RESUMO
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that is increasingly common all over the world with a high risk of progressive hyperglycemia and high microvascular and macrovascular complications. The currently used drugs in the treatment of T2DM have insufficient glucose control and can carry detrimental side effects. Several drug delivery systems have been investigated to decrease the side effects and frequency of dosage, and also to increase the effect of oral antidiabetic drugs. In recent years, the use of microbubbles in biomedical applications has greatly increased, and research into microactive carrier bubbles continues to generate more and more clinical interest. In this study, various monodisperse polymer nanoparticles at different concentrations were produced by bursting microbubbles generated using a T-junction microfluidic device. Morphological analysis by scanning electron microscopy, molecular interactions between the components by FTIR, drug release by UV spectroscopy, and physical analysis such as surface tension and viscosity measurement were carried out for the particles generated and solutions used. The microbubbles and nanoparticles had a smooth outer surface. When the microbubbles/nanoparticles were compared, it was observed that they were optimized with 0.3 wt % poly(vinyl alcohol) (PVA) solution, 40 kPa pressure, and a 110 µL/min flow rate, thus the diameters of the bubbles and particles were 100 ± 10 µm and 70 ± 5 nm, respectively. Metformin was successfully loaded into the nanoparticles in these optimized concentrations and characteristics, and no drug crystals and clusters were seen on the surface. Metformin was released in a controlled manner at pH 1.2 for 60 min and at pH 7.4 for 240 min. The process and structures generated offer great potential for the treatment of T2DM.
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Diabetes Mellitus Tipo 2 , Metformina , Nanopartículas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Metformina/química , Metformina/uso terapêutico , Microbolhas , Nanopartículas/química , PolímerosRESUMO
Aim: The purpose of this study was to design a sensor that could monitor the skin-cast contact surface pressure (SCCSP) of a limb under a cast and inform the user via a mobile application when the pressure increases. Methods: In this experimental study, an infant sphygmomanometer cuff was initially placed on the forearm of 10 volunteers. A pressure sensor with a Bluetooth chip was then placed on the volar aspect of the forearm. Short arm plaster was applied with synthetic cast material. The SCCSP under the plaster was measured by the sensor and the measured values were transmitted to a mobile application via a Bluetooth chip. The mobile application processed the data from the chip and converted it to mmHg. Results: Intracompartmental pressure (ICP) values were categorized as 0, 10, 20, 30, 40, 50, 60, and 75 mmHg. The highest SCCSP was 75 mmHg CP, while the lowest was 0 mmHg CP. The correlation coefficient of the mean pressure values was 0.993 (p ≤ 0.001) (SD 0.002, range 0.989-0.997), and there was a significant relationship between ICP and SCCSP values (p ≤ 0.05). Conclusion: We can monitor SCCSP, detect limb swelling, and notify the user via a mobile application by using Bluetooth pressure sensors.
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Aplicativos Móveis , Humanos , Monitorização Fisiológica , PressãoRESUMO
In this study, a dual spinneret electrospinning technique was applied to fabricate a series of polyurethane (PU) and polyvinyl alcohol-gelatin (PVA/Gel) nanofibrous scaffolds. The study aims to enhance the properties of PU/PVA-Gel NFs loaded with a low dose of nanoceria through the incorporation of cinnamon essential oil (CEO). The as-prepared nCeO2 were embedded into the PVA/Gel nanofibrous layer, where the cinnamon essential oil (CEO) was incorporated into the PU nanofibrous layer. The morphology, thermal stability, mechanical properties, and chemical composition of the produced NF mats were investigated by STEM, DSC, and FTIR. The obtained results showed improvement in the mechanical, and thermal stability of the dual-fiber scaffolds by adding CEO along with nanoceria. The cytotoxicity evaluation revealed that the incorporation of CEO to PU/PVA-Gel loaded with a low dose of nanoceria could enhance the cell population compared to using pure PU/PVA-Gel NFs. Moreover, the presence of CEO could inhibit the growth rate of S. aureus more than E. coli. To our knowledge, this is the first time such nanofibrous membranes composed of PU and PVA-Gel have been produced. The first time was to load the nanofibrous membranes with both CEO and nCeO2. The obtained results indicate that the proposed PU/PVA-Gel NFs represent promising platforms with CEO and nCeO2 for effectively managing diabetic wounds.
