Combining Electrospun Fiber Mats and Bioactive Coatings for Vascular Graft Prostheses.

The patency of small-diameter (<6 mm) synthetic vascular grafts (VGs) is still limited by the absence of a confluent, blood flow-resistant monolayer of endothelial cells (ECs) on the lumen and of vascular smooth muscle cell (VSMC) growth into the media layer. In this research, electrospinning has been combined with bioactive coatings based on chondroitin sulfate (CS) to create scaffolds that possess optimal morphological and bioactive properties for subsequent cell seeding. We fabricated random and aligned electrospun poly(ethylene terephthalate), ePET, mats with small pores (3.2 ± 0.5 or 3.9 ± 0.3 µm) and then investigated the effects of topography and bioactive coatings on EC adhesion, growth, and resistance to shear stress. Bioactive coatings were found to dominate the cell behavior, which enabled creation of a near-confluent EC monolayer that resisted physiological shear-flow conditions. CS is particularly interesting since it prevents platelet adhesion, a key issue to avoid blood clot formation in case of an incomplete EC monolayer or partial cell detachment. Regarding the media layer, circumferentially oriented nanofibers with larger pores (6.3 ± 0.5 µm) allowed growth, survival, and inward penetration of VSMCs, especially when the CS was further coated with tethered, oriented epithelial growth factor (EGF). In summary, the techniques developed here can lead to adequate scaffolds for the luminal and media layers of small-diameter synthetic VGs.

In Vitro and Pilot In Vivo Evaluation of a Bioactive Coating for Stent Grafts Based on Chondroitin Sulfate and Epidermal Growth Factor.

PURPOSE: To evaluate the potential of a bioactive coating based on chondroitin sulfate (CS) and tethered epidermal growth factor (EGF) for improvement of healing around stent grafts (SGs). MATERIALS AND METHODS: The impact of the bioactive coating on cell survival was tested in vitro on human vascular cells using polyethylene terephthalate films (PET) as a substrate. After being transferred onto a more "realistic" material (expanded polytetrafluoroethylene [ePTFE]), the durability and mechanical behavior of the coating and cell survival were studied. Preliminary in vivo testing was performed in a canine iliac aneurysm model reproducing type I endoleaks (three animals with one control and one bioactive SG for each). RESULTS: CS and EGF coatings significantly increased survival of human smooth muscle cells and fibroblasts compared with bare PET or ePTFE (P < .05). The coating also displayed good durability over 30 days according to enzyme-linked immunosorbent assay and cell survival tests. The coating did not affect mechanical properties of ePTFE and was successfully transferred onto commercial SGs for in vivo testing. No difference was observed on computed tomography and macroscopic examinations in endoleak persistence at 3 months, but the bioactive coating deposited on the abluminal surface of the SG (exposed to the vessel wall) increased the percentage of healed tissue in the aneurysm. No adverse effect, such as neointima formation or thrombosis, was observed. CONCLUSIONS: The bioactive coating promoted in vitro cell survival, displayed good durability, and was successfully transferred onto a commercial SG. Preliminary in vivo results suggest improved healing around bioactive SGs.

High-Resolution Additive Manufacturing of a Biodegradable Elastomer with A Low-Cost LCD 3D Printer.

Artificial organs and organs-on-a-chip (OoC) are of great clinical and scientific interest and have recently been made by additive manufacturing, but depend on, and benefit from, biocompatible, biodegradable, and soft materials. Poly(octamethylene maleate (anhydride) citrate (POMaC) meets these criteria and has gained popularity, and as in principle, it can be photocured and is amenable to vat-photopolymerization (VP) 3D printing, but only low-resolution structures have been produced so far. Here, a VP-POMaC ink is introduced and 3D printing of 80 µm positive features and complex 3D structures is demonstrated using low-cost (≈US$300) liquid-crystal display (LCD) printers. The ink includes POMaC, a diluent and porogen additive to reduce viscosity within the range of VP, and a crosslinker to speed up reaction kinetics. The mechanical properties of the cured ink are tuned to match the elastic moduli of different tissues simply by varying the porogen concentration. The biocompatibility is assessed by cell culture which yielded 80% viability and the potential for tissue engineering illustrated with a 3D-printed gyroid seeded with cells. VP-POMaC and low-cost LCD printers make the additive manufacturing of high resolution, elastomeric, and biodegradable constructs widely accessible, paving the way for a myriad of applications in tissue engineering and 3D cell culture as demonstrated here, and possibly in OoC, implants, wearables, and soft robotics.

