RESUMEN

The repair of large load-bearing bone defects requires superior mechanical strength, a feat that a single hydrogel scaffold cannot achieve. The objective is to seamlessly integrate optimal microarchitecture, mechanical robustness, vascularisation, and osteoinductive biological responses to effectively address these critical load-bearing bone defects. To confront this challenge, three-dimensional (3D) printing technology was employed to prepare a polycaprolactone (PCL)-based integrated scaffold. Within the voids of 3D printed PCL scaffold, a methacrylate gelatin (GelMA)/methacrylated silk fibroin (SFMA) composite hydrogel incorporated with parathyroid hormone (PTH) peptide-loaded mesoporous silica nanoparticles (PTH@MSNs) was embedded, evolving into a porous PTH@MSNs/GelMA/SFMA/PCL (PM@GS/PCL) scaffold. The feasibility of fabricating this functional scaffold with a customised hierarchical structure was confirmed through meticulous chemical and physical characterisation. Compression testing unveiled an impressive strength of 17.81 ± 0.83 MPa for the composite scaffold. Additionally, in vitro angiogenesis potential of PM@GS/PCL scaffold was evaluated through Transwell and tube formation assays using human umbilical vein endothelium, revealing the superior cell migration and tube network formation. The alizarin red and alkaline phosphatase staining assays using bone marrow-derived mesenchymal stem cells clearly illustrated robust osteogenic differentiation properties within this scaffold. Furthermore, the bone repair potential of the scaffold was investigated on a rat femoral defect model using micro-computed tomography and histological examination, demonstrating enhanced osteogenic and angiogenic performance. This study presents a promising strategy for fabricating a microenvironment-matched composite scaffold for bone tissue engineering, providing a potential solution for effective bone defect repair.

RESUMEN

Endodontic therapy, while generally successful, is primarily limited to mature teeth, hence the pressing need to explore regenerative approaches. Gelatin methacryloyl (GelMA) hydrogels have emerged as pivotal biomaterials, promising a bright future for dental pulp regeneration. Despite advancements in tissue engineering and biomaterials, achieving true pulp tissue regeneration remains a formidable task. GelMA stands out for its injectability, rapid gelation, and excellent biocompatibility, serving as the cornerstone of scaffold materials. In the pursuit of dental pulp regeneration, GelMA holds significant potential, facilitating the delivery of stem cells, growth factors, and other vital substances crucial for tissue repair. Presently, in the field of dental pulp regeneration, researchers have been diligently utilizing GelMA hydrogels as engineering scaffolds to transport various effective substances to promote pulp regeneration. However, existing research is relatively scattered and lacks comprehensive reviews and summaries. Therefore, the primary objective of this article is to elucidate the application of GelMA hydrogels as regenerative scaffolds in this field, thereby providing clear direction for future researchers. Additionally, this article provides a comprehensive discussion on the synthesis, characterization, and application of GelMA hydrogels in root canal therapy regeneration. Furthermore, it offers new application strategies and profound insights into future challenges, such as optimizing GelMA formulations to mimic the complex microenvironment of pulp tissue and enhancing its integration with host tissues.

Asunto(s)

Pulpa Dental , Gelatina , Hidrogeles , Endodoncia Regenerativa , Andamios del Tejido , Hidrogeles/química , Humanos , Andamios del Tejido/química , Gelatina/química , Pulpa Dental/citología , Metacrilatos/química , Ingeniería de Tejidos , Regeneración , Materiales Biocompatibles/química , Animales

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The synthesis of ideal bioceramics to guide the fate of cells and subsequent bone regeneration within the chemical, biological, and physical microenvironment is a challenging long-term task. This study developed amorphous calcium magnesium phosphate (ACMP) bioceramics via a simple co-precipitation method. The role of Mg2+ in the formation of ACMP is investigated using physicochemical and biological characterization at different Ca/Mg molar ratio of the initial reaction solution. Additionally, ACMP bioceramics show superior cytocompatibility and improved osteogenic differentiation of co-cultured MC3T3-E1 cells. Regulation of the microenvironment with Mg2+ can promote early-stage bone regeneration. For this, bioprinting technology is employed to prepare ACMP-modified 3D porous structures. Our hypothesis is that the incorporation of ACMP into methacrylated gelatin (GelMA) bioink can trigger the osteogenic differentiation of encapsulated preosteoblast and stimulate bone regeneration. The cell-laden ACMP composite structures display stable printability and superior cell viability and cell proliferation. Also, constructs loading the appropriate amount of ACMP bioceramic showed significant osteogenic differentiation activity compared to the pure GelMA. We demonstrate that the dissolved Mg2+ cation microenvironment in ACMP-modified composite constructs plays an effective biochemical role, and can regulate cell fate. Our results predict that GelMA/ACMP bioink has significant potential in patient-specific bone tissue regeneration.

