RESUMEN
As an emerging technology, microneedles offer advantages such as painless administration, good biocompatibility, and ease of self-administration, so as to effectively treat various diseases, such as diabetes, wound repair, tumor treatment and so on. How to regulate the release behavior of loaded drugs in polymer microneedles is the core element of transdermal drug delivery. As an emerging on-demand drug-delivery technology, intelligent responsive microneedles can achieve local accurate release of drugs according to external stimuli or internal physiological environment changes. This review focuses on the research efforts in smart responsive polymer microneedles at home and abroad in recent years. It summarizes the response mechanisms based on various stimuli and their respective application scenarios. Utilizing innovative, responsive microneedle systems offers a convenient and precise targeted drug delivery method, holding significant research implications in transdermal drug administration. Safety and efficacy will remain the key areas of continuous efforts for research scholars in the future.
Asunto(s)
Piel , Polímeros de Estímulo Receptivo , Administración Cutánea , Sistemas de Liberación de Medicamentos , Preparaciones Farmacéuticas , Polímeros/farmacologíaRESUMEN
Silk fibroin (SF) has attracted much attention due to its high, tunable mechanical strength and excellent biocompatibility. Imparting the ability to respond to external stimuli can further enhance its scope of application. In order to imbue stimuli-responsive behavior in silk fibroin, we propose a new conjugated material, namely cationic SF (CSF) obtained by chemical modification of silk fibroin with ε-Poly-(L-lysine) (ε-PLL). This pH-responsive CSF hydrogel was prepared by enzymatic crosslinking using horseradish peroxidase and H2O2. Zeta potential measurements and SDS-PAGE gel electrophoresis show successful synthesis, with an increase in isoelectric point from 4.1 to 8.6. Fourier transform infrared (FTIR) and X-ray diffraction (XRD) results show that the modification does not affect the crystalline structure of SF. Most importantly, the synthesized CSF hydrogel has an excellent pH response. At 10 wt.% ε-PLL, a significant change in swelling with pH is observed. We further demonstrate that the hydrogel can be glucose-responsive by the addition of glucose oxidase (GOx). At high glucose concentration (400 mg/dL), the swelling of CSF/GOx hydrogel is as high as 345 ± 16%, while swelling in 200 mg/dL, 100 mg/dL and 0 mg/dL glucose solutions is 237 ± 12%, 163 ± 12% and 98 ± 15%, respectively. This shows the responsive swelling of CSF/GOx hydrogels to glucose, thus providing sufficient conditions for rapid drug release. Together with the versatility and biological properties of fibroin, such stimuli-responsive silk hydrogels have great potential in intelligent drug delivery, as soft matter substrates for enzymatic reactions and in other biomedical applications.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Fibroínas/química , Glucosa/metabolismo , Hidrogeles/síntesis química , Materiales Biocompatibles/química , Liberación de Fármacos , Fibroínas/metabolismo , Glucosa/química , Peroxidasa de Rábano Silvestre/química , Peróxido de Hidrógeno/química , Concentración de Iones de Hidrógeno , Polilisina/química , Seda/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Difracción de Rayos XRESUMEN
It is important to design a long-period transparent bioactive material for corneal repair in the process of corneal tissue renovation. This article discusses the silk fibroin and formamide blend membranes as a corneal stroma repair material. Silk fibroin solution was mixed with formamide in different proportions to obtain insoluble transparent silk fibroin film by casting method. The blending membranes had excellent mechanical properties, cell compatibility and long-term transparent properties. Rabbit corneal stromal cells were seeded on the sterilized composite films. The rate of cell surface adhesion was over 90% after cells were placed on it for 5 hours. When cells were seeded on blend membranes from one day to seven days, Alma Blue was added to complete medium. Compared with the cell culture plate, there was no significant difference in cell proliferation on formamide/silk films. The results indicated that formamide/silk films might be used as a corneal stroma repair material and worth of further investigatinn
Asunto(s)
Materiales Biocompatibles/química , Córnea/citología , Fibroínas/química , Animales , Adhesión Celular , Proliferación Celular , Conejos , RegeneraciónRESUMEN
Highly absorbent polymers have a wide range of applications in biomaterials, agriculture, physiological products of daily uses, and others. Silk fibroin, as a natural biomaterial with excellent biocompatibility and tunable mechanical properties, shows good prospects in the field of biomedicine applications. However, the dried fibroin hydrogel has very low absorbency. In this work, silk fibroin protein is used as the carrier, riboflavin as the photosensitizer, and accordingly, the hydrogel is prepared by free radical cross-linking under ultraviolet light. The fibroin in the hydrogel contains mainly the random coil structure. The covalent bond cross-linking hinders the crystallization of the silk fibroin, thereby an amorphous silk fibroin hydrogel is obtained. After drying, this xerogel can absorb water 90 times more than its own mass and assimilates a good amount of water within a minute. In vitro and in vivo rabbit ear hemostasis experiments show that this fabricated xerogel has good hemostatic properties. Therefore, this xerogel exhibits good promise for rapid hemostasis of wounds and absorbing other body exudates.
