Silk Fibroin Gel Research Articles

Silk fibroin hydrogel promote burn wound healing through regulating TLN1 expression and affecting cell adhesion and migration.

Skin injury is a kind of common tissue damage in daily life and war. Silk fibroin (SF) is becoming an engineered material for skin wound repair due to its superior unique physical and chemical properties. The present study aimed to illustrate mechanism of SF hydrogel promoting skin repair in the second degree burn mice. Heat shock models were established. In vitro, cells were culture for 50 min at 44 °C water bath; while in vivo, the skin of anesthetic mice were treat with soldering iron at 90 °C. Then, they divided into silk fibroin gel group, purilon gel group and control (blank) group. The cellular activity of proliferation and apoptosis was detected by Kit-8, flow cytometry and HE-staining, and the migration and adhesion were detected by scratch test. qRT-PCR and WB were employed to detected adhesion and migration related genes and proteins expression. TLN1 siRNA and overexpression technologies were also employed to illustrate the potential mechanism of SF effects. Compared with the purilon gel group and control group, SF hydrogel could enhance cell proliferation, migration and adhesion and increase the expression of adhesion and migration related proteins (P < 0.05), which promote burn wound healing. Through the inhibition, overexpression and rescue experiments of Talin1, we proved that silk fibroin hydrogel promote burn wound healing through regulating TLN1 expression and affecting cell adhesion and migration.

Exploring the Gelation Mechanisms and Cytocompatibility of Gold (III)-Mediated Regenerated and Thiolated Silk Fibroin Hydrogels.

Accelerating the gelation of silk fibroin (SF) solution from several days or weeks to minutes or few hours is critical for several applications (e.g., cell encapsulation, bio-ink for 3D printing, and injectable controlled release). In this study, the rapid gelation of SF induced by a gold salt (Au3+) as well as the cytocompatibility of Au3+-mediated SF hydrogels are reported. The gelation behaviors and mechanisms of regenerated SF and thiolated SF (tSF) were compared. Hydrogels can be obtained immediately after mixing or within three days depending on the types of silk proteins used and amount of Au3+. Au3+-mediated SF and tSF hydrogels showed different color appearances. The color of Au-SF hydrogels was purple-red, whereas the Au-tSF hydrogels maintained their initial solution color, indicating different gelation mechanisms. The reduction of Au3+ by amino groups and further reduction to Au by tyrosine present in SF, resulting in a dityrosine bonding and Au nanoparticles (NPs) production, are proposed as underlying mechanisms of Au-SF gel formation. Thiol groups of the tSF reduced Au3+ to Au+ and formed a disulfide bond, before a formation of Au+-S bonds. Protons generated during the reactions between Au3+ and SF or tSF led to a decrease of the local pH, which affected the chain aggregation of the SF, and induced the conformational transition of SF protein to beta sheet. The cytocompatibility of the Au-SF and tSF hydrogels was demonstrated by culturing with a L929 cell line, indicating that the developed hydrogels can be promising 3D matrices for different biomedical applications.

Alcohol‐triggered silk fibroin hydrogels having random coil and β‐turn structures enhanced for cytocompatible cell response

ABSTRACTAlcohol additive is one of the stimulants that induces the fast gelation of silk fibroin solution. Based on our previous report, different alcohol types influence the gelation kinetic and the properties of resulting silk fibroin hydrogels. Here, the effects of alcohol concentrations on the silk fibroin gelation and cell response were reported. All fibroin hydrogels prepared with various alcohol additives showed cell biocompatibility, especially the fibroin hydrogel prepared with 10 wt % n‐butanol. Results on the mechanical properties of hydrogels, n‐butanol additive enhanced a higher compressive modulus up to ~ 22 times in comparison to non‐alcoholic fibroin hydrogel. Fourier transform infrared analysis and peak deconvolution showed a possible formation of more β‐turn linkage and random coil structure of fibroin segments in alcoholic fibroin hydrogel. So, the micro‐segmental structure of fibroin hydrogel caused the higher compressive modulus, prolonged deformation of the hydrogels, and efficient cell growth on the fibroin hydrogel. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48731.

Properties of interpenetrating polymer networks associating fibrin and silk fibroin networks obtained by a double enzymatic method.

