A Hydrogel Platform that Incorporates Laminin Isoforms for Efficient Presentation of Growth Factors - Neural Growth and Osteogenesis
A Hydrogel Platform that Incorporates Laminin Isoforms for Efficient Presentation of Growth Factors - Neural Growth and Osteogenesis
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DOI：
10.1002/adfm.202010225
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发表时间：
2021-03-21
影响因子：
19
通讯作者：
Salmeron-Sanchez, Manuel
中科院分区：
文献类型：
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作者：
Dobre, Oana;Oliva, Mariana A. G.;Salmeron-Sanchez, Manuel
层粘连蛋白 (LM) 是细胞外基质 (ECM) 的重要结构蛋白。每种 LM 同工型的丰度均依赖于组织，这表明 LM 具有组织特异性作用。 LM 结合生长因子 (GF)，生长因子是一种强大的细胞因子，因其控制干细胞分化的能力而广泛应用于组织工程中。目前，体外最常用的 ECM 模拟材料是 Matrigel，这是一种含有 LM 和各种 GF 的成分不明的基质，但存在批次差异且缺乏对理化性质的控制。受Matrigel的启发，提出了一种基于混合LM-聚乙二醇（PEG）水凝胶的全新且完全定义的水凝胶平台，具有可控刚度（1-25 kPa）和可降解性。不同的 LM 同工型用于结合并有效展示 GF（此处为骨形态发生蛋白 (BMP-2) 和 β-神经生长因子 (β-NGF)），使其能够以超低剂量固相呈现，从而特异性靶向一系列组织。该平台具有触发干细胞向成骨谱系分化并刺激神经细胞 3D 生长的潜力。这些水凝胶可实现 3D、合成、成分确定和可重复的细胞培养微环境，反映天然 ECM 的复杂性，其中 GF 与 LM 亚型结合产生细胞过程的全部多样性。
Laminins (LMs) are important structural proteins of the extracellular matrix (ECM). The abundance of every LM isoform is tissue-dependent, suggesting that LM has tissue-specific roles. LM binds growth factors (GFs), which are powerful cytokines widely used in tissue engineering due to their ability to control stem cell differentiation. Currently, the most commonly used ECM mimetic material in vitro is Matrigel, a matrix of undefined composition containing LM and various GFs, but subjected to batch variability and lacking control of physicochemical properties. Inspired by Matrigel, a new and completely defined hydrogel platform based on hybrid LM-poly(ethylene glycol) (PEG) hydrogels with controllable stiffness (1-25 kPa) and degradability is proposed. Different LM isoforms are used to bind and efficiently display GFs (here, bone morphogenetic protein (BMP-2) and beta-nerve growth factor (beta-NGF)), enabling their solid-phase presentation at ultralow doses to specifically target a range of tissues. The potential of this platform to trigger stem cell differentiation toward osteogenic lineages and stimulate neural cells growth in 3D, is demonstrated. These hydrogels enable 3D, synthetic, defined composition, and reproducible cell culture microenvironments reflecting the complexity of the native ECM, where GFs in combination with LM isoforms yield the full diversity of cellular processes.