Asunto(s)
Fibroínas , Animales , Materiales Biocompatibles , Hidrogeles , Polímeros , ConejosRESUMEN
We reported previously that regenerated Antheraea pernyi silk fibroin (A. pernyi SF) could support the attachment and growth of human bone marrow mesenchymal stem cells (hBMSCs). In this work, the immunosupressive effects of hBMSCs cultured on the A. pernyi SF films on T-cells were investigated in vitro. The production of IL-6, CD80, CD86 and HLA-DR by the hBMSCs was also observed. The study showed that hBMSCs cultured on the regenerated A. pernyi SF films still kept their immunosupression on T-cell proliferation and IL-2 secretion. Moreover, regenerated A. pernyi SF like regenerated Bombyx mori SF and collagen did not elicit T-cell proliferation but it could support the expression of IL-6 and surface antigen of hBMSCs. Regenerated A. pernyi SF can maintain the function of hBMSCs in immunomodulation and cytokines production, which has the potential utility of hBMSCs combined with A. pernyi SF in tissue replacement and repair.
Asunto(s)
Células de la Médula Ósea/inmunología , Fibroínas , Tolerancia Inmunológica/efectos de los fármacos , Tolerancia Inmunológica/inmunología , Terapia de Inmunosupresión , Células Madre Mesenquimatosas/inmunología , Animales , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Células de la Médula Ósea/metabolismo , Proliferación Celular , Antígenos HLA-DR/metabolismo , Humanos , Interleucina-2/metabolismo , Interleucina-6/metabolismo , Activación de Linfocitos/inmunología , Ensayo de Materiales , Membranas Artificiales , Células Madre Mesenquimatosas/metabolismo , Mariposas Nocturnas , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
A photocurable silk fibroin hydrogel is prepared, for the first time, using natural silk protein fibroin and biophotosensitizer riboflavin. Riboflavin is excited by ultraviolet light to generate a triplet state which is transferred to produce active oxygen radicals with singlet oxygen as the main component. Active oxygen radicals can induce chemical cross-linking of amino-, phenol- and other groups in the silk fibroin macromolecules to form a photocurable hydrogel. The different biophysical characterizations of the gelation of this modified fibroin protein solution were studied by using Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, microplate reader and texture analyzer. The aggregate structures, surface morphologies, mechanical properties, light transmission and degradation properties of the gel were studied. The investigations showed that the silk fibroin/riboflavin hydrogels predominantly have random coils or alpha helix structures. These gels show resilience up to 90% after 80% compression and a light transmission of up to 97%. The cell culture experiment exhibits that the hydrogel has a satisfactory cytocompatibility.
Asunto(s)
Materiales Biocompatibles/química , Fenómenos Químicos , Elasticidad , Hidrogeles/química , Seda/química , Animales , Proliferación Celular , Fibroínas/química , Fenómenos Mecánicos , Ratones , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
In this paper, a swelling-modified silk fibroin (SF) microneedle for transdermal drug delivery is presented. The microneedles undergo a phase transition from a dried and rigid state to a semi-solid, acerose hydrogel state with a controlled 3-dimensional (3D) porous network structure. Different micromolecular reagents have been studied for mixing with aqueous silk fibroin to endow a swellable and insoluble capacity to the SF. The aqueous SF composite is poured on a polydimethylsiloxane (PDMS) mold with arranged micropores on its surface to fabricate SF microneedles with high fidelity and mechanical robustness. The results demonstrate that 2-ethoxyethanol (ECS) modified SF microneedles can easily pierce porcine skin with a depth of â¼200µm in vitro, and transform into semi-solid hydrogels with 50-700nm porous network inside. These swelling-modified microneedles can accomplish a significantly enhanced transdermal drug release capacity in proportion to their swelling characteristics. The better swelling capacity of the microneedles produces larger pores, resulting in higher transdermal drug release kinetics. There is also a relationship between swollen pore dimensions and the molecular weights of encapsulated therapeutics. The controllable properties of these SF microneedles coupled with their high biocompatibility, render swell-to-release ECS/SF composites as viable transdermal delivery devices.
