Nanoengineered biomimetic hydrogels for guiding human stem cell osteogenesis in three dimensional microenvironments.
Nanoengineered biomimetic hydrogels for guiding human stem cell osteogenesis in three dimensional microenvironments.
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DOI：
10.1039/c5tb02745d
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发表时间：
2016-05-28
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影响因子：
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通讯作者：
Khademhosseini A
中科院分区：
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作者：
Paul A;Manoharan V;Krafft D;Assmann A;Uquillas JA;Shin SR;Hasan A;Hussain MA;Memic A;Gaharwar AK;Khademhosseini A
在缺乏骨形态发生蛋白（BMP-2）等外源性药物的情况下，在三维（3D）微环境中调节骨组织工程干细胞分化的能力仍然是一个挑战。在这项研究中，我们引入了模拟细胞外基质（ECM）的纳米复合水凝胶，在没有任何骨诱导因子的情况下，诱导人间充质干细胞（hMSCs）的成骨分化，用于骨再生。特别地，我们用圆盘状纳米硅酸盐（nSi）增强了光交联胶原基基质（明胶甲基丙烯酰，GelMA），这是一种新的二维（2D）纳米材料。我们发现纳米工程水凝胶支持被封装的hMSCs的迁移和增殖，没有细胞凋亡或炎症细胞因子反应的迹象。与未添加nSi的GelMA相比，添加nSi可显著增强包封的hMSCs的成骨分化，这可以从碱性磷酸盐（ALP）活性和生物矿化基质沉积的增加中看出。我们还表明，微制造纳米工程微凝胶可以用于模式和控制细胞行为。此外，我们还通过免疫活性大鼠模型的体内实验表明，纳米工程水凝胶具有很高的生物相容性。具体来说，水凝胶表现出最小的局部免疫反应，表明它具有组织工程应用的能力。总的来说，我们展示了负载二维纳米硅酸盐的纳米工程水凝胶在没有任何生长因子（如BMP-2）的情况下体外干细胞成骨分化的能力。我们的体内研究表明纳米复合材料具有很高的生物相容性，并显示出无生长因子骨再生的潜力。我们报道了一种富含硅酸盐纳米粘土的生物活性水凝胶的发展，以促进成体干细胞在三维微环境中的成骨分化。
The ability to modulate stem cell differentiation in a three dimensional (3D) microenvironment for bone tissue engineering in absence of exogenous pharmaceutical agents such as bone morphogenic protein (BMP-2) remains a challenge. In this study, we introduce extracellular matrix (ECM)-mimicking nanocomposite hydrogels to induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) for bone regeneration in absence of any osteoinducting factors. In particular, we have reinforced photocrosslinkable collagen-based matrix (gelatin methacryloyl, GelMA) used disk-shaped nanosilicates (nSi), a new class of two-dimensional (2D) nanomaterials. We show that nanoengineered hydrogels supported migration and proliferation of encapsulated hMSCs, with no signs of cell apoptosis or inflammatory cytokine responses. The addition of nSi significantly enhances osteogenic differentiation of encapsulated hMSCs as evident by the increase in alkaline phosphates (ALP) activity and deposition of biomineralized matrix compared to GelMA without nSi. We also show that microfabricated nanoengineered microgels can be used to pattern and control cellular behaviour. Furthermore, we also show that nanoengineered hydrogel have high biocompatibility as determined by in vivo experiments using immunocompetent rat model. Specifically, the hydrogels showed minimum localized immune responses, indicating it ability for tissue engineering applications. Overall, we showed the ability of nanoengineered hydrogels loaded with 2D nanosilicates for osteogenic differentiation of stem cells in vitro, in absence of any growth factors such as BMP-2. Our in vivo studies show high biocompatibility of nanocomposites and show the potential for growth factor free bone regeneration. We report development of a silicate nanoclay-rich bioactive hydrogel to promote osteogenic differentiation of adult stem cells in a three dimensional microenvironment.