ABSTRACT
In the therapy of early-stage osteoarthritis, to accomplish full infiltration of subchondral bone and cartilage, and to target osteoclast and chondrocyte simultaneously remain challenges in biomaterials design. Herein, a novel hierarchical drug delivery system is introduced, with micrometer-scale outer layer spheres composed of regenerated silk fibroin, characterized by connected porous structure through the n-butanol and regenerated silk fibroin combined emulsion route and freezing method. The design effectively resists clearance from the joint cavity, ensuring stable delivery and prolonged residence time within the joint space. Additionally, the system incorporates phenylboronic acid-enriched silk fibroin nanoparticles, stabilized through chemical cross-linking, which encapsulate isoliquiritin derived from Glycyrrhiza uralensis. These nanoparticles facilitate complete penetration of the cartilage extracellular matrix, exhibit pH-responsive behavior, neutralize reactive oxygen species, and enable controlled drug release, thereby enhancing therapeutic efficacy. The in vitro and in vivo experiments both demonstrate that the composite micro/nanospheres not only inhibit osteoclastogenesis with bone loss in subchondral bone and osteophyte formation, but also mitigate chondrocytes apoptosis, reduce oxidative stress associated with cartilage degeneration, and ameliorate neuropathic hyperalgesia, with the underlying mechanisms being elucidated. The study indicates that such an injectable strategy combining organic biomaterials with Chinese medicine holds substantial promise for the treatment of early osteoarthritis.
ABSTRACT
Topical hemostatic agents are preferred for application to sensitive bleeding sites because of their immediate locoregional effects with less tissue damage. However, the majority of commercial hemostatic agents fail to provide stable tissue adhesion to bleeding wounds or act as physical barriers against contaminants. Hence, it has become necessary to investigate biologically favorable materials that can be applied and left within the body post-surgery. In this study, a dual-sided nanofibrous dressing for topical hemostasis is electrospun using a combination of two protein materials: bioengineered mussel adhesive protein (MAP) and silk fibroin (SF). The wound-adhesive inner layer is fabricated using dihydroxyphenylalanine (DOPA)-containing MAP, which promotes blood clotting by aggregation of hemocytes and activation of platelets. The anti-adhesive outer layer is composed of alcohol-treated hydrophobic SF, which has excellent spinnability and mechanical strength for fabrication. Because both proteins are fully biodegradable in vivo and biocompatible, the dressing would be suitable to be left in the body. Through in vivo evaluation using a rat liver damage model, significantly reduced clotting time and blood loss are confirmed, successfully demonstrating that the proposed dual-sided nanofibrous dressing has the right properties and characteristics as a topical hemostatic agent having dual functionality of hemostasis and physical protection.
Subject(s)
Anti-Bacterial Agents , Bandages , Hemostasis , Hemostatics , Nanofibers , Animals , Nanofibers/chemistry , Hemostasis/drug effects , Hemostatics/chemistry , Hemostatics/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Rats , Fibroins/chemistry , Fibroins/pharmacology , Bivalvia/chemistry , Proteins/chemistry , Silk/chemistry , Rats, Sprague-DawleyABSTRACT
Development of stimulus-responsive materials is crucial for novel soft actuators. Among these actuators, the moisture-responsive actuators are known for their accessibility, eco-friendliness, and robust regenerative attributes. A major challenge of moisture-responsive soft actuators (MRSAs) is achieving significant bending curvature within short response times. Many plants naturally perform large deformation through a layered hierarchical structure in response to moisture stimuli. Drawing inspiration from the bionic structure of Delosperma nakurense (D. nakurense) seed capsule, here the fabrication of an ultrafast bi-directional bending MRSAs is reported. Combining a superfine silk fibroin rod (SFR) modified graphene oxide (GO) moisture-responsive layer with a moisture-inert layer of reduced graphene oxide (RGO), this actuator demonstrated large bi-directional bending deformation (-4.06 ± 0.09 to 10.44 ± 0.00 cm-1) and ultrafast bending rates (7.06 cm-1 s-1). The high deformation rate is achieved by incorporating the SFR into the moisture-responsive layers, facilitating rapid water transmission within the interlayer structure. The complex yet predictable deformations of this actuator are demonstrated that can be utilized in smart switch, robotic arms, and walking device. The proposed SFR modification method is simple and versatile, enhancing the functionality of hierarchical layered actuators. It holds the potential to advance intelligent soft robots for application in confined environments.
