Biology subjects

Ozbolat, I. T.

Publications and source records attributed to Ozbolat, I. T..

3 recordsLinked to original sources

bioRxiv2020

The role of concentration on drop formation and breakup of collagen, fibrinogen, and thrombin solutions during inkjet bioprinting

The influence of protein concentration on drop formation and breakup of aqueous solutions of fibrous proteins collagen, fibrinogen, and globular protein thrombin in different concentration regimes is investigated during drop-on-demand (DOD) inkjet bioprinting. The capillary-driven thinning and breakup of dilute (c/c* < 1, where c is the concentration and c* is the overlap concentration) collagen, fibrinogen, and thrombin solutions is predominantly resisted by inertial force on the initial onset of necking. The minimum diameter (Dfmin(t)) of the necked fluid up to the critical pinch-off time (tc) scales with time as Dfmin(t) [~] (tc - t)2/3, a characteristic of potential flows. Although the capillary-driven thinning and breakup of semidilute unentangled collagen (1 [≤] c/c* [≤] 4) and fibrinogen (1 [≤] c/c* [≤] 1.3) solutions is predominantly resisted by inertial force on the initial onset of necking, the breakup of droplets is delayed beyond tc, where the minimum diameter of the necked fluid decreases exponentially with time because of the resistance of elastic force. The resistance of viscous force to the necking of both the dilute and semidilute untangled protein solutions is negligible. Aggregates or subvisible particles (between 1 and 100 m) constantly disrupt the formation of droplets for the semidilute unentangled protein solutions, even when their inverse Ohnesorge number (Z) is within the printability range of 4 [≤] Z [≤] 14. Although aggregates are present in the dilute protein solutions, they do not disrupt the formation of droplets.

bioengineering↗

bioRxiv2020

3D bioprinting of co-cultured osteogenic spheroids for bone tissue fabrication

Conventional top-down approaches in tissue engineering involving cell seeding on scaffolds have been widely used in bone engineering applications. However, scaffold-based bone tissue constructs have had limited clinical translation due to constrains in supporting scaffolds, minimal flexibility in tuning scaffold degradation, and low achievable cell seeding density as compared with native bone tissue. Here, we demonstrate a pragmatic and scalable bottom-up method, inspired from embryonic developmental biology, to build three-dimensional (3D) scaffold-free constructs using spheroids as building blocks. Human umbilical vein endothelial cells (HUVECs) were introduced to human mesenchymal stem cells (hMSCs) (hMSC/HUVEC) and spheroids were fabricated by an aggregate culture system. Bone tissue was generated by induction of osteogenic differentiation in hMSC/HUVEC spheroids for 10 days, with enhanced osteogenic differentiation and cell viability in the core of the spheroids compared to hMSC-only spheroids. Aspiration-assisted bioprinting (AAB) is a new bioprinting technique which allows precise positioning of spheroids (11% with respect to the spheroid diameter) by employing aspiration to lift individual spheroids and bioprint them onto a hydrogel. AAB facilitated bioprinting of scaffold-free bone tissue constructs using the pre-differentiated hMSC/HUVEC spheroids. These constructs demonstrated negligible changes in their shape for two days after bioprinting owing to the reduced proliferative potential of differentiated stem cells. Bioprinted bone tissues showed interconnectivity with actin-filament formation and high expression of osteogenic and endothelial-specific gene factors. This study thus presents a viable approach for 3D bioprinting of complex-shaped geometries using spheroids as building blocks, which can be used for various applications including but not limited to, tissue engineering, organ-on-a-chip and microfluidic devices, drug screening and, disease modeling.

bioengineering↗

bioRxiv2020

Aspiration-assisted Freeform Bioprinting of Tissue Spheroids in a Yield-stress Gel

Bioprinting of cellular aggregates, such as tissue spheroids or organoids, in complex three-dimensional (3D) arrangements has been a major obstacle for scaffold-free fabrication of tissues and organs. In this research, we unveiled a new approach to the bioprinting of tissue spheroids in a yield stress granular gel, which exhibited unprecedented capabilities in freeform positioning of spheroids in 3D. Due to its Herschel-Bulkley and self-healing properties as well as its biological inertness, the granular gel supported both the positioning and self-assembly of tissue spheroids. We studied the underlying physical mechanism of the approach to elucidate the interactions between the aspirated spheroids and the gels yield-stress during the transfer of spheroids from cell media to the gel. We demonstrate the application of the proposed approach in the realization of various freeform shapes and self-assembly of human mesenchymal stem cell spheroids for the construction of cartilage and bone tissues.

bioengineering↗