Asunto(s)

Bioimpresión , Regeneración Ósea , Fosfatos de Calcio , Diferenciación Celular , Osteogénesis , Impresión Tridimensional , Andamios del Tejido , Regeneración Ósea/efectos de los fármacos , Ratones , Animales , Osteogénesis/efectos de los fármacos , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Diferenciación Celular/efectos de los fármacos , Bioimpresión/métodos , Andamios del Tejido/química , Proliferación Celular/efectos de los fármacos , Compuestos de Magnesio/química , Compuestos de Magnesio/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Supervivencia Celular/efectos de los fármacos , Línea Celular , Ingeniería de Tejidos/métodos , Osteoblastos/efectos de los fármacos , Osteoblastos/citología , Fosfatos/química , Fosfatos/farmacología

RESUMEN

Malignant melanoma is a challenging problem worldwide, because the remaining tumor cells and extensive skin defects following surgical resection are difficult to treat. Biomaterial-mediated immunotherapy has emerged as a superior strategy for anti-tumor applications in recent years. Herein, a unique double-layer MNP was developed to address the problem of malignant melanoma. Hydroxyapatite (HAP) and short-chain peptides from tumor cells were self-assembled to prepare the bioinspired nano-vaccine, and then they were loaded onto the microneedle tips of methacrylated gelatin (GelMA)-based MNP. The products (dubbed HVMN) demonstrated relatively good biocompatibility and immune activity, inhibiting the proliferation and inducing apoptosis of malignant melanoma in a B16 cell-bearing model of C57BL/6 mice, and promoting skin tissue regeneration in a full thickness skin defect model of SD rats in 15 days. The putative molecular pathways were examined preliminarily. In conclusion, this research will develop a competitive microneedle patch with dual anti-tumor and pro-regenerative properties for the postoperative treatment of malignant melanoma.

Asunto(s)

Melanoma , Neoplasias Cutáneas , Ratones , Ratas , Animales , Melanoma/tratamiento farmacológico , Nanovacunas , Ratas Sprague-Dawley , Ratones Endogámicos C57BL , Cicatrización de Heridas , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología

RESUMEN

BACKGROUND:Combining seed cells with 3D bioprinting technology enables the specific construction of various tissues and organs to meet the demands of tissue repair.However,further research is needed on the promotion of angiogenesis in damaged tissues. OBJECTIVE:By cultivating a 3D scaffold structure of methacrylated gelatin loaded with fibroblasts,obtaining the supernatant,and mixing it in different proportions with a complete culture medium to simulate the cellular microenvironment during tissue repair,this study aimed to explore the role of various cellular microenvironments in promoting angiogenesis in endothelial cells. METHODS:A methacrylated gelatin scaffold structure loaded with fibroblasts was prepared using an extrusion-based 3D bioprinting process.Hydrogel scaffold extract was prepared and mixed with a complete culture medium in ratios of 1:1,1:2,and 1:4 to obtain conditioned medium.Mouse embryonic fibroblasts BALB3T3 and human umbilical vein endothelial cells were co-cultured with complete medium(control group)and hydrogel scaffold extract,respectively.Cell proliferation was assessed using the CCK-8 assay and cell viability was analyzed using live/dead staining.Three kinds of conditioned medium and complete medium(control group)were used to co-culture with human umbilical vein endothelial cells for tube formulation assay,vascular genetic testing,and immunofluorescence staining of CD31. RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the methacrylated gelatin scaffold exhibited a porous structure,and rheological results demonstrated excellent mechanical properties of the hydrogel.CCK-8 assay and live/dead cell staining showed that the hydrogel scaffold extract had no obvious cytotoxicity.(2)Tube formulation assay indicated that the hydrogel showed the total length of cell tubules in 1:1 conditioned medium group was smaller than that in the control group(P<0.05).There were no statistical differences among the four groups in the number of vascular branches formed by endothelial cells(P>0.05).(3)qRT-PCR results showed that for vascular endothelial growth factor mRNA expression,the 1:2 conditioned medium group was lower than the 1:1 conditioned medium group on day 1(P<0.01).On day 3,the expression level of vascular endothelial growth factor in the 1:2 conditioned medium group was higher than that in the control group(P<0.01).On day 5,the cytokine expression level in the 1:2 conditioned medium group was significantly higher than that in the other three groups(P<0.01 or P<0.000 1).The expression in the 1:1 conditioned medium group was significantly lower than that in the other three groups(P<0.05 or P<0.01).On day 1,the expression level of basic fibroblast growth factor in the 1:1 conditioned medium group was significantly higher than that in the control group and 1:4 conditioned medium group(P<0.01,P<0.05).The expression was higher in the 1:2 conditioned medium group than that in the control group(P<0.05).On day 3,the expression levels of cytokines in the 1:4 conditioned medium group was higher than that in the control group(P<0.05).(4)On day 3,the expression of CD31 in the 1:2 conditioned medium group was higher than that in the control group and the 1:4 conditioned medium group(P<0.05).(5)The results indicate that the resulting conditioned media can simulate the microenvironment of vascular regeneration after tissue damage,promoting the vascularization process of endothelial cells.The best promotion of vascularization in endothelial cells was observed when the ratio of supernatant to complete culture medium was 1:2.

