Development of Organic/Inorganic Hybrid Materials for Fully Degradable Reactive Oxygen Species-Releasing Stents for Antirestenosis.

Despite innovative advances in stent technology, restenosis remains a crucial issue for the clinical implantation of stents. Reactive oxygen species (ROS) are known to potentially accelerate re-endothelialization and lower the risk of restenosis by selectively controlling endothelial cells and smooth muscle cells. Recently, several studies have been conducted to develop biodegradable polymeric stents. As biodegradable polymers are not electrically conductive, double metallic layers are required to constitute a galvanic couple for ROS generation. Here, we report a new biodegradable hybrid material composed of a biodegradable polymer substrate and double anodic/cathodic metallic layers for enhancing re-endothelialization and suppressing restenosis. Pure Zn and Mg films (3 µm thick) were deposited onto poly-l-lactic acid (PLLA) substrates by DC magnetron sputtering, and a long-term immersion test using biodegradable hybrid materials was performed in phosphate-buffered solution (PBS) for 2 weeks. The concentrations of superoxide anions and hydrogen peroxide generated by the corrosion of biodegradable metallic films were monitored every 1 or 2 days. Both superoxide anions and hydrogen peroxide were seamlessly generated even after the complete consumption of the anodic Mg layer. It was confirmed that the superoxide anions and hydrogen peroxide were formed not only by the galvanic corrosion between the anode and cathode layers but also by the corrosion of a single Mg or Zn layer. The corrosion products of the Mg and Zn films in PBS were phosphate, oxide, or chloride of the biodegradable metals. Thus, it is concluded that ROS generation by the corrosion of PLLA-based hybrid materials can be sustained until the exhaustion of the cathode metal layer.

Advanced Materials and Devices for Bioresorbable Electronics.

Recent advances in materials chemistry establish the foundations for unusual classes of electronic systems, characterized by their ability to fully or partially dissolve, disintegrate, or otherwise physically or chemically decompose in a controlled fashion after some defined period of stable operation. Such types of "transient" technologies may enable consumer gadgets that minimize waste streams associated with disposal, implantable sensors that disappear harmlessly in the body, and hardware-secure platforms that prevent unwanted recovery of sensitive data. This second area of opportunity, sometimes referred to as bioresorbable electronics, is of particular interest due to its ability to provide diagnostic or therapeutic function in a manner that can enhance or monitor transient biological processes, such as wound healing, while bypassing risks associated with extended device load on the body or with secondary surgical procedures for removal. Early chemistry research established sets of bioresorbable materials for substrates, encapsulation layers, and dielectrics, along with several options in organic and bio-organic semiconductors. The subsequent realization that nanoscale forms of device-grade monocrystalline silicon, such as silicon nanomembranes (m-Si NMs, or Si NMs) undergo hydrolysis in biofluids to yield biocompatible byproducts over biologically relevant time scales advanced the field by providing immediate routes to high performance operation and versatile, sophisticated levels of function. When combined with bioresorbable conductors, dielectrics, substrates, and encapsulation layers, Si NMs provide the basis for a broad, general class of bioresorbable electronics. Other properties of Si, such as its piezoresistivity and photovoltaic properties, allow other types of bioresorbable devices such as solar cells, strain gauges, pH sensors, and photodetectors. The most advanced bioresorbable devices now exist as complete systems with successful demonstrations of clinically relevant modes of operation in animal models. This Account highlights the foundational materials concepts for this area of technology, starting with the dissolution chemistry and reaction kinetics associated with hydrolysis of Si NMs as a function of temperature, pH, and ion and protein concentration. A following discussion focuses on key supporting materials, including a range of dielectrics, metals, and substrates. As comparatively low performance alternatives to Si NMs, bioresorbable organic semiconductors are also presented, where interest derives from their intrinsic flexibility, low-temperature processability, and ease of chemical modification. Representative examples of encapsulation materials and strategies in passive and active control of device lifetime are then discussed, with various device illustrations. A final section outlines bioresorbable electronics for sensing of various biophysical parameters, monitoring electrophysiological activity, and delivering drugs in a programmed manner. Fundamental research in chemistry remains essential to the development of this emerging field, where continued advances will increase the range of possibilities in sensing, actuation, and power harvesting. Materials for encapsulation layers that can delay water-diffusion and dissolution of active electronics in passively or actively triggered modes are particularly important in addressing areas of opportunity in clinical medicine, and in secure systems for envisioned military and industrial uses. The deep scientific content and the broad range of application opportunities suggest that research in transient electronic materials will remain a growing area of interest to the chemistry community.

