Bruce Panilaitis

Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics

Electronics that are capable of intimate, non-invasive integration with the soft, curvilinear surfaces of biological tissues offer important opportunities for diagnosing and treating disease and for improving brain/machine interfaces. This article describes a material strategy for a type of bio-interfaced system that relies on ultrathin electronics supported by bioresorbable substrates of silk fibroin. Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface. Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies. In vivo, neural mapping experiments on feline animal models illustrate one mode of use for this class of technology. These concepts provide new capabilities for implantable and surgical devices.

A Physically Transient Form of Silicon Electronics

Reversible Implants Silicon electronics are generally designed to be stable and robust—it would be counterproductive if the key parts of your computer or cell phone slowly dissolved away while you were using it. In order to develop transient electronics for use as medical implants, Hwang et al. (p. 1640, see the cover) produced a complete set of tools and materials that would be needed to make standard devices. Devices were designed to have a specific lifetime, after which the component materials, such as porous silicon and silk, would be resorbed by the body. A platform of materials and fabrication methods furnishes resorbable electronic devices for in vivo use. A remarkable feature of modern silicon electronics is its ability to remain physically invariant, almost indefinitely for practical purposes. Although this characteristic is a hallmark of applications of integrated circuits that exist today, there might be opportunities for systems that offer the opposite behavior, such as implantable devices that function for medically useful time frames but then completely disappear via resorption by the body. We report a set of materials, manufacturing schemes, device components, and theoretical design tools for a silicon-based complementary metal oxide semiconductor (CMOS) technology that has this type of transient behavior, together with integrated sensors, actuators, power supply systems, and wireless control strategies. An implantable transient device that acts as a programmable nonantibiotic bacteriocide provides a system-level example.

Macrophage responses to silk.

Silk fibers have potential biomedical applications beyond their traditional use as sutures. The physical properties of silk fibers and films make it a promising candidate for tissue engineering scaffold applications, particularly where high mechanical loads or tensile forces are applied or in cases where low rates of degradation are desirable. A critical issue for biomaterial scaffolds is biocompatibility. The direct inflammatory potential of intact silk fibers as well as extracts was studied in an in vitro system. The results indicate that silk fibers are largely immunologically inert in short- and long-term culture with RAW 264.7 murine macrophage cells while insoluble fibroin particles induced significant TNF release. Soluble sericin proteins extracted from native silk fibers did not induce significant macrophage activation. While sericin did not activate macrophages by itself, it demonstrated a synergistic effect with bacterial lipopolysaccharide. The low level of inflammatory potential of silk fibers makes them promising candidates in future biomedical applications.

Waterproof AlInGaP optoelectronics on stretchable substrates with applications in biomedicine and robotics

Inorganic light-emitting diodes and photodetectors represent important, established technologies for solid-state lighting, digital imaging and many other applications. Eliminating mechanical and geometrical design constraints imposed by the supporting semiconductor wafers can enable alternative uses in areas such as biomedicine and robotics. Here we describe systems that consist of arrays of interconnected, ultrathin inorganic light-emitting diodes and photodetectors configured in mechanically optimized layouts on unusual substrates. Light-emitting sutures, implantable sheets and illuminated plasmonic crystals that are compatible with complete immersion in biofluids illustrate the suitability of these technologies for use in biomedicine. Waterproof optical-proximity-sensor tapes capable of conformal integration on curved surfaces of gloves and thin, refractive-index monitors wrapped on tubing for intravenous delivery systems demonstrate possibilities in robotics and clinical medicine. These and related systems may create important, unconventional opportunities for optoelectronic devices.