ABSTRACT
Injectable bioadhesives are attractive for managing gastric ulcers through minimally invasive procedures. However, the formidable challenge is to develop bioadhesives that exhibit high injectability, rapidly adhere to lesion tissues with fast gelation, provide reliable protection in the harsh gastric environment, and simultaneously ensure stringent standards of biocompatibility. Here, a natural bioadhesive with tunable cohesion is developed based on the facile and controllable gelation between silk fibroin and tannic acid. By incorporating a hydrogen bond disruptor (urea or guanidine hydrochloride), the inherent network within the bioadhesive is disturbed, inducing a transition to a fluidic state for smooth injection (injection force <5 N). Upon injection, the fluidic bioadhesive thoroughly wets tissues, while the rapid diffusion of the disruptor triggers instantaneous in situ gelation. This orchestrated process fosters the formed bioadhesive with durable wet tissue affinity and mechanical properties that harmonize with gastric tissues, thereby bestowing long-lasting protection for ulcer healing, as evidenced through in vitro and in vivo verification. Moreover, it can be conveniently stored (≥3 m) postdehydration. This work presents a promising strategy for designing highly injectable bioadhesives utilizing natural feedstocks, avoiding any safety risks associated with synthetic materials or nonphysiological gelation conditions, and offering the potential for minimally invasive application.
Subject(s)
Hydrogen Bonding , Stomach Ulcer , Animals , Stomach Ulcer/drug therapy , Injections , Tissue Adhesives/chemistry , Adhesives/chemistry , Fibroins/chemistry , Tannins/chemistry , Rats, Sprague-DawleyABSTRACT
Inherent dendrite growth and side reactions of zinc anode caused by its unstable interface in aqueous electrolytes severely limit the practical applications of zinc-ion batteries (ZIBs). To overcome these challenges, a protective layer for Zn anode inspired by cytomembrane structure is developed with PVA as framework and silk fibroin gel suspension (SFs) as modifier. This PVA/SFs gel-like layer exerts similar to the solid electrolyte interphase, optimizing the anode-electrolyte interface and Zn2+ solvation structure. Through interface improvement, controlled Zn2+ migration/diffusion, and desolvation, this buffer layer effectively inhibits dendrite growth and side reactions. The additional SFs provide functional improvement and better interaction with PVA by abundant functional groups, achieving a robust and durable Zn anode with high reversibility. Thus, the PVA/SFs@Zn symmetric cell exhibits an ultra-long lifespan of 3150 h compared to bare Zn (182 h) at 1.0 mAh cm-2-1.0 mAh cm-2, and excellent reversibility with an average Coulombic efficiency of 99.04% under a large plating capacity for 800 cycles. Moreover, the PVA/SFs@Zn||PANI/CC full cells maintain over 20 000 cycles with over 80% capacity retention under harsh conditions at 5 and 10 A g-1. This SF-modified protective layer for Zn anode suggests a promising strategy for reliable and high-performance ZIBs.
ABSTRACT
Natural-derived biomaterials can be used as substrates for the growth, proliferation, and differentiation of cells. In this study, bovine vitreous humor as a biological material was cross-linked to silk fibroin with different concentration ratios to design a suitable substrate for corneal tissue regeneration. The cross-linked samples were evaluated with different analyses such as structural, physical (optical, swelling, and degradation), mechanical, and biological (viability, cell adhesion) assays. The results showed that all samples had excellent transparency, especially those with higher silk fibroin content. Increasing the ratio of vitreous humor to silk fibroin decreased mechanical strength and increased swelling and degradation, respectively. There was no significant difference in the toxicity of the samples, and with the increase in vitreous humor ratio, adhesion and cell proliferation increased. Generally, silk fibroin with vitreous humor can provide desirable characteristics as a transparent film for corneal wound healing.
