ABSTRACT
The treatment of tongue squamous cell carcinoma (TSCC) faces challenges because TSCC has an aggressive biological behavior and manifests usually as widespread metastatic disease. Therefore, it is particularly important to screen out and develop drugs that inhibit tumor invasion and metastasis. Two-dimensional (2D) cell culture has been used as in vitro models to study cellular biological behavior, but growing evidence now shows that the 2D systems can result in cell bioactivities that deviate appreciably the in vivo response. It is urgent to develop a novel 3D cell migration model in vitro to simulate the tumor microenvironment as much as possible and screen out effective anti-migration drugs. Sodium alginate, has a widely used cell encapsulation material, as significant advantages. We have designed a microfluidic device to fabricate a hollow alginate hydrogel microtube model. Based on the difference in liquid flow rate, TSCC cells (Cal27) were able to be evenly distributed in the hollow microtubes, which was confirmed though fluorescence microscope and laser scanning confocal microscope (LSCM). Our microfluidic device was cheap, and commercially available and could be assembled in a modular way, which are composed of a coaxial needle, silicone hose, and syringes. It was proved that the cells grow well in artificial microtubes with extracellular matrix (ECM) proteins by LSCM and flow cytometry. Periodic motility conferred a different motor state to the cells in the microtubes, more closely resembling the environment in vivo. The quantitative analysis of tumor cell migration could be achieved simply by determining the position of the cell in the microtube cross-section. We verified the anti-migration effects of three NSAIDs drugs (aspirin, indomethacin, and nimesulide) with artificial microtubes, obtaining the same results as conventional migration experiments. The results showed that among the three NSAIDs, nimesulide showed great anti-migration potential against TSCC cells. Our method holds great potential for application in the more efficient screening of anti-migration tumor drugs.
ABSTRACT
A body of evidence has suggested that tissue-engineered nerve grafts hold promise for the surgical repair of spinal cord injuries. In this study, a novel nerve graft was prepared to be implantated into a 5 mm gap which was caused by a complete transection of the rat spinal cord. The graft was featured by incorporation of neurotrophin-3 into a chitosan-based tube scaffold with a spinal cord-mimicking, partition-type architecture, which was prepared based on the morphometric insights of normal spinal cord anatomy. A set of behavioral, functional, and histological examinations were carried out to evaluate the repair. Results from Basso, Beattie, and Bresnahan tests, motor evoked potential measurements, anterograde tracing, and histological analyses suggested that the combined application of chitosan as the scaffold biomaterial, a spinal cord-mimicking partition-type as the scaffold architecture, and neurotrophin-3 (NT-3) as the bioactive component might probably create synergetic promotion on spinal cord regeneration. This composite nerve graft yielded significantly better results in axonal regeneration and function restoration as compared to its scaffold alone or other types of hollow tube scaffold alone.