Fibrin gels are of interest as biomaterials for regenerative medicine but present poor mechanical properties, undergo fast degradation and strongly contract in presence of cells. To face these drawbacks, a fibrin network can be associated with another polymer network, in an Interpenetrating Polymer Network (IPN) architecture. In this study, we report the properties of an IPN comprising a fibrin (Fb) network and a silk fibroin (SF) network. This IPN is synthesized through the action of 2 enzymes, each one being specific of one protein gelation, i.e. thrombin (Tb) for Fb gelation, and horseradish peroxidase (HRP) for SF gelation. The effective formation of both Fb and SF networks in an IPN architecture was first verified at qualitative and quantitative levels. The resulting IPN was easily manipulable, displayed high viscoelastic properties and showed homogeneous macro- and micro-structure. Then the degradability of the IPN by two proteases, thermolysin (TL) and trypsin (TRY), obeying different mechanisms was presented. Finally, two-dimensional culture of human fibroblasts on the IPN surface induced little material contraction, while fibroblasts showed healthy morphology, displayed high viability and produced mature extracellular matrix (ECM) proteins. Taken together, the results suggest that this new IPN have a strong potential for tissue engineering and regenerative medicine.

Gelation Process and Physicochemical Properties of Thai Silk Fibroin Hydrogels Induced by Various Anionic Surfactants for Controlled Release of Curcumin

AbstractHydrogels based on Thai silk fibroin (SF) were prepared by the induction of various anionic surfactants including sodium octyl sulfate (SOS), sodium dodecyl sulfate (SDS), and sodium tetradecyl sulfate (STS), which have a similar chemical structure but different alkyl chain lengths and charges. The effects of anionic surfactant types and their concentrations on the gelation mechanism and time of SF were systematically investigated. We found that SDS and STS that have long alkyl chain lengths and high negative charges could accelerate the gelation of SF to occur within 14–42 min in a concentration‐dependent manner. SOS that has a short alkyl chain length and low negative charge slowly induced SF to gel at around 113–144 h. The mechanisms of SF gelation induced by these three anionic surfactants were supposed to be combination of hydrophobic and electrostatic interactions, as well as the self‐transition of beta sheets. The SF + STS hydrogels were further employed to encapsulate curcumin for the controlled release application. The SF + 0.09% wt. STS hydrogel encapsulating curcumin showed a slow rate of degradation while sustained the release of curcumin. This hydrogel can be applied as a minimal invasive injectable hydrogel or as a hydrogel for topical treatment of diseases.

Facile Preparation of Mechanical Reinforced and Biocompatible Silk Gels

Nontoxic and controllable way to fabricate silk fibroin (SF) gel with high mechanical properties is of critical important to biomaterial in tissue engineering. Electrochemically triggered electrophoretic migration and electric charge of the silk molecules both contributed to SF microspheres and electronic gel (e-gel) formation by sol-gel transition. In this study, a novel silk pH e-gel with higher mechanical property was prepared by combining low-voltage electric fields with isoelectric point (pI) adjustment. This green process was mild and friendly without chemical crosslinker. Compressive modulus of the silk pH e-gel was up to 70 MPa that was significantly higher than that of SF gelation spontaneously. Furthermore, analysis of molecule conformation of the silk pH-e-gel demonstrated that most of random coil structures transformed into α-helix and a little β-sheet structures during this process. The silk pH e-gel was loaded with rhodamine B and showed an obvious sustainable release profile. Accumulation releasing amounts was approximately 60% at day 9. Cytocompatibility of the silk pH-e-gel was evaluated by epithelial cell. The results showed that the gels could support the cell growth and proliferation in vitro. Finally, gel biodegradation was assessed by protease XIV. After biodegradation for 28 days, remaining weight of the gel was about 20.23±2.59 wt%, indicating its good biodegradability. This novel process was established successfully by combining low voltage field with pH-control, which provided an alternative material for regenerative medicine.

Enhanced Osteogenesis of Bone Marrow-Derived Mesenchymal Stem Cells by a Functionalized Silk Fibroin Hydrogel for Bone Defect Repair.

Silk fibroin (SF) from Bombyx mori is a promising natural material for the synthesis of biocompatible and biodegradable hydrogels for use in biomedical applications from tissue engineering to drug delivery. However, weak gelation performance and the lack of biochemical cues to trigger cell proliferation and differentiation currently significantly limit its application in these areas. Herein, a biofunctional hydrogel containing SF (2.0%) and a small peptide gelator (e.g., NapFFRGD = 1.0 wt%) is generated via cooperative molecular self-assembly. The introduction of NapFFRGD to SF is shown to significantly improve its gelation properties by lowering both its threshold gelation concentration to 2.0% and gelation time to 20 min under physiological conditions (pH = 7.4, 37 °C), as well as functionalizing the SF hydrogel with cell-adhesive motifs (e.g., RGD). Besides mediating cell adhesion, the RGD ligands incorporated within the SF-RGD gel promote the osteogenic differentiation of bone marrow-derived mesenchymal stem cells encapsulated within the gel matrix, leading to bone regeneration in a mouse calvarial defect model, compared with a blank SF gel (2.0%, pH = 7.4). This work suggests that SF could be easily tailored with bioactive peptide gelators to afford bioactive hydrogels with favorable microenvironments for tissue regeneration applications.