ABSTRACT
In this study, a novel array electrospinning collector was devised to generate two distinct regenerated silk fibroin (SF) fibrous membranes: ordered and disordered. Leveraging electrostatic forces during the electrospinning process allowed precise control over the orientation of SF fiber, resulting in the creation of membranes comprising both aligned and randomly arranged fiber layers. This innovative approach resulted in the development of large-area membranes featuring exceptional stability due to their alternating patterned structure, achievable through expansion using the collector, and improving the aligned fiber membrane mechanical properties. The study delved into exploring the potential of these membranes in augmenting wound healing efficiency. Conducting in vitro toxicity assays with adipose tissue-derived mesenchymal stem cells (AD-MSCs) and normal human dermal fibroblasts (NHDFs) confirmed the biocompatibility of the SF membranes. We use dual perspectives on exploring the effects of different conditioned mediums produced by cells and structural cues of materials on NHDFs migration. The nanofibers providing the microenvironment can directly guide NHDFs migration and also affect the AD-MSCs and NHDFs paracrine effects, which can improve the chemotaxis of NHDFs migration. The ordered membrane, in particular, exhibited pronounced effectiveness in guiding directional cell migration. This research underscores the revelation that customizable microenvironments facilitated by SF membranes optimize the paracrine products of mesenchymal stem cells and offer valuable physical cues, presenting novel prospects for enhancing wound healing efficiency.
ABSTRACT
Osteoporotic bone defects, a severe complication of osteoporosis, are distinguished by a delayed bone healing process and poor repair quality. While bone marrow-derived mesenchymal stem cells (BMMSCs) are the primary origin of bone-forming osteoblasts, their mitochondrial function is impaired, leading to inadequate bone regeneration in osteoporotic patients. Melatonin is well-known for its antioxidant properties and regulation on bone metabolism. The present study postulated that melatonin has the potential to enhance the repair of osteoporotic bone defects by restoring the mitochondrial function of BMMSCs. In vitro administration of melatonin at varying concentrations (0.01, 1, and 100 µM) demonstrated a significant dose-dependent improvement in the mitochondrial function of BMMSCs obtained from ovariectomized rats (OVX-BMMSCs), as indicated by an elevation in mitochondrial membrane potential, adenosine triphosphate synthesis and expression of mitochondrial respiratory chain factors. Melatonin reduced the level of mitochondrial superoxide by activating the silent information regulator type 1 (SIRT1) and its downstream antioxidant enzymes, particularly superoxide dismutase 2 (SOD2). The protective effects of melatonin were found to be nullified upon silencing of Sirt1 or Sod2, underscoring the crucial role of the SIRT1-SOD2 axis in the melatonin-induced enhancement of mitochondrial energy metabolism in OVX-BMMSCs. To achieve a sustained and localized release of melatonin, silk fibroin scaffolds loaded with melatonin (SF@MT) were fabricated. The study involved the surgical creation of bilateral femur defects in OVX rats, followed by the implantation of SF@MT scaffolds. The results indicated that the application of melatonin partially restored the mitochondrial energy metabolism and osteogenic differentiation of OVX-BMMSCs by reinstating mitochondrial redox homeostasis. These findings suggest that the localized administration of melatonin through bone implants holds potential as a therapeutic approach for addressing osteoporotic bone defects.
Subject(s)
Melatonin , Mesenchymal Stem Cells , Osteoporosis , Humans , Rats , Animals , Osteogenesis , Melatonin/metabolism , Sirtuin 1/metabolism , Antioxidants/therapeutic use , Bone Marrow/metabolism , Osteoporosis/drug therapy , Cell Differentiation , Mitochondria/metabolism , Cells, CulturedABSTRACT
Brain damage is a common tissue damage caused by trauma or diseases, which can be life-threatening. Stem cell implantation is an emerging strategy treating brain damage. The stem cell is commonly embedded in a matrix material for implantation, which protects stem cell and induces cell differentiation. Cell differentiation induction by this material is decisive in the effectiveness of this treatment strategy. In this work, we present an injectable fibroin/MXene conductive hydrogel as stem cell carrier, which further enables in-vivo electrical stimulation upon stem cells implanted into damaged brain tissue. Cell differentiation characterization of stem cell showed high effectiveness of electrical stimulation in this system, which is comparable to pure conductive membrane. Axon growth density of the newly differentiated neurons increased by 290% and axon length by 320%. In addition, unfavored astrocyte differentiation is minimized. The therapeutic effect of this system is proved through traumatic brain injury model on rats. Combined with in vivo electrical stimulation, cavities formation is reduced after traumatic brain injury, and rat motor function recovery is significantly promoted.
