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3D Printed Cartilage-Like Tissue Constructs with Spatially Controlled Mechanical Properties

机译：具有空间控制的机械特性的3D打印软骨样组织构造

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摘要

Developing biomimetic cartilaginous tissues that support locomotion while maintaining chondrogenic behavior is a major challenge in the tissue engineering field. Specifically, while locomotive forces demand tissues with strong mechanical properties, chondrogenesis requires a soft microenvironment. To address this challenge, 3D cartilage-like tissue is fabricated using two biomaterials with different mechanical properties: a hard biomaterial to reflect the macromechanical properties of native cartilage, and a soft biomaterial to create a chondrogenic microenvironment. To this end, a bath composed of an interpenetrating polymer network (IPN) of polyethylene glycol (PEG) and alginate hydrogel (MPa order compressive modulus) is developed as an extracellular matrix (ECM) with self-healing properties. Within this bath supplemented with thrombin, human mesenchymal stem cell (hMSC) spheroids embedded in fibrinogen are 3D bioprinted, creating a soft microenvironment composed of fibrin (kPa order compressive modulus) that simulate cartilage's pericellular matrix and allow a fast diffusion of nutrients. The bioprinted hMSC spheroids present high viability and chondrogenic-like behavior without adversely affecting the macromechanical properties of the tissue. Therefore, the ability to locally bioprint a soft and cell stimulating biomaterial inside of a mechanically robust hydrogel is demonstrated, thereby uncoupling the micro- and macromechanical properties of the 3D printed tissues such as cartilage.
机译：在组织工程领域中，开发支持运动并保持软骨生成行为的仿生软骨组织是一项重大挑战。具体而言，尽管机车需要具有强机械性能的组织，但软骨形成需要柔软的微​​环境。为了应对这一挑战，使用两种具有不同机械特性的生物材料制造了3D软骨样组织：一种能反映天然软骨宏观力学特性的硬生物材料，以及一种能产生软骨微环境的软生物材料。为此，开发了由聚乙二醇（PEG）和藻酸盐水凝胶（MPa级压缩模量）互穿聚合物网络（IPN）组成的浴，作为具有自愈特性的细胞外基质（ECM）。在添加凝血酶的浴液中，将3D生物打印在纤维蛋白原中包埋的人间充质干细胞（hMSC）球状体进行3D生物打印，从而创建一个由纤维蛋白（kPa阶压缩模量）组成的柔软微环境，模拟软骨的细胞周围基质并允许营养物质快速扩散。生物打印的hMSC球体具有很高的生存能力和类似软骨的行为，而不会不利地影响组织的宏观力学性能。因此，证明了在机械坚固的水凝胶内部局部生物打印软的和刺激细胞的生物材料的能力，从而解开了3D打印组织（例如软骨）的微观和宏观力学特性。

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  • 来源
    《Advanced Functional Materials》 |2019年第51期|1906330.1-1906330.13|共13页
  • 作者

    de Melo Bruna A. G.; Jodat Yasamin A.; Mehrotra Shreya; Calabrese Michelle A.; Kamperman Tom; Mandal Biman B.; Santana Maria H. A.; Alsberg Eben; Leijten Jeroen; Shin Su Ryon;

  • 作者单位

    Harvard Med Sch Brigham & Womens Hosp Dept Med Div Engn Med Cambridge MA 02139 USA|Univ Estadual Campinas Sch Chem Engn Dept Engn Mat & Bioproc BR-13083852 Campinas SP Brazil;

    Harvard Med Sch Brigham & Womens Hosp Dept Med Div Engn Med Cambridge MA 02139 USA|Stevens Inst Technol Dept Mech Engn Hoboken NJ 07030 USA;

    Harvard Med Sch Brigham & Womens Hosp Dept Med Div Engn Med Cambridge MA 02139 USA|Indian Inst Technol Guwahati Dept Biosci & Bioengn Gauhati 781039 Assam India;

    Univ Minnesota Dept Chem Engn & Mat Sci 421 Washington Ave SE Minneapolis MN 55455 USA;

    Univ Twente Dept Dev BioEngn NL-7522 NB Enschede Overijssel Netherlands;

    Indian Inst Technol Guwahati Dept Biosci & Bioengn Gauhati 781039 Assam India;

    Univ Estadual Campinas Sch Chem Engn Dept Engn Mat & Bioproc BR-13083852 Campinas SP Brazil;

    Univ Illinois Dept Bioengn Chicago IL 60607 USA|Univ Illinois Dept Orthopaed Chicago IL 60607 USA;

    Harvard Med Sch Brigham & Womens Hosp Dept Med Div Engn Med Cambridge MA 02139 USA;

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  • 正文语种 eng
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  • 关键词

    bioprinting; cartilage; fibrin; IPN; spheroids;

    机译：生物印刷;软骨纤维蛋白IPN;球体;

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