RESUMEN

Scaffolds based on gelatin (Gel) play a crucial role in bone tissue engineering. However, the low mechanical properties, rapid biodegradation rate, insufficient osteogenic activity and lacking anti-infective properties limit their applications in bone regeneration. Herein, the incorporation of ibuprofen (IBU)-loaded zeolitic imidazolate framework-8 (ZIF-8) in a methacrylated gelatin (GelMA) matrix was proposed as a simple and effective strategy to develop the IBU-ZIF-8@GelMA scaffolds for enhanced bone regeneration capacity. Results indicated that the IBU-loaded ZIF-8 nanoparticles with tiny particle sizes were uniformly distributed in the GelMA matrix of the IBU-ZIF-8@GelMA scaffolds, and the IBU-loaded ZIF-8 growing in the scaffolds enabled the controlled and sustained releasing of Zn2+ and IBU in pH = 5.5 over a long period for efficient bone repair and long-term anti-inflammatory activity. Furthermore, the doping of the IBU-loaded ZIF-8 nanoparticles efficiently enhanced the compression performance of the GelMA scaffolds. In vitro studies indicated that the prepared scaffolds presented no cytotoxicity to MC3T3-E1 cells and the released Zn2+ during the degradation of the scaffolds promoted MC3T3-E1 cell osteogenic differentiation. Thus, the drug-loaded ZIF-8 modified 3D printed GelMA scaffolds demonstrated great potential in treating bone defects.

Asunto(s)

Osteogénesis , Andamios del Tejido , Andamios del Tejido/química , Gelatina/química , Regeneración Ósea , Ingeniería de Tejidos/métodos , Impresión Tridimensional

RESUMEN

The development of cell-laden bioinks that possess high biocompatibility and printability is crucial in the field of bioprinting for the creation of cell-embedded tissue engineering scaffolds. As widely known, methacrylated gelatin (GelMA) is one of the most commonly used photo-crosslinkable bioink for cell-laden bioprinting with different printing methods, but GelMA is the derivative of gelatin, so it loses the unique triple-helix molecular structure of collagen and may not be able to successfully activate the cellular pathways or facilitate cell-matrix interaction as effectively as collagen. Recently, methacrylated collagen (CMA) was developed to be an alternative photocrosslinkable bioink with a good bioactivity, but its low printability and biocompatibility limited that application in tissue engineering. In this study, the synthetic process for CMA was improved by synthesizing under 4 °C and using acidic aqueous solution as solvent. Our CMA bioinks were demonstrated a similar printability as GelMA in extrusion bioprinting, while a better formability in digital light processing (DLP). To further analyze the bioactive properties, CMA bioinks were encapsulated with Schwann cells (SCs) and bone mesenchymal stem cells (BMSCs) for printing. SCs-laden CMA bioinks had a significantly higher proliferation rate and expression of neural stem cell-associated genes than GelMA in DLP bioprinting. While, BMSCs-laden CMA bioinks demonstrated >95% cellular viability, better cell spreading and higher expression of osteogenesis-related genes than that of GelMA. Overall, we speculate that the CMA-based bioink developed in this study could be potential bioinks for 3D cell-laden bioprinting in the future.

