Synthetic hydrogels engineered to promote collecting lymphatic vessel sprouting.

Synthetic hydrogels engineered to promote collecting lymphatic vessel sprouting.
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DOI:
10.1016/j.biomaterials.2022.121483
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发表时间:
2022-05
期刊:
影响因子:
14
通讯作者:
--
中科院分区:
工程技术1区
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--
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淋巴管系统是身体循环的重要组成部分,提供了一个血管网络,将液体和蛋白质从组织空间返回到血液,促进免疫呼叫和抗原转运到淋巴结,并从肠道吸收膳食脂质。基于生物材料的策略的开发,以促进淋巴管的生长,无论是用于再生目的还是作为研究淋巴生物学的模型系统,仍处于起步阶段。特别是,促进集合管淋巴网络萌芽和形成的平台尤其不发达。通过实施基于聚乙二醇(PEG)的模块化水凝胶,我们探索了基质弹性、可降解性和粘附肽呈递对大鼠淋巴集合管植入段发芽的独立贡献。与其他物理化学基质特性相比,具有 680 Pa 弹性、2.0 mM RGD 粘合肽和对蛋白酶降解性完全敏感的工程水凝胶产生了最高水平的发芽。然后利用这种工程水凝胶作为支架,以促进供体血管的植入,该供体血管功能性地移植到宿主脉管系统中。这种水凝胶为促进体内淋巴管生成提供了一个有前途的平台,或作为了解收集淋巴管侧支过程中发芽过程中涉及的细胞机制的一种手段。设计了一种水凝胶来促进集合淋巴管的萌芽。对个体生物力学和生化凝胶特性的系统分析允许在体外平台中局部优化发芽淋巴管生成。
The lymphatic vasculature is an essential component of the body’s circulation providing a network of vessels to return fluid and proteins from the tissue space to the blood, to facilitate immune call and antigen transport to lymph nodes, and to take up dietary lipid from the intestine. The development of biomaterial based strategies to facilitate the growth of lymphatics either for regenerative purposes or as model system to study lymphatic biology is still in its nascent stages. In particular, platforms that encourage the sprouting and formation of lymphatic networks from collecting vessels are particularly underdeveloped. Through implementation of a modular, poly(ethylene glycol) (PEG)-based hydrogel, we explored the independent contributions of matrix elasticity, degradability, and adhesive peptide presentation on sprouting of implanted segments of rat lymphatic collecting vessels. An engineered hydrogel with 680 Pa elasticity, 2.0 mM RGD adhesive peptide, and full susceptibility to protease degradability produced the highest levels of sprouting relative to other physicochemical matrix properties. This engineered hydrogel was then utilized as a scaffold to facilitate the implantation of a donor vessel that functionally grafted into the host vasculature. This hydrogel provides a promising platform for facilitating lymphangiogenesis in vivo or as a means to understand the cellular mechanisms involved in the sprout process during collecting lymphatic vessel collateralization. A hydrogel was engineered to promote collecting lymphatic vessel sprouting. Systematic analysis of individual biomechanical and biochemical gel properties allowed local optimization of sprouting lymphangiogenesis in an in-vitro platform.
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