Silk Fibroin Concentration Research Articles

Tunable microphase-regulated silk fibroin/poly (lactic acid) biocomposite materials generated from ionic liquids

One of the most effective and promising strategies to develop novel biomaterials with unique, tunable structure and physicochemical properties is by creating composite materials that combine synthetic polymers with natural proteins using ionic liquids. In this study, biodegradable poly(d,l-lactic acid) (PDLLA) was blended with silk fibroin (SF) to create biocompatible films using an ionic liquid-based binary solvent system (1-butyl-3-methylimidazolium chloride/N,N-dimethylformamide), which can maintain the molecular weights of the proteins/polymers and encourage intermolecular interactions between the molecules. The effects of varying the ratio of PLA to SF were studied using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), water contact angle testing, and cytotoxicity analysis as well as enzymatic degradation. Results showed that the composite films were homogeneously blended on the macroscopic scale and exhibited typical fully miscible polymer blend characteristics. By increasing the SF content in the composites, the amounts of β-sheets in the films were significantly increased, allowing for SF to act as a physical crosslinker to maintain the stability of the protein-polymer network. Additionally, SF significantly improved the hydrophilicity and biocompatibility of the material and promoted the self-assembly of micelle structures in the biocomposites. Different topologies in the films also provided beneficial surface morphology for cell adhesion, growth, and proliferation. Overall, this study demonstrated an effective fabrication method for a fine-tuned polymer blends combining synthetic polymer and protein for a wide variety of biomedical and green material applications.

Impacts of Blended Bombyx mori Silk Fibroin and Recombinant Spider Silk Fibroin Hydrogels on Cell Growth.

Binary-blended hydrogels fabricated from Bombyx mori silk fibroin (SF) and recombinant spider silk protein eADF4(C16) were developed and investigated concerning gelation and cellular interactions in vitro. With an increasing concentration of eADF4(C16), the gelation time of SF was shortened from typically one week to less than 48 h depending on the blending ratio. The biological tests with primary cells and two cell lines revealed that the cells cannot adhere and preferably formed cell aggregates on eADF4(C16) hydrogels, due to the polyanionic properties of eADF4(C16). Mixing SF in the blends ameliorated the cellular activities, as the proliferation of L929 fibroblasts and SaOS-2 osteoblast-like cells increased with an increase of SF content. The blended SF:eADF4(C16) hydrogels attained the advantages as well as overcame the limitations of each individual material, underlining the utilization of the hydrogels in several biomedical applications.

Synthesis of highly fluorescent, amine-functionalized carbon dots from biotin-modified chitosan and silk-fibroin blend for target-specific delivery of antitumor agents

Carbon dots (CDs) have been a promising theranostic tool with high biocompatibility and a tailorable fluorescence profile. Herein, we report the synthesis of highly fluorescent amine-functionalized CDs from low molecular weight chitosan (LMWC) and silk-fibroin (SF) blends. The synthesized CDs were quasi-spherical in shape with a size of 3 ± 1.5 nm. A significant increase in fluorescent intensity and quantum yield was achieved upon increasing the SF content due to nitrogen doping. For inducing target specificity to cancer cells, biotin was covalently conjugated to the CDs, and the conjugation was determined by FTIR spectroscopy. The conjugate was further loaded with 5-fluorouracil (5-FU) as a model anti-cancer drug. The MTT assay showed increased cytotoxicity of the conjugated CDs in cancer cells compared to normal cells. The live-cell imaging in MCF-7 cell lines showed bright blue-colored fluorescence and increased internalization of the conjugated CDs than the non-conjugate ones due to receptor-mediated endocytosis.

