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1.
Exp Cell Res ; 443(1): 114289, 2024 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-39433171

RESUMO

Neuroblastoma (NB) is the most common pediatric extracranial solid tumor. It accounts for 50 % of cancers diagnosed in infants less than 1 year old, and 10 % of all pediatric cancer deaths in the United States. High-risk patients have a less than 50 % 5-year survival rate with current treatment strategies. The complex tumor microenvironment of NB makes the development of treatment strategies for high-risk patients challenging. There is increasing evidence that intratumoral immune suppression plays an important role in the progression and invasion of NB tumors. Few three-dimensional (3D) cancer models include components of the innate immune system. This work develops a preclinical 3D NB-immune co-culture model using SK-N-AS NB cells, NK-92 natural killer cells, and THP-1 derived macrophages, co-cultured on porous 3D silk scaffolds to provide tumor architecture. Conditioned media and indirect co-culturing showed changes in SK-N-AS gene expression associated with immunoregulatory signaling, and changes in NK-92 gene expression that are associated with reduced cytotoxicity. This motivated the development of a 3D direct co-culture system in which NB cells were seeded prior to immune cells to allow incorporation and deposition of extracellular matrix within the construct. Immune cells were then incorporated into the model to achieve direct co-culture with SK-N-AS cells. Changes in THP-1 macrophage polarization toward a more M2-like phenotype were observed in 3D direct co-culture, as well as altered NK-92 cell protein secretion and cytotoxic activity. Preliminary testing of immunotherapeutics within the model was conducted on both NB-macrophage and NB-NK co-cultures, but the model demonstrated limited response to immunotherapeutics. This work lays the foundation for building high-throughput therapeutic screening models for the improved treatment NB and other solid tumors.

2.
Small ; : e2403376, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39221643

RESUMO

Proteins are classified as biopolymers which share similar structural features with semi-crystalline polymers. Although their unique biocompatibility facilitates the universal applications of protein-based hydrogels in the biomedical field, the mechanical performances of protein-based hydrogels fall short of practical requirements. Conventional strategies for enhancing mechanical properties focus on forming regularly folded secondary structures as analogs of crystalline regions. This concept is based on proteins as the analogy of semi-crystalline polymers, in which crystalline regions profoundly contribute to the mechanical performances. Even though the contribution of the amorphous region is equally weighted for semi-crystalline polymers, their capacity to improve the mechanical performances of protein-based structures is still undervalued. Herein, the potential of promoting the mechanical performances is explored by controlling the state of amorphous regions in protein-based hydrogels. A fibril protein is chosen, regenerated silk fibroin (RSF), as a model molecule for its similar viscoelasticity with a semi-crystalline polymer. The amorphous regions in the RSF hydrogels are transformed from extended to entangled states through a double-crosslinking method. The formation of entanglement integrates new physically crosslinked points for remarkable improvement in mechanical performances. A robust hydrogel is not only developed but also intended to provide new insights into the structural-property relationship of protein-based hydrogels.

3.
Small ; : e2405049, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39101301

RESUMO

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.

4.
Small ; 20(25): e2309364, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38225691

RESUMO

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.

5.
Small ; 20(24): e2307628, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38191883

RESUMO

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.


Assuntos
Ligação de Hidrogênio , Úlcera Gástrica , Animais , Úlcera Gástrica/tratamento farmacológico , Injeções , Adesivos Teciduais/química , Adesivos/química , Fibroínas/química , Taninos/química , Ratos Sprague-Dawley
6.
Small ; 20(18): e2308833, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38185768

RESUMO

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.


Assuntos
Antibacterianos , Bandagens , Hemostasia , Hemostáticos , Nanofibras , Animais , Nanofibras/química , Hemostasia/efeitos dos fármacos , Hemostáticos/química , Hemostáticos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Ratos , Fibroínas/química , Fibroínas/farmacologia , Bivalves/química , Proteínas/química , Seda/química , Ratos Sprague-Dawley
7.
Small ; 20(34): e2400565, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38602450

RESUMO

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.

