Electrogenic Staphylococcus warneri in lactate-rich skin.

The electrogenicity of environmental bacteria has been thoroughly explored and has been known to have the unique capability of decomposing hazardous chemicals for environmental remediation. However, electrogenic bacteria in human skin in regards to their electrical properties and locations have not yet been determined. Here, electrodermal activities and metabolite compositions at different locations of arm skin were assessed. Compared to the uppermost part of arm, we found that the forearm elicited high electrodermal activity and carried abundant lactate and alpha-ketoglutarate, two components commonly present in sweat. Upon culturing bacteria from the forearm, an iron-resistant strain of Staphylococcus warneri (S. warneri) was identified through 16S ribosomal RNA sequencing. Voltage changes induced by S. warneri in the presence of glucose were detected by two voltmeters of different electrode materials, demonstrating the electrogenicity of skin bacteria. Furthermore, we discovered that S. warneri has the ability to metabolize lactate to generate electricity. The results of this study reveal changes in skin conductance caused by bacterial electricity that are mediated by skin endogenous molecules and may provide a novel method of monitoring environmental skin insults.

Chemotaxis-driven assembly of endothelial barrier in a tumor-on-a-chip platform.

The integration of three-dimensional micropatterning with microfluidics provides a unique opportunity to create perfusable tissue constructs in vitro. Herein, we have used this approach to create a tumor-on-a-chip with an endothelial barrier. Specifically, we photopatterned a mixture of endothelial cells and cancer spheroids within a gelatin methacrylate (GelMA) hydrogel inside a microfluidic device. The differential motility of endothelial and cancer cells in response to a controlled morphogen gradient across the cell-laden network drove the migration of endothelial cells to the periphery while maintaining the cancer cells within the interior of the hydrogel. The resultant endothelial cell layer forming cell-cell contact via VE-cadherin junctions was found to encompass the entire GelMA hydrogel structure. Furthermore, we have also examined the potential of such a tumor-on-a-chip system as a drug screening platform using doxorubicin, a model cancer drug.

3D cardiac µtissues within a microfluidic device with real-time contractile stress readout.

We present the development of three-dimensional (3D) cardiac microtissues within a microfluidic device with the ability to quantify real-time contractile stress measurements in situ. Using a 3D patterning technology that allows for the precise spatial distribution of cells within the device, we created an array of 3D cardiac microtissues from neonatal mouse cardiomyocytes. We integrated the 3D micropatterning technology with microfluidics to achieve perfused cell-laden structures. The cells were encapsulated within a degradable gelatin methacrylate hydrogel, which was sandwiched between two polyacrylamide hydrogels. The polyacrylamide hydrogels were used as "stress sensors" to acquire the contractile stresses generated by the beating cardiac cells. The cardiac-specific response of the engineered 3D system was examined by exposing it to epinephrine, an adrenergic neurotransmitter known to increase the magnitude and frequency of cardiac contractions. In response to exogenous epinephrine the engineered cardiac tissues exhibited an increased beating frequency and stress magnitude. Such cost-effective and easy-to-adapt 3D cardiac systems with real-time functional readout could be an attractive technological platform for drug discovery and development.

Biomimetic Material-Assisted Delivery of Human Embryonic Stem Cell Derivatives for Enhanced In Vivo Survival and Engraftment.

The ability of human embryonic stem cells (hESCs) and their derivatives to differentiate and contribute to tissue repair has enormous potential to treat various debilitating diseases. However, improving the in vivo viability and function of the transplanted cells, a key determinant of translating cell-based therapies to the clinic, remains a daunting task. Here, we develop a hybrid biomaterial consisting of hyaluronic acid (HA) grafted with 6-aminocaproic acid moieties (HA-6ACA) to improve cell delivery and their subsequent in vivo function using skeletal muscle as a model system. Our findings show that the biomimetic material-assisted delivery of hESC-derived myogenic progenitor cells into cardiotoxin-injured skeletal muscles of NOD/SCID mice significantly promotes survival and engraftment of transplanted cells in a dose-dependent manner. The donor cells were found to contribute to the regeneration of damaged muscle fibers and to the satellite cell (muscle specific stem cells) compartment. Such biomimetic cell delivery vehicles that are cost-effective and easy-to-synthesize could play a key role in improving the outcomes of other stem cell-based therapies.

Embedded 3D Photopatterning of Hydrogels with Diverse and Complex Architectures for Tissue Engineering and Disease Models.

Techniques that can create three-dimensional (3D) structures to provide architectural support for cells have a significant impact in generating complex and hierarchically organized tissues/organs. In recent times, a number of technologies, including photopatterning, have been developed to create such intricate 3D structures. In this study, we describe an easy-to-implement photopatterning approach, involving a conventional fluorescent microscope and a simple photomask, to encapsulate cells within spatially defined 3D structures. We have demonstrated the ease and the versatility of this approach by creating simple to complex as well as multilayered structures. We have extended this photopatterning approach to incorporate and spatially organize multiple cell types, thereby establishing coculture systems. Such cost-effective and easy-to-use approaches can greatly advance tissue engineering strategies.