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The aim of this study was to develop biocompatible, biodegradable dental implant coatings capable of withstanding the mechanical stresses imparted during implant placement. Two techniques were developed to deposit uniform silk fibroin protein coatings onto dental implants. Two novel coating techniques were implemented to coat titanium shims, studs, and implants. One technique involved electrodeposition of the silk directly onto the titanium substrates. The second technique consisted of melting electrogels and dispensing the melted gels onto the titanium to form the coatings. Both techniques were tested for coating reproducibility using a stylus profilometer and a dial thickness gauge. The mechanical strength of adhered titanium studs was assessed using a universal mechanical testing machine. Uniform, controllable coatings were obtained from both the electrodeposition and melted electrogel coating techniques, tunable from 35 to 1654 µm thick under the conditions studied, and able to withstand delamination during implantation into implant socket mimics. Mechanical testing revealed that the adhesive strength of electrogel coatings, 0.369 ± 0.09 MPa, rivaled other biologically derived coating systems such as collagen, hydroxyapatite, and chitosan (0.07–4.83 MPa). These novel silk-based techniques offer a unique approach to the deposition of safe, simple, mechanically robust, biocompatible, and degradable implant coatings. [ABSTRACT FROM AUTHOR]

Many chronic neuroscience studies require neural probes that can reliably record with a large number of electrodes in a densely configured array. Previous works have shown that adverse tissue reaction can be significantly reduced as probe shanks are scaled down toward subcellular dimensions. In addition, flexible probes can mitigate shear stress-induced tissue damage due to micromotion. However, both size reduction and flexibility compromise probe's ability to penetrate the pia mater, especially when many electrodes are distributed across multiple probe shanks. In this paper, we present a method to lithographically pattern a biodegradable silk coating that provides temporary mechanical stiffness for the surgical insertion of flexible probes without any conventional design constraints on the probe size, shape, or material. After insertion, the silk is completely dissolved in the tissue, only leaving the flexible minimum-geometry probes inside the brain. We validated the design by successfully inserting silk-backed 64-channel parylene probes into the motor cortex of Long-Evans rats (n = 6) and recorded in vivo neural activity for six weeks. [ABSTRACT FROM AUTHOR]

The goal of this study was to determine the impact of silk biomaterial structure (e.g. solution, hydrogel, film) on proteolytic susceptibility. In vitro enzymatic degradation of silk fibroin hydrogels and films was studied using a variety of proteases, including proteinase K, protease XIV, α-chymotrypsin, collagenase, matrix metalloproteinase-1 (MMP-1) and MMP-2. Hydrogels were used to assess bulk degradation while films were used to assess surface degradation. Weight loss, secondary structure determined by Fourier transform infrared spectroscopy and degradation products analyzed via sodium dodecyl sulfate–polyacrylamide gel electrophoresis were used to evaluate degradation over 5 days. Silk films were significantly degraded by proteinase K, while silk hydrogels were degraded more extensively by protease XIV and proteinase K. Collagenase preferentially degraded the β-sheet content in hydrogels while protease XIV and α-chymotrypsin degraded the amorphous structures. MMP-1 and MMP-2 degraded silk fibroin in solution, resulting in a decrease in peptide fragment sizes over time. The link between primary sequence mapping with protease susceptibility provides insight into the role of secondary structure in impacting proteolytic access by comparing solution vs. solid state proteolytic susceptibility. [ABSTRACT FROM AUTHOR]

Abstract: Silk fibroin (SF) is a biopolymer with distinguishing features from many other bio- as well as synthetic polymers. From a biomechanical and drug delivery perspective, SF combines remarkable versatility for scaffolding (solid implants, hydrogels, threads, solutions), with advanced mechanical properties and good stabilization and controlled delivery of entrapped protein and small molecule drugs, respectively. It is this combination of mechanical and pharmaceutical features which renders SF so exciting for biomedical applications. This pattern along with the versatility of this biopolymer has been translated into progress for musculoskeletal applications. We review the use and potential of silk fibroin for systemic and localized delivery of therapeutics in diseases affecting the musculoskeletal system. We also present future directions for this biopolymer as well as the necessary research and development steps for their achievement. [Copyright &y& Elsevier]