Mimicked Periosteum Layer Based on Deposited Particle Silk Fibroin Membrane for Osteogenesis and Guided Bone Regeneration in Alveolar Cleft Surgery: Formation and in Vitro Testing

ABSTRACT An alveolar cleft is a critical tissue defect often treated with surgery. In this research, the mimicked periosteum layer based on deposited silk fibroin membrane was fabricated for guided bone regeneration in alveolar cleft surgery. The deposited silk fibroin particle membranes were fabricated by spray-drying with different concentrations of silk fibroin (v/v): 0.5% silk fibroin (0.5% SFM), 1% silk fibroin (1% SFM), 2% silk fibroin (2% SFM), and 1% silk fibroin film (1% SFF) as the control. The membranes were then characterized and the molecular organization, structure, and morphology were observed with FT-IR, DSC, and SEM. Their physical properties, mechanical properties, swelling, and degradation were tested. The membranes were cultured with osteoblast cells and their biological performance, cell viability and proliferation, total protein, ALP activity, and calcium deposition were evaluated. The results demonstrated that the membranes showed molecular transformation of random coils to beta sheets and stable structures. The membranes had a porous layer. Furthermore, they had more stress and strain, swelling, and degradation than the film. They had more unique cell viability and proliferation, total protein, ALP activity, calcium deposition than the film. The results of the study indicated that 1% SFM is promising for guided bone regeneration for alveolar cleft surgery.

Effect of Silk Fibroin Concentration on the Properties of Polyethylene Glycol Dimethacrylates for Digital Light Processing Printing

The concentration of silk fibroin is varied and mixed with the light-curing resin polyethylene glycol methacrylate to create a bioink, and the hydrogel is printed by three-dimensional printing. The results, as described in the article number 2100487 by Fumio Narita and co-workers, indicate that it is possible to create a scaffold material with properties suitable for some tissue in the field of regenerative medicine.

Development of Metronidazole-loaded In situ Thermosensitive Hydrogel for Periodontitis Treatment

Periodontal treatment focuses on the thorough removal of specific periodontal pathogens, mainly anaerobic Gram-negative bacteria, by mechanical scaling and root planning. In case the periodontal abscess is detected after treatment, a high dose of antimicrobial agents is commonly applied via oral administration. However, this approach increases the risk of antibiotic resistance and systemic side effects and decreases efficacy. To overcome the aforementioned issues, this study focused on the development of thermosensitive hydrogel to deliver the antibiotic drug metronidazole (MTZ) directly and locally to the oral infection site. The thermosensitive hydrogels were prepared by blending 28% w/v Pluronic F127 with various concentrations of methylcellulose (MC) and silk fibroin (SF). The gel properties, such as sol-gel transition time, viscosity, and gel strength, were investigated. The drug dissolution profiles, together with their theoretical models and gel dissolution characteristics, were also determined. All hydrogel formulations exhibited sol-gel transitions at 37°C within 1 min. An increase in MC content proportionally increased the viscosity but decreased the gel strength of the hydrogel. By contrast, the SF content did not significantly affect the viscosity but increased the gel strength of the hydrogel. The thermosensitive hydrogels also showed prolonged MTZ release characteristics for 10 days in phosphate-buffered saline (PBS) at pH 6.6, which followed the Higuchi diffusion model. Moreover, MTZ-thermosensitive hydrogel exhibited delayed dissolution in PBS at 37°C for more than 9 days. MTZ-thermosensitive hydrogels could be considered a prospective local oral drug delivery system to achieve efficient sustained release and improve the drug pharmacological properties in periodontitis treatment.

