RESUMO
In clinical practice to treat complex injuries, the application of electrical stimulation (ES) directly to the skin complicates the wound. In this work, the effect of a conductive hydrogel mediated electric field on skin regeneration is investigated. Polypyrrole incorporated matrices of gelatin and silk fibroin were prepared by two-step interfacial polymerization. The maximum electrical conductivity of 10-4 S cm-1 was achieved when 200 mM polypyrrole was loaded. Mechanically stable and cytocompatible hydrogels were evidenced to have antioxidant and blood compatible characteristics. Human dermal fibroblast cells responded to pulsed stimulation of 100 or 300 mV mm-1 as observed from the increased expressions of TGFß1, αSMA, and COLIAI genes. Further, the increase in the αSMA protein expression with the magnitude of electrical stimulation also suggested transdifferentiation of the fibroblast to myofibroblast. Moreover, Raman spectroscopy identified two fingerprint regions (collagen and lipid) to differentiate ES treated and nontreated samples. Therefore, the combination of hydrogels and electrical stimulation has potential therapeutic effects for accelerating the rate of skin regeneration.
Assuntos
Estimulação Elétrica , Fibroblastos , Fibroínas , Gelatina , Hidrogéis , Polímeros , Pirróis , Pele , Pirróis/química , Pirróis/farmacologia , Fibroínas/química , Fibroínas/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Gelatina/química , Humanos , Polímeros/química , Polímeros/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/citologia , Pele/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Condutividade Elétrica , AnimaisRESUMO
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, É-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 É-amylase immobilized SFNs decreased the biofilm thickness by â¼98.84 % 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 HidrofílicasRESUMO
Vascular covered stents play a significant therapeutic role in cardiovascular diseases. However, the poor compliance and biological inertness of commercial materials cause post-implantation complications. Silk fibroin (SF), as a biomaterial, possesses satisfactory hemocompatibility and tissue compatibility. In this study, we developed a silk film for use in covered stents by employing a layer-by-layer self-assembly strategy with regenerated SF on silk braiding fabric. We investigated the effects on the mechanical properties of the silk films in detail, which were closely correlated with fabric parameters and layer-by-layer self-assembly. The results showed that there was a significant relationship between these factors and both the compliance and mechanical strength. The 1 × 2/90°/100/SF6 film exhibited excellent mechanical properties. Notably, compliance reached 2.6%/100 mmHg, matching that of the human saphenous vein. Thus, this strategy shows promise in developing a novel covered stent, with biocompatible and comprehensive mechanical properties, and significant potential for clinical applications.
Assuntos
Fibroínas , Teste de Materiais , Engenharia Tecidual , Engenharia Tecidual/métodos , Humanos , Fibroínas/química , Stents , Seda/química , Materiais Biocompatíveis/química , Animais , Células Endoteliais da Veia Umbilical Humana , Materiais Revestidos Biocompatíveis/química , Bombyx , Prótese VascularRESUMO
Silk fibroin is a fiber-forming protein derived from the thread of Bombyx mori silkworm cocoons. This biocompatible protein, under the kosmotropic influence of potassium phosphate, can undergo supramolecular self-assembly driven by a random coil to ß-sheet secondary structure transition. By leveraging concurrent nonspecific adsorption and self-assembly of silk fibroin, we demonstrate an interfacial phenomenon that yields adherent, defect-free nanothin protein coatings that grow continuously in time, without observable saturation in mass deposition. This noncovalent growth of silk fibroin coatings is a departure from traditionally studied protein adsorption phenomena, which generally yield adsorbed layers that saturate in mass with time and often do not completely cover the surface. Here, we explore the fundamental mechanisms of coating growth by examining the effects of coating solution parameters that promote or inhibit silk fibroin self-assembly. Results show a strong dependence of coating kinetics and structure on solution pH, salt species, and salt concentration. Moreover, coating growth was observed to occur in two stages: an early stage driven by protein-surface interactions and a late stage driven by protein-protein interactions. To describe this phenomenon, we developed a kinetic adsorption model with Langmuir-like behavior at early times and a constant steady-state growth rate at later times. Structural analysis by FTIR and photoinduced force microscopy show that small ß-sheet-rich structures serve as anchoring sites for absorbing protein nanoaggregates, which is critical for coating formation. Additionally, ß-sheets are preferentially located at the interface between protein nanoaggregates in the coating, suggesting their role in forming stable, robust coatings.