High-strength silk protein scaffolds for bone repair

Biomaterials for bone tissue regeneration represent a major focus of orthopedic research. However, only a handful of polymeric biomaterials are utilized today because of their failure to address critical issues like compressive strength for load-bearing bone grafts. In this study development of a high compressive strength (~13 MPa hydrated state) polymeric bone composite materials is reported, based on silk protein-protein interfacial bonding. Micron-sized silk fibers (10–600 µm) obtained utilizing alkali hydrolysis were used as reinforcement in a compact fiber composite with tunable compressive strength, surface roughness, and porosity based on the fiber length included. A combination of surface roughness, porosity, and scaffold stiffness favored human bone marrow-derived mesenchymal stem cell differentiation toward bone-like tissue in vitro based on biochemical and gene expression for bone markers. Further, minimal in vivo immunomodulatory responses suggested compatibility of the fabricated silk-fiber-reinforced composite matrices for bone engineering applications.

Silicon electronics on silk as a path to bioresorbable, implantable devices

Many existing and envisioned classes of implantable biomedical devices require high performance electronicssensors. An approach that avoids some of the longer term challenges in biocompatibility involves a construction in which some parts or all of the system resorbs in the body over time. This paper describes strategies for integrating single crystalline silicon electronics, where the silicon is in the form of nanomembranes, onto water soluble and biocompatible silk substrates. Electrical, bending, water dissolution, and animal toxicity studies suggest that this approach might provide many opportunities for future biomedical devices and clinical applications.

Functionalized Silk Biomaterials for Wound Healing

Silk protein-biomaterial wound dressings with epidermal growth factor (EGF) and silver sulfadiazine were studied with a cutaneous excisional mouse wound model. Three different material designs and two different drug incorporation techniques were studied to compare wound healing responses. Material formats included silk films, lamellar porous silk films and electrospun silk nanofibers, each studied with the silk matrix alone and with drug loading or drug coatings on the silk matrices. Changes in wound size and histological assessments of wound tissues showed that the functionalized silk biomaterial wound dressings increased wound healing rate, including reepithelialization, dermis proliferation, collagen synthesis and reduced scar formation, when compared to air-permeable Tegaderm tape (3M) (- control) and a commercial wound dressing, Tegaderm Hydrocolloid dressing (3M) (+ control). All silk biomaterials were effective for wound healing, while the lamellar porous films and electrospun nanofibers and the incorporation of EGF/silver sulfadiazine, via drug loading or coating, provided the most rapid wound healing responses. This systematic approach to evaluating functionalized silk biomaterial wound dressings demonstrates a useful strategy to select formulations for further study towards new treatment options for chronic wounds.

Stabilization of vaccines and antibiotics in silk and eliminating the cold chain

Sensitive biological compounds, such as vaccines and antibiotics, traditionally require a time-dependent “cold chain” to maximize therapeutic activity. This flawed process results in billions of dollars worth of viable drug loss during shipping and storage, and severely limits distribution to developing nations with limited infrastructure. To address these major limitations, we demonstrate self-standing silk protein biomaterial matrices capable of stabilizing labile vaccines and antibiotics, even at temperatures up to 60 °C over more than 6 months. Initial insight into the mechanistic basis for these findings is provided. Importantly, these findings suggest a transformative approach to the cold chain to revolutionize the way many labile therapeutic drugs are stored and utilized throughout the world.

Thin, Flexible Sensors and Actuators as ‘Instrumented’ Surgical Sutures for Targeted Wound Monitoring and Therapy

Sutures are among the simplest and most widely used devices in clinical medicine. All existing synthetic and natural forms use thread-like geometries, as purely passive, mechanical structures that are fl exible and resilient to tensile stress. Several recent reports describe strategies to incorporate advanced functionality into this platform through the employment of shape-memory polymers that offer mechanical actuation or through the release of bioresorbable compounds that carry growth factors and antibiotics to accelerate healing. [ 1–3 ]

Materials and designs for wirelessly powered implantable light-emitting systems

Strategies are presented to achieve bendable and stretchable systems of microscale inorganic light-emitting diodes with wireless powering schemes, suitable for use in implantable devices. The results include materials strategies, together with studies of the mechanical, electronic, thermal and radio frequency behaviors both in vitro and in in-vivo animal experiments.