Silk Hydrogels Research Articles

An ultra-thin transparent multi-functional sensor based on silk hydrogel for health monitoring

With the gradual improvement of people’s health awareness, wearable devices occupy an important position in daily health care and human physiological activity monitoring. As traditional silicon-based electronic products face problems such as interface mismatch, silk fibroin has gradually become an alternative choice for next-generation wearable electronic devices due to its excellent performance. Herein, an ultra-thin transparent and flexible multi-functional sensor based on silk hydrogel with self-patterned microstructure is proposed. The silk hydrogel exhibits superior transparency (>82%) and thin thickness (∼100 μm). Furthermore, the self-patterned microstructure on the silk hydrogel surface is beneficial for the high sensitivity of pressure sensing response (1.6 kPa−1). This device exhibits advantageous performance on temperature (top sensitivity of 6.25% °C−1) and humidity (top sensitivity of 0.16% RH−1) sensing response. It also shows fast response (0.16 s) and durable stability (over 2000 dynamic cycles). Moreover, this device can be applied to monitor human facial expression, joint movements, temperature change, breathing and other health indicators. It is worth mentioning that this multi-functional sensor can monitor the signal of breathing and throat, so it can be applied to the clinical physiological activity monitoring of patients with upper respiratory tract infection. In addition, we also demonstrate a grasping and relaxing experiment of intelligent manipulator to verify the pressure and temperature sensing performance, providing a possibility for its application in the field of prosthetics. According to these advantages, the reported ultra-thin transparent multi-functional sensor based on silk hydrogel has broad prospects in the fields of health monitoring, intelligent prosthetics, and electronic skin, etc.

Cytoprotection of Human Progenitor and Stem Cells through Encapsulation in Alginate Templated, Dual Crosslinked Silk and Silk-Gelatin Composite Hydrogel Microbeads.

Susceptibility of mammalian cells against harsh processing conditions limit their use in cell transplantation and tissue engineering applications. Besides modulation of the cell microenvironment, encapsulation of mammalian cells within hydrogel microbeads attract attention for cytoprotection through physical isolation of the encapsulated cells. The hydrogel formulations used for cell microencapsulation are largely dominated by ionically crosslinked alginate (Alg), which suffer from low structural stability under physiological culture conditions and poor cell-matrix interactions. Here the fabrication of Alg templated silk and silk/gelatin composite hydrogel microspheres with permanent or on-demand cleavable enzymatic crosslinks using simple and cost-effective centrifugation-based droplet processing are demonstrated. The composite microbeads display structural stability under ion exchange conditions with improved mechanical properties compared to ionically crosslinked Alg microspheres. Human mesenchymal stem and neural progenitor cells are successfully encapsulated in the composite beads and protected against environmental factors, including exposure to polycations, extracellular acidosis, apoptotic cytokines, ultraviolet (UV) irradiation, anoikis, immune recognition, and particularly mechanical stress. The microbeads preserve viability, growth, and differentiation of encapsulated stem and progenitor cells after extrusion in viscous polyethylene oxide solution through a 27-gauge fine needle, suggesting potential applications in injection-based delivery and three-dimensional bioprinting of mammalian cells with higher success rates.

Self-Assembling Imageable Silk Hydrogels for the Focal Treatment of Osteosarcoma.