3D Printable Soy/Silk Hybrid Hydrogels for Tissue Engineering Applications

The development of protein-based 3D printable hydrogel systems with tunable structure and properties is a critical challenge in contemporary biomedicine. Particularly, 3D printing of modular hydrogels comprising different types of protein tertiary structure, such as globular and fibrous, has not yet been achieved. Here we report the extrusion-based 3D printing of hybrid hydrogels photochemically co-cross-linked between globular soy protein isolate (SPI) and fibrous silk fibroin (SF) for the first time. The hierarchical structure and organization of pristine SPI and SF, and 1:3 (SPI/SF) hybrid inks under various shear stress were investigated using in situ rheology combined with small-/ultra-small-angle neutron scattering (Rheo-SANS/USANS). The hybrid ink exhibited an isotropic mass fractal structure that was stable between tested shear rates of 0.1 and 100 s-1 (near printing shear). The kinetics of sol-gel transition during the photo-cross-linking reaction and the micromechanical properties of fabricated hydrogels were investigated using photorheology and atomic force microscopy, where the hybrid hydrogels exhibited tunable storage and Young's moduli in the range of 13-29 and 214-811 kPa, respectively. The cross-link density and printing accuracy of hybrid hydrogels and inks were observed to increase with the increase in SF content. The 3D printed hybrid hydrogels exhibited a micropore size larger than that of solution casted hydrogels; where the 3D printed 1:3 (SPI/SF) hybrid hydrogel showed a pore size about 7.6 times higher than that of the casted hydrogel. Moreover, the fabricated hybrid hydrogels exhibit good mouse fibroblast cell attachment, viability, and proliferation, demonstrating their potential for tissue engineering applications.

A Carbodiimide Cross‐Linked Silk Fibroin/Sodium Alginate Composite Hydrogel with Tunable Properties for Sustained Drug Delivery

AbstractCarbodiimide cross‐linked silk fibroin (SF)/sodium alginate (SA) composite hydrogels with superior stability and tunable properties are developed by varying preparation parameters. SF/SA blend ratio modulation allows to achieve composite hydrogel gelation times of 18–65 min, and rheological analysis shows that the speed of gel formation, the hydrogel network's density, and the hydrogels’ compressive properties are closely related to the blend ratio. The G′ of different hydrogels varies substantially from 28 to 413 Pa, and the hydrogel with higher SF content has a greater stiffness. The composite hydrogels present appropriate porosity of 76.63–85.09% and pore size of 316–603 µm. Hydrogel stability improves significantly after cross‐linking, and substantial swelling occurs due to the hydrophilicity of SA. The 7/3 and 6/4 SF/SA hydrogels are more resistant to degradation in PBS, and cytotoxicity testing confirmed their biocompatibility. For release studies in vitro, two model compounds are used as drug models, tetracycline hydrochloride, and bovine serum albumin (BSA). Different ratios of SF/SA have a greater influence on the release of BSA. This study provides a practical preparation method for flexible SF/SA composite hydrogels, which can help design hydrogels with specific physicochemical properties for different applications, especially drug delivery.

Development and Evaluation of Gellan Gum/Silk Fibroin/Chondroitin Sulfate Ternary Injectable Hydrogel for Cartilage Tissue Engineering.

Hydrogel is in the spotlight as a useful biomaterial in the field of drug delivery and tissue engineering due to its similar biological properties to a native extracellular matrix (ECM). Herein, we proposed a ternary hydrogel of gellan gum (GG), silk fibroin (SF), and chondroitin sulfate (CS) as a biomaterial for cartilage tissue engineering. The hydrogels were fabricated with a facile combination of the physical and chemical crosslinking method. The purpose of this study was to find the proper content of SF and GG for the ternary matrix and confirm the applicability of the hydrogel in vitro and in vivo. The chemical and mechanical properties were measured to confirm the suitability of the hydrogel for cartilage tissue engineering. The biocompatibility of the hydrogels was investigated by analyzing the cell morphology, adhesion, proliferation, migration, and growth of articular chondrocytes-laden hydrogels. The results showed that the higher proportion of GG enhanced the mechanical properties of the hydrogel but the groups with over 0.75% of GG exhibited gelling temperatures over 40 °C, which was a harsh condition for cell encapsulation. The 0.3% GG/3.7% SF/CS and 0.5% GG/3.5% SF/CS hydrogels were chosen for the in vitro study. The cells that were encapsulated in the hydrogels did not show any abnormalities and exhibited low cytotoxicity. The biochemical properties and gene expression of the encapsulated cells exhibited positive cell growth and expression of cartilage-specific ECM and genes in the 0.5% GG/3.5% SF/CS hydrogel. Overall, the study of the GG/SF/CS ternary hydrogel with an appropriate content showed that the combination of GG, SF, and CS can synergistically promote articular cartilage defect repair and has considerable potential for application as a biomaterial in cartilage tissue engineering.