Asunto(s)
Materiales Biocompatibles/química , Sistemas de Liberación de Medicamentos/instrumentación , Glicoles de Etileno/química , Fibroínas/química , Hidrogeles/química , Administración Cutánea , Animales , Bombyx , Dextranos/metabolismo , Dextranos/farmacocinética , Dimetilpolisiloxanos/química , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Fluoresceína-5-Isotiocianato/farmacocinética , Cinética , Agujas , Transición de Fase , Porosidad , Piel/metabolismo , Porcinos , HumectabilidadRESUMEN
Hydrogels are becoming widely used in biomaterial applications. The available methods for the preparation of these materials are continually growing. The gelation time (GT) of silk protein fibroin is difficult to control by physical methods. The cross-linkers used in available chemical techniques are likely to impact the biocompatibility of the resultant materials. In this paper, we demonstrate that the addition of sodium N-lauroyl sarcosinate (an amino-acid-based surfactant) accelerates the formation of hydrogels from fibroin. GT, turbidity variations, changes of viscoelasticity during the gelation process, and the mechanical properties of the products are measured. The secondary structure was probed by Fourier transform infrared spectroscopy, X-ray diffraction and the morphologies of the products were investigated by scanning electron microscopy. Transformations in the ß-sheet content were monitored by the fluorescence of Thioflavine T and circular dichroism measurements. The relationship between the surface tension of sodium N-lauroyl sarcosinate and the GT was also explained. To investigate cell compatibility, fibroblast cells were seeded onto the surface of the hydrogels. The results indicate that the sodium N-lauroyl sarcosinate/fibroin GT can be controlled. This blend-hydrogel demonstrates excellent cell compatibility, good compression strength, and outstanding compression-recovery characteristics. Sodium N-lauroyl sarcosinate/silk fibroin hydrogels containing ß-sheets have considerable potential as replacement materials in addressing the tissue defects involved with repair surgery.
Asunto(s)
Materiales Biocompatibles/química , Fibroínas/química , Hidrogeles/química , Sarcosina/análogos & derivados , Animales , Línea Celular , Fenómenos Mecánicos , Ratones , Estructura Secundaria de Proteína , Reología , Sarcosina/química , Tensión Superficial , Andamios del Tejido/químicaRESUMEN
A series of porous silk fibroin-poly(vinyl alcohol) blend gels were prepared from corresponding aqueous mixtures by freeze- or air-drying, and their structure and mechanical properties were examined. The air-dried gels had higher crystallinity and much greater strengths than the freeze-dried gels, and therefore are suitable for mechanical uses. The freeze-dried gels had characteristic porous structure potentially useful as cell culture substrate. Its structure could be systematically varied by changing freezing temperature and freeze-thaw pretreatments before drying.
Asunto(s)
Fibroínas/química , Alcohol Polivinílico/química , Congelación , Geles , PorosidadRESUMEN
Cell-microstructure surface interactions play a significant role in tissue engineering to guide cell spreading and migration. However, the mechanisms underlying cell-topography interactions are complex and remain elusive. To address this topic, microsphere array patterns were prepared on silk fibroin films through polystyrene microsphere self-assembly, followed by culturing rat bone marrow derived mesenchymal stem cells on the films to study cell-substrate interactions. Filopodia sensed and anchored to the microspheres to form initial attachments before spreading. Importantly, the anchored filopodia converted into lamellipodia, and this conversion initiated the directional formation of lamellipodia. Therefore, the conversion of exploratory filopodia into lamellipodia was the main driving force for directional extension of the lamellipodia. Correspondingly, cell spreading, morphology, and migration were modulated by pseudopodial recognition and conversion. This finding demonstrated that filopodia not only act as an antenna to detect microenvironment but also serve as skeleton to guide lamellipodial extension for directing cell motions. The micropatterned films promoted cell adhesion and proliferation due to accelerated lamellipodia formation and cell spreading, with recognition and conversion of filopodia into lamellipodia as a critical role in cell response to surface topography.
