Design of electrocuring adhesives for medical implants

• Main Author: Manisha Singh
• Other Authors: Terry W.J. Steele
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2021
• Subjects: Engineering::Materials::Biomaterials
• Online Access: https://hdl.handle.net/10356/146405
• Institution: Nanyang Technological University

Soft tissue fixation of implants relies on mechanical means (e.g., sutures, staples, and screws), with associated complications of tissue perforation, scarring, and interfacial stress concentrations. Implant fixation with tissue adhesives may reduce host tissue damage and provide stress distribution, but current bioadhesive designs are toxic, do not support minimally invasive deployment, and their activation techniques prevent tunable mechanical modulus. On-demand, voltage-activated tissue adhesives (i.e., PAMAM-g-diazirine aka Voltaglue) offer a new strategy for implant fixation over underlying tissues, but their activation is currently limited to large, stiff electrodes that restrict minimally invasive transcatheter delivery and spatial activation. Herein, principles of solid-state bipolar electrochemistry are adopted in order to design electrodes that allow for homogenous and spatial activation of Voltaglue over flexible substrates. Two different electrode architectures are proposed for spatiotemporal activation of Voltaglue – (i) interdigitated anode/cathode and (ii) contiguous anode/cathode configuration. Electrorheometry and adhesion structure-activity relationships are explored with respect to electric voltage and current on synthesized electrodes. The voltage-activated bioadhesives when activated using interdigitated configuration are found to have gelation times of 60 s or less with maximum shear storage modulus (G′) of 3 kPa. Shear modulus mimics reported values for human soft tissues (0.1–10 kPa). It is found that Voltaglue activation is dependent on the gap thickness of interdigitated electrodes and decaying electrical field, all of which can change the mechanical properties of the bioadhesive unpredictably. Therefore, a continuous electrode is hypothesized to overcome these limitations by providing a potential gradient for enhanced distribution and strength of the bounded electric field. As a result, electrocuring migration is observed when direct current (DC) is applied, where curing commences near the cathode and progresses toward the anode. A spatiotemporal activation is achieved with a tunable lap shear adhesion of 20−65 kPa. It is found that direct currents are linearly correlated to the migration rates of electrocuring, but this is limited by high voltages exceeding 100 V with instances of incomplete curing of voltage-activated adhesives on contiguous electrodes. Alternative electrocuring strategies based on alternating current (AC), electrolyte ionic radius, and temperature are next evaluated herein. Square-waveform AC electric field is hypothesized to initiate a two-sided curing progression of Voltaglue, where initiation occurs at the cathode terminal. Numerous improvements in electrocuring are observed with AC stimulation vs direct current, including a 35% decrease in maximum voltage, 180% improvement in kinetic rates, and a 100% increase in lap-shear adhesion at 2 mA. Li+ ion electrolytes and curing at 4 °C shifts curing kinetics by +104% and −22% respectively, with respect to the control ion (Na+ ion at 24 °C), suggesting that electrolyte migration is the rate-limiting step. Li+ ion electrolytes and curing at 50 °C improve storage modulus by 110% and 470%, respectively. Further evaluations of electrocured matrices with 19F NMR, solid-state NMR, and infrared spectroscopy provide insights into the probable cross-linking mechanisms. Finally, to facilitate the clinical translation of voltage-activated adhesives, a device involving an electroceutical patch paired with a minimally invasive catheter with retractable electrodes is designed and tested against the repair of ex vivo lumen defects.