Preparation and characterization of silk fibroin/polyethylene oxide nanofiber membranes with antibacterial activity.

Bacterial infection is among the most common diseases that threaten human health. Antibiotics are effective in treating bacterial infections. However, the overuse of antibiotics will lead to an increase in bacterial resistance. To reduce the overuse of antibiotics and improve the effective use of antibiotics through slow release, silk fibroin (SF)/polyethylene oxide (PEO) nanofiber membranes with different SF and PEO proportions were prepared by electrospinning. The ecofriendly solvent ethanol solution was used for electrospinning for better protection of antibiotic activity. The SEM showed that the surface of SF/PEO (2:8) and SF/PEO (3:7) was smoother and more uniform. With the increase of SF content, the thermal stability and hydrophilicity of SF/PEO nanofiber membranes were improved. The SF/PEO (3:7) nanofiber membrane had the best mechanical property and its maximum stress and strain were 4.6 1 ± 0.24 MPa and 16.36 ± 0.41%, respectively. Based on these good properties, SF/PEO (3:7) nanofiber membrane was chosen for loading and releasing gentamicin sulfate (GS). The fabricated (GS)/SF/PEO (3:7) nanofiber membrane exhibited good release efficiency and showed the good antibacterial activity against Staphylococcus aureus and Escherichia coli. These investigations indicated the GS/SF/PEO (3:7) nanofiber membrane (GS/SF/PEO) has a great potential for application in antibacterial materials.

Effect of Thai Silk Fibroin on Mechanical Properties of Bioactive Glass Silk Fibroin Hybrid Bone Scaffolds

Bioactive glass (70 mol% Si and 30% Ca; 70S30C) has been used as tissue engineering scaffolds in various research despite its brittleness due to its easy-to-replicate formula, extensive interconnected pores and natural bone bonding property of bioactive glass (BG). Thai silk fibroin (SF) is natural polymer with many desirable properties; biocompatibility, mechanical strength, biodegradability. Using BG-SF hybrid scaffolds could employ the positive effects of both bioactive glass and silk fibroin. Serving as bone scaffolds, BG-SF scaffolds must resist compression and other types of mechanical load depending on the application. This study fabricates scaffolds with various ratios of BG:SF (BG:SF; 90:10, 80:20 with 100:0 as control), and their stress-strain profiles were investigated. As expected, the scaffolds with highest BG content exhibited the curve resembling that of porous foam while the elastomeric stress-strain profile was becoming more evident when the SF content was increased. This study hence demonstrated fine-tuning mechanical properties of the BG using locally enriched SF.

Strontium mineralized silk fibroin porous microcarriers with enhanced osteogenesis as injectable bone tissue engineering vehicles

In this paper, silk fibroin (SF) porous microcarriers containing strontium were constructed as injectable bone tissue engineering vehicles. The effects of SF concentration and strontium content on micromorphology, element distribution, strontium ion release and cellular behavior of the constructed microcarriers were investigated. The microcarriers with an open interconnected pore can be fabricated by controlling the concentration of SF. The strontium functionalized SF microcarriers showed the sustained release of strontium ion and allowed bone mesenchymal stem cells (BMSCs) to attach, proliferate and secrete extracellular matrix. Furthermore, the strontium functionalized SF microcarriers improved the osteogenic capability of BMSCs in vitro compared with those microcarriers without sustained release of strontium ion. This study presents a valuable approach to fabricate polymeric microcarriers with the capability of sustained release of strontium ion that show potential in bone tissue engineering applications.