8.
J Transl Med ; 22(1): 946, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39420402

RESUMO

BACKGROUND: Intracerebral hemorrhage (ICH) is a severe form of stroke characterized by high incidence and mortality rates. Currently, there is a significant lack of effective treatments aimed at improving clinical outcomes. Our research team has developed a three-dimensional (3D) biological scaffold that incorporates Bergenin, allowing for the sustained release of the compound. METHODS: This 3D biological scaffold was fabricated using a combination of photoinitiator, GEMA, silk fibroin, and decellularized brain matrix (dECM) to encapsulate Bergenin through advanced 3D bioprinting techniques. The kinetics of drug release were evaluated through both in vivo and in vitro studies. A cerebral hemorrhage model was established, and a 3D biological scaffold containing Bergenin was transplanted in situ. Levels of inflammatory response, oxidative stress, and apoptosis were quantified. The neurological function of rats with cerebral hemorrhage was assessed on days 1, 3, and 5 using the turning test, forelimb placement test, Longa score, and Bederson score. RESULTS: The 3D biological scaffold incorporating Bergenin significantly enhances the maintenance of drug concentration in the bloodstream, leading to a marked reduction in inflammatory markers such as IL-6, iNOS, and COX-2 levels in a cerebral hemorrhage model, primarily through the inhibition of the NF-κB pathway. Additionally, the scaffold effectively reduces the expression of hypoxia-inducible factor 1-alpha (HIF-1α) in primary cultured astrocytes, which in turn decreases the production of reactive oxygen species (ROS) and inhibits IL-6 production induced by hemin. Subsequent experiments reveal that the 3D biological scaffold containing Bergenin promotes the activation of the Nrf-2/HO-1 signaling pathway, both in vivo and in vitro, thereby preventing cell death. Moreover, the application of this 3D biological scaffold has been demonstrated to improve drug retention in the bloodstream. CONCLUSION: This strategy effectively mitigates inflammation, oxidative stress, and cell death in rats with cerebral hemorrhage by inhibiting the NF-κB pathway while concurrently activating the Nrf-2/HO-1 pathway.


Assuntos
Benzopiranos , Hemorragia Cerebral , Doenças Neuroinflamatórias , Animais , Masculino , Ratos , Apoptose/efeitos dos fármacos , Benzopiranos/farmacologia , Benzopiranos/uso terapêutico , Benzopiranos/química , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/complicações , Hemorragia Cerebral/patologia , Doenças Neuroinflamatórias/tratamento farmacológico , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Alicerces Teciduais/química
9.
Microb Pathog ; 196: 106999, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39395744

RESUMO

Biofilm formation is a major challenge in the treatment of tuberculosis, leading to poor treatment outcomes and latent infections. The complex and dense extracellular polymeric substances (EPS) of the biofilm provides safe harbour for bacterium enabling persistence against anti-TB antibiotics. In this study, we demonstrated that rifampicin-encapsulated silk fibroin nanoparticles immobilized with antibiofilm enzymes can disrupt the Mycobacterium smegmatis biofilm and facilitate the anti-bacterial action of Rifampicin (RIF). The EPS of M.smegmatis biofilm predominantly comprised of lipids (48.8 ± 1.32 %) and carbohydrates (34.8 ± 4.70 %), similar to tuberculosis biofilms. Pre-formed biofilm eradication screening revealed that hydrolytic enzymes such as ß-Glucosidase, Glucose oxidase, ɑ-Amylase, Acylase, and Phytase can exhibit biofilm eradication of M.smegmatis biofilms. The enzyme-mediated biofilm disruption was associated with a decrease in hydrophobicity of biofilm surfaces. Treatment with ß-glucosidase and Phytase demonstrated a putative biofilm eradication by reducing the total carbohydrates and lipid composition without causing any significant bactericidal activity. Further, Phytase (250 µg/ml) and ß-Glucosidase (112.5 ± 17.6 µg/ml) conjugated rifampicin-loaded silk fibroin nanoparticles (R-SFNs) exhibited an enhanced anti-bacterial activity against pre-formed M.smegmatis biofilms, compared to free rifampicin (32.5±7 µg/ml). Notably, treatment with ß-glucosidase, Phytase and ɑ-amylase immobilized SFNs decreased the biofilm thickness by ∼98.84 % at 6h, compared to control. Thus, the study highlights that coupling anti-mycobacterial drugs with biofilm-eradicating enzymes such as amylase, phytase or ß-glucosidase can be a potential strategy to improve the TB therapeutic outcomes.


