Implantable, Degradable, Therapeutic Terahertz Metamaterial Devices.

Metamaterial (MM) sensors and devices, usually consisting of artificially structured composite materials with engineered responses that are mainly determined by the unit structure rather than the bulk properties or composition, offer new functionalities not readily available in nature. A set of implantable and resorbable therapeutic MM devices at terahertz (THz) frequencies are designed and fabricated by patterning magnesium split ring resonators on drug-loaded silk protein substrates with controllable device degradation and drug release rates. To demonstrate proof-of-concept, a set of silk-based, antibiotics-loaded MM devices, which can serve as degradable antibacterial skin patches with capabilities to monitor drug-release in real time are fabricated. The extent of drug release, which correlates with the degradation of the MM skin patch, can be monitored by analyzing the resonant responses in reflection during degradation using a portable THz camera. Animal experiments are performed to demonstrate the in vivo degradation process and the efficacy of the devices for antibacterial treatment. Thus, the implantable and resorbable therapeutic MM devices do not need to be retrieved once implanted, providing an appealing alternative for in-vivo sensing and in situ treatment applications.

In Situ Regulation of Macrophage Polarization to Enhance Osseointegration Under Diabetic Conditions Using Injectable Silk/Sitagliptin Gel Scaffolds.

As a chronic inflammatory disease, diabetes mellitus creates a proinflammatory microenvironment around implants, resulting in a high rate of implant loosening or failure in osteological therapies. In this study, macroporous silk gel scaffolds are injected at the bone-implant interface for in situ release of sitagliptin that can regulate macrophage response to create a prohealing microenvironment in diabetes mellitus disease. Notably, it is discovered that sitagliptin induces macrophage polarization to the M2 phenotype and alleviates the impaired behaviors of osteoblasts on titanium (Ti) implants under diabetic conditions in a dose-dependent manner. The silk gel scaffolds loaded with sitagliptin elicite a stronger recruitment of M2 macrophages to the sites of Ti implants and a significant promotion of osteointegration, as compared to oral sitagliptin administration. The results suggest that injectable silk/sitagliptin gel scaffolds can be utilized to modulate the immune responses at the bone-implant interface, thus enhancing bone regeneration required for successful implantation of orthopedic and dental devices in diabetic patients.

PDMS-Parylene Hybrid, Flexible Micro-ECoG Electrode Array for Spatiotemporal Mapping of Epileptic Electrophysiological Activity from Multicortical Brain Regions.

Epilepsy detection and focus location are urgent issues that need to be solved in epilepsy research. A cortex conformable and fine spatial accuracy electrocorticogram (ECoG) sensor array, especially for real-time detection of multicortical functional regions and delineating epileptic focus remains a challenge. Here, we fabricated a polydimethylsiloxane (PDMS)-parylene hybrid, flexible micro-ECoG electrode array. The multiwalled carbon nanotubes (MWCNTs)/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) nanocomposite-modified electrode interface significantly improved the sensing performance with low impedance (20.68 ± 6.65 kΩ), stable phase offset, and high sensitivity. The electrophysiological activities of multicortical brain regions (somatosensory cortex, parietal association cortex, and visual cortex) were simultaneously monitored during normal and epileptic statuses. The epileptic ECoG activities spread spatiotemporally from the starting point toward the adjacent cortex. Significant variations of the waveform, power, and frequency band were observed. The ECoG potential (123 ± 23 µV) at normal status was prominently up to 417 ± 87 µV at the spike wave stage. Besides, the power for epileptic activity (11.049 ± 4.513 µW) was 10 times higher than that (1.092 ± 0.369 µW) for normal activity. In addition, the theta frequency band was found to be a characteristic frequency band of epileptic signals. These joint analysis results of multicortical regions indicated that the active micron-scale region on the parietal association cortex was more likely to be the epileptogenic focus. Cortical mapping with high spatial detail provides the accurate delineation of lesions. The flexible micro-ECoG electrode array is a powerful tool for constructing a spatiotemporal map of the cortex. It provides a technical platform for epileptic focus location, biomedical diagnosis, and brain-computer interaction.

"Self-Matched" Tribo/Piezoelectric Nanogenerators Using Vapor-Induced Phase-Separated Poly(vinylidene fluoride) and Recombinant Spider Silk.