Effect of Silk Fibroin Concentration on the Properties of Polyethylene Glycol Dimethacrylates for Digital Light Processing Printing

Attempts are made to use silk fibroin (SF), which is a protein produced by the silkworm, as a scaffold material in the field of regenerative medicine due to its high biocompatibility. Herein, the concentration of SF is varied and mixed with the light‐curing resin polyethylene glycol dimethacrylate (PEGDMA) to create a bioink, and the hydrogel is printed by digital light processing (DLP) 3D printing. Then, to investigate the properties of the printed hydrogel, scanning electron microscope (SEM) observation, swelling behavior measurement, and compression testing are conducted. The properties of hydrogels depend on the concentration of SF, and this result indicates that it is possible to create a scaffold with properties suitable for some tissue by controlling the amount of SF.

Conductive polypyrrole-encapsulated silk fibroin fibers for cardiac tissue engineering

Polypyrrole (PPy) has been utilized in smart scaffolds to improve the functionality of the engineered cardiac tissue. Compared to the commonly used aqueous coating, here, PPy was blended into silk fibroin (SF) solution to electrospin conductive PPy-encapsulated SF nanofibers. Combinations of various SF concentrations (5%, 7%, and 12%) and different PPy-to-SF ratios (15:85, 30:70, and 40:60) were compared. PPy reduced the fiber diameter (0.431 ± 0.060 μm), better-mimicking the myocardium fibrils. Conductive mats with 7% SF showed the closest mechanical properties (1.437 ± 0.044 MPa) to the native myocardium; meanwhile, a PPy-to-SF ratio of 15:85 exhibited sufficient electrical conductivity for cardiomyocytes (CMs). In vitro studies using three different types of CM demonstrated that the hybrid mats support CM contraction. Primary neonatal rat CMs on the mat with a PPy-to-SF ratio of 15:85 were elongated and orientated anisotropically with locally organized sarcomeric striations. By contrast, human-induced pluripotent stem cell derived-CMs on the mat with a PPy-to-SF ratio of 30:70 exhibited the strongest contractions. Contraction synchrony was further improved by external stimulation. Taken together, these findings indicated the great potential of the PPy-encapsulated SF electrospun mat for cardiac tissue engineering.

Application potential of three-dimensional silk fibroin scaffold using mesenchymal stem cells for cardiac regeneration

Cardiac tissue engineering focusing on biomaterial scaffolds incorporating cells from different sources has been explored to regenerate or repair damaged area as a lifesaving approach.The aim of this study was to evaluate the cardiomyocyte differentiation potential of human adipose mesenchymal stem cells (hAD-MSCs) as an alternative cell source on silk fibroin (SF) scaffolds for cardiac tissue engineering. The change in surface morphology of SF scaffolds depending on SF concentration (1-6%, w/v) and increase in their porosity upon application of unidirectional freezing were visualized by scanning electron microscopy (SEM). Swelling ratio was found to increase 2.4 fold when SF amount was decreased from 4% to 2%. To avoid excessive swelling, 4% SF scaffold with swelling ratio of 10% (w/w) was chosen for further studies.Biodegradation rate of SF scaffolds depended on enzymatic activity was found to be 75% weight loss of SF scaffolds at the day 14. The phenotype of hAD-MSCs and their multi-linage potential into chondrocytes, osteocytes, and adipocytes were shown by flow cytometry and immunohistochemical staining, respectively.The viability of hAD-MSCs on 3D SF scaffolds was determined as 90%, 118%, and 138% after 1, 7, and 14 days, respectively. The use of 3D SF scaffolds was associated with increased production of cardiomyogenic biomarkers: α-actinin, troponin I, connexin 43, and myosin heavy chain. The fabricated 3D SF scaffolds were proved to sustain hAD-MSCs proliferation and cardiomyogenic differentiation therefore, hAD-MSCs on 3D SF scaffolds may useful tool to regenerate or repair damaged area using cardiac tissue engineering techniques.

