Collagenase motors in gelatine-based hydrogels.

Nano/micromotors outperform Brownian motion due to their self-propulsive capabilities and hold promise as carriers for drug delivery across biological barriers such as the extracellular matrix. This study employs poly(2-(diethylamino)ethyl methacrylate) polymer brushes to enhance the collagenase-loading capacity of silica particle-based motors with the aim to systematically investigate the impact of gelatine viscosity, motors' size, and morphology on their propulsion velocity. Notably, 500 nm and 1 µm motors achieve similar speeds as high as ∼15 µm s-1 in stiff gelatine-based hydrogels when triggered with calcium. Taken together, our findings highlight the potential of collagenase-based motors for navigating the extracellular matrix, positioning them as promising candidates for efficient drug delivery.

Artificial Cells and HepG2 Cells in 3D-Bioprinted Arrangements.

Artificial cells are engineered units with cell-like functions for different purposes including acting as supportive elements for mammalian cells. Artificial cells with minimal liver-like function are made of alginate and equipped with metalloporphyrins that mimic the enzyme activity of a member of the cytochrome P450 family namely CYP1A2. The artificial cells are employed to enhance the dealkylation activity within 3D bioprinted structures composed of HepG2 cells and these artificial cells. This enhancement is monitored through the conversion of resorufin ethyl ether to resorufin. HepG2 cell aggregates are 3D bioprinted using an alginate/gelatin methacryloyl ink, resulting in the successful proliferation of the HepG2 cells. The composite ink made of an alginate/gelatin liquid phase with an increasing amount of artificial cells is characterized. The CYP1A2-like activity of artificial cells is preserved over at least 35 days, where 6 nM resorufin is produced in 8 h. Composite inks made of artificial cells and HepG2 cell aggregates in a liquid phase are used for 3D bioprinting. The HepG2 cells proliferate over 35 days, and the structure has boosted CYP1A2 activity. The integration of artificial cells and their living counterparts into larger 3D semi-synthetic tissues is a step towards exploring bottom-up synthetic biology in tissue engineering.

Cell-contact-mediated assembly of contractile airway smooth muscle rings.

Microtissues in the shape of toroidal rings provide an ideal geometry to better represent the structure and function of the airway smooth muscle present in the small airways, and to better understand diseases such as asthma. Here, polydimethylsiloxane devices consisting of a series of circular channels surrounding central mandrels are used to form microtissues in the shape of toroidal rings by way of the self-aggregation and -assembly of airway smooth muscle cell (ASMC) suspensions. Over time, the ASMCs present in the rings become spindle-shaped and axially align along the ring circumference. Ring strength and elastic modulus increase over 14 d in culture, without significant changes in ring size. Gene expression analysis indicates stable expression of mRNA for extracellular matrix-associated proteins, including collagen I and lamininsα1 andα4 over 21 d in culture. Cells within the rings respond to TGF-ß1 treatment, leading to dramatic decreases in ring circumference, with increases in mRNA and protein levels for extracellular matrix and contraction-associated markers. These data demonstrate the utility of ASMC rings as a platform for modeling diseases of the small airways such as asthma.