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Diabetes Mellitus , Nanofibras , Óleos Voláteis , Antibacterianos/química , Antibacterianos/farmacologia , Cério , Cinnamomum zeylanicum , Escherichia coli , Gelatina/química , Humanos , Nanofibras/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Poliuretanos/farmacologia , Álcool de Polivinil/química , Staphylococcus aureus , CicatrizaçãoRESUMO
PURPOSE: Extracellular vesicles (EVs) are responsible for intercellular communication. Mesenchymal stem cell-derived vesicles have been shown to have similar properties as functional mesenchymal stem cells. The aim of this study was to compare the therapeutic benefit of EVs obtained from adipose tissue-derived stem cells (ADSC) on bone repair whereas using ß-tricalcium phosphate (ß-TCP) biomaterial as a carrier. MATERIALS AND METHOD: A single critical size bone defect of 8âmm in diameter was created on the right side of rat calvarium using a custom-made punch needle. Animals were randomly divided into 5 groups: group 1 (no treatment), group 2 (bone graft), group 3 (ß-TCP + ADSC), group 4 (ß-TCP + EV), group 5 (ß-TCP). Eight weeks later, animals were sacrificed and histologic and radiologic evaluation was performed. RESULTS: Semiquantitative histologic scoring demonstrated significantly higher bone regeneration scores for groups 2, 3, and 4 compared to group 1. Radiologic imaging showed significantly higher bone mineral density for groups 2, 3, and 5 compared to group 1. There were no significant differences between treatment groups in either histologic or radiologic scoring. CONCLUSIONS: Our data showed that EVs provided from thermally induced ADSCs did not show any significant difference in bone regeneration when compared to ADSCs themselves. Future studies should focus on determining the optimum amount and content of EV application since these vary significantly depending on the microenvironment.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , Tecido Adiposo , Animais , Regeneração Óssea , Osteogênese , Ratos , Células-TroncoRESUMO
In this research, polyvinyl-alcohol (PVA)/gelatin (GEL)/propolis (Ps) biocompatible nanofiber patches were fabricated via electrospinning technique. The controlled release of Propolis, surface wettability behaviors, antimicrobial activities against the S. aureus and P. aeruginosa, and biocompatibility properties with the mesenchymal stem cells (MSCs) were investigated in detail. By adding 0.5, 1, and 3 wt.% GEL into the 13 wt.% PVA, the morphological and mechanical results suggested that 13 wt.% PVA/0.5 wt.% GEL patch can be an ideal matrix for 3 and 5 wt.% propolis addition. Morphological results revealed that the diameters of the electrospun nanofiber patches were increased with GEL (from 290 nm to 400 nm) and Ps addition and crosslinking process cause the formation of thicker nanofibers. The tensile strength and elongation at break enhancement were also determined for 13 wt.% PVA/0.5 wt.% GEL/3 wt.% Ps patch. Propolis was released quickly in the first hour and arrived at a plateau. Cell culture and contact angle results confirmed that the 3 wt.% addition of propolis reinforced mesenchymal stem cell proliferation and wettability properties of the patches. The antimicrobial activity demonstrated that propolis loaded patches had antibacterial activity against the S. aureus, but for P. aeruginosa, more studies should be performed.
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Anti-Infecciosos/administração & dosagem , Materiais Biocompatíveis , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Nanofibras , Própole/administração & dosagem , Materiais Biocompatíveis/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Testes de Sensibilidade Microbiana , Nanofibras/química , Nanofibras/ultraestrutura , Álcool de Polivinil/química , Própole/química , Pseudomonas aeruginosa/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Propriedades de SuperfícieRESUMO
Powders of ß-tricalcium phosphate [ß-TCP, ß-Ca3(PO4)2] and composite powders of ß-TCP and polyvinyl alcohol (PVA) were synthesized by using wet precipitation methods. First, the conditions for the preparation of single phase ß-TCP have been delineated. In the co-precipitation procedure, calcium nitrate and diammonium hydrogen phosphate were used as calcium and phosphorous precursors, respectively. The pH of the system was varied in the range 7-11 by adding designed amounts of ammonia solution. The filtered cakes were desiccated at 80 °C and subsequently calcined at different temperatures in the range between 700-1100 °C. Later on, rifampicin form II was used to produce drug-loaded ß-TCP and PVA/ß-TCP powders. All the synthesized materials have been characterized from morphological (by scanning electron microscopy) and structural-chemical (by X-ray diffraction and Fourier transform infrared spectroscopy) point of view. The drug loading capacity of the selected pure ß-TCP powder has been assessed. The biological performance (cytocompatibility in fibroblast cell culture and antibacterial efficacy against Escherichia coli and Staphylococcus aureus) has been tested with promising results. Application perspectives of the designed drug-bioceramic-polymer blends are advanced and discussed.