Subject(s)
Bombyx , Brain Injuries, Traumatic , Fibroins , Mesenchymal Stem Cells , Neural Stem Cells , Nitrites , Transition Elements , Rats , Animals , Fibroins/metabolism , Fibroins/pharmacology , Bombyx/metabolism , Hydrogels/pharmacology , Neurons/metabolism , Brain/metabolism , Brain Injuries, Traumatic/metabolismABSTRACT
Bioactive agents have demonstrated regenerative potential for cell-free bone tissue engineering. Nevertheless, certain challenges persist, including ineffective delivery methods and confined therapeutic potency. Here, we demonstrated that the biomimetic calcium phosphate coating system (BioCaP) could effectively uptake and slowly release the incorporated bioactive agents compared to the surface absorption system via osteoclast-mediated degradation of BioCaP coatings. The release kinetics were determined as a function of time. The release rate was stable without remarkable burst release during the first 1 day, followed by a sustained release from day 7 to day 19. Then, we developed the bi-functional BioCaP-coated silk fibroin scaffolds enabling the effective co-delivery of TGF-ß3 and BMP-2 (SFI-T/SFI-B) and the corresponding slow release of TGF-ß3 and BMP-2 exhibited superior potential in promoting chondrogenesis and osteogenesis without impairing cell vitality in vitro. The SFI-T/SFI-B scaffolds could improve cartilage and bone regeneration in 5 × 4 mm rabbit osteochondral (OC) defect. These findings indicate that the biomimetic calcium-phosphate coated silk fibroin scaffolds with slowly co-released TGF-ß3 and BMP-2 effectively promote the repair of OC defects, hence facilitating the future clinical translation of controlled drug delivery in tissue engineering.
Subject(s)
Bone Morphogenetic Protein 2 , Bone Regeneration , Calcium Phosphates , Fibroins , Osteogenesis , Tissue Engineering , Tissue Scaffolds , Transforming Growth Factor beta3 , Fibroins/chemistry , Fibroins/pharmacology , Animals , Bone Morphogenetic Protein 2/pharmacology , Transforming Growth Factor beta3/pharmacology , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Rabbits , Tissue Scaffolds/chemistry , Bone Regeneration/drug effects , Tissue Engineering/methods , Osteogenesis/drug effects , Chondrogenesis/drug effects , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Bombyx , MaleABSTRACT
Nanocomposites selectively induce cancer cell death, holding potential for precise liver cancer treatment breakthroughs. This study assessed the cytotoxicity of gold nanocomposites (Au NCs) enclosed within silk fibroin (SF), aptamer (Ap), and the myogenic Talaromyces purpureogenus (TP) against a human liver cancer cell (HepG2). The ultimate product, Ap-SF-TP@Au NCs, results from a three-step process. This process involves the myogenic synthesis of TP@Au NCs derived from TP mycelial extract, encapsulation of SF on TP@Au NCs (SF-TP@Au NCs), and the conjugation of Ap within SF-TP@Au NCs. The synthesized NCs are analyzed by various characteristic techniques. Ap-SF-TP@Au NCs induced potential cell death in HepG2 cells but exhibited no cytotoxicity in non-cancerous cells (NIH3T3). The morphological changes in cells were examined through various biochemical staining methods. Thus, Ap-SF-TP@Au NCs emerge as a promising nanocomposite for treating diverse cancer cells.
ABSTRACT
It is challenging to recapitulate the natural extracellular matrix's hierarchical nano/microfibrous three-dimensional (3D) structure with multilevel pores, good mechanical and hydrophilic properties, and excellent bioactivity for designing and developing advanced biomimetic materials. This work reports a new facile strategy for the scalable manufacturing of such a 3D architecture. Natural polymers in an aqueous solution are interpenetrated into a 3D microfibrous matrix with arbitrary shapes and property characteristics to self-assemble in situ into a nanofibrous network. The collagen fiber-like hierarchical structure and interconnected multilevel pores are achieved by self-assembly of the formed nanofibers within the 3D matrix, triggered by a simple cross-linking treatment. The as-prepared alginate/polypropylene biomimetic matrices are bioactive and have a tunable mechanical property (compressive modulus from â¼17 to â¼24 kPa) and a tunable hydrophilicity (water contact angle from â¼94° to 63°). This facile and versatile strategy allows eco-friendly and scalable manufacturing of diverse biomimetic matrices or modification of any existing porous matrices using different polymers.