Biodegradable elastomers and silicon nanomembranes/nanoribbons for stretchable, transient electronics, and biosensors.

Transient electronics represents an emerging class of technology that exploits materials and/or device constructs that are capable of physically disappearing or disintegrating in a controlled manner at programmed rates or times. Inorganic semiconductor nanomaterials such as silicon nanomembranes/nanoribbons provide attractive choices for active elements in transistors, diodes and other essential components of overall systems that dissolve completely by hydrolysis in biofluids or groundwater. We describe here materials, mechanics, and design layouts to achieve this type of technology in stretchable configurations with biodegradable elastomers for substrate/encapsulation layers. Experimental and theoretical results illuminate the mechanical properties under large strain deformation. Circuit characterization of complementary metal-oxide-semiconductor inverters and individual transistors under various levels of applied loads validates the design strategies. Examples of biosensors demonstrate possibilities for stretchable, transient devices in biomedical applications.

CVD-grown monolayer MoS2 in bioabsorbable electronics and biosensors.

Transient electronics represents an emerging technology whose defining feature is an ability to dissolve, disintegrate or otherwise physically disappear in a controlled manner. Envisioned applications include resorbable/degradable biomedical implants, hardware-secure memory devices, and zero-impact environmental sensors. 2D materials may have essential roles in these systems due to their unique mechanical, thermal, electrical, and optical properties. Here, we study the bioabsorption of CVD-grown monolayer MoS2, including long-term cytotoxicity and immunological biocompatibility evaluations in biofluids and tissues of live animal models. The results show that MoS2 undergoes hydrolysis slowly in aqueous solutions without adverse biological effects. We also present a class of MoS2-based bioabsorbable and multi-functional sensor for intracranial monitoring of pressure, temperature, strain, and motion in animal models. Such technology offers specific, clinically relevant roles in diagnostic/therapeutic functions during recovery from traumatic brain injury. Our findings support the broader use of 2D materials in transient electronics and qualitatively expand the design options in other areas.

Flexible Transient Optical Waveguides and Surface-Wave Biosensors Constructed from Monocrystalline Silicon.

Optical technologies offer important capabilities in both biological research and clinical care. Recent interest is in implantable devices that provide intimate optical coupling to biological tissues for a finite time period and then undergo full bioresorption into benign products, thereby serving as temporary implants for diagnosis and/or therapy. The results presented here establish a silicon-based, bioresorbable photonic platform that relies on thin filaments of monocrystalline silicon encapsulated by polymers as flexible, transient optical waveguides for accurate light delivery and sensing at targeted sites in biological systems. Comprehensive studies of the mechanical and optical properties associated with bending and unfurling the waveguides from wafer-scale sources of materials establish general guidelines in fabrication and design. Monitoring biochemical species such as glucose and tracking physiological parameters such as oxygen saturation using near-infrared spectroscopic methods demonstrate modes of utility in biomedicine. These concepts provide versatile capabilities in biomedical diagnosis, therapy, deep-tissue imaging, and surgery, and suggest a broad range of opportunities for silicon photonics in bioresorbable technologies.

Materials for programmed, functional transformation in transient electronic systems.

Materials and device designs are presented for electronic systems that undergo functional transformation by a controlled time sequence in the dissolution of active materials and/or encapsulation layers. Demonstration examples include various biocompatible, multifunctional systems with autonomous behavior defined by materials selection and layout.