RESUMEN

Biopolymer hydrogels have become an important group of biomaterials in experimental and clinical use. However, unlike metallic or mineral materials, they are quite sensitive to sterilization. The aim of this study was to compare the effects of gamma irradiation and supercritical carbon dioxide (scCO2) treatment on the physicochemical properties of different hyaluronan (HA)- and/or gelatin (GEL)-based hydrogels and the cellular response of human bone marrow-derived mesenchymal stem cells (hBMSC). Hydrogels were photo-polymerized from methacrylated HA, methacrylated GEL, or a mixture of GEL/HA. The composition and sterilization methods altered the dissolution behavior of the biopolymeric hydrogels. There were no significant differences in methacrylated GEL release but increased methacrylated HA degradation of gamma-irradiated samples. Pore size/form remained unchanged, while gamma irradiation decreased the elastic modulus from about 29 kPa to 19 kPa compared to aseptic samples. HBMSC proliferated and increased alkaline phosphatase activity (ALP) particularly in aseptic and gamma-irradiated methacrylated GEL/HA hydrogels alike, while scCO2 treatment had a negative effect on both proliferation and osteogenic differentiation. Thus, gamma-irradiated methacrylated GEL/HA hydrogels are a promising base for multi-component bone substitute materials.

RESUMEN

Transcatheter arterial radioembolization (TARE) is of great significance for the treatment of advanced hepatocellular carcinoma (HCC). However, the existing radioembolic microspheres still have problems such as non-degradability, non-uniform size, and inability to directly monitor in vivo, which hinders the development of TARE. In this paper, a novel radioembolic agent, 131 I-labeled methacrylated gelatin microspheres (131 I-GMs), is prepared for the treatment of HCC. Water-in-oil (W/O) emulsion templates are prepared by a simple one-step microfluidic method to obtain methacrylated gelatin microspheres (GMs) after UV irradiation. A series of GMs with uniform and controllable size is obtained by adjusting the flow rate of each fluid. Both air-dried and freeze-dried GMs can quickly restore their original shape and size, and still have good monodispersity, elasticity, and biocompatibility. The radiolabeling experiments show that 131 I can efficiently bind to GMs by chloramine-T method, and the obtained 131 I-GMs have good radioactive stability in vitro. The results of in vivo TARE treatment in rats show that 131 I-GMs can be well retained in the hepatic artery and have a good inhibitory effect on the progression of liver cancer, showing the potential for the treatment of HCC.

Asunto(s)

Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratas , Animales , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/radioterapia , Microesferas , Gelatina , Microfluídica

RESUMEN

Use of injectable hydrogels attract attention in the regeneration of dental pulp due to their ability to fill non-uniform voids such as pulp cavities. Here, gelatin methacrylate/thiolated pectin hydrogels (GelMA/PecTH) carrying electrospun core/shell fibers of melatonin (Mel)-polymethylmethacrylate (PMMA)/Tideglusib (Td)-silk fibroin (SF) were designed as an injectable hydrogel for vital pulp regeneration, through prolonged release of Td and Mel to induce proliferation and odontoblastic differentiation of dental pulp stem cells (DPSC). H NMR and FTIR confirmed methacrylation of Gel and thiolation of Pec. Addition of PMMA/SF increased degradation and water retention capacities of GelMA/PecTH. Rheological analyses and syringe tests proved the injectability of the hydrogel systems. Release studies indicated that Td and Mel were released from the fibers inside the hydrogels sequentially due to their specific locations. This release pattern from the hydrogels resulted in DPSC proliferation and odontogenic differentiation in vitro. Gene expression studies showed that the upregulation of DMP1, DSPP, and Axin-2 genes was promoted by GelMA/PecTH carrying PMMA/SF loaded with Mel (50 µg/mL) and Td (200 nM), respectively. Our results suggest that this hydrogel system holds promise for use in the regeneration of pulp tissue.