Tissue-engineered nerve graft using silk-fibroin/polycaprolactone fibrous mats decorated with bioactive cerium oxide nanoparticles.

The main aim of this study was to evaluate the efficacy of cerium oxide nanoparticles (CNPs) encapsulated in fabricated hybrid silk-fibroin (SF)/polycaprolactone (PCL) nanofibers as an artificial neural guidance conduit (NGC) applicable for peripheral nerve regeneration. The NGC was prepared by PCL and SF filled with CNPs. The mechanical properties, contact angle, and cell biocompatibility experiments showed that the optimized concentration of CNPs inside SF and SF/PCL wall of conduits was 1% (wt/wt). The SEM image analysis showed the nanoscale texture of the scaffold in different topologies depend on composition with fiber diameters at about 351 ± 54 nm and 420 ± 73 nm respectively for CNPs + SF and CNPs + SF/PCL fibrous mats. Furthermore, contact angle measurement confirmed the hydrophilic behavior of the membranes, ascribable to the SF content and surface modification through modified methanol treatment. The balance of morphological and biochemical properties of hybrid CNPs 1% (wt/wt) + SF/PCL construct improves cell adhesion and proliferation in comparison with lower concentrations of CNPs in nanofibrous scaffolds. The release of CNPs 1% (wt/wt) from both CNPs + SF and CNPs+ SF/PCL fibrous mats was highly controlled and very slow during the extended time of incubation until 60 days. Fabricated double-layered NGC using CNPs + SF and CNPs + SF/PCL fibers was consistent for application in nervous tissue engineering and regenerative medicine from a structural and biocompatible perspective.

Dual-Crystallizable Silk Fibroin/Poly(L-lactic Acid) Biocomposite Films: Effect of Polymer Phases on Protein Structures in Protein-Polymer Blends.

Biopolymer composites based on silk fibroin have shown widespread potential due to their brilliant applications in tissue engineering, medicine and bioelectronics. In our present work, biocomposite nanofilms with different special topologies were obtained through blending silk fibroin with crystallizable poly(L-lactic acid) (PLLA) at various mixture rates using a stirring-reflux condensation blending method. The microstructure, phase components, and miscibility of the blended films were studied through thermal analysis in combination with Fourier-transform infrared spectroscopy and Raman analysis. X-ray diffraction and scanning electron microscope were also used for advanced structural analysis. Furthermore, their conformation transition, interaction mechanism, and thermal stability were also discussed. The results showed that the hydrogen bonds and hydrophobic interactions existed between silk fibroin (SF) and PLLA polymer chains in the blended films. The secondary structures of silk fibroin and phase components of PLLA in composites vary at different ratios of silk to PLLA. The β-sheet content increased with the increase of the silk fibroin content, while the glass transition temperature was raised mainly due to the rigid amorphous phase presence in the blended system. This results in an increase in thermal stability in blended films compared to the pure silk fibroin films. This study provided detailed insights into the influence of synthetic polymer phases (crystalline, rigid amorphous, and mobile amorphous) on protein secondary structures through blending, which has direct applications on the design and fabrication of novel protein–synthetic polymer composites for the biomedical and green chemistry fields.

Photothermal-modulated drug release from a composite hydrogel based on silk fibroin and sodium alginate

