compared to other blends. The presence of a magnetic field during the gelation of the magnetic blends can significantly increase their stiffness.