Silk Fibroin Microneedles for Transdermal Vaccine Delivery.

Microneedles represent an exciting departure from the existing parenteral injection paradigm for drug delivery, particularly for the administration of vaccines. While the benefit of delivering vaccine antigens to immunocompetent tissue in the skin has been established, there have been varying degrees of success using microneedles to do so. Here, we investigate the use of silk fibroin protein to produce microneedles and evaluate their ability to deliver vaccines against influenza, , and .

A cellulosic responsive "living" membrane.

Bacterial cellulose has been demonstrated to be a remarkably versatile biomaterial and widely used in biomedical applications due to its unique physical properties. Here we reported for the first time a "living membrane" system based on recombinant Escherichia coli bacterial strains entrapped in cellulosic membranes produced by Gluconacetobacter xylinus. Biologically driven detection and identification of a range of target molecules presents unique challenges, and requires that detection methods are developed to be rapid, specific and sensitive.

Focal Infection Treatment using Laser-Mediated Heating of Injectable Silk Hydrogels with Gold Nanoparticles.

Medical treatment of subcutaneous bacterial abscesses usually involves systemic high-dose antibiotics and incision-drainage of the wound. Such an approach suffers from two main deficiencies: bacterial resistance to antibiotics and pain associated with multiple incision-drainage-wound packing procedures. Furthermore, the efficacy of high-dose systemic antibiotics is limited because of the inability to penetrate into the abscess.

Antibiotic-Releasing Silk Biomaterials for Infection Prevention and Treatment.

Effective treatment of infections in avascular and necrotic tissues can be challenging due to limited penetration into the target tissue and systemic toxicities. Controlled release polymer implants have the potential to achieve the high local concentrations needed while also minimizing systemic exposure. Silk biomaterials possess unique characteristics for antibiotic delivery including biocompatibility, tunable biodegradation, stabilizing effects, water-based processing and diverse material formats.

Sustained volume retention in vivo with adipocyte and lipoaspirate seeded silk scaffolds.

Current approaches to soft tissue regeneration include the use of fat grafts, natural or synthetic biomaterials as filler materials. Fat grafts and natural biomaterials resorb too quickly to maintain tissue regeneration, while synthetic materials do not degrade or regenerate tissue. Here, we present a simple approach to volume stable filling of soft tissue defects.

In vitro chondrogenesis with lysozyme susceptible bacterial cellulose as a scaffold.

A current focus of tissue engineering is the use of adult human mesenchymal stem cells (hMSCs) as an alternative to autologous chondrocytes for cartilage repair. Several natural and synthetic polymers (including cellulose) have been explored as a biomaterial scaffold for cartilage tissue engineering. While bacterial cellulose (BC) has been used in tissue engineering, its lack of degradability in vivo and high crystallinity restricts widespread applications in the field.

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.

Laminar silk scaffolds for aligned tissue fabrication.

3D-biomaterial scaffolds with aligned architecture are of vital importance in tissue regeneration. A generic method is demonstrated to produce aligned biomaterial scaffolds using the physics of directional ice freezing. Homogeneously aligned 3D silk scaffolds with high porosity and alignment are prepared.

Implantable, multifunctional, bioresorbable optics.

Advances in personalized medicine are symbiotic with the development of novel technologies for biomedical devices. We present an approach that combines enhanced imaging of malignancies, therapeutics, and feedback about therapeutics in a single implantable, biocompatible, and resorbable device. This confluence of form and function is accomplished by capitalizing on the unique properties of silk proteins as a mechanically robust, biocompatible, optically clear biomaterial matrix that can house, stabilize, and retain the function of therapeutic components.

A physically transient form of silicon electronics.

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.

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.

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.

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.

Silk fibroin and polyethylene glycol-based biocompatible tissue adhesives.

Tissue sealants have emerged in recent years as strong candidates for hemostasis. A variety of formulations are currently commercially available and though they satisfy many of the markets' needs there are still key aspects of each that need improvement. Here we present a new class of blends, based on silk fibroin and chemically active polyethylene glycols (PEGs) with strong adhesive properties.

N-acetylglucosamine 6-phosphate deacetylase (nagA) is required for N-acetyl glucosamine assimilation in Gluconacetobacter xylinus.

Metabolic pathways for amino sugars (N-acetylglucosamine; GlcNAc and glucosamine; Gln) are essential and remain largely conserved in all three kingdoms of life, i.e., microbes, plants and animals.

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.

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.

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.

Erratum: "Silicon electronics on silk as a path to bioresorbable, implantable devices" [Appl. Phys. Lett. 95, 133701 (2009)].

[This corrects the article on p. 133701 in vol. 95.

Emulsan-alginate beads for protein adsorption.

Emulsan-alginate beads were prepared and challenged using bovine serum albumin (BSA) to assess adsorption in comparison to alginate beads. BSA binding to the emulsan-alginate beads was improved over the alginate bead controls and protein adsorption was less sensitive to changes in ionic strength. BSA adsorption between pH 8.

Modifications and applications of the Acinetobacter venetianus RAG-1 exopolysaccharide, the emulsan complex and its components.

Since its discovery in the late 1970s, emulsan has been the subject of significant interest for fundamental biosynthesis and structure-function relationships as well as for its potential industrial applications. These studies initially examined the emulsification properties of the compound, while more recent efforts have focused on potential biomedical applications. As a result of this change of focus, it became necessary to more completely characterize the structure of the emulsan molecule and to develop a more reproducible purification process.

Discovery of the dual polysaccharide composition of emulsan and the isolation of the emulsion stabilizing component.

Emulsan has been reported as an emulsion stabilizing amphipathic lipoheteropolysaccharide secreted by the oil-degrading bacterium Acinetobacter venetianus RAG-1. Previously, emulsan was regarded as a single polymer. As a result of developing a new purification process, we have discovered that emulsan is a complex of approximately 80% (w/w) lipopolysaccharide (LPS) and 20% (w/w) high molecular weight exopolysaccharide (EPS).

Emulsan, a tailorable biopolymer for controlled release.

Microsphere hydrogels made with emulsan-alginate were used as carrier for the microencapsulation of blue dextran in order to study the effect of emulsan on the alginate bead stability. Blue dextran release studies indicated an increase of microsphere stability in presence of emulsan, as a coating agent. BSA adsorption by emulsan-alginate microspheres is also enhanced 40% compared to alginate alone.

Controlled release biopolymers for enhancing the immune response.

Controlled release of biologically active compounds in the context of drug and vaccine delivery is an important area of research with broad implications in many areas of medicine. In particular, the challenges of oral delivery are of specific interest to reduce the cost and potential health risks related to parenteral administration of pharmaceuticals and vaccine formulations. We discuss the biological activities of two biopolymers, beta-glucans and emulsans, both of which offer significant potential for individual formulations related to drug impact, while in combination offer synergistic opportunities in terms of formulation and delivery.