Assuntos
Bombyx , Fibroínas , Fosfatos , Fibroínas/química , Bombyx/química , Animais , Fosfatos/química , Adsorção , Nanoestruturas/química , Materiais Revestidos Biocompatíveis/química , Propriedades de Superfície , Cinética , Concentração de Íons de HidrogênioRESUMO
Bacterial keratitis (BK) is a serious ocular infection that can lead to vision impairment or blindness if not treated promptly. Herein, we report the development of a versatile composite hydrogel consisting of silk fibroin and sodium alginate, reinforced by antibiotic-loaded mesoporous silica nanoparticles (MSNs) for the treatment of BK. The drug delivery system is constructed by incorporating vancomycin- and ceftazidime-loaded MSNs into the hydrogel network. The synthesized MSNs were found to be spherical in shape with an average size of about 95 nm. The loading capacities of both drugs were approximately 45% and 43%, for vancomycin and ceftazidime respectively. Moreover, the formulation exhibited a sustained release profile, with 92% of vancomycin and 90% of ceftazidime released over a 24 h period. The cytocompatibility of the drug carrier was also confirmed by MTT assay results. In addition, we performed molecular dynamics (MD) simulations to better reflect the drug-drug and drug-MSN interactions. The results obtained from RMSD, number of contacts, and MSD analyses perfectly corroborated the experimental findings. In brief, the designed drug-MSN@hydrogel could mark an intriguing new chapter in the treatment of BK.
Assuntos
Antibacterianos , Portadores de Fármacos , Hidrogéis , Ceratite , Nanopartículas , Dióxido de Silício , Vancomicina , Dióxido de Silício/química , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas/química , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Portadores de Fármacos/química , Hidrogéis/química , Vancomicina/administração & dosagem , Vancomicina/química , Sistemas de Liberação de Medicamentos/métodos , Ceftazidima/administração & dosagem , Ceftazidima/química , Porosidade , Liberação Controlada de Fármacos , Simulação de Dinâmica Molecular , Alginatos/química , Fibroínas/química , HumanosRESUMO
Integrating biological material within soft microfluidic systems made of hydrogels offers countless possibilities in biomedical research to overcome the intrinsic limitations of traditional microfluidics based on solid, non-biodegradable, and non-biocompatible materials. Hydrogel-based microfluidic technologies have the potential to transformin vitrocell/tissue culture and modeling. However, most hydrogel-based microfluidic platforms are associated with device deformation, poor structural definition, reduced stability/reproducibility due to swelling, and a limited range in rigidity, which threatens their applicability. Herein, we describe a new methodological approach for developing a soft cell-laden microfluidic device based on enzymatically-crosslinked silk fibroin (SF) hydrogels. Its unique mechano-chemical properties and high structural fidelity, make this platform especially suited forin vitrodisease modelling, as demonstrated by reproducing the native dynamic 3D microenvironment of colorectal cancer and its response to chemotherapeutics in a simplistic way. Results show that from all the tested concentrations, 14 wt% enzymatically-crosslinked SF microfluidic platform has outstanding structural stability and the ability to perfuse fluid while displayingin vivo-like biological responses. Overall, this work shows a novel technique to obtain an enzymatically-crosslinked SF microfluidic platform that can be employed for developing soft lab-on-a-chipin vitromodels.