Background: The standard treatment for osteosarcoma comprises complete surgical resection and neoadjuvant chemotherapy, which may cause serious side effects and partial or total limb loss. Therefore, to avoid the disadvantages of traditional treatment, we developed self-assembling imageable silk hydrogels for osteosarcoma. Methods: We analysed whether iodine induced apoptosis in MG-63 and Saos-2 cells by using CCK-8 and flow cytometry assays and transmission electron microscopy. Western blotting was used to analyse the pathway of iodine-induced apoptosis in osteosarcoma cells. PEG400, silk fibroin solution, polyvinylpyrrolidone iodine (PVP-I), and meglumine diatrizoate (MD) were mixed to produce an imageable hydrogel. A nude mouse model of osteosarcoma was established, and the hydrogel was injected locally into the interior of the osteosarcoma with X-ray guidance. The therapeutic effect and biosafety of the hydrogel were evaluated. Results: Iodine treatment at 18 and 20 µM for 12 h resulted in cell survival rate reduced to 50 ± 2.1% and 50.5 ± 2.7% for MG-63 and Sao-2 cells, respectively (p < 0.01). The proportion of apoptotic cells was significantly higher in the iodine-treatment group than in the control group (p < 0.05), and apoptotic bodies were observed by transmission electron microscopy. Iodine could regulate the death receptor pathway and induce MG-63 and Saos-2 cell apoptosis. The hydrogels were simple to assemble, and gels could be formed within 38 min. A force of less than 50 N was required to inject the gels with a syringe. The hydrogels were readily loaded and led to sustained iodine release over 1 week. The osteosarcoma volume in the PEG-iodine-silk/MD hydrogel group was significantly smaller than that in the other three groups (p < 0.001). Caspase-3 and poly (ADP-ribose) polymerase (PARP) expression levels were significantly higher in the PEG-iodine-silk/MD hydrogel group than in the other three groups (p < 0.001). Haematoxylin and eosin (H&E) staining showed no abnormalities in the heart, liver, spleen, lung, kidney, pancreas or thyroid in any group. Conclusions: Self-assembling imageable silk hydrogels could be injected locally into osteosarcoma tissues with X-ray assistance. With the advantages of good biosafety, low systemic toxicity and minimal invasiveness, self-assembling imageable silk hydrogels provide a promising approach for improving the locoregional control of osteosarcoma.

Intraarticularly injectable silk hydrogel microspheres with enhanced mechanical and structural stability to attenuate osteoarthritis

A silk fibroin (silk) hydrogel was prepared by using diglycidyl ether (BDDE), a chemical crosslinker commonly used to generate Food and Drug Administration (FDA)-approved hyaluronic acid (HA) medical products. The silk/BDDE hydrogels exhibited high elasticity (compressive modulus of 166 ± 15.0 kPa), anti-fatigue properties, and stable structure and mechanical strength in aqueous solution. Chemical crosslinking was conducted in a high concentration (9.3 M) of lithium bromide (LiBr) solution, a salt that is commonly used to dissolve degummed silk fibers during silk solubilization. The unfolded and extended structure of silk molecules with these reaction conditions, as well as the unique ionic environment provided by LiBr facilitated a high degree of crosslinking in the hydrogel. Similar hydrogels were not obtained when the silk was dissolved in other silk fiber-dissolving reagents (e.g., Ajisawa's, formic acid (FA)/LiBr, FA/CaCl2 solutions), likely because partially folded silk structures and the ionic conditions with these reagents were less favorable for the crosslinking reaction. Based on these findings, silk/BDDE hydrogel spheres were prepared using an oil/water (o/w) emulsification method and biocompatibility and biodegradation were evaluated in vivo, along with other silk gel control systems (e.g., enzyme-catalyzed di-tyrosine and pulverized silk/BDDE gel particles with irregular shapes). Histological and immunohistochemical analyses demonstrated that the silk/BDDE hydrogel spheres were biocompatible and served as a bio-lubricant to treat osteoarthritis (OA). The intra-articular injection of the gel spheres reduced pain as measured with OA rats, reduced cartilage damage and resisted the digestive environment in the articular cavity for extended time frames (>4 weeks), suggesting utility for pain relief and sustained drug release for future OA treatments.

Preparation and Characterization of Natural Silk Fibroin Hydrogel for Protein Drug Delivery.

In recent years, hydrogels have been widely used as drug carriers, especially in the area of protein delivery. The natural silk fibroin produced from cocoons of the Bombyx mori silkworm possesses excellent biocompatibility, significant bioactivity, and biodegradability. Therefore, silk fibroin-based hydrogels are arousing widespread interest in biomedical research. In this study, a process for extracting natural silk fibroin from raw silk textile yarns was established, and three aqueous solutions of silk fibroin with different molecular weight distributions were successfully prepared by controlling the degumming time. Silk fibroin was dispersed in the aqueous solution as “spherical” aggregate particles, and the smaller particles continuously accumulated into large particles. Finally, a silk fibroin hydrogel network was formed. A rheological analysis showed that as the concentration of the silk fibroin hydrogel increased its storage modulus increased significantly. The degradation behavior of silk fibroin hydrogel in different media verified its excellent stability, and the prepared silk fibroin hydrogel had good biocompatibility and an excellent drug-loading capacity. After the protein model drug BSA was loaded, the cumulative drug release within 12 h reached 80%. We hope that these investigations will promote the potential utilities of silk fibroin hydrogels in clinical medicine.

