On-chip anticancer drug screening - Recent progress in microfluidic platforms to address challenges in chemotherapy.

There is an increasing need for advanced and inexpensive preclinical models to accelerate the development of anticancer drugs. While costly animal models fail to predict human clinical outcomes, in vitro models such as microfluidic chips ('tumor-on-chip') are showing tremendous promise at predicting and providing meaningful preclinical drug screening outcomes. Research on 'tumor-on-chips' has grown enormously worldwide and is being widely accepted by pharmaceutical companies as a drug development tool. In light of this shift in philosophy, it is important to review the recent literature on microfluidic devices to determine how rapidly the technology has progressed as a promising model for drug screening and aiding cancer therapy. We review the past five years of successful developments and capabilities in microdevice technology (cancer models) for use in anticancer drug screening. Microfluidic devices that are being designed to address current challenges in chemotherapy, such as drug resistance, combinatorial drug therapy, personalized medicine, and cancer metastasis are also reviewed in detail. We provide a perspective on how personalized 'tumor-on-chip', as well as high-throughput microfluidic platforms based on patient-specific tumor cells, can potentially replace the more expensive and 'non-human' animal models in preclinical anticancer drug development.

Enhanced osteodifferentiation of MSC spheroids on patterned electrospun fiber mats - An advanced 3D double strategy for bone tissue regeneration.

2D cell culture has been widely developed with various micropatterning and microfabrication techniques over the past few decades for creating and controlling cellular microenvironments including cell-matrix interactions, cell-cell interactions, and bio-mimicking the in-vivo tissue hierarchy and functions. However, the drawbacks of 2D culture have currently paved the way to 3D cell culture which is considered clinically and biologically more relevant. Here we report a 3D double strategy for osteodifferentiation of MSC spheroids on nano- and micro-patterned PLGA/Collagen/nHAp electrospun fiber mats. A comparison of cell alignment, proliferation and differentiation of 2D and 3D MSCs on patterned and non-patterned substrate was done. The study demonstrates the synergistic effect of geometric cues and 3D culture on differentiation of MSC spheroids into osteogenic lineage even in absence of osteoinduction medium.

Effect of patterned electrospun hierarchical structures on alignment and differentiation of mesenchymal stem cells: Biomimicking bone.

Considering the complex hierarchical structure of bone, biomimicking the micro and nano level features should be an integral part of scaffold fabrication for successful bone regeneration. We aim to biomimic the microstructure and nanostructure of bone and study the effect of physical cues on cell alignment, proliferation, and differentiation. To achieve this, we have divided the scaffolds into groups: electrospun SU-8 nanofibers, electrospun SU-8 nanofibers with UV treatment, and micropatterned (20 µm sized ridges and grooves) SU-8 nanofibers by photolithography with UV treatment. Two types of culture conditions were applied: with and without osteoinduction medium. In vitro cell proliferation assays, protein estimation, alkaline phosphatase osteodifferentiation assay, live dead assay, and cell alignment studies were performed on these micropatterned nanofiber domains. Our findings show that patterned surface induced an early osteodifferentiation of mesenchymal stem cells even in absence of osteoinduction medium. An interesting similarity with the helicoidal plywood model of the bone was observed. The cells showed layering and rotation along the patterns with time. This resembles the in vivo anisotropic multilamellar bone tissue architecture thus, closely mimicking the subcellular features of bone. This might serve as a smart biomaterial surface for mesenchymal stem cell differentiation in therapeutics where the addition of external chemical factors is a challenge.

Microfabrication of carbon structures by pattern miniaturization in resorcinol-formaldehyde gel.

A simple and novel method to fabricate and miniaturize surface and subsurface microstructures and micropatterns in glassy carbon is proposed and demonstrated. An aqueous resorcinol-formaldehyde (RF) sol is employed for micromolding of the master pattern to be replicated, followed by controlled drying and pyrolysis of the gel to reproduce an isotropically shrunk replica in carbon. The miniaturized version of the master pattern thus replicated in carbon is about 1 order of magnitude smaller than original master by repeating three times the above cycle of molding and drying. The microfabrication method proposed will greatly enhance the toolbox for a facile fabrication of a variety of carbon-MEMS and C-microfluidic devices.