Assuntos
Antibacterianos , Biofilmes , Enzimas Imobilizadas , Fibroínas , Mycobacterium smegmatis , Nanopartículas , Rifampina , Biofilmes/efeitos dos fármacos , Nanopartículas/química , Rifampina/farmacologia , Fibroínas/química , Fibroínas/farmacologia , Mycobacterium smegmatis/efeitos dos fármacos , Enzimas Imobilizadas/química , Enzimas Imobilizadas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , 6-Fitase/farmacologia , 6-Fitase/metabolismo , 6-Fitase/química , beta-Glucosidase/metabolismo , beta-Glucosidase/química , Testes de Sensibilidade Microbiana , Glucose Oxidase/farmacologia , Glucose Oxidase/metabolismo , Glucose Oxidase/química , Matriz Extracelular de Substâncias Poliméricas/química , Matriz Extracelular de Substâncias Poliméricas/efeitos dos fármacos , Matriz Extracelular de Substâncias Poliméricas/metabolismo , alfa-Amilases/metabolismo , alfa-Amilases/farmacologia , alfa-Amilases/antagonistas & inibidores , Interações Hidrofóbicas e Hidrofílicas
10.
Biopolymers ; : e23612, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38994706

RESUMO

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.

11.
Biotechnol Bioeng ; 121(10): 3224-3238, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38924076

RESUMO

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.


Assuntos
Fibroínas , Células-Tronco Mesenquimais , Cicatrização , Fibroínas/química , Humanos , Células-Tronco Mesenquimais/citologia , Fibroblastos/citologia , Células Cultivadas , Animais , Nanofibras/química , Alicerces Teciduais/química , Bombyx/química
12.
J Pineal Res ; 76(1): e12924, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37941528

RESUMO

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.


Assuntos
Melatonina , Células-Tronco Mesenquimais , Osteoporose , Humanos , Ratos , Animais , Osteogênese , Melatonina/metabolismo , Sirtuína 1/metabolismo , Antioxidantes/uso terapêutico , Medula Óssea/metabolismo , Osteoporose/tratamento farmacológico , Diferenciação Celular , Mitocôndrias/metabolismo , Células Cultivadas
13.
Environ Res ; 262(Pt 1): 119856, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39197485

RESUMO

Artificial biomanufacturing has been developed as a promising biotechnology for water pollution control. Effective bioimmobilization techniques are limited in application because of low productivity and the difficulty in achieving both mechanical strength and biocompatibility. Bioprinting technology, using biomaterials as bioink to enable the rapid on-demand production of bioactive structures, opens a new path for bioimmobilization. In this study, mimicking extracellular polysaccharide and protein of aerobic granular sludge (AGS), sodium alginate (SA) and silk fibroin methacryloyl (SilMA) were developed as the dual-component bioink with a suitable viscosity for bioprinting hydrogel. Interpenetrating network (IPN) hydrogel beads were manufactured using 1.5% (w/v) SA combined with 20% (w/v) SilMA through physical and covalent crosslinking, which exhibited excellent structural stability and bioactivity. The addition of SilMA provided a solution to the poor mechanical stability of SA-Ca hydrogels limited by Ca2+-Na+ ionic exchange. The unique structure of SilMA contributed to the reduction of hydrogel swelling as well as the prevention of SA loss. IPN hydrogels showed a swelling rate of less than 20% compared to the high swelling rate of more than 60% for SA hydrogels. On the other hand, SA controlled the hardening induced by excessive self-assembly of SilMA and improved mass transport in SilMA hydrogels. Compared to IPN hydrogels, SilMA hydrogels experienced a 15% volumetric shrinkage and exhibited a low water content of 92%. Sonication pretreatment of the dual-component bioink not only increased the intermolecular chain entanglement to form IPN, but also led to ß-sheet content in SiMA reaching 46%-48%, which resulted in the formation of stable IPN hydrogels dominated entirely by physical crosslinking. Satisfactory proliferation and viability were achieved for the encapsulated bacteria in IPN hydrogels (µmax 1.49-2.18 d-1). Further, the IPN biohydrogels could maintain structural stability as well as achieve pollutant removal for treating synthetic wastewater with high Na+ concentration of 300 mg/L. The novel SA/SilMA hydrogel bioprinting strategy established in this study offers a new direction for bioimmobilization in water pollution control and other environmental applications.

