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首页> 外文学位 >Engineering invitro cellular microenvironment using polyelectrolyte multilayer films to control cell adhesion and for drug delivery applications.
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Engineering invitro cellular microenvironment using polyelectrolyte multilayer films to control cell adhesion and for drug delivery applications.

机译：使用聚电解质多层膜工程化体外细胞微环境，以控制细胞粘附并用于药物递送应用。

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Over the past decades, the development of new methods for fabricating thin films that provide precise control of the three-dimensional topography and cell adhesion has generated lots of interest. These films could lead to significant advances in the fields of tissue engineering, drug delivery and biosensors which have become increasingly germane areas of research in the field of chemical engineering. The ionic layer-by-layer (LbL) assembly technique called "Polyelectrolyte Multilayers (PEMs)", introduced by Decher in 1991, has emerged as a versatile and inexpensive method of constructing polymeric thin films, with nanometer-scale control of ionized species. PEMs have long been utilized in such applications as sensors, eletrochromics, and nanomechanical thin films but recently they have also been shown to be excellent candidates for biomaterial applications. In this thesis, we engineered these highly customizable PEM thin films to engineer in vitro cellular microenvironments to control cell adhesion and for drug delivery applications.; PEM films were engineered to control the adhesion of primary hepatocytes and primary neurons without the aid of adhesive proteins/ligands. We capitalized upon the differential cell attachment and spreading of primary hepatocytes and neurons on poly(diallyldimethylammoniumchloride) (PDAC) and sulfonated polystyrene (SPS) surfaces to make patterned co-cultures of primary hepatocytes/fibroblasts and primary neurons/astrocytes on the PEM surfaces. In addition, we developed self-assembled monolayer (SAM) patterns of m-d-poly(ethylene glycol) (m-dPEG) acid molecules onto PEMs. The created m-dPEG acid monolayer patterns on PEMs acted as resistive templates, and thus prevented further deposits of consecutive poly(anion)/poly(cation) pairs of charged particles and resulted in the formation of three-dimensional (3-D) patterned PEM films or selective particle depositions atop the original multilayer thin films. These new patterned and structured surfaces have potential applications in microelectronic devices and electro-optical and biochemical sensors. The PEG patterns developed are tunable at certain salt conditions and be removed from the PEM surface without affecting the PEM layers underneath the patterns. These removable surfaces provide an alternative method to form patterns of multiple particles, proteins and cells. This new approach provides an environmentally friendly and biocompatible route to designing versatile salt tunable surfaces. Finally, we illustrate the use of PEM films to engineer aptamer and siRNA based drug delivery systems.
机译：在过去的几十年中，用于制造薄膜的新方法的发展引起了人们的极大兴趣，这些新方法提供了对三维形貌和细胞粘附的精确控制。这些薄膜可能会导致组织工程，药物输送和生物传感器领域的重大进步，这些领域已成为化学工程领域越来越紧密的研究领域。由Decher于1991年提出的称为“聚电解质多层（PEM）”的离子逐层（LbL）组装技术已成为一种通用且廉价的构造聚合物薄膜的方法，可对离子化物种进行纳米级控制。 PEM长期用于传感器，电致变色和纳米机械薄膜等应用，但近来它们也被证明是生物材料应用的极佳候选者。在本文中，我们设计了这些高度可定制的PEM薄膜，以设计体外细胞微环境，以控制细胞粘附并用于药物递送应用。 PEM膜经过工程设计，无需粘合剂蛋白/配体即可控制原代肝细胞和原代神经元的粘附。我们利用聚（二烯丙基二甲基氯化铵）（PDAC）和磺化聚苯乙烯（SPS）表面上原代肝细胞和神经元在细胞上的差异性细胞附着和扩散来在原代细胞表面上进行原代肝细胞/成纤维细胞和原代神经元/星形细胞的模式共培养。此外，我们在PEM上开发了m-d-聚（乙二醇）（m-dPEG）酸分子的自组装单层（SAM）模式。在PEM上创建的m-dPEG酸单层图案充当电阻模板，从而防止了带电粒子的连续聚（阴离子）/聚（阳离子）对的进一步沉积，并导致形成了三维（3-D）图案在原始多层薄膜之上的PEM膜或选择性颗粒沉积。这些新的图案化和结构化表面在微电子设备以及光电和生化传感器中具有潜在的应用。所形成的PEG图案在某些盐条件下是可调的，并且可以从PEM表面去除而不会影响图案下方的PEM层。这些可移动的表面提供了形成多种粒子，蛋白质和细胞的图案的替代方法。这种新方法为设计通用的盐可调表面提供了一种环境友好且生物相容的途径。最后，我们说明了使用PEM膜工程化适体和基于siRNA的药物递送系统。

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