Assuntos
Técnicas de Cocultura , Fibroínas , Hidrogéis , Dispositivos Lab-On-A-Chip , Fibroínas/química , Hidrogéis/química , Humanos , Biomimética , Técnicas de Cultura de Células em Três Dimensões , Animais , Microfluídica , Reagentes de Ligações Cruzadas/química , Materiais Biocompatíveis/química , Bombyx , Materiais Biomiméticos/química , Engenharia Tecidual/métodos , Seda/química , Neoplasias Colorretais/patologia , Linhagem Celular TumoralRESUMO
Controlled drug release systems are pivotal in optimizing therapeutic outcomes and mitigating side effects in treatment protocols. While traditional delivery vectors such as liposomes, micro/nanoparticles, and microspheres are effective, they often struggle with consistency in drug release rates. This study addresses these issues by integrating stimuli-responsive elements specifically magnetic, thermal, and pH-responsive components into drug delivery systems for precise control. Central to our approach is the use of silk fibroin (SF), chosen for its superior biocompatibility and tunable degradation kinetics. We developed uniform carrier microspheres (CMs) by embedding polydopamine nanoparticles (PDA NPs) into SF microspheres using a custom-designed microfluidic platform. The development process and the application of this platform are detailed, highlighting the precision in control achievable. These CMs showcased enhanced photothermal effects, with the thermal response finely adjustable by altering the PDA NPs concentration, achieving a notable temperature increase of 24.5°C at 7.4 wt% concentration. High drug loading capacity (7.5%) and encapsulation efficiency (91.6%) were achieved, along with a pH-responsive release profile under near-infrared irradiation, paving the way for targeted anticancer drug delivery systems using the model drug doxorubicin hydrochloride. These findings underscore the potential of the developed CMs for external topical application, offering promising prospects for targeted cancer therapy utilizing drug-loaded microspheres.
Assuntos
Antineoplásicos , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Fibroínas , Indóis , Microesferas , Nanopartículas , Polímeros , Fibroínas/química , Polímeros/química , Indóis/química , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Concentração de Íons de Hidrogênio , Nanopartículas/química , Portadores de Fármacos/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Humanos , Animais , Temperatura , Preparações de Ação Retardada/química , Materiais Biocompatíveis/químicaRESUMO
Treatment of articular cartilage remains a great challenge due to its limited self-repair capability. In tissue engineering, a scaffold with both mechanical strength and regenerative capacity has been highly desired. This study developed a double-network scaffold based on natural biomaterials of silk fibroin (SF) and methacrylated hyaluronic acid (MAHA) using three-dimensional (3D) printing technology. Structural and mechanical characteristics of the scaffold was first investigated. To enhance its ability of recruiting endogenous bone marrow mesenchymal stem cells (BMSCs), the scaffold was conjugated with a proven BMSC-specific-affinity peptide E7, and its biocompatibility and capacity of cell recruitment were assessed in vitro. Animal experiments were conducted to evaluate cartilage regeneration after transplantation of the described scaffolds. The SF/HA scaffolds exhibited a hierarchical macro-microporous structure with ideal mechanical properties, and offered a 3D spatial microenvironment for cell migration and proliferation. In vitro experiments demonstrated excellent biocompatibility of the scaffolds to support BMSCs proliferation, differentiation, and extracellular matrix production. In vivo, superior capacity of cartilage regeneration was displayed by the SF/MAHA + E7 scaffold as compared with microfracture and unconjugated SF/MAHA scaffold based on macroscopic, histologic and imaging evaluation. In conclusion, this structurally and functionally optimized SF/MAHA + E7 scaffold may provide a promising approach to repair articular cartilage lesions in situ.
Assuntos
Cartilagem Articular , Fibroínas , Ácido Hialurônico , Células-Tronco Mesenquimais , Impressão Tridimensional , Regeneração , Alicerces Teciduais , Fibroínas/química , Alicerces Teciduais/química , Cartilagem Articular/fisiologia , Ácido Hialurônico/química , Animais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Engenharia Tecidual/métodos , Proliferação de Células , Materiais Biocompatíveis/química , Diferenciação Celular , CoelhosRESUMO
Covalent organic frameworks designed as chromatic sensors offer opportunities to probe biological interfaces, particularly when combined with biocompatible matrices. Particularly compelling is the prospect of chemical tomography - or the 3D spatial mapping of chemical detail within the complex environment of living systems. Herein, we demonstrate a chromic Covalent Organic Framework (COF) integrated within silk fibroin (SF) microneedles that probe plant vasculature, sense the alkalization of vascular fluid as a biomarker for drought stress, and provide a 3D in-vivo mapping of chemical gradients using smartphone technology. A series of Schiff base COFs with tunable pKa ranging from 5.6 to 7.6 enable conical, optically transparent SF microneedles with COF coatings of 120 to 950 nm to probe vascular fluid and the surrounding tissues of tobacco and tomato plants. The conical design allows for 3D mapping of the chemical environment (such as pH) at standoff distances from the plant, enabling in-vivo chemical tomography. Chromatic COF sensors of this type will enable multidimensional chemical mapping of previously inaccessible and complex environments.