ABSTRACT
The traditional production mode of the sericulture industry is no longer suitable for the development requirements of modern agriculture; to facilitate the sustainable development of the sericulture industry, factory all-age artificial diet feeding came into being. Understanding the structural characteristics and properties of silk fibers obtained from factory all-age artificial diet feeding is an important prerequisite for application in the fields of textiles, clothing, biomedicine, and others. However, there have been no reports so far. In this paper, by feeding silkworms with factory all-age artificial diets (AD group) and mulberry leaves (ML group), silk fibers were obtained via two different feeding methods. The structure, mechanical properties, hygroscopic properties, and degradation properties were studied by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). Structurally, no new functional groups appeared in the AD group. Compared with the ML group, the structure of the two groups was similar, and there was no significant difference in mechanical properties and moisture absorption. The structure of degummed silk fibers is dominated by crystalline regions, but α-chymotrypsin hydrolyzes the amorphous regions of silk proteins, so that after 28 d of degradation, the weight loss of both is very small. This provides further justification for the feasibility of factory all-age artificial diets for silkworms.
Subject(s)
Bombyx , Silk , Animals , Silk/chemistry , Bombyx/chemistry , X-Ray Diffraction , Spectroscopy, Fourier Transform Infrared , Thermogravimetry , Morus/chemistryABSTRACT
The various wastes generated by silkworm silk textiles that are no longer in use are increasing, which is causing considerable waste and contamination. This issue has attracted widespread attention in countries that use a lot of silk. Therefore, enhancing the mechanical properties of regenerated silk fibroin (RSF) and enriching the function of silk are important directions to expand the comprehensive utilization of silk products. In this paper, the preparation of RSF/Al2O3 nanoparticles (NPs) hybrid fiber with different Al2O3 NPs contents by wet spinning and its novel performance are reported. It was found that the RSF/Al2O3 NPs hybrid fiber was a multifunctional fiber material with thermal insulation and UV resistance. Natural light tests showed that the temperature rise rate of RSF/Al2O3 NPs hybrid fibers was slower than that of RSF fibers, and the average temperature rose from 29.1 °C to about 35.4 °C in 15 min, while RSF fibers could rise to about 40.1 °C. UV absorption tests showed that the hybrid fiber was resistant to UV radiation. Furthermore, the addition of Al2O3 NPs may improve the mechanical properties of the hybrid fibers. This was because the blending of Al2O3 NPs promoted the self-assembly of ß-sheets in the RSF reaction mixture in a dose-dependent manner, which was manifested as the RSF/Al2O3 NPs hybrid fibers had more ß-sheets, crystallinity, and a smaller crystal size. In addition, RSF/Al2O3 NPs hybrid fibers had good biocompatibility and durability in micro-alkaline sweat environments. The above performance makes the RSF/Al2O3 NPs hybrid fibers promising candidates for application in heat-insulating and UV-resistant fabrics as well as military clothing.
Subject(s)
Aluminum Oxide , Fibroins , Nanoparticles , Ultraviolet Rays , Fibroins/chemistry , Nanoparticles/chemistry , Aluminum Oxide/chemistry , Animals , Bombyx , Hot Temperature , Humans , Silk/chemistryABSTRACT
BACKGROUND: The biocompatible amphiphilic silk fibroin, extracted from domesticated silkworms, can adsorb at the oil-water interface and form elastic interfacial layers. In this study, three surfactants (cationic cetyltrimethylammonium bromide, the nonionic polyoxyethylene sorbitan monolaurate, and the anionic sodium dodecyl sulfate) were selected to investigate, through interfacial shear rheology, the influences of surfactants on the interfacial viscoelasticity and stability of silk fibroin at the interfaces between water and two different oils. RESULTS: The presence of surfactant prolongs the equilibration time and enhances the interfacial elastic modulus and toughness of the interfacial silk fibroin layers, especially at the nonpolar dodecane-water interface. However, when the surfactant exceeds a critical concentration, the shear modulus and stability of interfacial silk fibroin layers begin to decrease due to the competitive adsorption of surfactant molecules and the weakening of the protein network. Owing to electrostatic interactions, the ionic surfactants cetyltrimethylammonium bromide and sodium dodecyl sulfate can form more hydrophobic complexes with silk fibroin, which results in higher shear moduli than for silk fibroin and silk fibroin-polyoxyethylene sorbitan monolaurate mixture. CONCLUSION: Both the surfactant type and oil polarity play important roles in the adsorption, shear viscoelasticity, and stability of silk fibroin at the oil-water interface. Enhanced interactions between a silk fibroin-surfactant mixture and the oil phase delay the equilibration of the adsorption layers but strengthen the stability of interfacial layers. © 2023 Society of Chemical Industry.
