Development of dopant-free conductive bioelastomers.

Conductive biodegradable materials are of great interest for various biomedical applications, such as tissue repair and bioelectronics. They generally consist of multiple components, including biodegradable polymer/non-degradable conductive polymer/dopant, biodegradable conductive polymer/dopant or biodegradable polymer/non-degradable inorganic additives. The dopants or additives induce material instability that can be complex and possibly toxic. Material softness and elasticity are also highly expected for soft tissue repair and soft electronics. To address these concerns, we designed a unicomponent dopant-free conductive polyurethane elastomer (DCPU) by chemically linking biodegradable segments, conductive segments, and dopant molecules into one polymer chain. The DCPU films which had robust mechanical properties with high elasticity and conductivity can be degraded enzymatically and by hydrolysis. It exhibited great electrical stability in physiological environment with charge. Mouse 3T3 fibroblasts survived and proliferated on these films exhibiting good cytocompatibility. Polymer degradation products were non-toxic. DCPU could also be processed into a porous scaffold and in an in vivo subcutaneous implantation model, exhibited good tissue compatibility with extensive cell infiltration over 2 weeks. Such biodegradable DCPU with good flexibility and elasticity, processability, and electrical stability may find broad applications for tissue repair and soft/stretchable/wearable bioelectronics.

Synthesis and characterization of conductive, biodegradable, elastomeric polyurethanes for biomedical applications.

Biodegradable conductive polymers are currently of significant interest in tissue repair and regeneration, drug delivery, and bioelectronics. However, biodegradable materials exhibiting both conductive and elastic properties have rarely been reported to date. To that end, an electrically conductive polyurethane (CPU) was synthesized from polycaprolactone diol, hexadiisocyanate, and aniline trimer and subsequently doped with (1S)-(+)-10-camphorsulfonic acid (CSA). All CPU films showed good elasticity within a 30% strain range. The electrical conductivity of the CPU films, as enhanced with increasing amounts of CSA, ranged from 2.7 ± 0.9 × 10(-10) to 4.4 ± 0.6 × 10(-7) S/cm in a dry state and 4.2 ± 0.5 × 10(-8) to 7.3 ± 1.5 × 10(-5) S/cm in a wet state. The redox peaks of a CPU1.5 film (molar ratio CSA:aniline trimer = 1.5:1) in the cyclic voltammogram confirmed the desired good electroactivity. The doped CPU film exhibited good electrical stability (87% of initial conductivity after 150 hours charge) as measured in a cell culture medium. The degradation rates of CPU films increased with increasing CSA content in both phosphate-buffered solution (PBS) and lipase/PBS solutions. After 7 days of enzymatic degradation, the conductivity of all CSA-doped CPU films had decreased to that of the undoped CPU film. Mouse 3T3 fibroblasts proliferated and spread on all CPU films. This developed biodegradable CPU with good elasticity, electrical stability, and biocompatibility may find potential applications in tissue engineering, smart drug release, and electronics. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2305-2314, 2016.

Superoxide inhibits guanine nucleotide exchange factor (GEF) action on Ras, but not on Rho, through desensitization of Ras to GEF.

Ras and Rho GTPases are molecular switches for various vital cellular signaling pathways. Overactivation of these GTPases often causes development of cancer. Guanine nucleotide exchange factors (GEFs) and oxidants function to upregulate these GTPases through facilitation of guanine nucleotide exchange (GNE) of these GTPases. However, the effect of oxidants on GEF functions, or vice versa, has not been known. We show that, via targeting Ras Cys(51), an oxidant inhibits the catalytic action of Cdc25-the catalytic domain of RasGEFs-on Ras. However, the enhancement of Ras GNE by an oxidant continues regardless of the presence of Cdc25. Limiting RasGEF action by an oxidant may function to prevent the pathophysiological overactivation of Ras in the presence of both RasGEFs and oxidants. The continuous exposure of Ras to nitric oxide and its derivatives can form S-nitrosated Ras (Ras-SNO). This study also shows that an oxidant not only inhibits the catalytic action of Cdc25 on Ras-SNO but also fails to enhance Ras-SNO GNE. This lack of enhancement then populates the biologically inactive Ras-SNO in cells, which may function to prevent the continued redox signaling of the Ras pathophysiological response. Finally, this study also demonstrates that, unlike the case with RasGEFs, an oxidant does not inhibit the catalytic action of RhoGEF-Vav or Dbs-on Rho GTPases such as Rac1, RhoA, RhoC, and Cdc42. This result explains the results of the previous study in which, despite the presence of an oxidant, the catalytic action of Dbs in cells continued to enhance RhoC GNE.