Making In Vitro Tumor Models Whole Again.

As a reductionist approach, patient-derived in vitro tumor models are inherently still too simplistic for personalized drug testing as they do not capture many characteristics of the tumor microenvironment (TME), such as tumor architecture and stromal heterogeneity. This is especially problematic for assessing stromal-targeting drugs such as immunotherapies in which the density and distribution of immune and other stromal cells determine drug efficacy. On the other end, in vivo models are typically costly, low-throughput, and time-consuming to establish. Ex vivo patient-derived tumor explant (PDE) cultures involve the culture of resected tumor fragments that potentially retain the intact  TME of the original tumor. Although developed decades ago, PDE cultures have not been widely adopted likely because of their low-throughput and poor long-term viability. However, with growing recognition of the importance of patient-specific TME in mediating drug response, especially in the field of immune-oncology, there is an urgent need to resurrect these holistic cultures. In this Review, the key limitations of patient-derived tumor explant cultures are outlined and technologies that have been developed or could be employed to address these limitations are discussed. Engineered holistic tumor explant cultures may truly realize the concept of personalized medicine for cancer patients.

Stretchable and Self-Adhesive PEDOT:PSS Blend with High Sweat Tolerance as Conformal Biopotential Dry Electrodes.

Dry epidermal electrodes that can always form conformal contact with skin can be used for continuous long-term biopotential monitoring, which can provide vital information for disease diagnosis and rehabilitation. But, this application has been limited by the poor contact of dry electrodes on wet skin. Herein, we report a biocompatible fully organic dry electrode that can form conformal contact with both dry and wet skin even during physical movement. The dry electrodes are prepared by drop casting an aqueous solution consisting of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS), poly(vinyl alcohol) (PVA), tannic acid (TA), and ethylene glycol (EG). The electrodes can exhibit a conductivity of 122 S cm-1 and a mechanical stretchability of 54%. Moreover, they are self-adhesive to not only dry skin but also wet skin. As a result, they can exhibit a lower contact impedance to skin than commercial Ag/AgCl gel electrodes on both dry and sweat skins. They can be used as dry epidermal electrodes to accurately detect biopotential signals including electrocardiogram (ECG) and electromyogram (EMG) on both dry and wet skins for the users at rest or during physical movement. This is the first time to demonstrate dry epidermal electrodes self-adhesive to wet skin for accurate biopotential detection.

Conductive polypyrrole-encapsulated silk fibroin fibers for cardiac tissue engineering.

Polypyrrole (PPy) has been utilized in smart scaffolds to improve the functionality of the engineered cardiac tissue. Compared to the commonly used aqueous coating, here, PPy was blended into silk fibroin (SF) solution to electrospin conductive PPy-encapsulated SF nanofibers. Combinations of various SF concentrations (5%, 7%, and 12%) and different PPy-to-SF ratios (15:85, 30:70, and 40:60) were compared. PPy reduced the fiber diameter (0.431 ± 0.060 µm), better-mimicking the myocardium fibrils. Conductive mats with 7% SF showed the closest mechanical properties (1.437 ± 0.044 MPa) to the native myocardium; meanwhile, a PPy-to-SF ratio of 15:85 exhibited sufficient electrical conductivity for cardiomyocytes (CMs). In vitro studies using three different types of CM demonstrated that the hybrid mats support CM contraction. Primary neonatal rat CMs on the mat with a PPy-to-SF ratio of 15:85 were elongated and orientated anisotropically with locally organized sarcomeric striations. By contrast, human-induced pluripotent stem cell derived-CMs on the mat with a PPy-to-SF ratio of 30:70 exhibited the strongest contractions. Contraction synchrony was further improved by external stimulation. Taken together, these findings indicated the great potential of the PPy-encapsulated SF electrospun mat for cardiac tissue engineering.