The additive manufacturing of highly ordered, micrometer-scale scaffolds is at the forefront of tissue engineering and regenerative medicine research. The fabrication of scaffolds for the regeneration of larger tissue volumes, in particular, remains a major challenge. A technology at the convergence of additive manufacturing and electrospinning-melt electrospinning writing (MEW)-is also limited in thickness/volume due to the accumulation of excess charge from the deposited material repelling and hence, distorting scaffold architectures. The underlying physical principles are studied that constrain MEW of thick, large volume scaffolds. Through computational modeling, numerical values variable working distances are established respectively, which maintain the electrostatic force at a constant level during the printing process. Based on the computational simulations, three voltage profiles are applied to determine the maximum height (exceeding 7 mm) of a highly ordered large volume scaffold. These thick MEW scaffolds have fully interconnected pores and allow cells to migrate and proliferate. To the best of the authors knowledge, this is the first study to report that z-axis adjustment and increasing the voltage during the MEW process allows for the fabrication of high-volume scaffolds with uniform morphologies and fiber diameters.

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Current in vivo models for investigating human primary bone tumors and cancer metastasis to the bone rely on the injection of human cancer cells into the mouse skeleton. This approach does not mimic species-specific mechanisms occurring in human diseases and may preclude successful clinical translation. We have developed a protocol to engineer humanized bone within immunodeficient hosts, which can be adapted to study the interactions between human cancer cells and a humanized bone microenvironment in vivo. A researcher trained in the principles of tissue engineering will be able to execute the protocol and yield study results within 4-6 months. Additive biomanufactured scaffolds seeded and cultured with human bone-forming cells are implanted ectopically in combination with osteogenic factors into mice to generate a physiological bone 'organ', which is partially humanized. The model comprises human bone cells and secreted extracellular matrix (ECM); however, other components of the engineered tissue, such as the vasculature, are of murine origin. The model can be further humanized through the engraftment of human hematopoietic stem cells (HSCs) that can lead to human hematopoiesis within the murine host. The humanized organ bone model has been well characterized and validated and allows dissection of some of the mechanisms of the bone metastatic processes in prostate and breast cancer.

We present a design rationale for stretchable soft network composites for engineering tissues that predominantly function under high tensile loads. The convergence of 3D-printed fibers selected from a design library and biodegradable interpenetrating polymer networks (IPNs) result in biomimetic tissue engineered constructs (bTECs) with fully tunable properties that can match specific tissue requirements. We present our technology platform using an exemplary soft network composite model that is characterized to be flexible, yet ∼125 times stronger (E = 3.19 MPa) and ∼100 times tougher (W = ∼2000 kJ m) than its hydrogel counterpart.

Melt electrowriting (MEW) combines the fundamental principles of electrospinning, a fibre forming technology, and 3D printing. The process, however, is highly complex and the quality of the fabricated structures strongly depends on the interplay of key printing parameter settings including processing temperature, applied voltage, collection speed, and applied pressure. These parameters act in unison, comprising the principal forces on the electrified jet: pushing the viscous polymer out of the nozzle and mechanically and electrostatically dragging it for deposition towards the collector. Although previous studies interpreted the underlying mechanism of electrospinning with polymer melts in a direct writing mode, contemporary devices used in laboratory environments lack the capability to collect large data reproducibly. Yet, a validated large data set is a condition sine qua non to design an in-process control system which allows to computer control the complexity of the MEW process. For this reason, we engineered an advanced automated MEW system with monitoring capabilities to specifically generate large, reproducible data volumes which allows the interpretation of complex process parameters. Additionally, the design of an innovative real-time MEW monitoring system identifies the main effects of the system parameters on the geometry of the fibre flight path. This enables, for the first time, the establishment of a comprehensive correlation between the input parameters and the geometry of a MEW jet. The study verifies the most stable process parameters for the highly reproducible fabrication of a medical-grade poly(ε-caprolactone) fibres and demonstrates how Printomics can be performed for the high throughput analysis of processing parameters for MEW.