A review on tragacanth gum: A promising natural polysaccharide in drug delivery and cell therapy.

Tragacanth is an abundant natural gum extracted from some plants and is dried for use in various applications from industry to biomedicines. It is a cost-effective and easily accessible polysaccharide with desirable biocompatibility and biodegradability, drawing much attention for use in new biomedical applications such as wound healing and tissue engineering. Moreover, this anionic polysaccharide with a highly branched structure has been used as an emulsifier and thickening agent in pharmaceutical applications. In addition, this gum has been introduced as an appealing biomaterial for producing engineering tools in drug delivery. Furthermore, the biological properties of tragacanth gum have made it a favorable biomaterial in cell therapies, and tissue engineering. This review aims to discuss the recent studies on this natural gum as a potential carrier for different drugs and cells.

Carrageenans for tissue engineering and regenerative medicine applications: A review.

Biomaterials are considered a substantial building block for tissue engineering, regenerative medicine, and drug delivery. Despite using both organic and inorganic biomaterials in these fields, polymeric biomaterials are the most promising candidates because of their versatility in their characteristics (i.e., physical, chemical, and biological). Mainly, naturally-derived polymers are of great interest due to their inherent bioactivity. Derived from red seaweeds, carrageenan (CG) is a naturally-occurring polysaccharide that has shown promise as a biopolymer for various biomedical applications. CG possesses unique characteristics, including antiviral, immunomodulatory, anticoagulant, antioxidant, and anticancer properties, making it an appealing candidate for tissue engineering and drug delivery research. This review summarizes the versatile properties of CG and the chemical modifications applied to it. In addition, it highlights some of the most promising research that takes advantage of CG to formulate and fabricate scaffolds and/or drug delivery systems with high potential for tissue repair and disease curing.

Toward Hierarchical Assembly of Aligned Cell Sheets into a Conical Cardiac Ventricle Using Microfabricated Elastomers.

Despite current efforts in organ-on-chip engineering to construct miniature cardiac models, they often lack some physiological aspects of the heart, including fiber orientation. This motivates the development of bioartificial left ventricle models that mimic the myofiber orientation of the native ventricle. Herein, an approach relying on microfabricated elastomers that enables hierarchical assembly of 2D aligned cell sheets into a functional conical cardiac ventricle is described. Soft lithography and injection molding techniques are used to fabricate micro-grooves on an elastomeric polymer scaffold with three different orientations ranging from -60° to +60°, each on a separate trapezoidal construct. The width of the micro-grooves is optimized to direct the majority of cells along the groove direction and while periodic breaks are used to promote cell-cell contact. The scaffold is wrapped around a central mandrel to obtain a conical-shaped left ventricle model inspired by the size of a human left ventricle 19 weeks post-gestation. Rectangular micro-scale holes are incorporated to alleviate oxygen diffusional limitations within the 3D scaffold. Cardiomyocytes within the 3D left ventricle constructs showed high viability in all layers after 7 days of cultivation. The hierarchically assembled left ventricle also provided functional readouts such as calcium transients and ejection fraction.

3D Printing of Vascular Tubes Using Bioelastomer Prepolymers by Freeform Reversible Embedding.