Subject(s)
Fibroins , Surface-Active Agents , Surface-Active Agents/chemistry , Fibroins/chemistry , Sodium Dodecyl Sulfate , Cetrimonium , Polysorbates , Water/chemistry , Oils/chemistryABSTRACT
Silk fibroin (SF) microparticles were administered in the diet of gilthead seabream with or without experimental skin wounds to study the effects on cellular immunity and liver. A commercially available diet was enriched with varying amount of SF: 0, 50 and 100 mg kg-1 (representing the control, SF50 and SF100 diets respectively). The animals were fed for 30 days and half of them were sampled. Similar experimental wounds were then performed on the rest of fish, and they continued to be fed the same diet. At 7 days post-wounding, samples were taken from the wounded fish. Cellular immunity was studied on head kidney leucocytes (phagocytosis, respiratory and peroxidase content) and liver status (histological study and gene expression) were studied. Our results showed that experimental wounds affect both cellular immunity (by decreasing leucocyte respiratory burst and peroxidase activity) and altered liver histology (by inducing vascularisation and congestion of blood vessels). In addition, it influences the expression of genes that serve as markers of oxidative stress, endoplasmic reticulum stress and apoptosis. The highest dose of SF (SF100) increased the phagocytic capacity of leucocytes the most, as well as the expression of genes related to blood vessel formation in the liver. Furthermore, increased expression of antioxidant genes (cat and gsr) and decreased expression of genes related to reticulum endoplasmic stress (grp94 and grp170) and apoptosis (nos and jnk) were detected in these fish fed with SF100 and wounded. In conclusion, fed fish with SF100 had many beneficial effects as cellular immunostimulant and hepatoprotection in wounded fish. Its use could be of great interest for stress management in farmed fish conditions.
Subject(s)
Fibroins , Immunity, Cellular , Liver , Sea Bream , Animals , Liver/drug effects , Sea Bream/immunology , Fibroins/chemistry , Immunity, Cellular/drug effects , Skin/drug effects , Skin/injuries , Gene Expression Regulation/drug effects , Animal Feed/analysis , Diet/veterinaryABSTRACT
Targeted drug delivery of biological molecules using the development of biocompatible, non-toxic and biodegradable nanocarriers can be a promising method for cancer therapy. In this study, silk fibroin protein nanoparticles (SFPNPs) were synthesized as a targeted delivery system for sulforaphane-rich broccoli sprout extract (BSE). The BSE-loaded SFPNPs were conjugated with polyethylene glycol and folic acid, and then their physicochemical properties were characterized via UV-Vis, XRD, FTIR, DLS, FE-SEM and EDX analyses. In vitro, the release profile, antioxidant and anticancer activities of NPs were also studied. The FE-SEM and DLS analyses indicated stable NPs with an average size of 88.5 nm and high zeta potential (-32 mV). The sulforaphane release profile from NPs was pH-dependent, with the maximum release value (70%) observed in simulated intestinal fluid (pH = 7.4). Encapsulation of BSE also decreased the release rate of sulforaphane from the capsules compared to free BSE. In vitro cytotoxicity of BSE and NPs on breast cancer cell lines (MCF-7) was concentration-dependent, and the IC50 for BSE and NPs were 54 and 210 µg ml-1, respectively. Moreover, the NPs demonstrated no appreciable cytotoxicity in normal mouse fibroblast (L929) cell lines. These results indicated that biocompatible NPs synthesized as controlled and long-term targeted drug delivery systems can be a potential candidate for breast cancer therapy.