Assuntos
Fibroínas , Fibroínas/química , Solanum lycopersicum , Tomografia/métodos , Tomografia/instrumentação , Nicotiana/química , Bases de Schiff/química , Imageamento Tridimensional/métodos , Estruturas Metalorgânicas/química , Concentração de Íons de Hidrogênio , AnimaisRESUMO
Medical plastic-appliance-based healthcare services, especially in dentistry, generate tremendous amounts of plastic waste. Given the physiological features of our mouth, it is desirable to substitute dental care plastics with viscoelastic and antimicrobial bioplastics. Herein, we develop a medical-grade and sustainable bioplastic that is viscoelastic enough to align the tooth positions, resists microbial contamination, and exhibits recyclable life cycles. In particular, we devise a molecular template involving entanglement-inducing and antimicrobial groups and prepare a silk fibroin-based dental care bioplastic. The generated compactly entangled structure endows great flexibility, toughness, and viscoelasticity. Therefore, a satisfactory orthodontic outcome is accomplished, as demonstrated by the progressive alignment of male rabbit incisors within the 2.5 mm range. Moreover, the prepared bioplastic exhibits resistance to pathogenic colonization of intraoral microbes such as Streptococcaceae and Veillonellaceae. Because the disentanglement of entangled domains enables selective separation and extraction of the components, the bioplastic can be recycled into a mechanically identical one. The proposed medical-grade and sustainable bioplastic could potentially contribute to a green healthcare future.
Assuntos
Anti-Infecciosos , Elasticidade , Animais , Coelhos , Viscosidade , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Masculino , Fibroínas/química , Assistência Odontológica , ReciclagemRESUMO
With the advancement of modern medical and brain-computer interface devices, flexible artificial nociceptors with tactile perception hold significant scientific importance and exhibit great potential in the fields of wearable electronic devices and biomimetic robots. Here, a bioinspired artificial intelligent nociceptive alarm system integrating sensing monitoring and transmission functions is constructed using a silk fibroin (SF) fibrous memristor. This memristor demonstrates high stability, low operating power, and the capability to simulate synaptic plasticity. As a result, an artificial pressure nociceptor based on the SF fibrous memristor can detect both fast and chronic pain and provide a timely alarm in the event of a fall or prolonged immobility of the carrier. Further, an array of artificial pressure nociceptors not only monitors the pressure distribution across various parts of the carrier but also provides direct feedback on the extent of long-term pressure to the carrier. This work holds significant implications for medical support in biological carriers or targeted maintenance of electronic carriers.