Bioelastomers have been extensively used in tissue engineering applications because of favorable mechanical stability, tunable properties, and chemical versatility. As these materials generally possess low elastic modulus and relatively long gelation time, it is challenging to 3D print them using traditional techniques. Instead, the field of 3D printing has focused preferentially on hydrogels and rigid polyester materials. To develop a versatile approach for 3D printing of elastomers, we used freeform reversible embedding of suspended prepolymers. A family of novel fast photocrosslinakble bioelastomer prepolymers were synthesized from dimethyl itaconate, 1,8-octanediol, and triethyl citrate. Tensile testing confirmed their elastic properties with Young's moduli in the range of 11-53 kPa. These materials supported cultivation of viable cells and enabled adhesion and proliferation of human umbilical vein endothelial cells. Tubular structures were created by embedding the 3D printed microtubes within a secondary hydrogel that served as a temporary support. Upon photocrosslinking and porogen leaching, the polymers were permeable to small molecules (TRITC-dextran). The polymer microtubes were assembled on the 96-well plates custom made by hot-embossing, as a tool to connect multiple organs-on-a-chip. The endothelialization of the tubes was performed to confirm that these microtubes can be utilized as vascular tubes to support parenchymal tissues seeded on them.

Facile Method for Fabrication of Meter-Long Multifunctional Hydrogel Fibers with Controllable Biophysical and Biochemical Features.

Hydrogel structures with microscale morphological features have extensive application in tissue engineering owing to their capacity to induce desired cellular behavior. Herein, we describe a novel biofabrication method for fabrication of grooved solid and hollow hydrogel fibers with control over their cross-sectional shape, surface morphology, porosity, and material composition. These fibers were further configured into three-dimensional structures using textile technologies such as weaving, braiding, and embroidering methods. Additionally, the capacity of these fibers to integrate various biochemical and biophysical cues was shown via incorporating drug-loaded microspheres, conductive materials, and magnetic particles, extending their application to smart drug delivery, wearable or implantable medical devices, and soft robotics. The efficacy of the grooved fibers to induce cellular alignment was evaluated on various cell types including myoblasts, cardiomyocytes, cardiac fibroblasts, and glioma cells. In particular, these fibers were shown to induce controlled myogenic differentiation and morphological changes, depending on their groove size, in C2C12 myoblasts.

One-Pot Synthesis of Unsaturated Polyester Bioelastomer with Controllable Material Curing for Microscale Designs.

Synthetic polyester elastomeric constructs have become increasingly important for a range of healthcare applications, due to tunable soft elastic properties that mimic those of human tissues. A number of these constructs require intricate mechanical design to achieve a tunable material with controllable curing. Here, the synthesis and characterization of poly(itaconate-co-citrate-co-octanediol) (PICO) is presented, which exhibits tunable formation of elastomeric networks through radical crosslinking of itaconate in the polymer backbone of viscous polyester gels. Through variation of reaction times and monomer molar composition, materials with modulation of a wide range of elasticity (36-1476 kPa) are generated, indicating the tunability of materials to specific elastomeric constructs. This correlated with measured rapid and controllable gelation times. As a proof of principle, scaffold support for cardiac tissue patches is developed, which presents visible tissue organization and viability with appropriate elastomeric support from PICO materials. These formulations present potential application in a range of healthcare applications with requirement for elastomeric support with controllable, rapid gelation under mild conditions.

A Facile Approach for the Mass Production of Submicro/Micro Poly (Lactic Acid) Fibrous Mats and Their Cytotoxicity Test towards Neural Stem Cells.

Despite many of the studies being conducted, the electrospinning of poly (lactic acid) (PLA), dissolved in its common solvents, is difficult to be continuously processed for mass production. This is due to the polymer solution droplet drying. Besides, the poor stretching capability of the polymer solution limits the production of small diameter fibers. To address these issues, we have examined the two following objectives: first, using an appropriate solvent system for the mass production of fibrous mats with fine-tunable fiber diameters; second, nontoxicity of the mats towards Neural Stem Cell (NSC). To this aim, TFA (trifluoroacetic acid) was used as a cosolvent, in a mixture with DCM (dichloromethane), and the solution viscosity, surface tension, electrical conductivity, and the continuity of the electrospinning process were compared with the solutions prepared with common single solvents. The binary solvent facilitated PLA electrospinning, resulting in a long lasting, stable electrospinning condition, due to the low surface tension and high conductivity of the binary-solvent system. The fiber diameter was tailored from nano to micro by varying effective parameters and examined by scanning electron microscopy (SEM) and image-processing software. Laminin-coated electrospun mats supported NSC expansion and spreading, as examined using AlamarBlue assay and fluorescent microscopy, respectively.