Bioprinting has emerged as a flexible technology in tissue engineering to mimic biological and functional organizational complexity of native tissues. Drop-on-Demand (DoD) bioprinting is one of the most promising technologies currently due to the unique characteristics of high-throughput efficiency and cost-effectiveness. Despite these significant advantages, DoD bioprinting has some drawbacks, including loss of cell viability impacted by shear stress. However, there are only very few studies discussed the variation of shear stress in DoD cell printing and its effects on cell behaviours. In this paper, a CFD simulation model of piezoelectric DoD print-head was developed to study shear stress in the nozzle during printing. Experiments were conducted to study the effect of shear stress on cell viability and cell proliferation. The mathematical model of piezoelectric effect is developed with CFD model to improve the simulation accuracy. Parametric studies on shear stress were also carried out. Simulation results demonstrated that (1) shear stress has a dramatic variation around the nozzle orifice mainly during the rise time and the following dwell time of voltage pulse in the episode; (2) the backflow fluid pushed the fluid entered from the inlet flowing down along the wall, increasing the wall shear stress simultaneously; (3) voltage, viscosity and nozzle diameter have important effects on both values and the effect range of shear stress. With simulation results of shear stress, experiments showed that both cell viability and cell proliferation are decreased with the increase of shear stress, whereby shear stress has a larger influence on cell proliferation than on cell viability. Through the proposed simulation model, the computed shear stress during DoD bioprinting is able to link with engineering characteristics, such as printing parameters, and cell characteristics, such as cell viability and cell proliferation. The simulation model can be used to improve cell viability and cell proliferation through optimizing printing parameters to decrease shear stress in piezoelectric DoD bioprinting.

The musculoskeletal system plays a critical role in providing the physical scaffold and movement to the mammalian body. Musculoskeletal disorders severely affect mobility and quality of life and pose a heavy burden to society. This new field of musculoskeletal tissue engineering has great potential as an alternative approach to treating large musculoskeletal defects. Natural and synthetic polymers are widely used in musculoskeletal tissue engineering owing to their good biocompatibility and biodegradability. Even more promising is the use of natural and synthetic polymer composites, as well as the combination of polymers and inorganic materials, to repair musculoskeletal tissue. Therefore, this review summarizes the progress of polymer-based scaffolds for applications of musculoskeletal tissue engineering and briefly discusses the challenges and future perspectives.

In situ tissue engineering is a powerful strategy for the treatment of bone defects. It could overcome the limitations of traditional bone tissue engineering, which typically involves extensive cell expansion steps, low cell survival rates upon transplantation, and a risk of immuno-rejection. Here, a porous scaffold polycaprolactone (PCL)/decellularized small intestine submucosa (SIS) was fabricated via cryogenic free-form extrusion, followed by surface modification with aptamer and PlGF-2_123-144*-fused BMP2 (pBMP2). The two bioactive molecules were delivered sequentially. The aptamer Apt19s, which exhibited binding affinity to bone marrow-derived mesenchymal stem cells (BMSCs), was quickly released, facilitating the mobilization and recruitment of host BMSCs. BMP2 fused with a PlGF-2_123-144 peptide, which showed “super-affinity” to the ECM matrix, was released in a slow and sustained manner, inducing BMSC osteogenic differentiation. In vitro results showed that the sequential release of PCL/SIS-pBMP2-Apt19s promoted cell migration, proliferation, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes. The in vivo results demonstrated that the sequential release system of PCL/SIS-pBMP2-Apt19s evidently increased bone formation in rat calvarial critical-sized defects compared to the sequential release system of PCL/SIS-BMP2-Apt19s. Thus, the novel delivery system shows potential as an ideal alternative for achieving cell-free scaffold-based bone regeneration in situ.