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Silk fibroin has applications in different medical fields such as tissue engineering, regenerative medicine, drug delivery and medical devices. Advances in silk chemistry and biomaterial designs have yielded exciting tools for generating new silk-based materials and technologies. Selective chemistries can enhance or tune the features of silk, such as mechanics, biodegradability, processability and biological interactions, to address challenges in medically relevant materials (hydrogels, films, sponges and fibres). This Review details the design and utility of silk biomaterials for different applications, with particular focus on chemistry. This Review consists of three segments: silk protein fundamentals, silk chemistries and functionalization mechanisms. This is followed by a description of different crosslinking chemistries facilitating network formation, including the formation of composite biomaterials. Utility in the fields of tissue engineering, drug delivery, 3D printing, cell coatings, microfluidics and biosensors are highlighted. Looking to the future, we discuss silk biomaterial design strategies to continue to improve medical outcomes., (© 2023. Springer Nature Limited.)

A variety of artificial spinning methods have been applied to produce regenerated silk fibers; however, how to spin regenerated silk fibers that retain the advantages of natural silks in terms of structural hierarchy and mechanical properties remains challenging. Here, we show a bioinspired approach to spin regenerated silk fibers. First, we develop a nematic silk microfibril solution, highly viscous and stable, by partially dissolving silk fibers into microfibrils. This solution maintains the hierarchical structures in natural silks and serves as spinning dope. It is then spun into regenerated silk fibers by direct extrusion in the air, offering a useful route to generate polymorphic and hierarchical regenerated silk fibers with physical properties beyond natural fiber construction. The materials maintain the structural hierarchy and mechanical properties of natural silks, including a modulus of 11 ± 4 GPa, even higher than natural spider silk. It can further be functionalized with a conductive silk/carbon nanotube coating, responsive to changes in humidity and temperature. [ABSTRACT FROM AUTHOR]

Obesity is a rising issue especially in the United States that can lead to heart problems, type II diabetes, and respiratory problems. Since the 1970s, obesity rates in the United States have more than doubled in adults and children. Recent evidence suggests that exposure to certain chemicals, termed 'obesogens,' in utero may alter metabolic processes, predisposing individuals to weight gain. There is a need to develop a three-dimensional human tissue system that is able to model the effects of obesogens in vitro in order to better understand the impact of obesogens on early development. Human embryonic-derived stem cells in three-dimensional collagen embedded silk scaffolds were exposed to three different obesogens: Bisphenol A (BPA), Bisphenol S (BPS), and Tributyltin (TBT). The exposed tissues accumulated triglycerides and increased expression of adipogenic genes (Perilipin (PLIN1), peroxisome proliferator-activated receptor gamma (PPARy), fatty acid binding protein 4 (FABP4)) compared to equivalent control cultures with no obesogen exposure. These cultures were also compared to human adult stem cell cultures, which did not respond the same upon addition of obesogens. These results demonstrate the successful development of a representative tissue model of in utero obesogen exposures. This tissue system could be used to determine mechanisms of action of current obesogens and to screen other potential obesogens. [ABSTRACT FROM AUTHOR]

Mechanical reinforcement of silk membranes by embedding silk microfibers was studied. Silk microfibers of 10-600 μm long were prepared by hydrolyzing degummed silk fibers in alkali solution. The silk microfibers were mixed with silk fibroin solution (continuous phase) at various ratios to fabricate silk microfiber-reinforced composite scaffolds (SMCSs). The morphology, mechanical properties, structural characteristics, biodegradation, and cytotoxicity of the composites were investigated. Silk microfiber-reinforced membranes with 1 wt% of microfibers displayed the most homogeneous distribution of microfibers in the membrane matrix. The tensile strength and elongation at break were 10.5 ± 2.7 MPa and 56.7 ± 7.8 %, respectively, comparable to human meniscus tissue. The presence of silk microfibers did not significantly impact the secondary structure and crystallization of SMCSs. Proteolytic degradation in vitro using protease XIV showed that the 1 % silk microfiber-reinforced membranes lost 90 % weight after 5 days, a longer time frame than plain silk membrane controls. The viability of human fibroblasts (Hs 865.Sk) on the SMCSs demonstrated no cytotoxicity. SMCSs may be useful as biomaterial systems as tissue substitutes where mechanical strength is critical for functional performance. [ABSTRACT FROM AUTHOR]

