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BACKGROUND: Latest tissue engineering strategies for musculoskeletal tissues regeneration focus on creating a biomimetic microenvironment closely resembling the natural topology of extracellular matrix. This paper presents a novel musculoskeletal tissue scaffold fabricated by hybrid additive manufacturing method. METHODS: The skeleton of the scaffold was 3D printed by fused deposition modeling, and a layer of random or aligned polycaprolactone nanofibers were embedded between two frames. A parametric study was performed to investigate the effects of process parameters on nanofiber morphology. A compression test was performed to study the mechanical properties of the scaffold. Human fibroblast cells were cultured in the scaffold for 7 days to evaluate the effect of scaffold microstructure on cell growth. RESULTS: The tip-to-collector distance showed a positive correlation with the fiber alignment, and the electrospinning time showed a negative correlation with the fiber density. With reinforced nanofibers, the hybrid scaffold demonstrated superior compression strength compared to conventional 3D-printed scaffold. The hybrid scaffold with aligned nanofibers led to higher cell attachment and proliferation rates, and a directional cell organization. In addition, there was a nonlinear relationship between the fiber diameter/density and the cell actinfilament density. CONCLUSION: This hybrid biofabrication process can be established as a highly efficient and scalable platform to fabricate biomimetic scaffolds with patterned fibrous microstructure, and will facilitate future development of clinical solutions for musculoskeletal tissue regeneration.

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There has been substantial progress in tissue engineering of biological substitutes for medical applications. One of the major challenges in development of complex tissues is the difficulty of creating vascular networks for engineered constructs. The diameter of current artificial vascular channels is usually at millimeter or submillimeter level, while human capillaries are about 5 to 10 µm in diameter. In this paper, a novel core-sheath electrospinning process was adopted to fabricate nanoporous microtubes to mimic the structure of fenestrated capillary vessels. A mixture of polylactic acid (PLA) and polyethylene glycol (PEO) was used as the sheath solution and PEO was used as the core solution. The microtubes were observed under a scanning electron microscope and the images were analyzed by ImageJ. The diameter of the microtubes ranged from 1–8 microns. The diameter of the nanopores ranged from 100 to 800 nm. The statistical analysis showed that the microtube diameter was significantly influenced by the PEO ratio in the sheath solution, pump rate, and the viscosity gradient between the sheath and the core solution. The electrospun microtubes with nanoscale pores highly resemble human fenestrated capillaries. Therefore, the nanoporous microtubes have great potential to support vascularization in engineered tissues.

The integration of nanomaterials in microfluidic devices has emerged as a new research paradigm. Microfluidic devices composed of ZnO nanowires have been developed for the collection of urine extracellular vesicles (EVs) at high efficiency and in situ extraction of various microRNAs (miRNAs). The devices can be used for diagnosing various diseases, including kidney diseases and cancers. A major research need for developing micro total analysis systems is to enhance extraction efficiency. This article presents a novel fabrication method for a herringbone-patterned microfluidic device anchored with ZnO nanowire arrays. The substrates with herringbone patterns were created by maskless photolithography. The ZnO nanowire arrays were grown on the substrates by chemical bathing. The patterned design was to introduce turbulent flows as opposed to laminar flow in traditional devices to increase the mixing and contact of the urine sample with ZnO nanowires. The device showed reduced flow rates compared with conventional planar microfluidic channels and successfully extracted urine EV-encapsulated miRNAs.