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NiCHE Platform: Nature-Inspired Catechol-Conjugated Hyaluronic Acid Environment Platform for Salivary Gland Tissue Engineering.
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2020-01-14 , DOI: 10.1021/acsami.9b20546
Sang-Woo Lee 1 , Ji Hyun Ryu 2 , Min Jae Do 3 , Eun Namkoong 1 , Haeshin Lee 3 , Kyungpyo Park 1
Affiliation  

Recently, there has been growing interest in replacing severely damaged salivary glands with artificial salivary gland functional units created in vitro by tissue engineering approaches. Although various materials such as poly(lactic-co-glycolic acid), polylactic acid, poly(glycolic acid), and polyethylene glycol hydrogels have been used as scaffolds for salivary gland tissue engineering, none of them is effective enough to closely recapitulate the branched structural complexity and heterogeneous cell population of native salivary glands. Instead of discovering new biomaterial candidates, we synthesized hyaluronic acid-catechol (HACA) conjugates to establish a versatile hyaluronic acid coating platform named "NiCHE (nature-inspired catechol-conjugated hyaluronic acid environment)" for boosting the salivary gland tissue engineering efficacy of the previously reported biomaterials. By mimicking hyaluronic acid-rich niche in the mesenchyme of embryonic submandibular glands (eSMGs) with NiCHE coating on substrates including polycarbonate membrane, stiff agarose hydrogel, and polycaprolactone scaffold, we observed significantly enhanced cell adhesion, vascular endothelial and progenitor cell proliferation, and branching of in vitro-cultured eSMGs. High mechanical stiffness of the substrate is known to inhibit eSMG growth, but the NiCHE coating significantly reduced such stiffness-induced negative effects, leading to successful differentiation of progenitor cells to functional acinar and myoepithelial cells. These enhancement effects of the NiCHE coating were due to the increased proliferation of vascular endothelial cells via interaction between CD44 and surface-immobilized HAs. As such, our NiCHE coating platform renders any kind of material highly effective for salivary gland tissue culture by mimicking in vivo embryonic mesenchymal HA. Based on our results, we expect the NiCHE coating to expand the range of biomaterial candidates for salivary glands and other branching epithelial organs.

中文翻译:

NiCHE平台:自然界中邻苯二酚共轭的透明质酸环境平台,用于唾液腺组织工程。

最近,人们越来越感兴趣的是用组织工程方法在体外创建的人工唾液腺功能单元来替代严重受损的唾液腺。尽管聚乳酸-乙醇酸共聚物,聚乳酸,聚乙醇酸和聚乙二醇水凝胶等各种材料已被用作唾液腺组织工程的支架,但它们均不能有效地使分支的器官重塑唾液腺的结构复杂性和异质细胞群。我们没有发现新的生物材料候选物,而是合成了透明质酸-邻苯二酚(HACA)共轭物,从而建立了一个多功能的透明质酸涂层平台,命名为“ NiCHE(自然启发型邻苯二酚共轭的透明质酸环境)”。增强先前报道的生物材料的唾液腺组织工程功效。通过在包括聚碳酸酯膜,坚硬的琼脂糖水凝胶和聚己内酯支架在内的底物上用NiCHE涂层模拟胚胎下颌腺(eSMG)的间充质中富含透明质酸的利基,我们观察到细胞粘附力显着增强,血管内皮和祖细胞增殖以及分支体外培养的eSMG。已知基材的高机械刚度会抑制eSMG的生长,但是NiCHE涂层显着降低了这种刚度诱导的负面影响,从而成功地使祖细胞分化为功能性腺泡和肌上皮细胞。NiCHE涂层的这些增强作用归因于通过CD44和表面固定的HA之间的相互作用增加了血管内皮细胞的增殖。因此,我们的NiCHE涂层平台通过模仿体内胚胎间充质HA,为唾液腺组织培养提供了非常有效的材料。根据我们的结果,我们期望NiCHE涂层能够扩大唾液腺和其他分支上皮器官的生物材料候选物范围。
更新日期:2020-01-15
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