Asunto(s)
Movimiento Celular , Proliferación Celular , Fibroínas/química , Membranas Artificiales , Células Madre Mesenquimatosas/metabolismo , Seudópodos/metabolismo , Animales , Adhesión Celular , Masculino , Células Madre Mesenquimatosas/citología , Poliestirenos/química , Ratas , Ratas Sprague-DawleyRESUMEN
The fabrication of new dermal substitutes providing mechanical support and cellular cues is urgently needed in dermal reconstruction. Silk fibroin (SF)/chondroitin sulfate (CS)/hyaluronic acid (HA) ternary scaffolds (95-248µm in pore diameter, 88-93% in porosity) were prepared by freeze-drying. By the incorporation of CS and HA with the SF solution, the chemical potential and quantity of free water around ice crystals could be controlled to form smaller pores in the SF/CS/HA ternary scaffold main pores and improve scaffold equilibrium swelling. This feature offers benefits for cell adhesion, survival and proliferation. In vivo SF, SF/HA and SF/CS/HA (80/5/15) scaffolds as dermal equivalents were implanted onto dorsal full-thickness wounds of Sprague-Dawley rats to evaluate wound healing. Compared to SF and SF/HA scaffolds, the SF/CS/HA (80/5/15) scaffolds promoted dermis regeneration, related to improved angiogenesis and collagen deposition. Further, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) expression in the SF/CS/HA (80/5/15) groups were investigated by immunohistochemistry to assess the mechanisms involved in the stimulation of secretion of VEGF, PDGF and bFGF and accumulation of these growth factors related to accelerated wound process. These new three-dimensional ternary scaffolds offer potential for dermal tissue regeneration.
Asunto(s)
Sulfatos de Condroitina/química , Fibroínas/química , Ácido Hialurónico/química , Piel Artificial , Piel/lesiones , Andamios del Tejido , Heridas Penetrantes/cirugía , Animales , Materiales Biocompatibles/síntesis química , Procedimientos Quirúrgicos Dermatologicos/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , Masculino , Ensayo de Materiales , Ratas , Ratas Sprague-Dawley , Procedimientos de Cirugía Plástica/instrumentación , Piel/patología , Piel/fisiopatología , Resultado del Tratamiento , Cicatrización de Heridas/fisiología , Heridas Penetrantes/patología , Heridas Penetrantes/fisiopatologíaRESUMEN
Besides excellent biocompatibility and biodegradability, a useful tissue engineering scaffold should provide suitable macropores and nanofibrous structure, similar to extracellular matrix (ECM), to induce desired cellular activities and to guide tissue regeneration. In the present study, a mild process to prepare porous and nanofibrous silk-based scaffolds from aqueous solution is described. Using collagen to control the self-assembly of silk, nanofibrous silk scaffolds were firstly achieved through lyophilization. Water annealing was used to generate insolubility in the silk-based scaffolds, thereby avoiding the use of organic solvents. The nano-fibrils formed in the silk-collagen scaffolds had diameters of 20-100 nm, similar with native collagen in ECM. The silk-collagen scaffolds dissolved slowly in PBS solution, with about a 28% mass lost after 4 weeks. Following the dissolution or degradation, the nanofibrous structure inside the macropore walls emerged and interacted with cells directly. During in vitro cell culture, the nanofibrous silk-collagen scaffolds containing 7.4% collagen demonstrated significantly improved cell compatibility when compared with salt-leached silk scaffolds and silk-collagen scaffolds containing 20% collagen that emerged less nano-fibrils. Therefore, this new process provides useful scaffolds for tissue engineering applications. Furthermore, the process involves all-aqueous, room temperature and pressure processing without the use of toxic chemicals or solvents, offering new green chemistry approaches, as well as options to load bioactive drugs or growth factors into process.
Asunto(s)
Fibroínas/ultraestructura , Nanofibras/ultraestructura , Andamios del Tejido/química , Animales , Materiales Biocompatibles/química , Bombyx/química , Células Cultivadas , Colágeno/química , Colágeno/ultraestructura , Matriz Extracelular/química , Fibroblastos/citología , Fibroblastos/fisiología , Fibroínas/química , Humanos , Ensayo de Materiales , Porosidad , Ingeniería de Tejidos/instrumentación , Ingeniería de Tejidos/métodos , Agua/químicaRESUMEN
Silk fibroin of the silkworm Bombyx mori has been studied extensively, while the research on Antheraea pernyi silk fibroin (A. pernyi SF) in biomaterials is only at an early stage. In this study, the attachment, morphology, growth and phenotype of human bone marrow derived mesenchymal stem cells (hBMSCs) cultured on the regenerated A. pernyi SF films were studied in vitro. The results indicated that the attachment of hBMSCs on the regenerated A. pernyi SF films was almost the same as that on the collagen films. MTT and cell counting analyses demonstrated that the growth of hBMSCs on the regenerated A. pernyi SF films was better than that on controls. Moreover, electron scanning microscopy and fluorescence-activated cell sorting assays showed that the regenerated A. pernyi SF supported hBMSCs growth and functional maintenance compared with the controls. These data suggest that the regenerated A. pernyi SF, like Bombyx mori silk fibroin (B. mori SF) and collagen, can support hBMSCs attachment, growth and phenotypic maintenance, and has better biocompatibilities for hBMSCs in vitro culture.