14.
J Nanobiotechnology ; 22(1): 453, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080653

RESUMO

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.


Assuntos
Proteína Morfogenética Óssea 2 , Regeneração Óssea , Fosfatos de Cálcio , Fibroínas , Osteogênese , Engenharia Tecidual , Alicerces Teciduais , Fator de Crescimento Transformador beta3 , Fibroínas/química , Fibroínas/farmacologia , Animais , Proteína Morfogenética Óssea 2/farmacologia , Fator de Crescimento Transformador beta3/farmacologia , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Coelhos , Alicerces Teciduais/química , Regeneração Óssea/efeitos dos fármacos , Engenharia Tecidual/métodos , Osteogênese/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Bombyx , Masculino
15.
J Nanobiotechnology ; 22(1): 111, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486273

RESUMO

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.


Assuntos
Bombyx , Lesões Encefálicas Traumáticas , Fibroínas , Células-Tronco Mesenquimais , Células-Tronco Neurais , Nitritos , Elementos de Transição , Ratos , Animais , Fibroínas/metabolismo , Fibroínas/farmacologia , Bombyx/metabolismo , Hidrogéis/farmacologia , Neurônios/metabolismo , Encéfalo/metabolismo , Lesões Encefálicas Traumáticas/metabolismo
16.
Biotechnol Lett ; 46(5): 871-885, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38676857

RESUMO

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.


Assuntos
Antineoplásicos , Apoptose , Aptâmeros de Nucleotídeos , Proliferação de Células , Fibroínas , Ouro , Nanocompostos , Fibroínas/química , Fibroínas/farmacologia , Ouro/química , Ouro/farmacologia , Humanos , Camundongos , Nanocompostos/química , Células Hep G2 , Animais , Apoptose/efeitos dos fármacos , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/farmacologia , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Células NIH 3T3 , Nanopartículas Metálicas/química
17.
Nano Lett ; 23(18): 8602-8609, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37706635

RESUMO

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 ∼17 to ∼24 kPa) and a tunable hydrophilicity (water contact angle from ∼94° 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.

18.
Int J Mol Sci ; 25(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39273212

RESUMO

The use of biodegradable materials combined with natural metabolites in wound dressings has received much attention. Flavonoids (FLs) from green cocoons, as metabolites, have antibacterial, antioxidant, anti-inflammatory, and other pharmacological effects. In this study, composite membranes of FL-loaded polylactic glycolic acid (PLGA)/silk fibroin (SF) were prepared by an electrospinning method. The prepared membranes, including SF, exhibited a good slow-release effect and cytocompatibility. An in vitro evaluation of the FL-loaded PLGA/SF membranes demonstrated good antioxidant, antibacterial, and anti-inflammatory properties. Animal experiments showed that the wound healing rate of PLGA/SF-2.5FL membranes within 15 days was 97.3%, and that of the control group was 72.5%. The PLGA/SF-2.5FL membranes shortened the inflammatory period of a full-layer wound model and promoted skin regeneration and wound healing by downregulating expression of the pro-inflammatory cytokines IL-1ß and TNF-α and promoting expression of the growth factors VEGF, TGF-ß, and EGF. In summary, the PLGA/SF-2.5FL composite nanofibre membrane with anti-inflammatory properties is an ideal wound dressing to promote acute wound healing.


Assuntos
Fibroínas , Flavonoides , Nanofibras , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Cicatrização , Fibroínas/química , Fibroínas/farmacologia , Cicatrização/efeitos dos fármacos , Nanofibras/química , Animais , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Flavonoides/química , Flavonoides/farmacologia , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Antioxidantes/farmacologia , Antioxidantes/química , Antibacterianos/farmacologia , Antibacterianos/química , Ratos , Masculino , Membranas Artificiais , Bandagens , Humanos
19.
Int J Mol Sci ; 25(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38892315

RESUMO

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.


Assuntos
Bombyx , Seda , Animais , Seda/química , Bombyx/química , Difração de Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Morus/química
20.
Molecules ; 29(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38731513

RESUMO

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.


Assuntos
Óxido de Alumínio , Fibroínas , Nanopartículas , Raios Ultravioleta , Fibroínas/química , Nanopartículas/química , Óxido de Alumínio/química , Animais , Bombyx , Temperatura Alta , Humanos , Seda/química
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