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Fosfatos de Cálcio/química , Osteócitos/fisiologia , Animais , Antibacterianos , Substitutos Ósseos , Proliferação de Células , Sobrevivência Celular , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Teste de Materiais , Osteogênese , Álcool de Polivinil , Rifampina , Engenharia Tecidual , Alicerces TeciduaisRESUMO
Natural calcium phosphates derived from fish wastes are a promising material for biomedical application. However, their sintered ceramics are not fully characterized in terms of mechanical and biological properties. In this study, natural calcium phosphate was synthesized through a thermal calcination process from salmon fish bone wastes. The salmon-derived calcium phosphates (sCaP) were sintered at different temperatures to obtain natural calcium phosphate bioceramics and then were investigated in terms of their microstructure, mechanical properties and biocompatibility. In particular, this work is concerned with the effects of grain size on the relative density and microhardness of the sCaP bioceramics. Ca/P ratio of the sintered sCaP ranged from 1.73 to 1.52 when the sintering temperature was raised from 1000 to 1300 °C. The crystal phase of all the sCaP bioceramics obtained was biphasic and composed of hydroxyapatite (HA) and tricalcium phosphate (TCP). The density and microhardness of the sCaP bioceramics increased in the temperature interval 1000-1100 °C, while at temperatures higher than 1100 °C, these properties were not significantly altered. The highest compressive strength of 116 MPa was recorded for the samples sintered at 1100 °C. In vitro biocompatibility was also examined in the behavior of osteosarcoma (Saos-2) cells, indicating that the sCaP bioceramics had no cytotoxicity effect. Salmon-derived biphasic calcium phosphates (BCP) have the potential to contribute to the development of bone substituted materials.
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Materiais Biocompatíveis/química , Neoplasias Ósseas/patologia , Substitutos Ósseos/química , Osso e Ossos/química , Fosfatos de Cálcio/farmacologia , Cerâmica/farmacologia , Osteossarcoma/patologia , Animais , Neoplasias Ósseas/tratamento farmacológico , Fosfatos de Cálcio/química , Proliferação de Células , Cerâmica/química , Humanos , Teste de Materiais , Osteossarcoma/tratamento farmacológico , Salmão , Propriedades de Superfície , Células Tumorais CultivadasRESUMO
In this study, the main aim was to fabricate propolis (Ps)-containing wound dressing patches using 3D printing technology. Different combinations and structures of propolis (Ps)-incorporated sodium alginate (SA) scaffolds were developed. The morphological studies showed that the porosity of developed scaffolds was optimized when 20% (v/v) of Ps was added to the solution. The pore sizes decreased by increasing Ps concentration up to a certain level due to its adhesive properties. The mechanical, swelling-degradation (weight loss) behaviors, and Ps release kinetics were highlighted for the scaffold stability. An antimicrobial assay was employed to test and screen antimicrobial behavior of Ps against Escherichia coli and Staphylococcus aureus strains. The results show that the Ps-added scaffolds have an excellent antibacterial activity because of Ps compounds. An in vitro cytotoxicity test was also applied on the scaffold by using the extract method on the human dermal fibroblasts (HFFF2) cell line. The 3D-printed SA-Ps scaffolds are very useful structures for wound dressing applications.
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Alginatos/química , Antibacterianos , Escherichia coli/crescimento & desenvolvimento , Fibroblastos/metabolismo , Teste de Materiais , Impressão Tridimensional , Própole/química , Staphylococcus aureus/crescimento & desenvolvimento , Alicerces Teciduais/química , Antibacterianos/química , Antibacterianos/farmacologia , Linhagem Celular , HumanosRESUMO
Cinnamon-containing polycaprolactone (PCL) bandages were produced by pressurised gyration and their anti-fungal activities against Candida albicans were investigated. It was found that by preparing and spinning polymer solutions of cinnamon with PCL, fibres capable of inhibiting fungal growth could be produced, as observed in disk diffusion tests for anti-fungal susceptibility. Fascinatingly, compared with raw cinnamon powder, the novel cinnamon-loaded fibres had outstanding long-term activity. The results presented here are very promising and may indeed accelerate a new era of using completely natural materials in biomedical applications, especially in wound healing.