Engineered Tough Silk Hydrogels through Assembling β-Sheet Rich Nanofibers Based on a Solvent Replacement Strategy.

β-Sheet rich silk nanofiber hydrogels are suitable scaffolds in tissue regeneration and carriers for various drugs. However, unsatisfactory mechanical performance limits its applications. Here, insight into the silk nanofibers stimulates the remodeling of previous solvent systems to actively regulate the assembly of silk nanofibers. Formic acid, a solvent of regenerated silk fibroin, is used to shield the charge repulsion of silk nanofibers to facilitate the nanofiber assembly under concentrated solutions. Formic acid was replaced with water to solidify the assembly, which induced the formation of a tough hydrogel. The hydrogels generated with this process possessed a modulus of 5.88 ± 0.82 MPa, ultimate stress of 1.55 ± 0.06 MPa, and toughness of 0.85 ± 0.03 MJ m-3, superior to those of previous silk hydrogels prepared through complex cross-linking processes. Benefiting from the dense gel network and high β-sheet content, these silk nanofiber hydrogels had good stability and antiswelling ability. The modulus could be modulated via changing the silk nanofiber concentration to provide differentiation signals to stem cells. Improved mechanical and bioactive properties with these hydrogels suggest utility in biomedical and engineering fields. More importantly, our present study reveals that the in-depth understanding of silk nanofibers could infuse power into traditional fabrication systems to achieve more high performance biomaterials, which is seldom considered in silk material studies.

Upregulation of biochemical and biophysical properties of cell-laden microfiber, silk-hyaluronic acid composite

Cell-laden filament-like hydrogels are advantageous for many applications including drug screening, tissue engineering, and regenerative medicine. However, most of the designed filament vehicles hold weak mechanical properties, which hinder their applications in specific tissue engineering. We present a binary hybrid silk and hyaluronic acid hydrogel microfiber generated through a microfluidic system to encapsulate cells with superior mechanical properties and biocompatibility. Cell-laden hydrogel microfibers were continuously produced through coaxial double orifice microfluidic device and horseradish peroxidase mediated crosslinking, which conjugated introduce phenolic moieties in the backbone of silk fibroin and HA derivatives (Silk-Ph and HA-Ph, respectively). The iterative hybrid Silk-Ph + HA-Ph fibers were fabricated in tunable size distribution between 195 and 680 μm through control of outer flow velocity. Tensile strength and maximum stain of prepared Silk-Ph + HA-Ph sample upregulated more than three times higher than the single HA-Ph sample, which demonstrated significant impacts of synthesized silk derivative in hydrogel fiber composition. The proteolytic degradation of microfibers manipulated by hyaluronidase and collagenase treatment. Encapsulation process and crosslinking did not insert any harmful effect on cell viability (> 90%) and the cells maintained their growth ability after encapsulation process. Cellular filament-like tissue fabricated from proliferation of cells in Silk-Ph + HA-Ph microfiber.

An injectable photo-cross-linking silk hydrogel system augments diabetic wound healing in orthopaedic surgery through spatiotemporal immunomodulation

BackgroundThe complicated hyperglycaemic and chronic inflammation of diabetic wounds in orthopaedic surgery leads to dysregulated immune cell function and potential infection risk. Immune interventions in diabetic wounds face a possible contradiction between simultaneous establishment of the pro-inflammatory microenvironment in response to potential bacterial invasion and the anti-inflammatory microenvironment required for tissue repair. To study this contradiction and accelerate diabetic-wound healing, we developed a photocurable methacryloxylated silk fibroin hydrogel (Sil-MA) system, co-encapsulated with metformin-loaded mesoporous silica microspheres (MET@MSNs) and silver nanoparticles (Ag NPs).ResultsThe hydrogel system (M@M–Ag–Sil-MA) enhanced diabetic-wound healing via spatiotemporal immunomodulation. Sil-MA imparts a hydrogel system with rapid in situ Ultra-Violet-photocurable capability and allows preliminary controlled release of Ag NPs, which can inhibit bacterial aggregation and create a stable, sterile microenvironment. The results confirmed the involvement of Met in the immunomodulatory effects following spatiotemporal dual-controlled release via the mesoporous silica and Sil-MA. Hysteresis-released from Met shifts the M1 phenotype of macrophages in regions of diabetic trauma to an anti-inflammatory M2 phenotype. Simultaneously, the M@M–Ag–Sil-MA system inhibited the formation of neutrophil extracellular traps (NETs) and decreased the release of neutrophil elastase, myeloperoxidase, and NETs-induced pro-inflammatory factors. As a result of modulating the immune microenvironmental, the M@M–Ag–Sil-MA system promoted fibroblast migration and endothelial cell angiogenesis in vivo, with verification of enhanced diabetic-wound healing accompanied with the spatiotemporal immunoregulation of macrophages and NETs in a diabetic mouse model.ConclusionsOur findings demonstrated that the M@M–Ag–Sil-MA hydrogel system resolved the immune contradiction in diabetic wounds through spatiotemporal immunomodulation of macrophages and NETs, suggesting its potential as a promising engineered nano-dressing for the treatment of diabetic wounds in orthopaedic surgery.Graphical

