Photodynamic therapy (PDT) is a promising cancer treatment modality that can selectively target unresectable tumors through optical activation of cytotoxic agents, thus reducing many side effects associated with systemic administration of chemotherapeutic drugs. However, limited light penetration into most biological tissues have so far prevented its widespread adoption beyond dermatology and a few other oncological applications in which a fiber optic can be threaded to the desired locations via an endoscopic approach (e.g., bladder). In this paper, we introduce an ultrasonically powered implantable microlight source, μLight, which enables in-situ localized light delivery to deep-seated solid tumors. Ultrasonic powering allows for small receiver form factor (mm-scale) and power transfer deep into the tissue (several centimeters). The implants consist of piezoelectric transducers measuring 2 × 2 × 2 mm3 and 2 × 4 × 2 mm3 with surface-mounted miniature red and blue LEDs. When energized with 185 mW/cm2 of transmitted acoustic power at 720 kHz, μLight can generate 0.048 to 6.5 mW/cm2 of optical power (depending on size of the piezoelectric element and light wavelength spectrum). This allows powering multiple receivers to a distance of 10 cm at therapeutic light output levels (a delivery of 20–40 J/cm2 light radiation dose in 1–2 hours). In vitro tests show that HeLa cells irradiated with μLights undergo a 70% decrease in average cell viability as compared to the control group. In vivo tests in mice implanted with 4T1-induced tumors (breast cancer) show light delivery capability at therapeutic dose levels. Overall, results indicate implanting multiple µLights and operating them for 1–2 hours can achieve cytotoxicity levels comparable to the clinically reported cases using external light sources.

No abstract

Blast-induced traumatic brain injury (bTBI) has been linked to a multitude of delayed-onset neurodegenerative and neuropsychiatric disorders, but complete understanding of their pathogenesis remains elusive. To develop mechanistic relationships between bTBI and post-blast neurological sequelae, it is imperative to characterize the initiating traumatic mechanical events leading to eventual alterations of cell, tissue, and organ structure and function. This paper presents a wireless sensing system capable of monitoring the intracranial brain deformation in real-time during the event of a bTBI. The system consists of an implantable soft magnet and an external head-mounted magnetic sensor that is able to measure the field in three dimensions. The change in the relative position of the soft magnet WITH respect to the external sensor as the result of the blast wave induces changes in the magnetic field. The magnetic field data in turn is used to extract the temporal and spatial motion of the brain under the blast wave in real-time. The system has temporal and spatial resolutions of 5 μs and 10 μm. Following the characterization and validation of the sensor system, we measured brain deformations in a live rodent during a bTBI.

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.

Transient implantable medical devices based on biodegradable electronics can be used for diagnostic and therapeutic purposes for a desired duration and undergo biodegradation, unlike their conventional counterparts. However, powering transient implants through biodegradable power sources remains underexplored. Here, we report biodegradable piezoelectric transducer fabricated using 0-3 composite film made of barium titanate nanoparticles and poly (L-lactic-co-glycolic) acid polymer (BT-PLGA). The proposed BT-PLGA can be utilized in two different powering schemes; ultrasonic powering and energy harvesting from low frequency acoustic waves. We demonstrated that the power density of the BT-PLGA transducer can reach up to 10 mW/cm 2 in ultrasonic powering. The energy harvesting from low frequency acoustic waves could also readily generate sufficient power for small electronics. The fabricated transducers underwent complete biodegradation in physiological conditions within 100 days. The development of the biodegradable piezoelectric transducer potentially provides a reliable power source for transient implants, especially for deeply seated bioelectronics. The output performance, biocompatibility, and tunable biodegradation of BT-PLGA transducer demonstrate its potential as a biodegradable power source for transient implantable devices.INDEX TERMS Biodegradable materials, implants, piezoelectric transducers, wireless power transmission.

electrolytic ablation (eA) is a promising nonthermal tumor ablation technique that destroys malignant cells through induction of a locoregional pH change. eA is typically performed by inserting needle electrodes inside the tumor followed by application of direct current (Dc), thus inducing electrolysis and creating localized pH changes around the electrodes. in this paper, we report an ultrasonically powered implantable eA microprobe that may increase the clinical relevance of eA by allowing wireless control over device operation (capability to remotely turn the device on and off) and providing flexibility in treatment options (easier to administer fractionated doses over a longer period). the wireless eA microprobe consists of a millimeter-sized piezoelectric ultrasonic receiver, a rectifier circuit, and a pair of platinum electrodes (overall size is 9 × 3 × 2 mm 3). once implanted through a minimally invasive procedure, the microprobe can stay within a solid tumor and be repeatedly used as needed. Ultrasonic power allows for efficient power delivery to mm-scale devices implanted deep within soft tissues of the body. The microprobe is capable of producing a direct current of 90 µA at a voltage of 5 V across the electrodes under low-intensity ultrasound (~200 mW/cm 2). the Dc power creates acidic (pH < 2) and alkaline (pH > 12.9) regions around the anode and the cathode, respectively. The pH change, measured using tissue-mimicking agarose gel, extends to 0.8 cm 3 in volume within an hour at an expansion rate of 0.5 mm 3 /min. The microprobe-mediated EA ablative capability is demonstrated in vitro in cancer cells and ex vivo in mouse liver.

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

No abstract