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Antifúngicos/química , Bandagens , Candida albicans/efeitos dos fármacos , Cinnamomum zeylanicum/química , Extratos Vegetais/química , Poliésteres/químicaRESUMO
Background and Objectives: A coaxial electrospinning technique was used to produce core/shell nanofibers of a polylactic acid (PLA) as a shell and a polyvinyl alcohol (PVA) containing metformin hydrochloride (MH) as a core. Materials and Methods: Fish sarcoplasmic protein (FSP) was extracted from fresh bonito and incorporated into nanofiber at various concentrations to investigate the influence on properties of the coaxial nanofibers. The morphology, chemical structure and thermal properties of the nanofibers were studied. Results: The results show that uniform and bead-free structured nanofibers with diameters ranging from 621 nm to 681 nm were obtained. A differential scanning calorimetry (DSC) analysis shows that FSP had a reducing effect on the crystallinity of the nanofibers. Furthermore, the drug release profile of electrospun fibers was analyzed using the spectrophotometric method. Conclusions: The nanofibers showed prolonged and sustained release and the first order kinetic seems to be more suitable to describe the release. MTT assay suggests that the produced drug and protein loaded coaxial nanofibers are non-toxic and enhance cell attachment. Thus, these results demonstrate that the produced nanofibers had the potential to be used for diabetic wound healing applications.
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Metformina/administração & dosagem , Nanofibras , Animais , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Técnicas In Vitro , Metformina/farmacocinética , Nanofibras/química , Nanofibras/ultraestrutura , Álcool de Polivinil , Retículo Sarcoplasmático , Espectroscopia de Infravermelho com Transformada de Fourier , AtumRESUMO
Electrospun nanofibrous scaffolds are promising regenerative wound dressing options but have yet to be widely used in practice. The challenge is that nanofibre productions rely on bench-top apparatuses, and the delicate product integrity is hard to preserve before reaching the point of need. Timing is critically important to wound healing. The purpose of this investigation is to produce novel nanofibrous scaffolds using a portable, hand-held "gun", which enables production at the wound site in a time-dependent fashion, thereby preserving product integrity. We select bacterial cellulose, a natural hydrophilic biopolymer, and polycaprolactone, a synthetic hydrophobic polymer, to generate composite nanofibres that can tune the scaffold hydrophilicity, which strongly affects cell proliferation. Composite scaffolds made of 8 different ratios of bacterial cellulose and polycaprolactone were successfully electrospun. The morphological features and cell-scaffold interactions were analysed using scanning electron microscopy. The biocompatibility was studied using Saos-2 cell viability test. The scaffolds were found to show good biocompatibility and allow different proliferation rates that varied with the composition of the scaffolds. A nanofibrous dressing that can be accurately moulded and standardised via the portable technique is advantageous for wound healing in practicality and in its consistency through mass production.
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Bandagens , Celulose/uso terapêutico , Nanofibras/uso terapêutico , Poliésteres/uso terapêutico , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos , Alicerces Teciduais , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cicatrização/fisiologiaRESUMO
BACKGROUND: We evaluated the Bovine hydroxyapatite (BHA) structure. BHA powder was admixed with 5 and 10 wt% natural pumice (NP). Compression strength, Vickers micro hardness, Fourier transform infrared spectroscopy, scanning electron microscopy (SEM) and X-ray diffraction studies were performed on the final NP-BHA composite products. The cells proliferation was investigated by MTT assay and SEM. Furthermore, the antimicrobial activity of NP-BHA samples was interrogated. RESULTS: Variances in the sintering temperature (for 5 wt% NP composites) between 1000 and 1300 °C, reveal about 700 % increase in the microhardness (~100 and 775 HV, respectively). Composites prepared at 1300 °C demonstrate the greatest compression strength with comparable result for 5 wt% NP content (87 MPa), which are significantly better than those for 10 wt% and those that do not include any NP (below 60 MPa, respectively). CONCLUSION: The results suggested the optimal parameters for the preparation of NP-BHA composites with increased mechanical properties and biocompatibility. Changes in micro-hardness and compression strength can be tailored by the tuning the NP concentration and sintering temperature. NP-BHA composites have demonstrated a remarkable potential for biomedical engineering applications such as bone graft and implant.