Silk Hydrogel-Mediated Delivery of Bone Morphogenetic Protein 7 Directly to Subcutaneous White Adipose Tissue Increases Browning and Energy Expenditure.

Objective: Increasing the mass and/or activity of brown adipose tissue (BAT) is one promising avenue for treating obesity and related metabolic conditions, given that BAT has a high potential for energy expenditure and is capable of improving glucose and lipid homeostasis. BAT occurs either in discrete “classical” depots, or interspersed in white adipose tissue (WAT), termed “inducible/recruitable” BAT, or ‘beige/brite’ adipocytes. We and others have demonstrated that bone morphogenetic protein 7 (BMP7) induces brown adipogenesis in committed and uncommitted progenitor cells, resulting in increased energy expenditure and reduced weight gain in mice. BMP7 is therefore a reliable growth factor to induce browning of WAT. Methods: In this study, we sought to deliver BMP7 specifically to subcutaneous (sc)WAT in order to induce tissue-resident progenitor cells to differentiate into energy-expending recruitable brown adipocytes, without off-target effects like bone formation, which can occur when BMPs are in the presence of bone progenitor cells (outside of WAT). BMP7 delivery directly to WAT may also promote tissue innervation, or directly activate mitochondrial activity in brown adipocytes, as we have demonstrated previously. We utilized silk protein in the form of an injectable hydrogel carrying BMP7. Silk scaffolds are useful for in vivo delivery of substances due to favorable material properties, including controlled release of therapeutic proteins in an active form, biocompatibility with minimal immunogenic response, and prior FDA approval for some medical materials. For this study, the silk was engineered to meet desirable release kinetics for BMP7 in order to mimic our prior in vitro brown adipocyte differentiation studies. Fluorescently-labeled silk hydrogel loaded with BMP7 was directly injected into WAT through the skin and monitored by non-invasive in vivo whole body imaging, including in UCP1-luciferase reporter mice, thereby enabling an approach that is translatable to humans. Results: Injection of the BMP7-loaded silk hydrogels into the subcutaneous WAT of mice resulted in “browning”, including the development of multilocular, uncoupling protein 1 (UCP1)-positive brown adipocytes, and an increase in whole-body energy expenditure and skin temperature. In diet-induced obese mice, BMP7-loaded silk delivery to subcutaneous WAT resulted in less weight gain, reduced circulating glucose and lower respiratory exchange ratio (RER). Conclusions: In summary, BMP7 delivery via silk scaffolds directly into scWAT is a novel translational approach to increase browning and energy expenditure, and represents a potential therapeutic avenue for delivering substances directly to adipose depots in pursuit of metabolic treatments.