Silk materials with different nanostructures have been developed without the understanding of the inherent transformation mechanism. Here we attempt to reveal the conversion road of the various nanostructures and determine the critical regulating factors. The regulating conversion processes influenced by a hierarchical charge distribution were investigated, showing different transformations between molecules, nanoparticles and nanofibers. Various repulsion and compressive forces existed among silk fibroin molecules and aggregates due to the exterior and interior distribution of charge, which further controlled their aggregating and deaggregating behaviors and finally formed nanofibers with different sizes. Synergistic action derived from molecular mobility and concentrations could also tune the assembly process and final nanostructures. It is suggested that the complicated silk fibroin assembly processes comply a same rule based on charge distribution, offering a promising way to develop silk-based materials with designed nanostructures. [ABSTRACT FROM AUTHOR]

Various techniques have been employed to entrap fragrant oils within microcapsules or microparticles in the food, pharmaceutical, and chemical industries for improved stability and delivery. In the present work, we describe the use of silk protein microparticles for encapsulating fragrant oils using ambient processing conditions to form an all-natural biocompatible matrix. These microparticles are stabilized via physical crosslinking, requiring no chemical agents, and are prepared with aqueous and ambient processing conditions using polyvinyl alcohol-silk emulsions. The particles were loaded with fragrant oils via direct immersion of the silk particles within an oil bath. The oil-containing microparticles were coated using alternating silk and polyethylene oxide layers to control the release of the oil from the microspheres. Particle morphology and size, oil loading capacity, release rates as well as silk-oil interactions and coating treatments were characterized. Thermal analysis demonstrated that the silk coatings can be tuned to alter both retention and release profiles of the encapsulated fragrance. These oil-containing particles demonstrate the ability to adsorb and controllably release oils, suggesting a range of potential applications including cosmetic and fragrance utility. [ABSTRACT FROM AUTHOR]

The article focuses on an in vivo and in vitro study conducted to assess the biocompatibility of silk gel for cervical injection during pregnancy. It mentions injection of silk gel into cervix of rats pregnant with 13 days and the use of culture of human cervical fibroblasts on silk gel and tissue culture plastic to evaluate cell viability, proliferation, metabolic activity and gene expression, and the conclusion that silk gel can be used as an alternative to cervical cerclage.

Collagen and silk materials, in neat forms and as silica composites, were flown for 18 months on the International Space Station [Materials International Space Station Experiment (MISSE)-6] to assess the impact of space radiation on structure and function. As natural biomaterials, the impact of the space environment on films of these proteins was investigated to understand fundamental changes in structure and function related to the future utility in materials and medicine in space environments. About 15% of the film surfaces were etched by heavy ionizing particles such as atomic oxygen, the major component of the low-Earth orbit space environment. Unexpectedly, more than 80% of the silk and collagen materials were chemically crosslinked by space radiation. These findings are critical for designing next-generation biocompatible materials for contact with living systems in space environments, where the effects of heavy ionizing particles and other cosmic radiation need to be considered. [ABSTRACT FROM AUTHOR]

Objective: New therapies to prevent preterm birth are needed. Our objective was to study an injectable biomaterial for human cervical tissue as an alternative to cervical cerclage. Study Design: Human cervical tissue specimens were obtained from premenopausal gynecological hysterectomies for benign indications. A 3-part biomaterial was formulated, consisting of silk protein solution blended with a 2-part polyethylene glycol gelation system. The solutions were injected into cervical tissue and the tissue was evaluated for mechanical properties, swelling, cytocompatibility, and histology. Results: The stiffness of cervical tissue more than doubled after injection (P = .02). Swelling properties of injected tissue were no different than native tissue controls. Cervical fibroblasts remained viable for at least 48 hours when cultured on the biomaterial. Conclusions: We report a silkbased, biocompatible, injectable biomaterial that increased the stiffness of cervical tissue compared to uninjected controls. Animal studies are needed to assess this biomaterial in vivo. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Control of silk structural and morphological features is reported for fibroin protein films via all aqueous processing, with and without polyethylene oxide (PEO). Silk films with thicknesses from 500 nm to 50 μm were generated with controllable surface morphologies by employing soft-lithography surface patterning or by adjusting PEO concentrations. FTIR analysis indicated that water-annealing, used to cure or set the films, resulted in increased β-sheet and α-helix content within the films. Steam sterilization provided an additional control point by increasing β-sheet content, while reducing random coil and turn structures, yet retaining film transparency and material integrity. Increased PEO concentration used during processing resulted in decreased sizes of surface globule structures, while simultaneously increasing uniformity of these features. The above results indicate that both surface and bulk morphologies and structures can be controlled by adjusting PEO concentration. The combined tool set for controlling silk film geometry and structure provides a foundation for further study of novel silk film biomaterial systems. These silk film biomaterials have potential applicability for a variety of optical and regenerative medicine applications due to their optical clarity, impressive mechanical properties, slow degradability, and biocompatibility. [ABSTRACT FROM AUTHOR]