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Materiais Biocompatíveis/química , Engenharia Biomédica , Durapatita/química , Silicatos/química , Animais , Bovinos , Linhagem Celular Tumoral , Humanos , Teste de Materiais , Fenômenos Mecânicos , Porosidade , TemperaturaRESUMO
INTRODUCTION: Microneedles (MNs) are miniaturized, painless, and minimally invasive platforms that have attracted significant attention over recent decades across multiple fields, such as drug delivery, disease monitoring, disease diagnosis, and cosmetics. Several manufacturing methods have been employed to create MNs; however, these approaches come with drawbacks related to complicated, costly, and time-consuming fabrication processes. In this context, employing additive manufacturing (AM) technology for MN fabrication allows for the quick production of intricate MN prototypes with exceptional precision, providing the flexibility to customize MNs according to the desired shape and dimensions. Furthermore, AM demonstrates significant promise in the fabrication of sophisticated transdermal drug delivery systems and medical devices through the integration of MNs with various technologies. AREAS COVERED: This review offers an extensive overview of various AM technologies with great potential for the fabrication of MNs. Different types of MNs and the materials utilized in their fabrication are also discussed. Recent applications of 3D-printed MNs in the fields of transdermal drug delivery and biosensing are highlighted. EXPERT OPINION: This review also mentions the critical obstacles, including drug loading, biocompatibility, and regulatory requirements, which must be resolved to enable the mass-scale adoption of AM methods for MN production, and future trends.
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Administração Cutânea , Sistemas de Liberação de Medicamentos , Microinjeções , Agulhas , Impressão Tridimensional , Sistemas de Liberação de Medicamentos/instrumentação , Humanos , Microinjeções/instrumentação , Animais , Desenho de Equipamento , Técnicas Biossensoriais , Preparações Farmacêuticas/administração & dosagem , Tecnologia FarmacêuticaRESUMO
The aim of this study is to provide an overview of the current state-of-the-art in the fabrication of bioceramic scaffolds for bone tissue engineering, with an emphasis on the use of three-dimensional (3D) technologies coupled with generative design principles. The field of modern medicine has witnessed remarkable advancements and continuous innovation in recent decades, driven by a relentless desire to improve patient outcomes and quality of life. Central to this progress is the field of tissue engineering, which holds immense promise for regenerative medicine applications. Scaffolds are integral to tissue engineering and serve as 3D frameworks that support cell attachment, proliferation, and differentiation. A wide array of materials has been explored for the fabrication of scaffolds, including bioceramics (i.e., hydroxyapatite, beta-tricalcium phosphate, bioglasses) and bioceramic-polymer composites, each offering unique properties and functionalities tailored to specific applications. Several fabrication methods, such as thermal-induced phase separation, electrospinning, freeze-drying, gas foaming, particle leaching/solvent casting, fused deposition modeling, 3D printing, stereolithography and selective laser sintering, will be introduced and thoroughly analyzed and discussed from the point of view of their unique characteristics, which have proven invaluable for obtaining bioceramic scaffolds. Moreover, by highlighting the important role of generative design in scaffold optimization, this review seeks to pave the way for the development of innovative strategies and personalized solutions to address significant gaps in the current literature, mainly related to complex bone defects in bone tissue engineering.
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New gelatin methacryloyl (GelMA)-strontium-doped nanosize hydroxyapatite (SrHA) composite hydrogel scaffolds were developed using UV photo-crosslinking and 3D printing for bone tissue regeneration, with the controlled delivery capacity of strontium (Sr). While Sr is an effective anti-osteoporotic agent with both anti-resorptive and anabolic properties, it has several important side effects when systemic administration is applied. Multi-layer composite scaffolds for bone tissue regeneration were developed based on the digital light processing (DLP) 3D printing technique through the photopolymerization of GelMA. The chemical, morphological, and biocompatibility properties of these scaffolds were investigated. The composite gels were shown to be suitable for 3D printing. In vitro cell culture showed that osteoblasts can adhere and proliferate on the surface of the hydrogel, indicating that the GelMA-SrHA hydrogel has good cell viability and biocompatibility. The GelMA-SrHA composites are promising 3D-printed scaffolds for bone repair.