Biodegradable and injectable poly(vinyl alcohol) microspheres in silk sericin-based hydrogel for the controlled release of antimicrobials: application to deep full-thickness burn wound healing

Biodegradable and injectable poly(vinyl alcohol) microspheres in silk sericin-based hydrogel for the controlled release of antimicrobials: application to deep full-thickness burn wound healing

Multiphysics modeling and experiments on ultrasound-triggered drug delivery from silk fibroin hydrogel for Wilms tumor

In this study, silk fibroin hydrogel is employed as a carrier for vincristine and ultrasound as a method to accelerate the drug release. The Acoustic, deformation, swelling, and diffusion fields are coupled in a multi-physics model to optimize the drug delivery. A transient acoustic structure model and a chemically controlled mechanism are implemented, while a coupled model of deformation and diffusion takes the impact of mechanical forces into account. An evaluation of the model is made through experiments. To monitor the drug release rate over 40 days following injection of silk hydrogel syringes containing vincristine, they were triggered by ultrasound in some selected time intervals. Drug release rates were determined using different power intensities and induction times. Computed simulation results and laboratory experiments revealed that ultrasound could cause a significant improvement in drug release rate, with an increase of up to 10 times over a release without ultrasound stimulation. By increasing the ultrasound power and induction time up to their peak value, the drug release rate rises and drops then. Predictions of the drug release rate by the model were in good agreement with those observed in experiments. This makes the model a valuable tool for potential predictions. Results showed that the ultrasound triggers the increased cell death rates, but the Wilms tumor cells were resistant to higher concentrations of released drugs.

Fe3O4-doped silk fibroin-polyacrylamide hydrogel for selective and highly efficient absorption of cationic dyes pollution in water

Overuse of organic dyes has caused serious threats to the ecosystem and human health. However, the development of high-efficient, environmentally friendly, selective, and degradable cationic dye adsorbents remains a huge challenge. In this work, a novel Fe3O4 nanoparticles doped silk fibroin-polyacrylamide magnetic hybrid hydrogel (Fe3O4@SF-PAAM) was successfully fabricated by combining free radical polymerization to prepare hydrogels and in situ co-precipitation to prepare nanoparticles. The obtained Fe3O4@SF-PAAM hydrogel shows strong magnetic performance with saturated magnetic of 10.2 emu mg−1 and excellent swelling properties with a swelling ratio of 55867%. In addition, Fe3O4@SF-PAAM can adsorb cationic dyes such as methylene blue (MB), crystal violet, and Rhodamine B, but has no adsorption effect on anionic dyes such as methyl orange, congo red, and carmine, indicating that Fe3O4@SF-PAAM has good selective adsorption properties for cationic dyes. Interestingly, the adsorption capacity of Fe3O4@SF-PAAM was approached 2025 mg g–1 for MB (MB, a typical cation dye) at 25 °C and neutral. Meanwhile, the hybrid hydrogel is reusable, the removal rate for MB is still over 90% after the five adsorption–desorption cycles. The fabricated magnetic hybrid hydrogel is a kind of a highly-efficiency and eco-friendly adsorbent and presents great potential applications in water purification and environmental protection.

Microporosity engineered printable silk/graphene hydrogels and their cytocompatibility evaluations

In this work, regenerated silk fibroin (RSF)/reduced graphene oxide (rGO) hybrid ink system was fabricated in aqueous phase, extrusion printed and photocrosslinked to hydrogels with tunable physicochemical properties and cell-gel interactions. Aqueous isopropyl alcohol was used to disperse the rGO into RSF matrix, where the RSF molecules showed relatively increased radius of gyration with IPA resulting in increased pore size and water uptake capacity of the photocrosslinked hydrogels. Incorporation of IPA along with increase in rGO content systematically decreased the viscosity, contact angle and printing accuracy of RSF/rGO hybrid inks, where the ink with highest rGO content exhibited relatively loose network structure at printing shear rate. However, no secondary structural change and fibrillogenesis was observed under printing shear stress, making it a suitable system for bioprinting silk hydrogel scaffolds. In addition, increase in rGO content systematically increased the crosslink density, β-sheet content, and mechanical properties of RSF/rGO hybrid hydrogels, whereas decreased the micropore size and water uptake capacity. Moreover, with increase in rGO content, the hybrid and bioprinted hydrogels showed good biocompatibility with marginal difference in cell viability on hybrid and bioprinted gels. The developed hydrogel systems could be potentially applied for tissue engineering and other functional applications.

Synergetic integrations of bone marrow stem cells and transforming growth factor-β1 loaded chitosan nanoparticles blended silk fibroin injectable hydrogel to enhance repair and regeneration potential in articular cartilage tissue.

