1,720,971 research outputs found

    Biomaterial-Assisted 3D In Vitro Tumor Models: From Organoid towards Cancer Tissue Engineering Approaches

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    : Cancers are a leading cause of death around the world, accounting for nearly 10 million deaths yearly [...]

    3D printing of methylcellulose-based hydrogels

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    Methylcellulose-based (MC) hydrogels are optimal substrates to obtain cell sheets for regenerative medicine applications. However, current MC-based hydrogel preparation methods only allow for the obtainment of MC substrates with standardized and simple geometries (i.e., geometry of the container where the hydrogel is produced). Here, we propose the 3D printing of a MC-based hydrogel to obtain substrates with desired and controlled geometries. First, we optimize the printing temperature (i.e., T = 21 °C) of the MC-based hydrogel, so to obtain printed strands reproducing the designed geometry without defects. We investigate the influence of the printing parameters (i.e., needle size, deposition speed and extrusion multiplier) on the printed strands diameters and printing accuracy. A decrease in the sol-gel transition temperature was evidenced, together with an increase in water uptake at 37 °C, for printed MC-based hydrogels compared to not printed samples; the stability at 37 °C and achieved rheological properties were suitable for cell sheet engineering applications. In addition, cell viability higher than 90% was detected after embedding cells in the MC-based hydrogel; moreover, the optimized printing parameters allowed to bioprint C2C12 cells embedded in the MC-based hydrogel with a viability higher than 80%. The printing parameters we optimized could be used to produce MC substrates for cell sheet engineering or cell delivery applications with controlled and complex-shaped geometries

    Plant Tissues as 3D Natural Scaffolds for Adipose, Bone and Tendon Tissue Regeneration

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    Decellularized tissues are a valid alternative as tissue engineering scaffolds, thanks to the three-dimensional structure that mimics native tissues to be regenerated and the biomimetic microenvironment for cells and tissues growth. Despite decellularized animal tissues have long been used, plant tissue decellularized scaffolds might overcome availability issues, high costs and ethical concerns related to the use of animal sources. The wide range of features covered by different plants offers a unique opportunity for the development of tissue-specific scaffolds, depending on the morphological, physical and mechanical peculiarities of each plant. Herein, three different plant tissues (i.e., apple, carrot, and celery) were decellularized and, according to their peculiar properties (i.e., porosity, mechanical properties), addressed to regeneration of adipose tissue, bone tissue and tendons, respectively. Decellularized apple, carrot and celery maintained their porous structure, with pores ranging from 70 to 420 μm, depending on the plant source, and were stable in PBS at 37°C up to 7 weeks. Different mechanical properties (i.e., Eapple = 4 kPa, Ecarrot = 43 kPa, Ecelery = 590 kPa) were measured and no indirect cytotoxic effects were demonstrated in vitro after plants decellularization. After coating with poly-L-lysine, apples supported 3T3-L1 preadipocytes adhesion, proliferation and adipogenic differentiation; carrots supported MC3T3-E1 pre-osteoblasts adhesion, proliferation and osteogenic differentiation; celery supported L929 cells adhesion, proliferation and guided anisotropic cells orientation. The versatile features of decellularized plant tissues and their potential for the regeneration of different tissues are proved in this work

    Chemically crosslinked gelatin hydrogels as scaffolding materials for adipose tissue engineering