Assuntos
Fibroínas , Fibroínas/química , Humanos , Dispositivos Eletrônicos Vestíveis , Nociceptores/fisiologia , Materiais Biomiméticos/química , Biomimética/instrumentação , Biomimética/métodos , Robótica/instrumentaçãoRESUMO
Tyrosinase is a copper-containing polyphenol oxidase widely applied in the food, cosmetics, pharmaceutical, and other industries. Currently, the production of commercial tyrosinase primarily relies on extraction from fungi, which has high costs, low purity, low specific activity, and poor stability. The objective of this study is to obtain highly expressed bacterial tyrosinase with potential for industrial applications. The bacterial tyrosinases from five different sources were heterologously expressed in Escherichia coli BL21(DE3), and the tyrosinases TyrBm and TyrVs derived from Bacillus megaterium and Verrucomicrobium spinosum were obtained with the enzyme activities of (16.1±0.2) U/mL and (48.6±0.9) U/mL, respectively. After protein purification, we compared the enzymatic properties of TyrBm and TyrVs, which revealed that TyrVs exhibited better thermal stability and higher substrate specificity than TyrBm. On the basis of characterizing TyrVs with high catalytic performance, we established a biological hair dyeing system based on TyrVs catalysis to achieve in-situ catalytic hair dyeing. The color washing fastness test measured the ∆E value less than 7.38±0.64 after simulated 14-day cleaning. To facilitate the rapid separation of catalytic products and enzymes, we successfully constructed an immobilized enzyme TyrVs-CipA dependent on self-assembly label CipA and applied this enzyme in the DOPA modification of hydrolyzed silk fibroin (HSF). The immobilized enzyme continuously catalyzed HSF for more than seven cycles, resulting in a single DOPA modification degree exceeding 70.00%. Further investigations demonstrated that DOPA modification enhances the scavenging activity of HSF towards DPPH and O2- radicals by 507.80% and 78.23%, respectively. This study provides a technical foundation for the development of environmentally friendly biological hair dye based on tyrosinase and biomaterials for tissue engineering.
Assuntos
Bacillus megaterium , Escherichia coli , Fibroínas , Monofenol Mono-Oxigenase , Monofenol Mono-Oxigenase/metabolismo , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/química , Escherichia coli/genética , Escherichia coli/metabolismo , Bacillus megaterium/enzimologia , Bacillus megaterium/genética , Fibroínas/química , Fibroínas/biossíntese , Fibroínas/genética , Fibroínas/metabolismo , Di-Hidroxifenilalanina/metabolismo , Di-Hidroxifenilalanina/química , Di-Hidroxifenilalanina/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/química , Corantes/metabolismo , Corantes/química , HidróliseRESUMO
Biological water-responsive materials that deform with changes in relative humidity have recently demonstrated record-high actuation energy densities, showing promise as high-performance actuators for various engineering applications. However, there is a lack of theories capable of explaining or predicting the stress generated during water-responsiveness. Here, we show that the nanoscale confinement of water dominates the macroscopic dehydration-induced stress of the regenerated silk fibroin. We modified silk fibroin's secondary structure, which leads to various distributions of bulk-like mobile and tightly bound water populations. Interestingly, despite these structure variations, all silk samples start to exert force when the bound-to-mobile (B/M) ratio of confined water reaches the same level. This critical B/M water ratio suggests a common threshold above which the chemical potential of water instigates the actuation. Our findings serve as guidelines for predicting and engineering silk's WR behavior and suggest the potential of describing the WR behavior of biopolymers through confined water.
Assuntos
Fibroínas , Seda , Água , Água/química , Fibroínas/química , Seda/química , Bombyx/química , Animais , UmidadeRESUMO
Bacterial cellulose (BC) is an ideal candidate for wound dressings due to its natural origin, exceptional water-holding capacity, pliability, biocompatibility, and high absorption capability. However, the lack of essential antimicrobial activity limits its biomedical applications. This study reported BC-based wound dressings containing silk fibroin protein (SF), offering the potential for biomimetic properties, and (-)-epigallocatechin-3-gallate (EGCG) for polyphenol-assisted surface modification to promote infectious wound healing. Glycerol was used as the carbon source to promote the formation of an adhesive layer by facilitating the ß-sheet folding of SF, and different concentrations of EGCG were employed to interact with SF through strong hydrogen bonding facilitated by the polyphenolic groups. The functionalized membrane exhibited outstanding water-holding capacity, swelling ratio, and degradation properties, along with enhanced hydrophilicity, adhesiveness, and a remarkable free radical scavenging ability. Both in vitro and in vivo experiments confirmed its potent bacteriostatic activity. The composite membrane displayed excellent biocompatibility, including cellular and hemocompatibility. Importantly, it effectively promoted wound healing in murine back infections. These findings suggest the significant feasibility of the innovative modification approach, and that functionalized membranes have great potential as wound-dressing materials for infection management in future clinical applications.
