Karl Svennersten

Organic bioelectronics in nanomedicine

BACKGROUND Nanomedicine is a research area with potential to shape, direct, and change future medical treatments in a revolutionary manner over the next decades. While the common goal with other fields of biomedicine is to solve medical problems, this area embraces an increasing number of technology platforms as they become miniaturized. Organic electronics has over the past two decades developed into an exciting and thriving area of research. SCOPE OF REVIEW Today, the organic electronics field stands at the interface with biology. As the area of organic bioelectronics advances, it holds promise to make major contributions to nanomedicine. The progress made in this direction is the topic of this review. MAJOR CONCLUSIONS We describe the inherent features of conducting polymers, and explain the usefulness of these materials as active scaffolds in cell biology and tissue engineering. We also explain how the combined ionic and electronic conductive nature of the polymers is used to precisely control the delivery of signal substances. This unique feature is key in novel devices for chemical communication with cells and tissues. GENERAL SIGNIFICANCE This review highlights the results from the creative melting pot of interdisciplinary research in organic bioelectronics. This article is part of a Special Issue entitled Nanotechnologies - Emerging Applications in Biomedicine.

Electrochemical modulation of epithelia formation using conducting polymers

Conducting polymers are soft, flexible materials, exhibiting material properties that can be reversibly changed by electrochemically altering the redox state. Surface chemistry is an important determinant for the molecular events of cell adhesion. Therefore, we analyzed whether the redox state of the conducting polymer PEDOT:Tosylate can be used to control epithelial cell adhesion and proliferation. A functionalized cell culture dish comprising two adjacent electrode surfaces was developed. Upon electronic addressing, reduced and oxidized surfaces are created within the same device. Simultaneous analysis of how a homogenous epithelial MDCK cell population responded to the electrodes revealed distinct surface-specific differences. Presentation of functional fibronectin on the reduced electrode promoted focal adhesion formation, involving alpha(v)beta(3) integrin, cell proliferation, and ensuing formation of polarized monolayers. In contrast, the oxidized surface harbored only few cells with deranged morphology showing no indication of proliferation. This stems from the altered fibronectin conformation, induced by the different surface chemistry of the PEDOT:Tosylate electrode in the oxidized state. Our results demonstrate a novel use of PEDOT:Tosylate as a cell-hosting material in multiple-electrode systems, where cell adhesion and proliferation can be controlled by electrochemical modulation of surface properties.

Active Control of Epithelial Cell‐Density Gradients Grown Along the Channel of an Organic Electrochemical Transistor

Complex patterning of the extracellular matrix, cells, and tissues under in situ electronic control is the aim of the technique presented here. The distribution of epithelial cells along the channel of an organic electrochemical transistor is shown to be actively controlled by the gate and drain voltages, as electrochemical gradients are formed along the transistor channel when the device is biased..

Electronic control of cell detachment using a self-doped conducting polymer.

An electronic detachment technology based on thin films of a poly(3,4-ethylene-dioxythiophene) derivative is evaluated for controlled release of human epithelial cells. When applying a potential of ...

Localization of P2X receptor subtypes 2, 3 and 7 in human urinary bladder

BackgroundVoiding dysfunctions are a common problem that has a severe negative impact on the quality of life. Today there is a need for new drug targets for these conditions. The role of ATP receptors in bladder physiology has been studied for some time, primarily in animal models. The aim of this work is to investigate the localization of the ATP receptors P2X2, P2X3 and P2X7 and their colocalization with vimentin and actin in the human urinary bladder.MethodsImmunohistochemical analysis was conducted on full-thickness bladder tissues from fundus and trigonum collected from 15 patients undergoing open radical cystectomy due to chronic cystitis, bladder cancer or locally advanced prostate cancer. Colocalization analyses were performed between the three different P2X subtypes and the structural proteins vimentin and actin. Specimens were examined using epifluorescence microscopy and correlation coefficients were calculated for each costaining as well as the mean distance from the laminin positive basal side of the urothelium to the vimentin positive cells located in the suburothelium.ResultsP2X2 was expressed in vimentin positive cells located in the suburothelium. Less distinct labelling of P2X2 was also observed in actin positive smooth muscle cells and in the urothelium. P2X3 was expressed in vimentin positive cells surrounding the smooth muscle, and in vimentin positive cells located in the suburothelium. Weaker P2X3 labelling was seen in the urothelium. P2X7 was expressed in the smooth muscle cells and the urothelium. In the suburothelium, cells double positive for P2X2 and vimentin where located closer to the urothelium while cells double positive for P2X3 and vimentin where located further from the urothelium.ConclusionThe results from this study demonstrate that there is a significant difference in the expression of the purinergic P2X2, P2X3 and P2X7 receptors in the different histological layers of the human urinary bladder.

Receptors involved in the modulation of guinea pig urinary bladder motility by prostaglandin D2

We have described a urothelium‐dependent release of PGD2‐like activity which had inhibitory effects on the motility of guinea pig urinary bladder. Here, we have pharmacologically characterized the receptors involved and localized the sites of PGD2 formation and of its receptors.