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    The design of scaffolding materials that mimic the properties of the target tissue to be regenerated is a mandatory requirement to engineer a successful scaffold; however, the heterogeneous properties of adipose tissue (AT), strictly dependent on the AT depot, are often underestimated when engineering AT scaffolds. Moreover, a scaffolding material with versatile properties, suitable for the regeneration of different AT depots, is currently missing. Chemically crosslinked gelatin hydrogels are here prepared, and their properties tuned by varying gelatin concentration and reaction stoichiometry to obtain hydrogels suitable for AT regeneration. All hydrogel formulations are stable in water at 37 °C, showing swelling behavior dependent on synthesis parameters. The mechanical compressive response mimics the viscoelastic response typical of native AT, with elastic modulus values covering the range of breast and heel pad AT. The rheological properties vary among the hydrogel formulations, showing a typical shear thinning response, comparable to other AT scaffolds described in literature. In vitro cytotoxicity tests using 3T3-L1 preadipocytes show no cytotoxic effects up to 7 days. 3T3-L1 cells seeded on the hydrogels show good adhesion, proliferation, and adipogenic differentiation, confirmed by an increase in peroxisome proliferator-activated receptor gamma gene expression and lipid droplets accumulation observed by Oil Red O staining. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47104

    Characterization of gelatin hydrogels derived from different animal sources

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    Gelatin hydrogels are a valid alternative to produce scaffolds, wound dressings, and drug delivery systems. However, the animal source from which collagen is extracted to obtain gelatin and its treatment are often underestimated despite they can influence the properties of the obtained gelatin hydrogels. Here, three gelatin powders derived from different animal sources (i.e., porcine, bovine and cold water fish) are chemically crosslinked by two reactions and their physico-mechanical properties investigated. The non-cytotoxic hydrogels swelled differently in water (i.e., porcine > fish > bovine), which in turn influenced the mechanical properties of the obtained hydrogels, highlighting the importance of properly selecting the gelatin source when preparing gelatin hydrogels

    Post forming analysis and in vitro biological characterization of AZ31B processed by incremental forming and coated with electrospun polycaprolactone

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    Main problems related to the adoption of magnesium alloys for temporary orthopedic prostheses manufacturing are (i) the need of an efficient production process and (ii) the high corrosion rate compared with the bone healing time. In this work, the single-point incremental forming (SPIF) process, an effective and flexible solution for manufacturing very small batches even composed by one piece, was investigated. Tests were conducted on AZ31B-H24 sheets and were aimed at understanding the effect of temperature on the mechanical characteristics (microstructure, hardness, and roughness) of the sheet after the above-mentioned forming process and their correlation with both the corrosion rate and the cytocompatibility. In addition, after the forming process, samples processed by SPIF were coated by electrospun polycaprolactone (PCL) to reduce the corrosion rate and to further improve the cytocompatibility. Grain refinement was achieved thanks to the combined effect of temperature and strain rate during forming and finer grain size resulted to improve the magnesium corrosion resistance. In simulated body fluids, the electrospun PCL-coated samples exhibited a slower pH increase compared with uncoated samples. No indirect cytotoxic effects were detected in vitro for MC3T3-E1 cells for both coated and uncoated samples. However, cells colonization was observed only on electrospun PCL-coated samples, suggesting the importance of the polymeric coating in promoting the adhesion and survival of seeded MC3T3-E1 cells on the implant surface

    Crosslinked gelatin hydrogels as carriers for controlled heparin release

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    The application of heparin as anticoagulant, anti-inflammatory and growth factor regulating agent is currently limited by its narrow therapeutic window. Here, we describe the use of chemically crosslinked gelatin hydrogels as delivery platform to achieve the control of heparin release over time. Different hydrogel formulations and two strategies for heparin loading were tested. The synergic electrostatic interactions between heparin and gelatin hydrogels resulted in a sustained release until 60 h, demonstrated by toluidine blue tests. Platelets adhesion was significantly reduced in heparin-loaded hydrogels, thus proving good heparin bioactivity after processing. Our heparin-loaded hydrogels represent a possible valid option to develop coating for catheters and cardiovascular devices, or skin dressings