Thai silk fibroin gelation process enhancing by monohydric and polyhydric alcohols

Silk fibroin hydrogel is an interesting natural material in various biomedical applications. However, the self-assembled gelation takes a long time. In this work, different alcohol types are used as gelation enhancers for aqueous silk fibroin solution. Monohydric alcohols having carbon chain length from C1 to C4 and polyhydric alcohols with the number of mono- to tri- hydroxyl groups were used as the enhancers which are effective for rapid gelation. The addition of monohydric alcohol distinctively reduced the gelation time, comparing to the polyhydric alcohol. The gelation process is directly dependent on the polarity of alcohol and hydrophobicity. The alcohol mediated gelation imparts strong viscoelastic property and enhanced compressive modulus of resulting hydrogels. This is due to the effective formation of self-assembled beta sheet network of the silk fibroin chains facilitates the gelation process.

Cooperative Assembly of a Peptide Gelator and Silk Fibroin Afford an Injectable Hydrogel for Tissue Engineering.

Silk fibroin (SF) from Bombyx mori has received increasing interest in biomedical fields, because of its slow biodegradability, good biocompatibility, and low immunogenicity. Although SF-based hydrogels have been studied intensively as a potential matrix for tissue engineering, weak gelation performance and low mechanical strength are major limitations that hamper their widespread applicability. Therefore, searching for new strategies to improve the SF gelation property is highly desirable in tissue engineering research. Herein, we report a facile approach to induce rapid gelation of SF by a small peptide gelator (e.g., NapFF). Following the simple mixing of SF and NapFF in water, a stable hydrogel of SF was obtained in a short time period at physiological pH, and the minimum gelation concentration of SF can reach as low as 0.1%. In this process of gelation, NapFF not only can behave itself as a gelator for supramolecular self-assembly, but also can trigger the conformational transition of the SF molecule from random coil to β-sheet structure via hydrophobic and hydrogen-bonding interactions. More importantly, for the generation of a scaffold with favorable cell-surface interactions, a new peptide gelator (NapFFRGD) with Arg-Gly-Asp (RGD) domain was applied to functionalize SF hydrogel with improved bioactivity for cell adhesion and growth. Following encapsulating the vascular endothelial growth factor (VEGF), the SF gel was subcutaneously injected in mice, and served as an effective matrix to trigger the generation of new blood capillaries in vivo.

Sodium oleate induced rapid gelation of silk fibroin

Silk fibroin has acquired increasing interest in the last years for application in medicine and namely in tissue engineering. Several methods have been developed to process fibroin and for the fabrication of nets, sponges, films and gels. This paper deals with the fabrication and characterization of fibroin hydrogels obtained by using sodium oleate as gelation agent. Gels have been prepared by mixing Silk fibroin (SF) and Sodium oleate (SO) water solutions in different concentrations, and a quite wide frame of compositions have been explored. Rheological tests have been performed to determine the gelation times, scanning electron microscopies have been made to evaluate morphologies, FTIR analysis has been done to determine the conformation of the starting materials and of the resulting gels, water content has been measured and cytotoxicity tests have been performed to validate the potential biomedical use of the hydrogels. Depending on the SF and SO different gelation times have been obtained thanks to the formation of intermolecular bonds between the fibroin chains. The obtained fastest gelation of about 80 s could make this specific formulation compatible with in situ gelation. By changing composition, gels with different morphologies, rheological properties and water contents have been prepared.

