Project Grant R01HL171633

3D PRINTED SOFT AND STRETCHABLE TISSUE-LIKE BIOADHESIVE ELECTRONIC DEVICE ENABLED NEUROMODULATION FOR RESISTANT HYPERTENSION THERAPY - PROJECT SUMMARY THE OBJECTIVE OF THIS PROPOSAL IS TO DEVELOP A SOFT AND STRETCHABLE TISSUE-LIKE BIOADHESIVE ELECTRONIC DEVICE FOR THE TREATMENT OF RESISTANT HYPERTENSION. HYPERTENSION IS A MAJOR BURDEN ON HEALTHCARE SYSTEMS AND AN IMPORTANT CONTRIBUTOR TO GLOBAL MORBIDITY AND MORTALITY. ALTHOUGH A NUMBER OF MEDICINES HAVE BEEN USED FOR THE TREATMENT OF HYPERTENSION, A LARGE PORTION OF PATIENTS (MORE THAN 10 MILLION) ARE RESISTANT TO MEDICATIONS. ELECTRICAL ACTIVATION OF THE CAROTID SINUS BAROREFLEX (CSB) HAS BEEN PROVEN TO A PROMISING STRATEGY TO REDUCE BLOOD PRESSURE (BP) IN DRUG-RESISTANT HYPERTENSION PATIENTS. NEVERTHELESS, EXISTING COMMERCIAL DEVICES FOR CSB ACTIVATION HAVE SIGNIFICANT LIMITATIONS THAT PRECLUDES THEIR PRACTICAL APPLICATIONS. THEY ARE STIFF AND UNABLE TO STRETCH IN RESPONSE TO THE CAROTID WALL'S PERIODIC EXPANSION AND CONTRACTION, WHICH CAUSES TISSUE DAMAGE AND INFLAMMATION. BESIDES, THEY ALSO REQUIRE TO BE SUTURED TO THE CAROTID WALL AND INTRODUCE FURTHER DAMAGE. OVERALL, THESE LIMITATIONS OF EXISTING DEVICES CAUSE SIGNIFICANT PATIENT DISCOMFORT, ILLNESS, AND FAILURE OF DEVICES OVER TIME, WHICH PRECLUDES THEIR WIDE APPLICATION IN HYPERTENSION THERAPY. THE DEVELOPMENT OF A MINIMALLY INVASIVE DEVICE FOR LONG-TERM CSB ACTIVATION THAT DOES NOT CAUSE HARM IS AN URGENT UNMET NEED. OUR GOAL IS TO DEVELOP A NEXT- GENERATION DEVICE FOR DRUG-RESISTANT HYPERTENSION THERAPY THAT CAN ENABLE LONG-TERM EFFICIENT, SAFE, AND MINIMALLY INVASIVE NON-PHARMACOLOGICAL NEUROMODULATION THERAPIES FOR HYPERTENSION. WE ADOPT SOFT, STRETCHABLE, YET RESILIENT HYDROGEL-BASED MATERIALS FOR THE FABRICATION OF THE DEVICES TO MATCH THE MECHANICAL PROPERTIES OF TISSUES AND SIGNIFICANTLY REDUCE TISSUE DAMAGE AND INFLAMMATION. OWING TO ITS INTRINSIC STRETCHABILITY, THE WHOLE DEVICE CAN DEFORM WITH THE CONTRACTION AND EXPANSION OF CAROTID WALLS AND THUS MINIMIZE CONSTRAINT AND DAMAGE TO THE CAROTID. WE WILL ALSO ADOPT A BIOADHESIVE COMPONENT IN THE PROPOSED SYSTEM TO ELIMINATE THE NEED FOR SUTURING OF ELECTRICAL DEVICES ON CAROTID WALLS, THUS SIGNIFICANTLY DECREASING THE INVASIVENESS OF IMPLANTED DEVICES AND INCREASING THE STABILITY OF THE DEVICE-TISSUE INTERFACE. WE PROPOSE THE FOLLOWING SPECIFIC AIMS TO ENSURE SUCCESSFUL COMPLETION OF THE PROJECT. AIM 1) TO DEVELOP STRETCHABLE AND PRINTABLE BIOADHESIVE MATERIALS FOR SUTURE-FREE IN VIVO INCORPORATION AND CHARACTERIZATION. WE WILL FABRICATE 3D-PRINTABLE STRETCHABLE BIOADHESIVE MATERIALS TO ENABLE STABLE LONG-TERM INTERFACING BETWEEN MEDICAL DEVICES AND IN VIVO TISSUE. AIM 2) TO OPTIMIZE SOFT AND STRETCHABLE TISSUE-LIKE BIOELECTRONIC DEVICE DESIGNS FOR OPTIMAL LONG-TERM TISSUE-RESPONSE ON DYNAMIC TISSUE. BY OPTIMIZING DEVICE DESIGNS AND MATERIALS, WE WILL IMPROVE THE LONG-TERM TISSUE RESPONSE OF TISSUE-LIKE BIOELECTRONIC DEVICES IMPLANTED ON THE CAROTID SINUS. AIM 3) TO OPTIMIZE THE ACUTE AND LONG-TERM EFFECTIVENESS OF TISSUE-LIKE BIOELECTRONIC DEVICE FOR ELECTRICAL STIMULATION OF CAROTID SINUS BAROREFLEX (CSB). WE HAVE AN INTERDISCIPLINARY TEAM WITH EXPERTISE IN TISSUE-LIKE BIOELECTRONICS, SOFT MATERIALS, BIOADHESIVES, ADDITIVE MANUFACTURING, RESISTANT-HYPERTENSION, AND CAROTID SINUS BAROREFLEX STIMULATION THERAPY FOR TREATMENT OF HYPERTENSION TO GUARANTEE THE SUCCESS OF THIS PROJECT. THE SUCCESS OF THIS WORK WILL PROVIDE A NOVEL DEVICE FOR MINIMALLY INVASIVE AND LONG-TERM ACTIVATION OF THE CAROTID SINUS BAROREFLEX FOR THE TREATMENT OF RESISTANT HYPERTENSION. THIS DEVICE WILL HAVE AN IMPORTANT POSITIVE IMPACT BECAUSE IT INTRODUCES REDUCED TISSUE INFLAMMATION/DAMAGE AND SIGNIFICANTLY INCREASED STABILITY AND SAFETY, WHICH BENEFITS MILLIONS OF HYPERTENSION PATIENTS. 1