Asunto(s)

Fibroínas , Melatonina , Polimetil Metacrilato , Gelatina/química , Fibroínas/farmacología , Fibroínas/química , Pulpa Dental , Melatonina/farmacología , Hidrogeles/farmacología , Hidrogeles/química , Pectinas/farmacología , Regeneración

RESUMEN

BACKGROUND: Traumatic impacts to the articular joint surface are known to lead to cartilage degeneration, as in post-traumatic osteoarthritis (PTOA). Limited progress in the development of disease-modifying OA drugs (DMOADs) may be due to insufficient mechanistic understanding of human disease onset/progression and insufficient in vitro models for disease and therapeutic modeling. In this study, biomimetic hydrogels laden with adult human mesenchymal stromal cells (MSC) are used to examine the effects of traumatic impacts as a model of PTOA. We hypothesize that MSC-based, engineered cartilage models will respond to traumatic impacts in a manner congruent with early PTOA pathogenesis observed in animal models. METHODS: Engineered cartilage constructs were fabricated by encapsulating adult human bone marrow-derived mesenchymal stem cells in a photocross-linkable, biomimetic hydrogel of 15% methacrylated gelatin and promoting chondrogenic differentiation for 28 days in a defined medium and TGF-ß3. Constructs were subjected to traumatic impacts with different strains or 10 ng/ml IL-1ß, as a common comparative method of modeling OA. Cell viability and metabolism, elastic modulus, gene expression, matrix protein production and activation of catabolic enzymes were assessed. RESULTS: Cell viability staining showed that traumatic impacts of 30% strain caused an appropriate level of cell death in engineered cartilage constructs. Gene expression and histo/immunohistochemical analyses revealed an acute decrease in anabolic activities, such as COL2 and ACAN expression, and a rapid increase in catabolic enzyme expression, e.g., MMP13, and inflammatory modulators, e.g., COX2. Safranin O staining and GAG assays together revealed a transient decrease in matrix production 24 h after trauma that recovered within 7 days. The decrease in elastic modulus of engineered cartilage constructs was coincident with GAG loss and mediated by the encapsulated cells. The acute and transient changes observed after traumatic impacts contrasted with progressive changes observed using continual IL-1ß treatment. CONCLUSIONS: Traumatic impacts delivered to engineered cartilage constructs induced PTOA-like changes in the encapsulated cells. While IL-1b may be appropriate in modeling OA pathogenesis, the results of this study indicate it may not be appropriate in understanding the etiology of PTOA. The development of a more physiological in vitro PTOA model may contribute to the more rapid development of DMOADs.

Asunto(s)

Cartílago Articular , Células Madre Mesenquimatosas , Osteoartritis , Adulto , Animales , Cartílago/metabolismo , Cartílago Articular/metabolismo , Células Cultivadas , Condrogénesis/genética , Humanos , Hidrogeles/farmacología , Células Madre Mesenquimatosas/metabolismo , Osteoartritis/metabolismo

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The investigation of novel hydrogel systems allows for the study of relationships between biomaterials, cells, and other factors within osteochondral tissue engineering. Three-dimensional (3D) printing is a popular research method that can allow for further interrogation of these questions via the fabrication of 3D hydrogel environments that mimic tissue-specific, complex architectures. However, the adaptation of promising hydrogel biomaterial systems into 3D-printable bioinks remains a challenge. Here, we delineated an approach to that process. First, we characterized a novel methacryloylated gelatin composite hydrogel system and assessed how calcium phosphate and glycosaminoglycan additives upregulated bone- and cartilage-like matrix deposition and certain genetic markers of differentiation within human mesenchymal stem cells (hMSCs), such as RUNX2 and SOX9. Then, new assays were developed and utilized to study the effects of xanthan gum and nanofibrillated cellulose, which allowed for cohesive fiber deposition, reliable droplet formation, and non-fracturing digital light processing (DLP)-printed constructs within extrusion, inkjet, and DLP techniques, respectively. Finally, these bioinks were used to 3D print constructs containing viable encapsulated hMSCs over a 7 d period, where DLP printed constructs facilitated the highest observed increase in cell number over 7 d (∼2.4×). The results presented here describe the promotion of osteochondral phenotypes via these novel composite hydrogel formulations, establish their ability to bioprint viable, cell-encapsulating constructs using three different 3D printing methods on multiple bioprinters, and document how a library of modular bioink additives affected those physicochemical properties important to printability.