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Chronic skin wounds pose a global clinical challenge, necessitating effective treatment strategies. This study explores the potential of 3D printed Poly Lactic Acid (PLA) scaffolds, enhanced with Whey Protein Concentrate (WPC) at varying concentrations (25, 35, and 50% wt), for wound healing applications. PLA's biocompatibility, biodegradability, and thermal stability make it an ideal material for medical applications. The addition of WPC aims to mimic the skin's extracellular matrix and enhance the bioactivity of the PLA scaffolds. Fourier Transform Infrared Spectroscopy results confirmed the successful loading of WPC into the 3D printed PLA-based scaffolds. Scanning Electron Microscopy (SEM) images revealed no significant differences in pore size between PLA/WPC scaffolds and pure PLA scaffolds. Mechanical strength tests showed similar tensile strength between pure PLA and PLA with 50% WPC scaffolds. However, scaffolds with lower WPC concentrations displayed reduced tensile strength. Notably, all PLA/WPC scaffolds exhibited increased strain at break compared to pure PLA. Swelling capacity was highest in PLA with 25% WPC, approximately 130% higher than pure PLA. Scaffolds with higher WPC concentrations also showed increased swelling and degradation rates. Drug release was found to be prolonged with increasing WPC concentration. After seven days of incubation, cell viability significantly increased in PLA with 50% WPC scaffolds compared to pure PLA scaffolds. This innovative approach could pave the way for personalized wound care strategies, offering tailored treatments and targeted drug delivery. However, further studies are needed to optimize the properties of these scaffolds and validate their effectiveness in clinical settings.
Assuntos
Bandagens , Materiais Biocompatíveis , Poliésteres , Impressão Tridimensional , Resistência à Tração , Alicerces Teciduais , Proteínas do Soro do Leite , Cicatrização , Proteínas do Soro do Leite/química , Poliésteres/química , Alicerces Teciduais/química , Cicatrização/efeitos dos fármacos , Humanos , Materiais Biocompatíveis/química , Teste de Materiais , Espectroscopia de Infravermelho com Transformada de Fourier , Microscopia Eletrônica de Varredura , Sobrevivência Celular/efeitos dos fármacos , Porosidade , Liberação Controlada de Fármacos , Pele/metabolismoRESUMO
Although different fabrication methods and biomaterials are used in scaffold development, hydrogels and electrospun materials that provide the closest environment to the extracellular matrix have recently attracted considerable interest in tissue engineering applications. However, some of the limitations encountered in the application of these methods alone in scaffold fabrication have increased the tendency to use these methods together. In this study, a bilayer scaffold was developed using 3D-printed gelatin methacryloyl (GelMA) hydrogel containing ciprofloxacin (CIP) and electrospun polycaprolactone (PCL)-collagen (COL) patches. The bilayer scaffolds were characterized in terms of chemical, morphological, mechanical, swelling, and degradation properties; drug release, antibacterial properties, and cytocompatibility of the scaffolds were also studied. In conclusion, bilayer GelMA-CIP/PCL-COL scaffolds, which exhibit sufficient porosity, mechanical strength, and antibacterial properties and also support cell growth, are promising potential substitutes in tissue engineering applications.
Assuntos
Antibacterianos , Materiais Biocompatíveis , Ciprofloxacina , Gelatina , Hidrogéis , Teste de Materiais , Metacrilatos , Poliésteres , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Gelatina/química , Ciprofloxacina/farmacologia , Ciprofloxacina/química , Poliésteres/química , Antibacterianos/farmacologia , Antibacterianos/química , Materiais Biocompatíveis/química , Hidrogéis/química , Porosidade , Metacrilatos/química , Colágeno/química , Animais , Humanos , Proliferação de Células/efeitos dos fármacosRESUMO
[This corrects the article DOI: 10.1021/acsomega.3c00914.].