Subject(s)
Brassica , Fibroins , Isothiocyanates , Nanoparticles , Plant Extracts , Sulfoxides , Fibroins/chemistry , Brassica/chemistry , Humans , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Plant Extracts/pharmacology , Isothiocyanates/chemistry , Isothiocyanates/pharmacology , Isothiocyanates/administration & dosage , Nanoparticles/chemistry , MCF-7 Cells , Drug Carriers/chemistry , Drug Delivery Systems/methods , Drug Liberation , Animals , Particle Size , Antioxidants/pharmacology , Antioxidants/administration & dosage , Antioxidants/chemistryABSTRACT
PURPOSE: Dry eye syndrome (DES), arising from various etiologic factors, leads to tear film instability and ocular surface damage. Given its anti-inflammatory effects, cyclosporine A (CsA) has been widely used as a short-term treatment option for DES. However, poor bioavailability and solubility of CsA in aqueous phase make the development of a cyclosporine A-based eye drop for ocular topical application a huge challenge. METHODS: In this study, a novel strategy for preparing cyclosporine A-loaded silk fibroin nanoemulsion gel (CsA NBGs) was proposed to address these barriers. Additionally, the rheological properties, ocular irritation potential, tear elimination kinetics, and pharmacodynamics based on a rabbit dry eye model were investigated for the prepared CsA NBGs. Furthermore, the transcorneal mechanism across the ocular barrier was also investigated. RESULTS: The pharmacodynamics and pharmacokinetics of CsA NBGs exhibited superior performance compared to cyclosporine eye drops, leading to a significant enhancement in the bioavailability of CsA NBGs. Furthermore, our investigation into the transcorneal mechanism of CsA NBGs revealed their ability to be absorbed by corneal epithelial cells via the paracellular pathway. CONCLUSION: The CsA NBG formulation exhibits promising potential for intraocular drug delivery, enabling safe, effective, and controlled administration of hydrophobic drugs into the eye. Moreover, it enhances drug retention within the ocular tissues and improves systemic bioavailability, thereby demonstrating significant clinical translational prospects.
Subject(s)
Biological Availability , Cyclosporine , Dry Eye Syndromes , Fibroins , Gels , Ophthalmic Solutions , Rabbits , Animals , Fibroins/chemistry , Cyclosporine/administration & dosage , Cyclosporine/pharmacokinetics , Cyclosporine/chemistry , Dry Eye Syndromes/drug therapy , Ophthalmic Solutions/administration & dosage , Drug Delivery Systems/methods , Administration, Ophthalmic , Solubility , Male , Emulsions/chemistry , Cornea/metabolism , Cornea/drug effects , Disease Models, AnimalABSTRACT
Repairing skin wounds has always been challenging in clinical practice. The new skin tissue engineering scaffold provides innovative ways to address these challenges with a good chance of success because of its stable mechanical properties, biodegradability, and antibacterial properties. This paper presents the fabrication and evaluation of a three-dimensional composite scaffold made with sulfated silk fibroin, chitosan, and hydroxyapatite (SSF/CS/HAP). An electron microscope shows that the scaffold has an aperture of 15-20 µm, while an absorption performance test shows that its expansion index reaches 779%. The co-culture of L929 cells and the CCK-8 experiments demonstrated good cell compatibility and low scaffold cytotoxicity, respectively. Meanwhile, in vivo experiments demonstrate that rats with SSF/CS/HAP scaffold-treated neck wounds heal faster. In the wound skin tissue of the SSF/CS/HAP scaffold group, immunohistochemistry indicates a more rapid and mature development of hair follicles. This study successfully developed a novel skin tissue engineering scaffold material with high moisture retention, high tissue compatibility, and low cytotoxicity, demonstrating its ability to improve wound repair with promising potential for tissue engineering applications.
Subject(s)
Chitosan , Fibroins , Rats , Animals , Tissue Engineering/methods , Fibroins/chemistry , Chitosan/chemistry , Durapatite/chemistry , Sulfates , Tissue Scaffolds/chemistry , Silk/chemistry , Biocompatible Materials/chemistryABSTRACT
Silk methacrylate (SilMA) has been studied extensively due to its ability to modify Silk fibroin (SF) by increasing the water solubility and enhancing the mechanical properties of SF hydrogels. However, SilMA hydrogels are generally soft with weak mechanical properties. In order to enhance the mechanical properties of hydrogel scaffolds, we used liquid nitrogen to modify SilMA to obtain a novel N2-SilMA/gelatin-methacryloyl (GelMA) composite hydrogel. N2-SilMA was successfully detected by Fourier transform infrared (FTIR) spectroscopy and 1H nuclear magnetic resonance. Scanning electron microscope showed that the composite hydrogel still had certain arrangement characteristics of SF and dense pores which met the necessary conditions for the cell scaffold. The mechanical tests showed that the mechanical properties of SilMA were greatly enhanced after modification at ultra-low temperature. We evaluated its cytocompatibility and biocompatibility, and the results showed that the composite scaffold promoted the growth of cells. Different types of composite hydrogels were injected into ICR mice and the results showed a stable scaffold structure in vivo, suggesting their ability to promote angiogenesis. In conclusion, the N2-SilMA/GelMA composite hydrogel had better mechanical properties, excellent cytocompatibility, and biological properties compared to the other groups.