Approaches to Treat Sensorineural Hearing Loss by Hair-Cell Regeneration: The Current State of Therapeutic Developments and Their Potential Impact on Audiological Clinical Practice.

Sensorineural hearing loss (SNHL) is typically a permanent and often progressive condition that is commonly attributed to sensory cell loss. All vertebrates except mammals can regenerate lost sensory cells. Thus, SNHL is currently only treated with hearing aids or cochlear implants.

Improved Speech Intelligibility in Subjects With Stable Sensorineural Hearing Loss Following Intratympanic Dosing of FX-322 in a Phase 1b Study.

Objectives: There are no approved pharmacologic therapies for chronic sensorineural hearing loss (SNHL). The combination of CHIR99021+valproic acid (CV, FX-322) has been shown to regenerate mammalian cochlear hair cells ex vivo. The objectives were to characterize the cochlear pharmacokinetic profile of CV in guinea pigs, then measure FX-322 in human perilymph samples, and finally assess safety and audiometric effects of FX-322 in humans with chronic SNHL.

The Yale Center for Biomedical Innovation and Technology (CBIT): One Model to Accelerate Impact From Academic Health Care Innovation.

The process of translating academic biomedical advances into clinical care improvements is difficult, risky, expensive, and poorly understood. Notably, many clinicians who identify health care problems do not have the time or expertise to solve the problems, and many academic researchers are unaware of important gaps in clinical care to which their expertise may apply.Recognizing an opportunity to connect people who can identify health care problems with those who can solve them, the Yale Center for Biomedical Innovation and Technology (CBIT) was established in 2014 to educate and enhance the impact of health care innovators.

Anti-infection trauma devices with drug release and nonfouling surface modification.

Objectives: By coupling an antimicrobial release with a highly nonfouling betaine modification on titanium, this approach innovatively addresses the initial bacterial challenge and the longer term biofilm formation on trauma devices.

Methods: Titanium substrates were modified to obtain a polymer reservoir for chlorhexidine (CHX) and a polybetaine surface layer. The surface was characterized by infrared spectroscopy, scanning electron microscopy, laser confocal scanning microscopy, and a radiolabeled fibrinogen assay.

Polybetaine modification of PDMS microfluidic devices to resist thrombus formation in whole blood.

Assembled polydimethylsiloxane microfluidic devices were modified with a sulfobetaine polymer through continuous "tip-to-tip" modification, significantly reducing blood clotting and extending device patency under blood flow. This technology can be designed to enable the development of devices that can continuously work in whole blood, especially in an extracorporeal or in vivo environment.

Rapid, nondestructive estimation of surface polymer layer thickness using attenuated total reflection fourier transform infrared (ATR FT-IR) spectroscopy and synthetic spectra derived from optical principles.

We have developed a rapid, nondestructive analytical method that estimates the thickness of a surface polymer layer with high precision but unknown accuracy using a single attenuated total reflection Fourier transform infrared (ATR FT-IR) measurement. Because the method is rapid, nondestructive, and requires no sample preparation, it is ideal as a process analytical technique. Prior to implementation, the ATR FT-IR spectrum of the substrate layer pure component and the ATR FT-IR and real refractive index spectra of the surface layer pure component must be known.

Vascular catheters with a nonleaching poly-sulfobetaine surface modification reduce thrombus formation and microbial attachment.

Adherence of proteins, cells, and microorganisms to the surface of venous catheters contributes to catheter occlusion, venous thrombosis, thrombotic embolism, and infections. These complications lengthen hospital stays and increase patient morbidity and mortality. Current technologies for inhibiting these complications are limited in duration of efficacy and may induce adverse side effects.

Controlling the release of peptide antimicrobial agents from surfaces.

Medical conditions are often exacerbated by the onset of infection caused by hospital dwelling bacteria such as Staphylococcus aureus. Antibiotics taken orally or intravenously can require large and frequent doses, further contributing to the sharp rise in resistant bacteria observed over the past several decades. These existing antibiotics are also often ineffective in preventing biofilm formation, a common cause of medical device failure.

Optimization of protein fusion partner length for maximizing in vitro translation of peptides.

Using protein fusion partners for in vitro translation may increase solubility, assist in purification, or allow detection of small proteins and peptides. Here we show that the molar yield of peptide in a batch reaction may be maximized by optimizing the length of the translated product, which is composed of the fusion partner plus the peptide. Using truncated versions of GFP as a series of fusion partners, the molar yield increased approximately 3-fold as the length of the translated product was reduced from 250 to 100 amino acids.

A linguistic model for the rational design of antimicrobial peptides.

Antimicrobial peptides (AmPs) are small proteins that are used by the innate immune system to combat bacterial infection in multicellular eukaryotes. There is mounting evidence that these peptides are less susceptible to bacterial resistance than traditional antibiotics and could form the basis for a new class of therapeutic agents. Here we report the rational design of new AmPs that show limited homology to naturally occurring proteins but have strong bacteriostatic activity against several species of bacteria, including Staphylococcus aureus and Bacillus anthracis.