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A middle ear infection occurs due to the presence of several microorganisms behind the eardrum (tympanic membrane) and is very challenging to treat due to its unique location and requires a well-designed treatment. If not treated properly, the infection can result in severe symptoms and unavoidable side effects. In this study, excellent biocompatible ethyl cellulose (EC) and biodegradable polyhydroxybutyrate (PHB) biopolymer were used to fabricate drug-loaded nanofiber scaffolds using an electrospinning technique to overcome antibiotic overdose and insufficient efficacy of drug release during treatment. PHB polymer was produced from Halomonas sp., and the purity of PHB was found to around be 90 %. Additionally, ciprofloxacin (CIP) and amoxicillin (AMX) are highly preferable since both drugs are highly effective against gram-negative and gram-positive bacteria to treat several infections. Obtained smooth nanofibers were between 116.24 and 171.82 nm in diameter and the addition of PHB polymer and antibiotics improved the morphology of the nanofiber scaffolds. Thermal properties of the nanofiber scaffolds were tested and the highest Tg temperature resulted at 229 °C. The mechanical properties of the scaffolds were tested, and the highest tensile strength resulted in 4.65 ± 6.33 MPa. Also, drug-loaded scaffolds were treated against the most common microorganisms that cause the infection, such as S.aureus, E.coli, and P.aeruginosa, and resulted in inhibition zones between 10 and 21 mm. MTT assay was performed by culturing human adipose-derived mesenchymal stem cells (hAD MSCs) on the scaffolds. The morphology of the hAD MSCs' attachment was tested with SEM analysis and hAD MSCs were able to attach, spread, and live on each scaffold even on the day of 7. The cumulative drug release kinetics of CIP and AMX from drug-loaded scaffolds were analysed in phosphate-buffered saline (pH: 7.4) within different time intervals of up to 14 days using a UV spectrophotometer. Furthermore, the drug release showed that the First-Order and Korsmeyer-Peppas models were the most suitable kinetic models. Animal testing was performed on SD rats, matrix and collagen deposition occurred on days 5 and 10, which were observed using Hematoxylin-eosin and Masson's trichrome staining. At the highest drug concentration, a better repair effect was observed. Results were promising and showed potential for novel treatment.
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Amoxicilina , Antibacterianos , Celulose , Ciprofloxacina , Nanofibras , Celulose/química , Celulose/análogos & derivados , Ciprofloxacina/farmacologia , Ciprofloxacina/química , Nanofibras/química , Animais , Ratos , Amoxicilina/farmacologia , Amoxicilina/química , Antibacterianos/farmacologia , Antibacterianos/química , Hidroxibutiratos/química , Hidroxibutiratos/farmacologia , Humanos , Otite Média/tratamento farmacológico , Otite Média/microbiologia , Poliésteres/química , Liberação Controlada de Fármacos , Alicerces Teciduais/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Proibitinas , Portadores de Fármacos/química , MasculinoRESUMO
Tympanic membrane (TM) perforations, primarily induced by middle ear infections, the introduction of foreign objects into the ear, and acoustic trauma, lead to hearing abnormalities and ear infections. We describe the design and fabrication of a novel composite patch containing photocrosslinkable gelatin methacryloyl (GelMA) and keratin methacryloyl (KerMA) hydrogels. GelMA-KerMA patches containing conical microneedles in their design were developed using the digital light processing (DLP) 3D printing approach. Following this, the patches were biofunctionalized by applying a coaxial coating with PVA nanoparticles loaded with gentamicin (GEN) and fibroblast growth factor (FGF-2) with the Electrohydrodynamic Atomization (EHDA) method. The developed nanoparticle-coated 3D-printed patches were evaluated in terms of their chemical, morphological, mechanical, swelling, and degradation behavior. In addition, the GEN and FGF-2 release profiles, antimicrobial properties, and biocompatibility of the patches were examined in vitro. The morphological assessment verified the successful fabrication and nanoparticle coating of the 3D-printed GelMA-KerMA patches. The outcomes of antibacterial tests demonstrated that GEN@PVA/GelMA-KerMA patches exhibited substantial antibacterial efficacy against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Furthermore, cell culture studies revealed that GelMA-KerMA patches were biocompatible with human adipose-derived mesenchymal stem cells (hADMSC) and supported cell attachment and proliferation without any cytotoxicity. These findings indicated that biofunctional 3D-printed GelMA-KerMA patches have the potential to be a promising therapeutic approach for addressing TM perforations.