Abstract: In recent studies silk fibroin has been explored as a new material platform for biosensors. Based on these developments, a procedure for the immobilization of antibodies on silk fibroin substrates was developed as a route to functionalizing these biosensor systems. By controlling the conformational transition of the silk fibroin, a primary antibody was immobilized and enriched at the surface of silk fibroin substrates under mild reaction conditions to maintain antibody function. Compared to chemical crosslinking, the immobilization efficiency in the present approach was increased significantly. This method, achieving high loading of antibody while retaining function, improves the feasibility of silk fibroin as a platform material for biosensor applications. [Copyright &y& Elsevier]

Curcumin is a natural antioxidant that is isolated from turmeric ( Curcuma longa ) and exhibits strong free radical scavenging activity, thus functional for anti-aging. However, poor stability and low solubility of curcumin in aqueous conditions limit its biomedical applications. Previous studies have shown that the anti-oxidation activity of curcumin embedded in silk fibroin films could be well preserved, resulting in the promoted adipogenesis from human mesenchymal stem cells (hMSCs) cultured on the surface of the films. In the present study, curcumin was encapsulated in both silk fibroin films (silk/cur films) and nanoparticles (silk/cur NPs), and their anti-aging effects were compared with free curcumin in solution, with an aim to elucidate the mechanism of anti-aging of silk-associated curcumin and to better serve biomedical applications in the future. The morphology and structure of silk/cur film and silk/cur NP were characterized using SEM, FTIR and DSC, indicating characteristic stable beta-sheet structure formation in the materials. Strong binding of curcumin molecules to the beta-sheet domains of silk fibroin resulted in the slow release of curcumin with well-preserved activity from the materials. For cell aging studies, rat bone marrow mesenchymal stem cells (rBMSCs) were cultured in the presence of free curcumin (FC), silk/cur film and silk/cur NP, and cell proliferation and markers of aging (P53, P16, HSP70 gene expression and β-Galactosidase activity) were examined. The results indicated that cell aging was retarded in all FC, silk/cur NP and silk/cur film samples, with the silk-associated curcumin superior to the FC. [ABSTRACT FROM AUTHOR]

An inkjet printing approach is presentedfor the facile fabricationof microscopic arrays of biocompatible silk “nests”capable of hosting live cells for prospective biosensors. The patterningof silk fibroin nests were constructed by the layer-by-layer (LbL)assembly of silk polyelectrolytes chemically modified with poly-(l-lysine) and poly-(l-glutamic acid) side chains. Theinkjet-printed silk circular regions with a characteristic “nest”shape had diameters of 70–100 μm and a thickness severalhundred nanometers were stabilized by ionic pairing and by the formationof the silk II crystalline secondary structure. These “locked-in”silk nests remained anchored to the substrate during incubation incell growth media to provide a biotemplated platform for printing-in,immobilization, encapsulation and growth of cells. The process ofinkjet-assisted printing is versatile and can be applied on any typeof substrate, including rigid and flexible, with scalability and facileformation. [ABSTRACT FROM AUTHOR]

Abstract: Due to its unique properties, silk fibroin was studied as a biodegradable polymer vehicle for sustained, local delivery of the anticonvulsant adenosine from encapsulated reservoirs. Silk is a biologically derived protein polymer that is biocompatible, mechanically strong and degrades to non-toxic products in vivo. To achieve local, sustained, controlled adenosine release from fully degradable implants, solid adenosine powder reservoirs were coated with silk fibroin. Material properties of the silk coating including thickness, crystallinity and morphology were investigated to assess the relationships between silk coating biomaterial features and adenosine release from silk encapsulated reservoirs. Reservoir coating thickness was varied through manipulation of the silk coating solution concentration and number of coatings applied. Release studies were also performed in proteinase type XIV to model the effects of degradation. Increasing the barrier to diffusion, either by increasing coating thickness or crystallinity was found to delay adenosine burst, decrease average daily release rate, and increase duration of release. In the case of encapsulated reservoirs coated with eight layers of 8% (w/v) silk, a linear release profile was observed and adenosine release was sustained for 14days. The ability to achieve nearly constant release for 2weeks for adenosine via control of the silk coating suggests these encapsulated reservoirs represent a novel system for delivering adenosine. We anticipate that this approach could also be extended to other implant needs and small-molecule drugs to treat a range of clinical needs. [Copyright &y& Elsevier]