3D freeform printing of silk fibroin

Freeform fabrication has emerged as a key direction in printing biologically-relevant materials and structures. With this emerging technology, complex structures with microscale resolution can be created in arbitrary geometries and without the limitations found in traditional bottom-up or top-down additive manufacturing methods. Recent advances in freeform printing have used the physical properties of microparticle-based granular gels as a medium for the submerged extrusion of bioinks. However, most of these techniques require post-processing or crosslinking for the removal of the printed structures (Miller et al., 2015; Jin et al., 2016) [1,2]. In this communication, we introduce a novel method for the one-step gelation of silk fibroin within a suspension of synthetic nanoclay (Laponite) and polyethylene glycol (PEG). Silk fibroin has been used as a biopolymer for bioprinting in several contexts, but chemical or enzymatic additives or bulking agents are needed to stabilize 3D structures. Our method requires no post-processing of printed structures and allows for in situ physical crosslinking of pure aqueous silk fibroin into arbitrary geometries produced through freeform 3D printing. Statement of Significance3D bioprinting has emerged as a technology that can produce biologically relevant structures in defined geometries with microscale resolution. Techniques for fabrication of free-standing structures by printing into granular gel media has been demonstrated previously, however, these methods require crosslinking agents and post-processing steps on printed structures. Our method utilizes one-step gelation of silk fibroin within a suspension of synthetic nanoclay (Laponite), with no need for additional crosslinking compounds or post processing of the material. This new method allows for in situ physical crosslinking of pure aqueous silk fibroin into defined geometries produced through freeform 3D printing.

Silk fibroin/collagen protein hybrid cell-encapsulating hydrogels with tunable gelation and improved physical and biological properties

Cell encapsulating hydrogels with tunable mechanical and biological properties are of special importance for cell delivery and tissue engineering. Silk fibroin and collagen, two typical important biological proteins, are considered potential as cell culture hydrogels. However, both have been used individually, with limited properties (e.g., collagen has poor mechanical properties and cell-mediated shrinkage, and silk fibroin from Bombyx mori (mulberry) lacks cell adhesion motifs). Therefore, the combination of them is considered to achieve improved mechanical and biological properties with respect to individual hydrogels. Here, we show that the cell-encapsulating hydrogels of mulberry silk fibroin / collagen are implementable over a wide range of compositions, enabled simply by combining the different gelation mechanisms. Not only the gelation reaction but also the structural characteristics, consequently, the mechanical properties and cellular behaviors are accelerated significantly by the silk fibroin / collagen hybrid hydrogel approach. Of note, the mechanical and biological properties are tunable to represent the combined merits of individual proteins. The shear storage modulus is tailored to range from 0.1 to 20 kPa along the iso-compositional line, which is considered to cover the matrix stiffness of soft-to-hard tissues. In particular, the silk fibroin / collagen hydrogels are highly elastic, exhibiting excellent resistance to permanent deformation under different modes of stress; without being collapsed or water-squeezed out (vs. not possible in individual proteins) – which results from the mechanical synergism of interpenetrating networks of both proteins. Furthermore, the role of collagen protein component in the hybrid hydrogels provides adhesive sites to cells, stimulating anchorage and spreading significantly with respect to mulberry silk fibroin gel, which lacks cell adhesion motifs. The silk fibroin / collagen hydrogels can encapsulate cells while preserving the viability and growth over a long 3D culture period. Our findings demonstrate that the silk / collagen hydrogels possess physical and biological properties tunable and significantly improved (vs. the individual protein gels), implying their potential uses for cell delivery and tissue engineering. Statement of SignificanceDevelopment of cell encapsulating hydrogels with excellent physical and biological properties is important for the cell delivery and cell-based tissue engineering. Here we communicate for the first time the novel protein composite hydrogels comprised of ‘Silk’ and ‘Collagen’ and report their outstanding physical, mechanical and biological properties that are not readily achievable with individual protein hydrogels. The properties include i) gelation accelerated over a wide range of compositions, ii) stiffness levels covering 0.1 kPa to 20 kPa that mimic those of soft-to-hard tissues, iii) excellent elastic behaviors under various stress modes (bending, twisting, stretching, and compression), iv) high resistance to cell-mediated gel contraction, v) rapid anchorage and spreading of cells, and vi) cell encapsulation ability with a long-term survivability. These results come from the synergism of individual proteins of alpha-helix and beta-sheet structured networks. We consider the current elastic cell-encapsulating hydrogels of silk-collagen can be potentially useful for the cell delivery and tissue engineering in a wide spectrum of soft-to-hard tissues.