Assuntos
Bandagens , Celulose , Polifenóis , Cicatrização , Cicatrização/efeitos dos fármacos , Celulose/química , Celulose/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Animais , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Fibroínas/química , Humanos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/prevenção & controle , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologiaRESUMO
Root caries is the main cause of oral pain and tooth loss in the elderly. Protecting root lesions from environmental disturbances, resisting pathogens, and facilitating remineralization over time are essential for addressing root caries, but are challenging due to the irregular root surface and the complex oral environment. Hagfish secretes slime when facing danger, which converts into gels upon contact with seawater, suffocating the predators. Inspired by hagfish's defense mechanism, a fluid-hydrogel conversion strategy is proposed to establish a mechanical self-regulating multifunctional platform for root caries treatment. The fluid system (silk fibroin-tannic acid-black phosphorene-urea, ST-BP-U), in which urea disrupts the hydrogen bonds between silk fibroin and tannic acid, can easily spread on the irregular root surface and permeate into dentinal tubules. Upon contact with the surrounding water, urea diffuses, prompting the hydrogel re-formation and creating intimate attachments with micromechanical inlay locks. Meanwhile, BP increases the crosslinking of the re-formed hydrogel network, resulting in reinforced cohesion for robust wet adhesion to the tooth root. This process establishes a structured platform for effective antimicrobial phototherapy and dentin remineralization promotion. This water-responsive fluid-hydrogel conversion system adapts to the irregular root surface in the dynamic wet environment, holding promise for addressing root caries. STATEMENT OF SIGNIFICANCE: Root caries bring a heavy burden to the aging society, but the irregular root surface and dynamic moist oral environment always hinder non-surgical therapeutic effects. Here, we propose a water-responsive fluid-hydrogel conversion strategy aimed at mechanical self-regulation on the irregular and wet root interface to construct a functional structural platform. The liquid system (ST-BP-U) that prebreak intermolecular hydrogen bonds can easily spread on irregular surfaces and dentin tubules. When encountering water, hydrogen bonds re-form, and BP increases the crosslinking of the hydrogel formed in situ. Based on this firm wet-adhesion platform, it provides powerful phototherapy effects and promotes dentin remineralization. This fluid-hydrogel conversion system turns the disadvantages of wet environment into advantages, offering a promising strategy for root caries.
Assuntos
Hidrogéis , Cárie Radicular , Remineralização Dentária , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Cárie Radicular/terapia , Cárie Radicular/tratamento farmacológico , Fototerapia , Ureia/química , Ureia/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Taninos/química , Taninos/farmacologia , Humanos , Fibroínas/químicaRESUMO
Objective: To describe the research progress of silk-based biomaterials in peripheral nerve repair and provide useful ideals to accelerate the regeneration of large-size peripheral nerve injury. Methods: The relative documents about silk-based biomaterials used in peripheral nerve regeneration were reviewed and the different strategies that could accelerate peripheral nerve regeneration through building bioactive microenvironment with silk fibroin were discussed. Results: Many silk fibroin tissue engineered nerve conduits have been developed to provide multiple biomimetic microstructures, and different microstructures have different mechanisms of promoting nerve repair. Biomimetic porous structures favor the nutrient exchange at wound sites and inhibit the invasion of scar tissue. The aligned structures can induce the directional growth of nerve tissue, while the multiple channels promote the axon elongation. When the fillers are introduced to the conduits, better growth, migration, and differentiation of nerve cells can be achieved. Besides biomimetic structures, different nerve growth factors and bioactive drugs can be loaded on silk carriers and released slowly at nerve wounds, providing suitable biochemical cues. Both the biomimetic structures and the loaded bioactive ingredients optimize the niches of peripheral nerves, resulting in quicker and better nerve repair. With silk biomaterials as a platform, fusing multiple ways to achieve the multidimensional regulation of nerve microenvironments is becoming a critical strategy in repairing large-size peripheral nerve injury. Conclusion: Silk-based biomaterials are useful platforms to achieve the design of biomimetic hierarchical microstructures and the co-loading of various bioactive ingredients. Silk fibroin nerve conduits provide suitable microenvironment to accelerate functional recovery of peripheral nerves. Different optimizing strategies are available for silk fibroin biomaterials to favor the nerve regeneration, which would satisfy the needs of various nerve tissue repair. Bioactive silk conduits have promising future in large-size peripheral nerve regeneration.