In order to realize effective controlled release of medicine to specific sites, the near-infrared (NIR) light responsive hydrogel has recently attracted noticeable attention as an innovative vehicle for a reserving and releasing the drug remotely “on demand” via stimuli-responsive NIR irradiation on/off. Herein, a modulated drug delivery platform was developed based on a silk fibroin (SF)/sodium alginate (SA) composite hydrogel incorporated with indocyanine green (ICG) as components. The gelation time of the crosslinked composite hydrogel ranged from 15 to 35 min, mainly depending on the concentration of SF. These materials are typical elastic hydrogels display stiffness between 260 and 2210 Pa. Besides, the compressive modulus E of the hydrogels varied in the range of 0.89–1.71 kPa by changing blend ratios. Scanning electron microscope (SEM) revealed the hydrogels showed highly porous (~89%) and tailored pore size in the range of 132–215 µm. And SF mainly remained silk I structure in the composite hydrogel and bovine serum albumin (BSA) and tetracycline hydrochloride (TH) still kept their own structure after encapsulation. SF/SA@ICG hydrogels exhibited desirable stability and swelling properties. Additionally, these hydrogel extracts displayed good cellular compatibility in vitro. Under near-infrared (NIR) radiation exposure, the hydrogels exhibited photothermal properties such as temperature rise by 8 °C, sufficient to stimulate drug release. Furthermore, hydrogels demonstrated NIR stimulated drug release, which was evaluated using BSA and TH, the drug loaded photothermal hydrogels can effectively increase the amount of drug released under NIR light trigger for just 1 min. The NIR-responsive hydrogels can provide a new option for developing natural ploymer based delivery vehicles to regulate drug release on demond using NIR irradiation remotely.

Electroencapsulation of Trans-resveratrol in Nanoparticles Composed of Silk Fibroin and Soluble Eggshell Membrane Protein

The beneficial effects of trans-resveratrol on health are widely accepted. However, when exposed to heat and UV light, the degradation of trans-resveratrol to less active form cis-resveratrol limits its use in industrial applications. Due to this reason, it is crucial to preserve the stability of trans-resveratrol by using carrier systems. This study aimed to encapsulate the trans-resveratrol in core/shell nanoparticles composed of eggshell membrane proteins and silk fibroin, respectively, using a coaxial electrospraying technique to preserve its stability. The size of the nanoparticles ranged from 8.2 to 254 nm. Keeping the encapsulation yield at the maximum level (96.9%), electroencapsulation process parameters which minimize the average particle diameter (23.8 nm) were found to be A (silk fibroin concentration) = 30.7 mg/ml, B (ratio of flow rates) = 0.72, C (applied voltage) = 18.8 kV, and D (distance) = 12.2 cm. Encapsulation efficiency varied between 40.05 and 96.41%. Detection of antioxidant capacity of released trans-resveratrol suggested that nanoparticles could be a suitable delivery system for sustained release of trans-resveratrol with preserved thermal and UV photostability. Central composite design (CCD) and the response surface methodology (RSM) were successfully used to optimize the electroencapsulation process parameters for the preparation of trans-resveratrol loaded core/shell nanoparticles. It was found that these parameters seemed to be varied depending on the response required. Therefore, an optimum process should be investigated to obtain desired responses such as high encapsulation yield, high encapsulation efficiency, and small average particle size while preserving the thermal and UV stabilities at reasonable levels.

Rheological characterization, compression, and injection molding of hydroxyapatite-silk fibroin composites

Traditional bone fixation devices made from inert metal alloys provide structural strength for bone repair but are limited in their ability to actively promote bone healing. Although several naturally derived bioactive materials have been developed to promote ossification in bone defects, it is difficult to translate small-scale benchtop fabrication of these materials to high-output manufacturing. Standard industrial molding processes, such as injection and compression molding, have typically been limited to use with synthetic polymers since most biopolymers cannot withstand the harsh processing conditions involved in these techniques. Here we demonstrate injection and compression molding of a bioceramic composite comprised of hydroxyapatite (HA) and silk fibroin (SF) from Bombyx mori silkworm cocoons. Both the molding behavior of the HA-SF slurry and final scaffold mechanics can be controlled by modulating SF protein molecular weight, SF content, and powder-to-liquid ratio. HA-SF composites with up to 20 weight percent SF were successfully molded into stable three-dimensional structures using high pressure molding techniques. The unique durability of silk fibroin enables application of common molding techniques to fabricate composite silk-ceramic scaffolds. This work demonstrates the potential to move bone tissue engineering one step closer to large-scale manufacturing of natural protein-based resorbable bone grafts and fixation devices.