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Polysaccharides on gelatin-based hydrogels differently affect chondrogenic differentiation of human mesenchymal stromal cells

机译:在明胶基水凝胶上的多糖对人间充质基质细胞的软骨形成分化

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摘要

Selection of feasible hybrid-hydrogels for best chondrogenic differentiation of human mesenchymal stromal cells (hMSCs) represents an important challenge in cartilage regeneration. In this study, three-dimensional hybrid hydrogels obtained by chemical crosslinking of poly (ethylene glycol) diglycidyl ether (PEGDGE), gelatin (G) without or with chitosan (Ch) or dextran (Dx) polysaccharides were developed. The hydrogels, namely G-PEG, GPEG-Ch and G-PEG-Dx, were prepared with an innovative, versatile and cell-friendly technique that involves two preparation steps specifically chosen to increase the degree of crosslinking and the physical-mechanical stability of the product: a first homogeneous phase reaction followed by directional freezing, freeze-drying and postcuring. Chondrogenic differentiation of human bone marrow mesenchymal stromal cells (hBM-MSC) was tested on these hydrogels to ascertain whether the presence of different polysaccharides could favor the formation of the native cartilage structure. We demonstrated that the hydrogels exhibited an open pore porous morphology with high interconnectivity and the incorporation of Ch and Dx into the G-PEG common backbone determined a slightly reduced stiffness compared to that of G-PEG hydrogels. We demonstrated that G-PEG-Dx showed a significant increase of its anisotropic characteristic and G-PEG-Ch exhibited higher and faster stress relaxation behavior than the other hydrogels. These characteristics were associated to absence of chondrogenic differentiation on G-PEG-Dx scaffold and good chondrogenic differentiation on G-PEG and G-PEG-Ch. Furthermore, G-PEG-Ch induced the minor collagen proteins and the formation of collagen fibrils with a diameter like native cartilage.This study demonstrated that both anisotropic and stress relaxation characteristics of the hybrid hydrogels were important features directly influencing the chondrogenic differentiation potentiality of hBM-MSC.
机译:用于最佳有软骨性分化的可行杂交水凝胶的选择是人间充质基质细胞(HMSCs)的最佳化学分化代表了软骨再生中的重要挑战。在该研究中,开发了通过聚(乙二醇)二缩水甘油醚(PEGDGE),明胶(G)的化学交联获得的三维杂化水凝胶,没有或与壳聚糖(CH)或葡聚糖(DX)多糖。用创新的通用和细胞友好的技术制备水凝胶,即G-PEG,GPEG-CH和G-PEG-DX,其涉及专门选择的两种准备步骤,以提高交联程度和物理机械稳定性该产品:第一种均相反应,然后是定向冷冻,冷冻干燥和后皮。在这些水凝胶上测试人骨髓间充质细胞(HBM-MSC)的软骨切片分化,以确定不同多糖的存在是否有利于本机软骨结构的形成。我们证明水凝胶具有高互连的开放孔隙多孔形态,并将CH和DX掺入G-PEG常见骨架中,与G-PEG水凝胶相比,确定略微减小的刚度。我们证明G-PEG-DX显示出其各向异性特征和G-PEG-CH的显着增加,而不是其他水凝胶的应力松弛行为更高。这些特征与G-PEG-DX支架上有软骨性分化的缺乏相关,G-PEG和G-PEG-CH上的良好软骨分化。此外,G-PEG-CH诱导小胶原蛋白蛋白质和胶原型原纤维的形成,其直径像天然软骨一样。本研究表明,杂交水凝胶的各向异性和应力松弛特性是直接影响HBM的软骨性分化潜力的重要特征-msc。

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  • 来源
    《Materials science & engineering》 |2021年第7期|112175.1-112175.12|共12页
  • 作者单位

    Univ Studi Brescia Dipartimento Ingn Meccan & Ind Via Branze 38 I-25123 Brescia Italy;

    IRCCS Ist Ortopedico Rizzoli SC Lab Immunoreumatol Rigeneraz Tissutale Via Barbiano 1-10 I-40136 Bologna Italy;

    IRCCS Ist Ortopedico Rizzoli SC Lab Immunoreumatol Rigeneraz Tissutale Via Barbiano 1-10 I-40136 Bologna Italy;

    Univ Studi Brescia Dipartimento Ingn Meccan & Ind Via Branze 38 I-25123 Brescia Italy|Univ Chittagong Dept Appl Chem & Chem Engn Fac Sci Chittagong 4331 Bangladesh;

    IRCCS Ist Ortopedico Rizzoli SC Lab Immunoreumatol Rigeneraz Tissutale Via Barbiano 1-10 I-40136 Bologna Italy;

    Univ Studi Brescia Dipartimento Ingn Meccan & Ind Via Branze 38 I-25123 Brescia Italy;

    CNR Inst Mol Genet Luigi Luca Cavalli Sforza Unit Bologna Via Barbiano 1-10 I-40136 Bologna Italy|IRCCS Ist Ortoped Rizzoli Via Barbiano 1-10 I-40136 Bologna Italy;

    ASST Spedali Civili Lab Stem Cells Manipulat & Cryopreservat Dept Transfus Med P Spedali Civili 1 I-25123 Brescia Italy;

    Brescia Univ Unit Blood Dis & Bone Marrow Transplantat DPT Clin & Expt Sci Ple Spedali Civili 1 I-25123 Brescia Italy|ASST Spedali Civili Brescia Unit Blood Dis & Bone marrow Transplantat DPT Clin & Expt Sci Ple Spedali Civili 1 I-25123 Brescia Italy;

    Brescia Univ Unit Blood Dis & Bone Marrow Transplantat DPT Clin & Expt Sci Ple Spedali Civili 1 I-25123 Brescia Italy|ASST Spedali Civili Brescia Unit Blood Dis & Bone marrow Transplantat DPT Clin & Expt Sci Ple Spedali Civili 1 I-25123 Brescia Italy;

    IRCCS Ist Ortopedico Rizzoli SC Lab Immunoreumatol Rigeneraz Tissutale Via Barbiano 1-10 I-40136 Bologna Italy|Univ Bologna DIMEC Alma Mater Studiorum Via Massarenti 9 I-40138 Bologna Italy;

    IRCCS Ist Ortopedico Rizzoli SC Lab Immunoreumatol Rigeneraz Tissutale Via Barbiano 1-10 I-40136 Bologna Italy;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Chitosan; dextran-based scaffold; Stress relaxing hydrogel; Human mesenchymal stromal cells; Tissue engineering; Cartilage regeneration;

    机译:壳聚糖;基于葡聚糖的支架;应激松弛水凝胶;人间充质基质细胞;组织工程;软骨再生;

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