Assuntos
Fibroínas , Regeneração Nervosa , Traumatismos dos Nervos Periféricos , Nervos Periféricos , Engenharia Tecidual , Traumatismos dos Nervos Periféricos/terapia , Seda/química , Nervos Periféricos/fisiologia , Alicerces Teciduais , Fibroínas/química , Fator de Crescimento Neural , Materiais Biocompatíveis , HumanosRESUMO
Biological scaffolds are plagued by poor biomechanical properties and untimely degradation. These limitations have yet to be addressed without compromising their biocompatibility. It is desirable to avoid inflammation and have degradation with concomitant host collagen deposition or even site-appropriate in situ regeneration for the successful outcome of an implanted biological scaffold. This work aims to achieve this by utilizing a biocompatible method to modify acellular scaffolds by impregnating alkaline-catalyzed citric acid (CA) cross-linking between the extracellular matrix proteins and silk fibroin (SF)/SF-gelatin (SFG) blends. Combinatorial detergent decellularization was employed to prepare a decellularized porcine liver scaffold (DPL). After proving the decellularization efficiency, the scaffold underwent modification by vacuum impregnation with CA containing SF (SF100DPL) and SFG blends (SFG5050DPL and SFG3070DPL) following pre-cross-linking, drying, and post-cross-linking. The subsequent strength augmentation was demonstrated by significant improvement in tensile strength from 2.4 ± 0.4 MPa (DPL) to, 3.8 ± 0.7 MPa (SF100DPL), 3.4 ± 0.7 MPa (SFG5050DPL), and 3.5 ± 0.2 MPa (SFG3070DPL); Young's modulus from 8.7 ± 1.8 MPa (DPL) to 20 ± 1.9 MPa (SF100DPL), 13.3 ± 2.6 MPa (SFG5050DPL), and 16 ± 1.2 MPa (SFG3070DPL); and suture retention strength from 0.9 ± 0.08 MPa (DPL) to 2.3 ± 0.2 MPa (SF100DPL), 2.8 ± 1.2 MPa (SFG5050DPL), and 2.6 ± 0.9 MPa (SFG3070DPL). The degradation resistance of the modified scaffolds was also markedly improved. Being cytocompatible, its ability to incite tolerable inflammatory and immune responses was confirmed by rat subcutaneous implantation for 14, 30, and 90 days, in terms of inflammatory cell infiltration, neoangiogenesis, and in vitro cytokine release to assess B-cell and T-cell activation. Such ECM composite scaffolds with appropriate strength and biocompatibility offer great promise in soft tissue repair applications such as skin grafting.
Assuntos
Materiais Biocompatíveis , Fibroínas , Teste de Materiais , Alicerces Teciduais , Fibroínas/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Alicerces Teciduais/química , Suínos , Tamanho da Partícula , Resistência à Tração , Matriz Extracelular/química , Matriz Extracelular/metabolismo , HumanosRESUMO
The endowment of guided bone regeneration (GBR) membranes with the ability to activate the endogenous regenerative capability of bone to regenerate bone defects is of clinical significance. Herein we explored the preparation of the calcium compound (CC) (calcium sulfate (CaSL), calcium hydrophosphate (CaHP), or tricalcium phosphate (TCaP)) loaded ultrathin silk fibroin (SF)/gelatin (G) fibre membranes via electrospinning as the GBR membranes to regenerate the calvarial bone defects. The in vitro experiments demonstrated that the CaSL-loaded ultrathin fibrous membranes could simulate optimally the bone remodelling microenvironment in comparison with the CaHP- and TCaP-loaded fibrous membranes, displaying the highest activity to regulate the migration, proliferation, and differentiation of mesenchymal stem cells (MSCs). Also, the in vivo experiments demonstrated that the CaSL-loaded fibrous membranes presented the highest intrinsic osteoinduction to guide in situ regeneration of bone. Furthermore, the in vivo experiments demonstrated that the as-prepared composite fibrous membranes possessed good degradability. In summary, our results suggested that the CaSL-loaded fibrous membranes with high intrinsic osteoinduction and good degradability have potential to translate into clinical practice.