Human bone is a three-dimensional composite structure consisting of inorganic apatite crystals and organic collagen fibers. An attractive strategy for fabricating mimics of these types of composite biomaterials is to selectively grow apatite on polymers with control of structure, mechanical properties, and function. In the present study, silk/apatite composites were prepared by growing apatite on functionalized nanodiameter silk fibroin fibers prepared by electrospinning. The functionalized fibers were spun from an aqueous solution of silk/polyethylene oxide (PEO) (78/22 wt/wt) containing poly(L-aspartate) (poly-Asp), which was introduced as an analogue of noncollageous proteins normally found in bone. Silk fibroin associated with the acidic poly-Asp and acted as template for mineralization. Apatite mineral growth occurred preferentially along the longitudinal direction of the fibers, a feature that was not present in the absence of the combination of components at appropriate concentrations. Energy dispersive spectroscopy and x-ray diffraction confirmed that the mineral deposits were apatite. The results suggest that this approach can be used to form structures with potential utility for bone-related biomaterials based on the ability to control the interface wherein nucleation and crystal growth occur on the silk fibroin. With this level of inorganic-organic control, coupled with the unique mechanical properties, slow rates of biodegradation, and polymorphic features of this type of proteins, new opportunities emerge for utility of biomaterials. [ABSTRACT FROM AUTHOR]

Silk spinning by insects and spiders leads to the formation of fibres that exhibit high strength and toughness. The lack of understanding of the protein processing in silk glands has prevented the recapitulation of these properties in vitro from reconstituted or genetically engineered silks. Here we report the identification of emulsion formation and micellar structures from aqueous solutions of reconstituted silkworm silk fibroin as a first step in the process to control water and protein-protein interactions. The sizes (100-200?nm diameter) of these structures could be predicted from hydrophobicity plots of silk protein primary sequence. These micelles subsequently aggregated into larger ‘globules’ and gel-like states as the concentration of silk fibroin increased, while maintaining solubility owing to the hydrophilic regions of the protein interspersed among the larger hydrophobic regions. Upon physical shearing or stretching structural transitions, increased birefringence and morphological alignment were demonstrated, indicating that this process mimics the behaviour of similar native silk proteins in vivo. Final morphological features of these silk materials are similar to those observed in native silkworm fibres. [ABSTRACT FROM AUTHOR]

The article focuses on the use of silk in connecting the worlds of optics and biology. The use of silk will open opportunities for a new class of biophotonics devices like bioactive optical filters, photonic crystals, and biodetectors. It discusses that the availability of a free-standing biological matrix that has the material toughness to endure room-temperature use under ordinary environmental conditions while concurrently showing high optical quality as well as biological activity is unique.

The article offers insights on the relationship between the structures and functions in orb webs regarding hierarchical structure of silk proteins. Illustrated are the mechanical properties of spider-silk fibres and webs through combinations of modelling and experiments. Noted are the primary sequence of silk proteins as the answer in response to nonlinear responses from the proteic structure of silk.

Reports that Lazaris et al. have heterologously expressed and isolated a spider-silk protein from mammalian epithelial cells, successfully spinning the protein into fibers whose properties closely resemble those of native silk fibers. Mechanical properties of silk fibers; Genetic organization related to different silks in different spiders; Technical barriers to the duplication of the silk's native mechanical properties in an environmentally compatible process.