    3D Bioprinting of Pectin-Cellulose Nanofibers Multicomponent Bioinks

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    Pectin has found extensive interest in biomedical applications, including wound dressing, drug delivery, and cancer targeting. However, the low viscosity of pectin solutions hinders their applications in 3D bioprinting. Here, we developed multicomponent bioinks prepared by combining pectin with TEMPO-oxidized cellulose nanofibers (TOCNFs) to optimize the inks’ printability while ensuring stability of the printed hydrogels and simultaneously print viable cell-laden inks. First, we screened several combinations of pectin (1%, 1.5%, 2%, and 2.5% w/v) and TOCNFs (0%, 0.5%, 1%, and 1.5% w/v) by testing their rheological properties and printability. Addition of TOCNFs allowed increasing the inks’ viscosity while maintaining shear thinning rheological response, and it allowed us to identify the optimal pectin concentration (2.5% w/v). We then selected the optimal TOCNFs concentration (1% w/v) by evaluating the viability of cells embedded in the ink and eventually optimized the writing speed to be used to print accurate 3D grid structures. Bioinks were prepared by embedding L929 fibroblast cells in the ink printed by optimized printing parameters. The printed scaffolds were stable in a physiological-like environment and characterized by an elastic modulus of E = 1.8 ± 0.2 kPa. Cells loaded in the ink and printed were viable (cell viability >80%) and their metabolic activity increased in time during the in vitro culture, showing the potential use of the developed bioinks for biofabrication and tissue engineering applications

    Additive Manufacturing Approaches for Hydroxyapatite-Reinforced Composites

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    Additive manufacturing (AM) techniques have gained interest in the tissue engineering field, thanks to their versatility and unique possibilities of producing constructs with complex macroscopic geometries and defined patterns. Recently, composite materials—namely, heterogeneous biomaterials identified as continuous phase (matrix) and reinforcement (filler)—have been proposed as inks that can be processed by AM to obtain scaffolds with improved biomimetic and bioactive properties. Significant efforts have been dedicated to hydroxyapatite (HA)-reinforced composites, especially targeting bone tissue engineering, thanks to the chemical similarities of HA with respect to mineral components of native mineralized tissues. Herein, applications of AM techniques to process HA-reinforced composites and biocomposites for the production of scaffolds with biological matrices, including cellular tissues, are reviewed. The primary outcomes of recent investigations in terms of morphological, structural, and in vitro and in vivo biological properties of the materials are discussed. The approaches based on the nature of the matrices employed to embed the HA reinforcements and produce the tissue substitutes are classified, and a critical discussion is provided on the presented state of the art as well as the future perspectives, to offer a comprehensive picture of the strategies investigated as well as challenges in this emerging field of materiomics

    In vitro cell delivery by gelatin microspheres prepared in water-in-oil emulsion

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    The regeneration of injured or damaged tissues by cell delivery approaches requires the fabrication of cell carriers (e.g., microspheres, MS) that allow for cell delivery to limit cells spreading from the injection site. Ideal MS for cell delivery should allow for cells adhesion and proliferation on the MS before the injection, while they should allow for viable cells release after the injection to promote the damaged tissue regeneration. We optimized a water-in-oil emulsion method to obtain gelatin MS crosslinked by methylenebisacrylamide (MBA). The method we propose allowed obtaining spherical, chemically crosslinked MS characterized by a percentage crosslinking degree of 74.5 ± 2.1%. The chemically crosslinked gelatin MS are characterized by a diameter of 70.9 ± 17.2 μm in the dry state and, at swelling plateau in culture medium at 37 °C, by a diameter of 169.3 ± 41.3 μm. The MS show dimensional stability up to 28 days, after which they undergo complete degradation. Moreover, during their degradation, MS release gelatin that can improve the engraftment of cells in the injured site. The produced MS did not induce any cytotoxic effect in vitro and they supported viable L929 fibroblasts adhesion and proliferation. The MS released viable cells able to colonize and proliferate on the tissue culture plastic, used as release substrate, potentially proving their ability in supporting a simplified in vitro wound healing process, thus representing an optimal tool for cell delivery applications. [Figure not available: see fulltext.
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