The cartilage repair and regeneration show inadequate self‐healing capability and have some complications, which are inordinate challenges in clinical therapy. Biopolymeric injectable hydrogels, a prominent type of cell‐carrier as well tissue engineering scaffolding materials, establish promising therapeutic potential of stem cell‐based cartilage‐regeneration treatment. In addition, injectable scaffolding biomaterial should have rapid gelation properties with adequate rheological and mechanical properties. In the present investigation, we developed and fabricated the macromolecular silk fibroin blended with polylysine modified chitosan polymer (SF/PCS) using thermal‐sensitive glycerophosphate (GP), which contains effective gelation ability, morphology, porosity and also has enhanced mechanical properties to induce physical applicability, cell proliferation and nutrient exchange in the cell‐based treatment. The developed and optimised injectable hydrogel group has good biocompatibility with human fibroblast (L929) cells and bone marrow‐derived mesenchymal stem cells (BMSCs). Additionally, it was found that SF/PCS hydrogel group could sustainably release TGF‐β1 and efficiently regulate cartilage‐specific and inflammatory‐related gene expressions. Finally, the cartilage‐regeneration potential of the hydrogel groups embedded with and without BMSCs were evaluated in SD rat models under histopathological analysis, which showed promising cartilage repair. Overall, we conclude that the TGF‐β1‐SF/PCS injectable hydrogel demonstrates enhanced in vitro and in vivo tissue regeneration properties, which lead to efficacious therapeutic potential in cartilage regeneration.

Impact of silk hydrogel secondary structure on hydrogel formation, silk leaching and in vitro response

Silk can be processed into a broad spectrum of material formats and is explored for a wide range of medical applications, including hydrogels for wound care. The current paradigm is that solution-stable silk fibroin in the hydrogels is responsible for their therapeutic response in wound healing. Here, we generated physically cross-linked silk fibroin hydrogels with tuned secondary structure and examined their ability to influence their biological response by leaching silk fibroin. Significantly more silk fibroin leached from hydrogels with an amorphous silk fibroin structure than with a beta sheet-rich silk fibroin structure, although all hydrogels leached silk fibroin. The leached silk was biologically active, as it induced vitro chemokinesis and faster scratch assay wound healing by activating receptor tyrosine kinases. Overall, these effects are desirable for wound management and show the promise of silk fibroin and hydrogel leaching in the wider healthcare setting.

Multifunctional polyphenol-based silk hydrogel alleviates oxidative stress and enhances endogenous regeneration of osteochondral defects

In osteochondral defects, oxidative stress caused by elevated levels of reactive oxygen species (ROS) can disrupt the normal endogenous repair process. In this study, a multifunctional hydrogel composed of silk fibroin (SF) and tannic acid (TA), the FDA-approved ingredients, was developed to alleviate oxidative stress and enhance osteochondral regeneration. In this proposed hydrogel, SF first interacts with TA to form a hydrogen-bonded supramolecular structure, which is subsequently enzymatically crosslinked to form a stable hydrogel. Furthermore, TA had multiple phenolic hydroxyl groups that formed interactions with the therapeutic molecule E7 peptide for controlled drug delivery. In vitro investigations showed that SF-TA and SF-TA-E7 hydrogels exhibited a multitude of biological effects including scavenging of ROS, maintaining cell viability, and promoting the proliferation of bone marrow mesenchymal stem cells (BMSCs) against oxidative stress. The proteomic analysis indicated that SF-TA and SF-TA-E7 hydrogels suppressed oxidative stress, which in turn improved cell proliferation in multiple proliferation and apoptosis-related pathways. In rabbit osteochondral defect model, SF-TA and SF-TA-E7 hydrogels promoted enhanced regeneration of both cartilage and subchondral bone as compared to hydrogel without TA incorporation. These findings indicated that the multifunctional SF-TA hydrogel provided a microenvironment suitable for the endogenous regeneration of osteochondral defects.

Impact of Cell Loading of Recombinant Spider Silk Based Bioinks on Gelation and Printability

Front Cover: Dragline silk proteins of the European Garden spider are the basis for recombinant spider silk proteins. Spider silk hydrogels are used as matrix for cell encapsulation and 3D bioprinting into stable scaffolds. With spider silk bioinks complex shapes can be printed such as a human aortic valve. This is reported by Annika Lechner, Vanessa T. Trossmann, and Thomas Scheibel in article number 2100390.