Curcumin-loaded silk fibroin e-gel scaffolds for wound healing applications

Recently, silk fibroin gel systems (e-gel), formed with weak electric fields have been prepared for various tissue-engineering applications such as neural, cartilage and bone. Here, we demonstrated the effectiveness of an electroresponsive silk fibroin (SF) hydrogel, which is a 3-D scaffold formed and used as a wound dressing material. SEM studies revealed that the curcumin (CUR)-loaded SF (CUR-SF) consisted of a 3-D porous structure with a porosity percent of 80% and a swelling ratio over 100%. Colony forming unit assay confirmed that CUR-SF e-gel scaffolds produced a reduction in viable bacteria compared to bare SF scaffolds. In vitro studies performed with immortalized human keratinocyte (HaCaT) indicated no toxicity of CUR-loaded SF e-gel scaffolds to healthy cells. Taking all the results together, it was suggested that the CUR-SF e-gel scaffolds could improve the wound healing activity in comparison to SF without curcumin and be potentially used as a wound dressing material.

Preparation and characterization of silk fibroin hydrogel as injectable implants for sustained release of Risperidone

The principal objective of the present study is to achieve a depot formulation of Risperidone by gelation of silk fibroin (SF). For this purpose, hydrochloric acid (HCl)/acetone-based and methanol-based hydrogels were prepared with different drug/polymer ratios (1:3, 1:6, and 1:15). For all the drug-loaded methanol-based hydrogels, gel transition of SF solutions occurred immediately and the gelation time was 1 min, while the gelation time of HCL/acetone-based hydrogels was around 360 min. According to the results obtined from Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) spectra, solvent systems and Risperidone could induce β-sheet structure, but HCL/acetone system had the lowest effect on induction of β-sheets. The crystallinity was increased by increasing the amount of Risperidone, and drug to polymer ratio of 1:3 possessed the highest crystallinity. Thermogravimetric analysis (TGA) indicated that increasing the amount of drug in formulation increased the stability of hydrogels, and methanol-based hydrogel with a ratio of 1:3 had the most stable structure. The release rate of Risperidone from methanol-based hydrogel at ratio of 1:3 was lower than that for HCl/acetone-based one, and it decreased by increasing the amount of Risperidone. The release of Risperidone from methanol hydrogel at ratios 1:3 and 1:6 continued up to 25 d which is acceptable for depot form of Risperidone and shows that the extended release of Risperidone was achieved successfully. In conclusion, SF hydrogel with the ability to respond to the environmental stimuli is an excellent candidate for injectable implants for extended release of Risperidone.

Cellulose–silk fibroin hydrogels prepared in a lithium bromide aqueous solution

Here, we present a new process for the preparation of cellulose–silk fibroin hydrogels using a concentrated lithium bromide (LiBr) aqueous solution. After mixing, the solutions of cellulose and silk fibroin that had each been dissolved separately in aqueous LiBr, the cellulose forms a gel as the solution cools to approximately 70°C, and silk fibroin is regenerated via treatment in methanol. Three grades of cellulose–silk fibroin hydrogels are prepared by controlling the amounts of cellulose and silk fibroin. The gels have highly porous, three-dimensional networks composed of long, interconnected fibrils. Through X-ray diffraction and ATR-FTIR analysis we show that the dissolution-regeneration of cellulose and silk fibroin induces a structural change in the crystal structure of cellulose II and silk II. While the porosity and swelling ratio of cellulose–silk fibroin gels is significantly reduced with the increased silk fibroin content, all the gels show high water uptake. The enzymatic degradation rates of cellulose–silk fibroin gels obviously reflect differences in the silk fibroin content, and cell adhesion and growth on cellulose–silk fibroin gels is enhanced with increased silk fibroin content. These cellulose–silk fibroin gels could provide novel properties that would be useful for biomaterial matrix applications.

Self‐Healing Silk Fibroin‐Based Hydrogel for Bone Regeneration: Dynamic Metal‐Ligand Self‐Assembly Approach

Despite advances in the development of silk fibroin (SF)‐based hydrogels, current methods for SF gelation show significant limitations such as lack of reversible crosslinking, use of nonphysiological conditions, and difficulties in controlling gelation time. In the present study, a strategy based on dynamic metal‐ligand coordination chemistry is developed to assemble SF‐based hydrogel under physiological conditions between SF microfibers (mSF) and a polysaccharide binder. The presented SF‐based hydrogel exhibits shear‐thinning and autonomous self‐healing properties, thereby enabling the filling of irregularly shaped tissue defects without gel fragmentation. A biomineralization approach is used to generate calcium phosphate‐coated mSF, which is chelated by bisphosphonate ligands of the binder to form reversible crosslinkages. Robust dually crosslinked (DC) hydrogel is obtained through photopolymerization of acrylamide groups of the binder. DC SF‐based hydrogel supports stem cell proliferation in vitro and accelerates bone regeneration in cranial critical size defects without any additional morphogenes delivered. The developed self‐healing and photopolymerizable SF‐based hydrogel possesses significant potential for bone regeneration application with the advantages of injectability and fit‐to‐shape molding.