Dissolution chemistry and biocompatibility of silicon- and germanium-based semiconductors for transient electronics.

Semiconducting materials are central to the development of high-performance electronics that are capable of dissolving completely when immersed in aqueous solutions, groundwater, or biofluids, for applications in temporary biomedical implants, environmentally degradable sensors, and other systems. The results reported here include comprehensive studies of the dissolution by hydrolysis of polycrystalline silicon, amorphous silicon, silicon-germanium, and germanium in aqueous solutions of various pH values and temperatures. In vitro cellular toxicity evaluations demonstrate the biocompatibility of the materials and end products of dissolution, thereby supporting their potential for use in biodegradable electronics. A fully dissolvable thin-film solar cell illustrates the ability to integrate these semiconductors into functional systems.

Water-soluble thin film transistors and circuits based on amorphous indium-gallium-zinc oxide.

This paper presents device designs, circuit demonstrations, and dissolution kinetics for amorphous indium-gallium-zinc oxide (a-IGZO) thin film transistors (TFTs) comprised completely of water-soluble materials, including SiNx, SiOx, molybdenum, and poly(vinyl alcohol) (PVA). Collections of these types of physically transient a-IGZO TFTs and 5-stage ring oscillators (ROs), constructed with them, show field effect mobilities (∼10 cm2/Vs), on/off ratios (∼2×10(6)), subthreshold slopes (∼220 mV/dec), Ohmic contact properties, and oscillation frequency of 5.67 kHz at supply voltages of 19 V, all comparable to otherwise similar devices constructed in conventional ways with standard, nontransient materials. Studies of dissolution kinetics for a-IGZO films in deionized water, bovine serum, and phosphate buffer saline solution provide data of relevance for the potential use of these materials and this technology in temporary biomedical implants.

Biodegradable materials for multilayer transient printed circuit boards.

Biodegradable printed circuit boards based on water-soluble materials are demonstrated. These systems can dissolve in water within 10 mins to yield end-products that are environmentally safe. These and related approaches have the potential to reduce hazardous waste streams associated with electronics disposal.

25th anniversary article: materials for high-performance biodegradable semiconductor devices.

We review recent progress in a class of silicon-based electronics that is capable of complete, controlled dissolution when immersed in water or bio-fluids. This type of technology, referred to in a broader sense as transient electronics, has potential applications in resorbable biomedical devices, eco-friendly electronics, environmental sensors, secure hardware systems and others. New results reported here include studies of the kinetics of hydrolysis of nanomembranes of single crystalline silicon in bio-fluids and aqueous solutions at various pH levels and temperatures. Evaluations of toxicity using live animal models and test coupons of transient electronic materials provide some evidence of their biocompatibility, thereby suggesting potential for use in bioresorbable electronic implants.

Triggered transience of metastable poly(phthalaldehyde) for transient electronics.

Triggerable transient electronics are demonstrated with the use of a metastable poly(phthalaldehyde) polymer substrate and encapsulant. The rate of degradation is controlled by the concentration of the photo-acid generator and UV irradiance. This work expands on the materials that can be used for transient electronics by demonstrating transience in response to a preselected trigger without the need for solution-based degradation.

Dissolution chemistry and biocompatibility of single-crystalline silicon nanomembranes and associated materials for transient electronics.

Single-crystalline silicon nanomembranes (Si NMs) represent a critically important class of material for high-performance forms of electronics that are capable of complete, controlled dissolution when immersed in water and/or biofluids, sometimes referred to as a type of "transient" electronics. The results reported here include the kinetics of hydrolysis of Si NMs in biofluids and various aqueous solutions through a range of relevant pH values, ionic concentrations and temperatures, and dependence on dopant types and concentrations. In vitro and in vivo investigations of Si NMs and other transient electronic materials demonstrate biocompatibility and bioresorption, thereby suggesting potential for envisioned applications in active, biodegradable electronic implants.