Project Grant R44DC022208

REDUCING INFLAMMATION AND IMPROVING ELECTRICAL PERFORMANCE OF COCHLEAR IMPLANTS THROUGH ZWITTERIONIC SURFACE MODIFICATION - PROJECT SUMMARY/ABSTRACT. POLYDIMETHYLSILOXANE (PDMS), COMMONLY KNOWN AS SILICONE, IS THE PREDOMINANT BIOMATERIAL USED IN MEDICAL IMPLANTS DUE TO ITS FLEXIBILITY, BIOCOMPATIBILITY, AND EASE OF MANUFACTURING. DESPITE THESE ADVANTAGES, PDMS ELICITS A SIGNIFICANT FOREIGN BODY RESPONSE (FBR) THAT LEADS TO FIBROTIC ENCAPSULATION OF IMPLANTED DEVICES, THEREBY COMPROMISING THEIR FUNCTIONALITY, SAFETY, AND LONGEVITY. FOR COCHLEAR IMPLANTS (CIS), THIS FIBROTIC TISSUE RESULTS IN INCREASED IMPEDANCE, INFLAMMATION, NON-TARGETED NEURONAL STIMULATION, ELEVATED RISK OF INFECTION, AND DAMAGES TO RESIDUAL ACOUSTIC HEARING. FURTHERMORE, PDMS-BASED IMPLANTS SUCH AS CIS ARE PRONE TO BACTERIAL ADHESION AND BIOFILM FORMATION, CONTRIBUTING TO THE $30 BILLION ANNUAL COST OF DEVICE-ASSOCIATED INFECTIONS IN THE US HEALTHCARE SYSTEM. ZWICOAT MATERIALS INNOVATIONS (ZCMI) PROPOSES A PHASE II SBIR PROJECT TO COMMERCIALIZE ZWIGUARD, AN ULTRA-LOW-FOULING, LUBRICIOUS COATING FOR CIS COMPRISED OF A CROSSLINKED, ZWITTERIONIC POLYMER HYDROGEL NETWORK. THIS "BIOLOGICAL TEFLON" ADDRESSES MULTIPLE CHALLENGES SIMULTANEOUSLY: REDUCING FIBROTIC CAPSULE FORMATION BY 50-70%, DECREASING INSERTION FORCES BY OVER 50%, AND LOWERING IMPEDANCE BY APPROXIMATELY 50%. WHILE ZWITTERIONIC POLYMERS DEMONSTRATE EXCEPTIONAL ANTIFOULING PROPERTIES, THEY HAVE YET TO BE WIDELY INCORPORATED INTO COMMERCIAL MEDICAL DEVICES DUE TO WEAK SUBSTRATE ADHESION, INADEQUATE MECHANICAL DURABILITY, AND MANUFACTURING COMPLEXITY. ZCMI HAS OVERCOME THESE BARRIERS THROUGH OUR SINGLE-STEP, SCALABLE PHOTOGRAFTING PROCESS THAT CREATES COVALENT BONDS BETWEEN ZWITTERIONIC HYDROGELS AND PDMS SURFACES. DURING OUR SUCCESSFUL PHASE I, WE DEMONSTRATED SCALABLE COATING METHODS FOR CIS THAT MAINTAINED 100% SURFACE COVERAGE AFTER RIGOROUS ENVIRONMENTAL STRESSORS INCLUDING BENDING, STERILIZATION, PACKAGING, SURGICAL INSERTION, DESICCATION/REHYDRATION, AND ELECTRICAL STIMULUS. OUR PHASE II WILL ADVANCE ZWIGUARD-COATED CIS THROUGH THREE AIMS: (1) QUALITY-CONTROLLED MANUFACTURING OF ZWIGUARD-COATED CIS VIA SPECIALIZED LED CURING STATIONS, COATING PARAMETER OPTIMIZATION, AND IMPLEMENTATION OF FDA-COMPLIANT QUALITY CONTROL SYSTEMS; (2) OPTIMIZATION OF RINSING, DESICCATION, PACKAGING, AND STERILIZATION PROCESSES THROUGH EXTRACTABLES AND LEACHABLES TESTING, STERILITY ASSURANCE LEVEL VALIDATION, AND ACCELERATED AGING STUDIES; AND (3) LONG-TERM PERFORMANCE VALIDATION AND SAFETY ASSESSMENT THROUGH ACCELERATED AGING TESTS, ELECTRICAL CHARACTERIZATION IN HUMAN CADAVERS, A 3-MONTH SHEEP IMPLANTATION STUDY, AND COMPREHENSIVE BIOCOMPATIBILITY TESTING. THIS PROJECT WILL ESTABLISH MANUFACTURING READINESS AND PRECLINICAL VALIDATION FOR ZWIGUARD-COATED CIS, SETTING THE STAGE FOR SUBSEQUENT HUMAN CLINICAL TRIALS AND REGULATORY APPROVAL. ZWIGUARD ADDRESSES A CRITICAL UNMET NEED IN THE $2.6 BILLION GLOBAL CI MARKET BY ENHANCING DEVICE PERFORMANCE, PRESERVING RESIDUAL HEARING, AND IMPROVING CLINICAL OUTCOMES FOR THE ONE MILLION PEOPLE WORLDWIDE WHO RELY ON CIS FOR HEARING. BEYOND CIS, SUCCESSFUL DEMONSTRATION OF ZWIGUARD HAS MUCH BROADER IMPLICATIONS FOR IMPLANTABLE MEDICAL DEVICES-POTENTIALLY REVOLUTIONIZING THE CURRENT PARADIGM WHEREIN FIBROSIS AND INFECTION ARE VIEWED AS INEVITABLE CONSEQUENCES OF MEDICAL IMPLANTATION.