Reversibility of strain stiffening in silk fibroin gels

We investigate the linear and nonlinear viscoelastic properties as well as the reversibility of strain-stiffening behavior of silk fibroin gels. The gels are prepared from 4.2w/v% fibroin solution in the presence of butanediol diglycidyl ether and N,N,N',N'-tetramethylethylenediamine (TEMED) as a cross-linker and catalyst, respectively. By changing the concentration of TEMED in the gelation system, fibroin gels exhibiting a storage modulus G’ between 10−1–105Pa and a loss factor tan δ between 10−2 and 10° could be obtained. We observe a strong stiffening (up to 900%) in fibroin gels with increasing strain above 10% deformation, but reversibly if the strain is removed, the gel recovers its initial viscoelastic properties. The strain induced formation of transient intermolecular domains acting as reversible cross-links are responsible for the stiffening behavior of fibroin gels. These additional cross-links formed in the hardened fibroin gels have a temporary nature with lifetimes of the order of seconds. The nonlinear behavior of fibroin gels can be reproduced by a wormlike chain model taking into account the entropic elasticity of fibroin molecules and the strain induced increase in the cross-link density of fibroin gels.

Gelation Behaviors and Mechanism of Silk Fibroin According to the Addition of Nitrate Salts.

Silk fibroin (SF) is a typical fibrous protein that is secreted by silkworms and spiders. It has been used in a variety of areas, and especially for tissue-engineering scaffolds, due to its sound processability, mechanical properties, biodegradability, and biocompatibility. With respect to gelation, the SF gelation time is long in aqueous solutions, so a novel approach is needed to shorten this time. The solubility of regenerated SF is sound in formic acid (FA), which is a carboxylic acid of the simplest structure. In this study, SF was dissolved in formic acid, and the addition of salts then induced a rapid gelation that accompanied a solution-color change. Based on the gelation behaviors of the SF solution according to different SF and salt concentrations, the gelation mechanism was investigated.

Programing Performance of Silk Fibroin Materials by Controlled Nucleation

To examine the mechanism of the network formation of silk fibroin (SF), monodispersed colloidal particles (MDCPs) are used as well defined foreign substrates to quantify their effect on the primary nucleation of β‐crystallites in molecular networks (silk nanofibrils) and the hierarchical network formation of SF. It follows that MDCPs are capable of accelerating the SF gelation by reducing the multistep nucleation barrier, which gives rise to a high density of silk fibril domain networks due to the increase of primary nucleation sites. Consequently, through governing the change in the hierarchical mesoscopic structure, the macroscopic performance of silk materials (e.g., the rheological properties of SF hydrogels and the tensile stress of fibers) can be controlled directly. As SF hydrogels represent a typical example of weak fibril domain–domain network interactions, the increase of fibril domain density leads to weaker gels. On the other hand, SF fibers correspond to strong fibril domain–domain network interactions, the increase of fibril domain density ends up with much tougher fibers. The knowledge obtained provides a facile strategy in controlling the complex hierarchical structure and macroscopic performance of SF materials, and offers useful routes for general design and functionalization of soft materials.

Silk Fibroin-Sophorolipid Gelation: Deciphering the Underlying Mechanism.

Silk fibroin (SF) protein, produced by silkworm Bombyx mori, is a promising biomaterial, while sophorolipid (SL) is an amphiphilic functional biosurfactant synthesized by nonpathogenic yeast Candida bombicola. SL is a mixture of two forms, acidic (ASL) and lactonic (LSL), which when added to SF results in accelerated gelation of silk fibroin. LSL is known to have multiple biological functionalities and hence hydrogels of these green molecules have promising applications in the biomedical sector. In this work, SANS, NMR, and rheology are employed to examine the assembling properties of individual and mixed SLs and their interactions with SF to understand the mechanism that leads to rapid gelation. SANS and NMR studies show that ASL assembles to form charged micelles, while LSL forms micellar assemblies and aggregates of a mass fractal nature. ASL and LSL together form larger mixed micelles, all of which interact differently with SF. It is shown that preferential binding of LSL to SF causes rapid unfolding of the SF chain leading to the formation of intermolecular beta sheets, which trigger fast gelation. Based on the observations, a mechanism for gelation of SF in the presence of different sophorolipids is proposed.