Asunto(s)

Bioimpresión , Bioimpresión/métodos , Gelatina/química , Humanos , Hidrogeles/química , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Andamios del Tejido/química

RESUMEN

The advances in the field of tissue engineering and regenerative medicine have opened new vistas for the repair of alveolar clefts. However, the currently available biomaterials used for the repair of alveolar clefts have poor mechanical properties and biocompatibility, which hinders the treatment outcomes. Here, we aimed to develop 3D printed biomimetic scaffolds that fuses ß-tricalcium phosphate (ß-TCP) and bone marrow mesenchymal stem cells (BMSCs) for improving the repair of alveolar clefts. The methacrylate gelatin (GelMA) was mixed with ß-TCP for the preparation of GelMA/ß-TCP hybrid scaffolds via 3D printing platform and chemically cross-linking with UV light. The physicochemical properties of the hydrogel scaffolds were characterized. Moreover, the survival state, proliferation ability, morphological characteristics, and osteogenic induction of BMSCs were examined. The prepared hybrid scaffolds showed good biocompatibility and mechanical properties. BMSCs attached well to the scaffolds and proliferated, survived, differentiated, and stimulated osteogenesis for the reconstruction of alveolar clefts. We expect that use of the prepared hybrid hydrogel scaffold can improve the outcomes of alveolar cleft repair in clinic and expand the application of hybrid hydrogel in tissue engineering repair.

RESUMEN

In recent decades, 3Din vitrocultures of primary human hepatocytes (PHHs) have been increasingly developed to establish models capable of faithfully mimicking main liver functions. The use of 3D bioprinting, capable of recreating structures composed of cells embedded in matrix with controlled microarchitectures, is an emergent key feature for tissue engineering. In this work, we used an extrusion-based system to print PHH in a methacrylated gelatin (GelMa) matrix. PHH bioprinted in GelMa rapidly organized into polarized hollow spheroids and were viable for at least 28 d of culture. These PHH were highly differentiated with maintenance of liver differentiation genes over time, as demonstrated by transcriptomic analysis and functional approaches. The cells were polarized with localization of apico/canalicular regions, and displayed activities of phase I and II biotransformation enzymes that could be regulated by inducers. Furthermore, the implantation of the bioprinted structures in mice demonstrated their capability to vascularize, and their ability to maintain human hepatic specific functions for at least 28 d was illustrated by albumin secretion and debrisoquine metabolism. This model could hold great promise for human liver tissue generation and its use in future biotechnological developments.

Asunto(s)

Bioimpresión , Animales , Bioimpresión/métodos , Gelatina/química , Hepatocitos/metabolismo , Humanos , Hidrogeles/química , Ratones , Impresión Tridimensional , Ingeniería de Tejidos/métodos , Andamios del Tejido/química

RESUMEN

The pandemic of the coronavirus disease 2019 (COVID-19) has made biotextiles, including face masks and protective clothing, quite familiar in our daily lives. Biotextiles are one broad category of textile products that are beyond our imagination. Currently, biotextiles have been routinely utilized in various biomedical fields, like daily protection, wound healing, tissue regeneration, drug delivery, and sensing, to improve the health and medical conditions of individuals. However, these biotextiles are commonly manufactured with fibers with diameters on the micrometer scale (> 10 µm). Recently, nanofibrous materials have aroused extensive attention in the fields of fiber science and textile engineering because the fibers with nanoscale diameters exhibited obviously superior performances, such as size and surface/interface effects as well as optical, electrical, mechanical, and biological properties, compared to microfibers. A combination of innovative electrospinning techniques and traditional textile-forming strategies opens a new window for the generation of nanofibrous biotextiles to renew and update traditional microfibrous biotextiles. In the last two decades, the conventional electrospinning device has been widely modified to generate nanofiber yarns (NYs) with the fiber diameters less than 1000 nm. The electrospun NYs can be further employed as the primary processing unit for manufacturing a new generation of nano-textiles using various textile-forming strategies. In this review, starting from the basic information of conventional electrospinning techniques, we summarize the innovative electrospinning strategies for NY fabrication and critically discuss their advantages and limitations. This review further covers the progress in the construction of electrospun NY-based nanotextiles and their recent applications in biomedical fields, mainly including surgical sutures, various scaffolds and implants for tissue engineering, smart wearable bioelectronics, and their current and potential applications in the COVID-19 pandemic. At the end, this review highlights and identifies the future needs and opportunities of electrospun NYs and NY-based nanotextiles for clinical use.

