Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, United States.
Department of Biological Sciences, University at Albany, State University of New York, United States.
Acta Biomater. 2017 Oct 15;62:116-127. doi: 10.1016/j.actbio.2017.08.009. Epub 2017 Aug 8.
Development of electrospun nanofibers that mimic the structural, mechanical and biochemical properties of natural extracellular matrices (ECMs) is a promising approach for tissue regeneration. Electrospun fibers of synthetic polymers partially mimic the topography of the ECM, however, their high stiffness, poor hydrophilicity and lack of in vivo-like biochemical cues is not optimal for epithelial cell self-organization and function. In search of a biomimetic scaffold for salivary gland tissue regeneration, we investigated the potential of elastin, an ECM protein, to generate elastin hybrid nanofibers that have favorable physical and biochemical properties for regeneration of the salivary glands. Elastin was introduced to our previously developed poly-lactic-co-glycolic acid (PLGA) nanofiber scaffolds by two methods, blend electrospinning (EP-blend) and covalent conjugation (EP-covalent). Both methods for elastin incorporation into the nanofibers improved the wettability of the scaffolds while only blend electrospinning of elastin-PLGA nanofibers and not surface conjugation of elastin to PLGA fibers, conferred increased elasticity to the nanofibers measured by Young's modulus. After two days, only the blend electrospun nanofiber scaffolds facilitated epithelial cell self-organization into cell clusters, assessed with nuclear area and nearest neighbor distance measurements, leading to the apicobasal polarization of salivary gland epithelial cells after six days, which is vital for cell function. This study suggests that elastin electrospun nanofiber scaffolds have potential application in regenerative therapies for salivary glands and other epithelial organs.
Regenerating the salivary glands by mimicking the extracellular matrix (ECM) is a promising approach for long term treatment of salivary gland damage. Despite their topographic similarity to the ECM, electrospun fibers of synthetic polymers lack the biochemical complexity, elasticity and hydrophilicity of the ECM. Elastin is an ECM protein abundant in the salivary glands and responsible for tissue elasticity. Although it's widely used for tissue regeneration of other organs, little is known about its utility in regenerating the salivary tissue. This study describes the use of elastin to improve the elasticity, hydrophilicity and biochemical complexity of synthetic nanofibers and its potential in directing in vivo-like organization of epithelial salivary cells which helps the design of efficient salivary gland regeneration scaffolds.
开发模仿天然细胞外基质（ECM）结构、力学和生化特性的静电纺纳米纤维，是组织再生的一种很有前途的方法。合成聚合物的静电纺纤维在一定程度上模拟了 ECM 的形貌，然而，其高刚性、低亲水性和缺乏类似体内的生化线索，不利于上皮细胞的自我组织和功能。为了寻找唾液腺组织再生的仿生支架，我们研究了弹性蛋白作为 ECM 蛋白的潜力，以生成具有有利于唾液腺再生的有利物理和生化特性的弹性蛋白杂化纳米纤维。通过两种方法，即共混静电纺丝（EP-共混）和共价接枝（EP-共价），将弹性蛋白引入到我们之前开发的聚乳酸-共-羟基乙酸（PLGA）纳米纤维支架中。这两种将弹性蛋白纳入纳米纤维的方法都提高了支架的润湿性，而只有弹性蛋白-PLGA 纳米纤维的共混静电纺丝，而不是弹性蛋白与 PLGA 纤维的表面接枝，提高了纳米纤维的弹性，通过杨氏模量测量。两天后，只有共混静电纺丝纳米纤维支架促进了上皮细胞自我组织成细胞簇，通过核面积和最近邻距离测量进行评估，导致六天后唾液腺上皮细胞的顶端-基底极化，这对于细胞功能至关重要。这项研究表明，弹性蛋白静电纺纳米纤维支架在唾液腺和其他上皮器官的再生治疗中有潜在的应用。
通过模拟细胞外基质（ECM）来再生唾液腺，是治疗唾液腺损伤的一种很有前途的长期方法。尽管它们的形貌与 ECM 相似，但合成聚合物的静电纺纤维缺乏 ECM 的生化复杂性、弹性和亲水性。弹性蛋白是一种 ECM 蛋白，在唾液腺中含量丰富，负责组织弹性。尽管它被广泛用于其他器官的组织再生，但关于它在再生唾液组织中的应用知之甚少。本研究描述了使用弹性蛋白来提高合成纳米纤维的弹性、亲水性和生化复杂性，并探讨了其在指导上皮唾液细胞体内样组织中的潜在应用，这有助于设计有效的唾液腺再生支架。