Flexible conductive silk-PPy hydrogel toward wearable electronic strain sensors

Conductive hydrogels have been studied as promising materials for the flexible and wearable bioelectronics, because of their unique electrical and mechanical properties. Addition of conducting polymers in biomaterial-based hydrogel matrix is a simple yet effective way to construct hydrogels with good conductivity and flexibility. In this work, a conductive hydrogel composed by a silk hydrogel and a conducting polymer, polypyrrole (PPy), is developed via in situ polymerization of pyrrole into the silk fibroin network. The silk-PPy hydrogel shows high conductivity (26 S m−1), as well as sensitive and fast responses to corresponding conformation changes. Taking advantages of these properties, flexible and wearable strain sensors are proposed for the monitoring of various body movements, which can detect both the large and subtle human motions with good sensitivity, reproducibility and stability. The hybridization of biomaterials and conducting polymers endows the multifunctions of the conductive hydrogels, thus showing considerable potentials in the advancement of the wearable electronics.

Exosomes derived from hypoxia preconditioned mesenchymal stem cells laden in a silk hydrogel promote cartilage regeneration via the miR-205–5p/PTEN/AKT pathway

Tissue engineering has promising prospects for cartilage regeneration. However, there remains an urgent need to harvest high quality seed cells. Bone marrow mesenchymal cells (BMSCs), and in particular their exosomes, might promote the function of articular chondrocytes (ACs) via paracrine mechanisms. Furthermore, preconditioned BMSCs could provide an enhanced therapeutic effect. BMSCs naturally exist in a relatively hypoxic environment (1%–5% O2); however, they are usually cultured under higher oxygen concentrations (21% O2). Herein, we hypothesized that hypoxia preconditioned exosomes (H-Exos) could improve the quality of ACs and be more conducive to cartilage repair. In our study, we compared the effects of exosomes derived from BMSCs preconditioned with hypoxia and normoxia (N-Exos) on ACs, demonstrating that H-Exos significantly promoted the proliferation, migration, anabolism and anti-inflammation effects of ACs. Furthermore, we confirmed that hypoxia preconditioning upregulated the expression of miR-205–5p in H-Exos, suggesting that ACs were promoted via the miR-205–5p/PTEN/AKT pathway. Finally, an injectable silk fibroin (SF) hydrogel containing ACs and H-Exos (SF/ACs/H-Exos) was utilized to repair cartilage defects and effectively promote cartilage regeneration in vivo. The application of SF/ACs/H-Exos hydrogel in cartilage regeneration therefore has promising prospects. Statement of significanceCartilage tissue engineering (CTE) has presented a promising prospect. However, the quality of seed cells is an important factor affecting the repair efficiency. Our study demonstrates for the first time that the exosomes derived from hypoxia preconditioned BMSCs (H-Exos) effectively promote the proliferation, migration and anabolism of chondrocytes and inhibit inflammation through miR-205–5p/PTEN/AKT pathway. Furthermore, we fabricated an injectable silk fibrion (SF) hydrogel to preserve and sustained release H-Exos. A complex composed of SF hydrogel, H-Exos and chondrocytes can effectively promote the regeneration of cartilage defects. Therefore, this study demonstrates that hypoxia pretreatment could optimize the therapeutic effects of BMSCs-derived exosomes, and the combination of exosomes and SF hydrogel could be a promising therapeutic method for cartilage regeneration.

MSC‐Laden Composite Hydrogels for Inflammation and Angiogenic Regulation for Skin Flap Repair

AbstractPressure‐driven, spreadable, deferoxamine (DFO)‐laden hydrogels are developed toward treatment for improved skin flap tissue repair. Further, mesenchymal stem cells (MSCs) are incorporated into silk nanofiber systems and then added to silk hydrogels to optimize angiogenesis and moderate inflammatory reactions in skin flap tissues for repair. The combined (composite) systems result in improved tissue outcomes. For example, the DFO release from the hydrogels is maintained while the system moderated negative influences of DFO on cells at the skin flap site with improved vasculization and for control of immune reactions. Both in vitro and in vivo results reveal improved outcomes with these composite hydrogel systems when MSCs are included. The synergistic action of DFO‐laden silk nanofibers combined with MSC‐laden microgels results in improved functional recovery of skin flaps in vivo when compared to control systems. Considering the ease of use of this system toward clinical applications, these new hydrogels are candidates for skin flap regeneration in surgical settings.