RESUMEN

The vast majority of patients with corneal blindness cannot recover their vision due to the serious shortage of donor cornea. However, the technology to construct a feasible corneal substitute is a promising treatment method for corneal blindness. In this paper, methacrylated gelatin (GelMA)-methacrylated hyaluronic acid (HAMA) double network (GHDN) hydrogels were prepared by modifying gelatin and hyaluronic acid with methacrylate anhydride (MA). GHDN hydrogel was compared with GelMA single network and HAMA single network hydrogels through characterization experiments of mechanical properties, optical properties, hydrophilicity and in-situ degradation in vitro. At the same time, the biocompatibility of hydrogel was tested by inoculating rabbit corneal epithelial cells (CEpCs) epidermal cells on hydrogels using CCK-8 test, live/dead staining, immunofluorescence staining and qRT-PCR. It was found that the GHDN hydrogel has optical transparency in the visible region, and its mechanical properties are better than those of GelMA and HAMA hydrogels, and its hydrophilicity is similar to that of normal human corneas. The results of in vitro hydrogel culture of CEpCs showed that the proliferation of CEpCs on GHDN hydrogel was two times higher than that of HAMA hydrogel, and the expression of specific marker Cytokeratin 3 (CK3) and Cytokeratin 12 (CK12) could be better maintained on GHDN hydrogel. All the experimental results proved that GHDN hydrogel has good physical properties and biocompatibility and is a potential candidate for corneal tissue engineering scaffolds.

Asunto(s)

Epitelio Corneal , Ingeniería de Tejidos , Animales , Ceguera , Gelatina , Humanos , Ácido Hialurónico , Hidrogeles , Conejos , Ingeniería de Tejidos/métodos

RESUMEN

@#Tissue engineering provides a new possibility for pulp regeneration. As one of the three elements of tissue engineering, scaffolds have attracted increasing attention. Because the root canal system is limited by the unique anatomical structure of the long and narrow lumen, the preformed scaffold cannot be completely covered with the whole root canal space, although it is convenient to apply, so the injectable scaffold may be an ideal choice for pulp tissue engineering. Hydrogels are hydrophilic polymer networks with physical properties similar to soft tissues. They can provide a porous hydrophilic microenvironment, which facilitates the diffusion of oxygen and nutrients. In recent years, researchers have used injectable hydrogels with different mechanical properties and/or loaded biologically active ingredients as scaffolds to promote revascularization and the regeneration of pulp. The results show that natural polymer hydrogels, synthetic polymer hydrogels, and composite hydrogels combining natural and synthetic polymers all have excellent biocompatibility. The types and mechanical properties of hydrogels and the addition of bioactive ingredients can influence the behavior of stem cells, and gelatin-based hydrogels and fibrin-based hydrogels can also achieve rapid vascularization, which creates the conditions for the formation of pulp-like tissues. Among them, photocrosslinked methacrylated gelatin/hyaluronic acid hydrogels, two/multicomponent hydrogels combined with chitosan with antibacterial and temperature-sensitive properties and new self-assembled peptides have become major research topics in recent years due to their excellent properties. To develop suitable hydrogel scaffolds and promote their application in pulp regeneration, this article reviews the research progress in the types, preparation, and application of injectable hydrogels used for dental pulp regeneration.

RESUMEN

Reconstruction of bone defects is still a significant challenge. The aim of this study was to evaluate the effect of application of photobiomodulation (PBM) to enhance in vivo bone regeneration and osteogenic differentiation potential of adipose-derived stem cells (ADSCs) encapsulated in methacrylated gelatin (GEL-MA) hydrogels. Thirty-six Sprague-Dawley rats were randomly separated into 3 experimental groups (n = 12 each). The groups were control/blank defect (I), GEL-MA hydrogel (II), and ADSC-loaded GEL-MA (GEL-MA+ADSC) hydrogel (III). Biparietal critical sized bone defects (6 mm in size) are created in each animal. Half of the animals from each group (n = 6 each) were randomly selected for PBM application using polychromatic light in the near infrared region, 600-1200 nm. PBM was administered from 10 cm distance cranially in 48 h interval. The calvaria were harvested at the 20th week, and macroscopic, microtomographic, and histologic evaluation were performed for further analysis. Microtomographic evaluation demonstrated the highest result for mineralized matrix formation (MMF) in group III. PBM receiving samples of group III showed mean MMF of 79.93±3.41%, whereas the non-PBM receiving samples revealed mean MMF of 60.62±6.34 % (p=0.002). In terms of histologic evaluation of bone defect repair, the higher scores were obtained in the groups II and III when compared to the control group (2.0 for both PBM receiving and non-receiving specimens; p<0.001). ADSC-loaded microwave-induced GEL-MA hydrogels and periodic application of photobiomodulation with polychromatic light appear to have beneficial effect on bone regeneration and can stimulate ADSCs for osteogenic differentiation.