Prostaglandin D2 effects and DP1/DP2 receptor distribution in guinea pig urinary bladder out‐flow region

The proximal urethra and urinary bladder trigone play important roles in continence. We have previously shown that PGD2 is released from guinea pig bladder urothelium/suburothelium and can inhibit detrusor contractile responses. We presently wished to investigate PGD2 actions in guinea pig out‐flow region and the distribution of DP1/DP2 receptors. The effects of PGD2 on urothelium‐intact trigone and proximal urethra contractility were studied in organ bath experiments. Expression of DP1/DP2 receptor proteins was analysed by western blot. Immunohistochemistry was used to identify distribution of DP1/DP2 receptors. PGD2 in a dose‐dependent manner inhibited trigone contractions induced by electrical field stimulation (EFS) and inhibited spontaneous contractions of the proximal urethra. PGD2 was equally (trigone) or slightly less potent (urethra) compared with PGE2. Expression of DP1 and DP2 receptors was found in male guinea pig bladder trigone, neck and proximal urethra. In the trigone and proximal urethra, DP1 receptors were found on the membrane of smooth muscle cells and weak immunoreactivty was observed in the urothelium. DP2 receptors were distributed more widespread, weakly and evenly in the urothelium and smooth muscles. Inhibitory effects by PGD2 on motor activity of guinea pig trigone and proximal urethra are consistent with finding DP1 and DP2 receptors located in the urothelium and smooth muscle cells of the trigone and proximal urethra, and PGD2 may therefore be a modulator of the bladder out‐flow region, possibly having a function in regulation of micturition and a role in overactive bladder syndrome.

Inhibitory Effects of Urothelium-related Factors

The urothelium of the bladder has long been recognized as a protective barrier between detrusor and urine. In recent years, it has become more evident that the urothelium plays a role as an active source of mediators. The urothelium can release neurotransmitters and modulators such as acetylcholine, ATP, nitric oxide, prostaglandins and neuropeptides. They exert both excitatory and inhibitory effects in modulating urinary tract motility. In addition, several studies have reported the existence of an urothelium‐derived unknown inhibitory factor in the urinary bladder. By the use of a new serial cascade superfusion bioassay on guinea pig ureter, recent studies confirm that the guinea pig bladder urothelium releases a substance with inhibitory bioactivity, which was resistant to treatment with nitric oxide synthase inhibitor and cyclooxygenase inhibitor and to adenosine A1/A2 receptor blockade. Lately, a marked and quickly inactivated novel release of PGD2 from the bladder urothelium was discovered, together with localization of prostaglandin D synthase therein. PGD2 was found to have an inhibitory influence on nerve‐induced contractions in guinea pig urinary bladder and on spontaneous contractions in the out‐flow region. An altered release of excitatory and inhibitory factors is likely to play an important part in bladder motility disturbances, of which the prostanoids are a notable group. Due to the fact that the bladder is relaxed 99% of the time, not only excitatory mechanisms in the bladder are necessary to study, but also inhibitory mechanisms need considerable attention, which will contribute to the discovery of new targets to treat bladder motility disorders.

Electroactive surfaces based on conducting polymers for controlling cell adhesion, signaling, and proliferation

We report on a variety of electroactive surfaces for the control of in vitro cell adhesion, proliferation, and stimulation. Planar cell culture substrates have been coated with the conducting polymer PEDOT and by switching the redox state, adhesion and proliferation of MDCK epithelial cells was controlled as well as stem cell seeding density. Electronically active 3D-scaffolds based on electrospun PET nano-fibers coated with PEDOT have been used as a substrate to culture SH-SY5Y neuroblastoma cells and to induce Ca2+ signaling. Finally, we report on micromechanical stimulation of cells using an electroactive topography surface based on micropattened polypyrrole.

Author Correction: Redox-active conducting polymers modulate Salmonella biofilm formation by controlling availability of electron acceptors

In the original published article, the author list did not include Karl Svennersten, Kristin Persson, Edwin Jager and Magnus Berggren. After publication, we were notified by the corresponding author that the author list did not accurately reflect the contributions made, and these authors have been added to the author list. The original “Author Contributions” stated that “S.G.C., M.R., and A.R.D. designed research; S.G.C. performed all experiments…” this has been updated to read “S.G.C., K.S., K.M.P., E.W.H.J., M.B., M.R., and A.R.D. designed research; K.S., K.M.P., and E.W.H.J. performed experiments; S.G.C. performed all reported experiments…”. The “Acknowledgements” previously read “We thank K. Svennersten, A. Kader, K. Persson, and M. Berggren for fruitful discussions, and S. Löffler for insightful comments on the manuscript…” and have been updated to state “We thank A. Kader for fruitful discussions and S. Loffler for insightful comments on the manuscript…”. The “Competing Interests” section did not require any amendments. All authors have agreed with this correction statement and authorship change.