Flexible biocompatible mechanical energy harvesters are drawing increasing interest because of their high energy-harvesting efficiency for powering wearable/implantable devices. Here, a type of "self-matched" tribo-piezoelectric nanogenerators composed of genetically engineered recombinant spider silk protein and piezoelectric poly(vinylidene fluoride) (PVDF)-decorated poly(ethylene terephthalate) (PET) layers is reported. The PET layer serves as a shared structure and electrification layer for both piezoelectric and triboelectric nanogenerators. Importantly, the PVDF generates a strong piezo-potential that modifies the surface potential of the PET layer to match the electron-transfer direction of the spider silk during triboelectrification. A "vapor-induced phase-separation" process is developed to enhance the piezoelectric performance in a facile and "green" roll-to-roll manufacturing fashion. The devices show exceptional output performance and energy transformation efficiency among currently existing energy harvesters of similar sizes and exhibit the potential for large-scale fabrication and various implantable/wearable applications.

A rewritable optical storage medium of silk proteins using near-field nano-optics.

Nanoscale lithography and information storage in biocompatible materials offer possibilities for applications such as bioelectronics and degradable electronics for which traditional semiconductor fabrication techniques cannot be used. Silk fibroin, a natural protein renowned for its strength and biocompatibility, has been widely studied in this context. Here, we present the use of silk film as a biofunctional medium for nanolithography and data storage. Using tip-enhanced near-field infrared nanolithography, we demonstrate versatile manipulation and characterize the topography and conformation of the silk in situ. In particular, we fabricate greyscale and dual-tone nanopatterns with full-width at half-maximum resolutions of ~35 nm, creating an erasable 'silk drive' that digital data can be written to or read from. As an optical storage medium, the silk drive can store digital and biological information with a capacity of ~64 GB inch-2 and exhibits long-term stability under various harsh conditions. As a proof-of-principle demonstration, we show that this silk drive can be biofunctionalized to exhibit chromogenic reactions, resistance to bacterial infection and heat-triggered, enzyme-assisted decomposition.

Skin-Friendly Electronics for Acquiring Human Physiological Signatures.

Epidermal sensing devices offer great potential for real-time health and fitness monitoring via continuous characterization of the skin for vital morphological, physiological, and metabolic parameters. However, peeling them off can be difficult and sometimes painful especially when these skin-mounted devices are applied on sensitive or wounded regions of skin due to their strong adhesion. A set of biocompatible and water-decomposable "skin-friendly" epidermal electronic devices fabricated on flexible, stretchable, and degradable protein-based substrates are reported. Strong adhesion and easy detachment are achieved concurrently through an environmentally benign, plasticized protein platform offering engineered mechanical properties and water-triggered, on-demand decomposition lifetime (transiency). Human experiments show that multidimensional physiological signals can be measured using these innovative epidermal devices consisting of electro- and biochemical sensing modules and analyzed for important physiological signatures using an artificial neural network. The advances provide unique, versatile capabilities and broader applications for user- and environmentally friendly epidermal devices.

"Genetically Engineered" Biofunctional Triboelectric Nanogenerators Using Recombinant Spider Silk.

Self-powered electronics using triboelectric nanogenerators (TENGs) is drawing increasing efforts and rapid advancements in eco/biocompatible energy harvesting, intelligent sensing, and biomedical applications. Currently, the triboelectric performances are mainly determined by the pair materials' inherent electron affinity difference, and merely tuned by chemical or physical methods, which significantly limit the optional variety and output capability, especially for natural-biomaterial-based TENGs. Herein, a biocompatible triboelectric material with a programmable triboelectric property, multiple functionalization, large-scale-fabrication capability, and transcendent output performance is designed, by genetically engineering recombinant spider silk proteins (RSSP). Featuring totally "green" large-scale manufacturing, the water lithography technique is introduced to the RSSP-TENG with facilely adjustable surface morphology, chemically modifiable surface properties, and controllable protein conformation. By virtue of the high electrical power, a proof-of-principle drug-free RSSP-patch is built, showing outstanding antibacterial performances both in vitro and in vivo. This work provides a novel high-performance biomaterial-based TENG and extends its potential for multifunctional applications.

The Use of Functionalized Silk Fibroin Films as a Platform for Optical Diffraction-Based Sensing Applications.

A set of biocompatible, biodegradable, and biofunctionalizable diffractive optical elements (DOEs) using silk proteins as the building materials is reported. The diffraction pattern of a DOE is highly sensitive to the surrounding environment and the structural integrity, offering numerous opportunities for biosensing applications.