Asunto(s)

Hidrogeles , Osteogénesis , Tejido Adiposo , Animales , Regeneración Ósea , Gelatina , Ratas , Ratas Sprague-Dawley , Células Madre

RESUMEN

Functional tissue engineered heart valves (TEHV) have been an elusive goal for nearly 30 years. Among the persistent challenges are the requirements for engineered valve leaflets that possess nonlinear elastic tissue biomechanical properties, support quiescent fibroblast phenotype, and resist osteogenic differentiation. Nanocellulose is an attractive tunable biological material that has not been employed to this application. In this study, we fabricated a series of photocrosslinkable composite hydrogels mNCC-MeGel (mNG) by conjugating TEMPO-modified nanocrystalline cellulose (mNCC) onto the backbone of methacrylated gelatin (MeGel). Their structures were characterized by FTIR, 1 HNMR and uniaxial compression testing. Human adipose-derived mesenchymal stem cells (HADMSC) were encapsulated within the material and evaluated for valve interstitial cell phenotypes over 14 days culture in both normal and osteogenic media. Compared to the MeGel control group, the HADMSC encapsulated within mNG showed decreased alpha smooth muscle actin (αSMA) expression and increased vimentin and aggrecan expression, suggesting the material supports a quiescent fibroblastic phenotype. Under osteogenic media conditions, HADMSC within mNG hydrogels showed lower expression of osteogenic genes, including Runx2 and osteocalcin, indicating resistance toward calcification. As a proof of principle, the mNG hydrogel, combined with a viscosity enhancing agent, was used to 3D bioprint a tall, self-standing tubular structure that sustained cell viability. Together, these results identify mNG as an attractive biomaterial for TEHV applications.

Asunto(s)

Hidrogeles , Osteogénesis , Diferenciación Celular , Celulosa/farmacología , Válvulas Cardíacas , Hidrogeles/química , Hidrogeles/farmacología , Ingeniería de Tejidos/métodos , Andamios del Tejido/química

RESUMEN

Biomaterials that can harness the intrinsic osteogenic potential of stem cells offer a promising strategy to accelerate bone regeneration and repair. Previously, we had used methacrylated gelatin (GelMA)-based scaffolds to achieve bone formation from human mesenchymal stem cells (hMSCs). In this study, we aimed to further enhance hMSC osteogenesis by incorporating graphene oxide (GO)-based nanosheets into GelMA. In vitro results showed high viability and metabolic activities in hMSCs encapsulated in the newly developed nanocomposites. Incorporation of GO markedly increased mineralization within hMSC-laden constructs, which was further increased by replacing GO with silica-coated graphene oxide (SiGO). Mechanistic analysis revealed that the nanosheet enhanced the production, retention, and biological activity of endogenous bone morphogenetic proteins (BMPs), resulting in robust osteogenesis in the absence of exogenous osteoinductive growth factors. Specifically, the osteoinductive effect of the nanosheets was abolished by inhibiting the BMP signaling pathway with LDN-193189 treatment. The bone formation potential of the technology was further tested in vivo using a mouse subcutaneous implantation model, where hMSCs-laden GO/GelMA and SiGO/GelMA samples resulted in bone volumes 108 and 385 times larger, respectively, than the GelMA control group. Taken together, these results demonstrate the biological activity and mechanism of action of GO-based nanosheets in augmenting the osteogenic capability of hMSCs, and highlights the potential of leveraging nanomaterials such as GO and SiGO for bone tissue engineering applications.

Asunto(s)

Células Madre Mesenquimatosas , Nanocompuestos , Diferenciación Celular , Grafito , Humanos , Osteogénesis , Transducción de Señal , Andamios del Tejido