Self-controllable proteinic antibacterial coating with bacteria-triggered antibiotic release for prevention of periprosthetic infection.

Periprosthetic infection is a devastating postimplantation complication in which a biofilm layer harboring invasive microorganisms forms around orthopedic implants, leading to severe implant failure and patient morbidity. Despite the development of several infection-triggered antibiotic release approaches, most current antibacterial coatings are susceptible to undesired antibiotic leakage or mechanical disintegration during prosthesis installation. Herein, we propose a self-controllable proteinic antibacterial coating capable of both long-lasting adherence onto titanium implant substrates over the implant fixation period and instantaneous bacterial eradication. Importantly, the pH-dependent reversible metal coordination of mussel adhesive protein (MAP) enabled bacterial concentration-dependent antibiotic delivery in response to infection-induced acidification. In addition, the MAP coating exhibited superior self-healable adhesive properties and scratch resistance, which enabled to avert issues associated with mechanical damages, including peeling and cracking, often occurring in conventional implant coating systems. The gentamicin-loaded MAP coating exhibited complete inhibition of bacterial growth in vivo against Staphylococcus aureus penetrations during implantation surgery (immediate infection) and even 4 weeks after implantation (delayed infection). Thus, our antibiotic-loaded MAP hydrogel coating can open new avenues for self-defensive antibiotic prophylaxis to achieve instant and sustainable bacteriocidal activity in orthopedic prostheses. © 2017 Elsevier Inc. All rights reserved.

A Perfluoropolyether Microfluidic Device for Cell-Based Drug Screening with Accurate Quantitative Analysis.

Microfluidic drug screening technologies have been extensively explored to evaluate the pharmacology and therapeutic implications of promising chemical compounds in multiplexed physiological microenvironments in vivo. However, conventional poly(dimethylsiloxane) microchips are susceptible to adsorption by hydrophobic molecules on channel surfaces and permeation in the matrix. These can significantly compromise the drug availability and accuracy of dose-dependent quantitative analyses. Here, we prepared a perfluorinated polyether (PFPE) microchip via digital light processing 3D printing as a quantitative drug screening platform for precise concentration-dependent pharmaceutical assays. Cells cultured on PFPE microchips exhibited excellent viability with a spread morphology as well as superior proliferative capability. Importantly, PFPE constructions with a low surface energy significantly prevented the nonspecific molecular adsorption into their surfaces or permeation into the matrix. In particular, the PFPE multibranched channel preserved the concentration of the pharmaceutical drug during the perfusion process and generated a linear concentration gradient, resulting in a dose-dependent chemotherapeutic effect. We suggest that the biocompatible and nonadsorbing PFPE microchannel can provide a cell-based drug screening platform for concentration-dependent quantitative analyses.

Preclinical evaluation of a regenerative immiscible bioglue for vesico-vaginal fistula.

Currently, there are no clinically available tissue adhesives that work effectively in the fluid-rich and highly dynamic environments of the human body, such as the urinary system. This is especially relevant to the management of vesico-vaginal fistula, and developing a high-performance tissue adhesive for this purpose could vastly expand urologists' surgical repertoire and dramatically reduce patient discomfort. Herein, we developed a water-immiscible mussel protein-based bioadhesive (imWIMBA) with significantly improved properties in all clinical respects, allowing it to achieve rapid and strong underwater adhesion with tunable rheological properties. We evaluated in vivo potential of imWIMBA for sealing thermally injured fistula tracts between the bladder and vagina. Importantly, the use of imWIMBA in the presence of prolonged bladder drainage resulted in perfect closure of the vesico-vaginal fistula in operated pigs. Thus, imWIMBA could be successfully used for many surgical applications and improve treatment efficacy when combined with conventional surgical methods. STATEMENT OF SIGNIFICANCE: Vesico-vaginal fistula (VVF) is an abnormal opening between the bladder and the vagina, which is a stigmatized disease in many developing countries. Leakage of urine into internal organs can induce serious complications and delay wound repair. Conventional VVF treatment requires skillful suturing to provide a tension-free and watertight closure. In addition, there is no clinically approved surgical glue that works in wet and highly dynamic environments such as the urinary system. In this work, for potential clinical VVF closure and regeneration, we developed an advanced immiscible mussel protein-based bioglue with fast, strong, wet adhesion and tunable rheological properties. This regenerative immiscible bioglue could be successfully used for sealing fistulas and further diverse surgical applications as an adjuvant for conventional suture methods.

Schizophrenia-associated dysbindin modulates axonal mitochondrial movement in cooperation with p150glued.

Mitochondrial movement in neurons is finely regulated to meet the local demand for energy and calcium buffering. Elaborate transport machinery including motor complexes is required to deliver and localize mitochondria to appropriate positions. Defects in mitochondrial transport are associated with various neurological disorders without a detailed mechanistic information. In this study, we present evidence that dystrobrevin-binding protein 1 (dysbindin), a schizophrenia-associated factor, plays a critical role in axonal mitochondrial movement. We observed that mitochondrial movement was impaired in dysbindin knockout mouse neurons. Reduced mitochondrial motility caused by dysbindin deficiency decreased the density of mitochondria in the distal part of axons. Moreover, the transport and distribution of mitochondria were regulated by the association between dysbindin and p150glued. Furthermore, altered mitochondrial distribution in axons led to disrupted calcium dynamics, showing abnormal calcium influx in presynaptic terminals. These data collectively suggest that dysbindin forms a functional complex with p150glued that regulates axonal mitochondrial transport, thereby affecting presynaptic calcium homeostasis.