Assuntos
Regeneração Óssea , Remodelação Óssea , Hidrogéis , Células-Tronco Mesenquimais , Regeneração Óssea/efeitos dos fármacos , Animais , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Hidrogéis/química , Hidrogéis/farmacologia , Remodelação Óssea/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Membranas Artificiais , Ratos , Ratos Sprague-Dawley , Compostos de Cálcio/química , Compostos de Cálcio/farmacologia , Fibroínas/química , Fibroínas/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologiaRESUMO
Open wounds present a significant challenge in healthcare, requiring careful management to prevent infection and promote wound healing. Advanced wound dressings are critical need to enhance their hemostatic capabilities, antimicrobial properties, and ability to support angiogenesis and sustained moisture for optimal healing. This study introduces a flexible hemostatic dressing designed for open wounds, integrating chitosan (CS) for hemostasis and biocompatibility, silk fibroin (SF) for mechanical strength, and montmorillonite (MMT) for enhanced drug transport. The CSSF@MMT dressings showed promising mechanical strength and swift hemostasis. The CIP-loaded CSSF@MMT demonstrated sustained release for up to one week, exhibiting antibacterial properties against both Gram-positive and Gram-negative bacteria. In vitro cell migration assay demonstrated that erythropoietin-loaded CSSF@MMT dressings promoted the proliferation and migration of endothelial cells. Similarly, the chick embryo chorioallantoic membrane study indicated the same dressings exhibited a significant increase in vascular regeneration. This research suggests that the CSSF@MMT sponge dressing, incorporated with CIP and erythropoietin, holds promise in effectively halting bleeding, creating a protective environment, diminishing inflammation, and fostering wound tissue regeneration. This potential makes it a significant advancement in open wound care, potentially lowering the need for limb amputation and decreasing wound care burden worldwide.
Assuntos
Bandagens , Bentonita , Quitosana , Fibroínas , Hemostasia , Neovascularização Fisiológica , Cicatrização , Quitosana/química , Quitosana/farmacologia , Fibroínas/química , Fibroínas/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Bentonita/química , Bentonita/farmacologia , Humanos , Neovascularização Fisiológica/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Embrião de Galinha , Antibacterianos/farmacologia , Antibacterianos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , AngiogêneseRESUMO
In recent years, biological 3D printing has garnered increasing attention for tissue and organ repair. The challenge with 3D-printing inks is to combine mechanical properties as well as biocompatibility. Proteins serve as vital structural components in living systems, and utilizing protein-based inks can ensure that the materials maintain the necessary biological activity. In this study, we incorporated two natural biomaterials, silk fibroin (SF) and collagen (COL), into a low-concentration sodium alginate (SA) solution to create novel composite inks. SF and COL were modified with glycidyl methacrylate (GMA) to impart photo-cross-linking properties. The UV light test and 1H NMR results demonstrated successful curing of silk fibroin (SF) and collagen (COL) after modification and grafting. Subsequently, the printability of modified silk fibroin (RSFMA)/SA with varying concentration gradients was assessed using a set of three consecutive printing models, and the material's properties were tested. The research results prove that the addition of RSFMA and ColMA enhances the printability of low-concentration SA solutions, with the Pr values increasing from 0.85 ± 0.02 to 0.90 ± 0.03 and 0.92 ± 0.02, respectively, and the mechanical strength increasing from 0.19 ± 0.01 to 0.28 ± 0.01 and 0.38 ± 0.01 MPa; cytocompatibility has also been improved. Furthermore, rheological tests indicated that all of the inks exhibited shear thinning properties. CCK-8 experiments demonstrated that the addition of ColMA increased the cytocompatibility of the ink system. Overall, the utilization of SF and COL-modified SA materials as inks represents a promising advancement in 3D-printed ink technology.