Bimodal Nanocomposite Platform with Antibiofilm and Self-Powering Functionalities for Biomedical Applications.

Advances in microelectronics and nanofabrication have led to the development of various implantable biomaterials. However, biofilm-associated infection on medical devices still remains a major hurdle that substantially undermines the clinical applicability and advancement of biomaterial systems. Given their attractive piezoelectric behavior, barium titanate (BTO)-based materials have also been used in biological applications. Despite its versatility, the feasibility of BTO-embedded biomaterials as anti-infectious implantable medical devices in the human body has not been explored yet. Here, the first demonstration of clinically viable BTO-nanocomposites is presented. It demonstrates potent antibiofilm properties against Streptococcus mutans without bactericidal effect while retaining their piezoelectric and mechanical behaviors. This antiadhesive effect led to ∼10-fold reduction in colony-forming units in vitro. To elucidate the underlying mechanism for this effect, data depicting unfavorable interaction energy profiles between BTO-nanocomposites and S. mutans using the classical and extended Derjaguin, Landau, Verwey, and Overbeek theories is presented. Direct cell-to-surface binding force data using atomic force microscopy also corroborate reduced adhesion between BTO-nanocomposites and S. mutans. Interestingly, the poling process on BTO-nanocomposites resulted in asymmetrical surface charge density on each side, which may help tackle two major issues in prosthetics-bacterial contamination and tissue integration. Finally, BTO-nanocomposites exhibit superior biocompatibility toward human gingival fibroblasts and keratinocytes. Overall, BTO-embedded composites exhibit broad-scale potential to be used in biological settings as energy-harvestable antibiofilm surfaces.

Implantable Cisplatin Synthesis Microdevice for Regional Chemotherapy.

Cisplatin, the first platinum chemotherapy agent to obtain Food and Drug Administration (FDA) approval in 1978, is widely used for a number of cancers. However, the painful side effects stemming from systemic delivery are the inevitable limitation of cisplatin. A possible solution is regional chemotherapy using various drug delivery systems, which reduces the systemic toxicity and increases drug accumulation in the tumor. In this paper, a rice-grain sized, ultrasonically powered, and implantable microdevice that can synthesize cisplatin in situ is presented. The microdevice produces 0.7 mg of cisplatin within 1 h under ultrasonic irradiation (400 mW cm-2 ). The effect of the microdevice-synthesized cisplatin is evaluated using in vitro murine breast cancer cells and ex vivo liver tissue. The results suggest that cytotoxic activities of the microdevice-mediated cisplatin delivery are significantly higher in both in vitro and ex vivo experiments. Overall, the proposed cisplatin synthesis microdevice represents a strong alternative treatment option for regional chemotherapy.

A Hydrogel-Based Ultrasonic Backscattering Wireless Biochemical Sensing.

Wireless monitoring of the physio-biochemical information is becoming increasingly important for healthcare. In this work, we present a proof-of-concept hydrogel-based wireless biochemical sensing scheme utilizing ultrasound. The sensing system utilizes silica-nanoparticle embedded hydrogel deposited on a thin glass substrate, which presents two prominent interfaces for ultrasonic backscattering (tissue/glass and hydrogel/glass). To overcome the effect of the varying acoustic properties of the intervening biological tissues between the sensor and the external transducer, we implemented a differential mode of ultrasonic back-scattering. Here, we demonstrate a wireless pH measurement with a resolution of 0.2 pH level change and a wireless sensing range around 10 cm in a water tank.

Hydrogel-Fractal Piezoelectric Bilayer Transducer for Wireless Biochemical Sensing.

This paper reports on a novel transducer for wireless biochemical sensing. The bilayer transducer consists of a fractal piezoelectric membrane and pH-sensitive chemo-mechanical hydrogel, which overcomes many shortcomings in the chemical and biochemical sensing. The fractal design on the piezoelectric membrane enhances frequency response and linearity by employing periodically repeated pore architecture. As a basis of the pore, a Hilbert space-filling curve with modifications is used. On the surface of the fractal piezoelectric membrane, the hydrogel is laminated. When the bilayer transducer is introduced to a pH environment (e.g., pH = 4, 8, and 12), the hydrogel swells (or shrinks) and induces the curling of the bilayer transducer (10.47°/pH). The curvature then exhibits various ultrasound responses when the bilayer transducer was excited. The measured voltage outputs using an ultrasonic receiver were 0.393, 0.341, 0.250 mV/cm2 when curvature angles were 30°, 60°, and 120°, respectively. Overall pH sensitivity was 0.017 mV/cm2/pH. Ultimately, the biochemical sensing principle using a novel bilayer ultrasound transducer suggests a simple, low-cost, battery-less, and long-range wireless readout system as compared to traditional biochemical sensing.

Human Oral Motion-Powered Smart Dental Implant (SDI) for In Situ Ambulatory Photo-biomodulation Therapy.

Peri-implant disease is an inflammatory condition affecting the soft and hard tissues surrounding a dental implant. However, current preventative methods are insufficient due to the limited bioactivity on the dental implant and poor patient compliance. Recently, photo-biomodulation (PBM) therapy that can recover and regenerate peri-implant soft tissue has attracted considerable attention in dentistry. In this paper, a seamless human oral motion-powered dental implant system (called Smart Dental Implant or SDI) is presented as an ambulatory PBM therapy modality. SDI allows the in situ light delivery, which is enabled by the energy harvesting from dynamic human oral motions (chewing and brushing) via an engineered piezoelectric dental crown, an associated circuit, and micro light emitting diodes (LEDs). The SDI also offers adequate mechanical strength as the clinical standards. Using primary human gingival keratinocytes (HGKs) as a model host organism and Pseudomonas aeruginosa lipopolysaccharides (LPS) as a model inflammatory stimulus, effective SDI-mediated PBM therapy is demonstrated. A new class of dental implants could be an ambulatory PBM therapy platform for the prevention of peri-implant disease without patient dependency, warranting long-lasting dental implants.

A Comprehensive Analysis of Near-Contact Photobiomodulation Therapy in the Host-Bacteria Interaction Model Using 3D-Printed Modular LED Platform.

One well-studied bacterial factor recognized by the host immune system is lipopolysaccharides (LPS) that stimulate host cells, resulting in cell inflammation. Although photobiomodulation (PBM) therapy demonstrates its potency on anti-inflammatory activity, the complete mechanism of action in the host-bacteria interaction model is still elusive. In addition, many studies were performed regarding a distance between the light source and biological sample (non-contact therapy) that may result in disparate reports on the efficacy of PBM therapy. Thus, it is critical to clearly understand the effect of this approach to maximize efficacy and minimize side effects. Here, a custom-built light-emitting diode (LED) platform that mimics near-contact therapy is developed. The effect and mechanism of PBM therapy on epithelial cells in response to LPS is systematically investigated under various conditions (wavelength, irradiation-time, pulse-frequency). The data show that the irradiation of near-infrared (NIR-LED) significantly improves the viability of inflamed cells. It reveals that NIR-LED inhibits the production of reactive oxygen species by regulating the Nox4-NF-κB pathway. Interestingly, however, high-pulse frequency stimulus causes the collapse of the mitochondrial membrane potential (ΔΨm) of cells, resulting in cell death. These results suggest that the optimized "PBM condition" is critical to assist the healthy immune system of the host against bacterial invasion.