Molecular Imprinting to Control Cell Responses

描述（由申请人提供）：理想情况下，植入物的设计应能够通过促进特定蛋白质和/或细胞对生物材料的识别来诱导特定的生物反应，从而促进所需的细胞和组织行为。在骨接触材料的情况下，这将意味着在植入后，装置将立即被成骨细胞谱系的细胞识别，并且细胞随后将被诱导以在表面上或紧邻表面形成骨。这可以避免纤维包裹，纤维包裹通常会阻挡植入物，并可能导致更好地融入周围骨。该项目的总体目标是开发表面改性策略，以创建对特定细胞表面分子具有选择性的生物材料。假设这些生物特异性表面可以在组织-植入物界面处诱导期望的生物分子和细胞事件。要研究的方法涉及压印表面具有选择性识别位点具有特定的形状，并与一个定义的功能基团的安排。在具体目标1中，将开发多功能配方，用于在骨科和牙科生物材料上形成粘附性分子印迹涂层。具有离子、极性和疏水末端官能团的烷氧基硅烷将用于增强单体的非共价组装，并导致印迹表面和模板生物分子之间更大的互补性。模拟骨形态发生受体IA（BMPR-IA）配体结合区的肽将被印迹。将对涂层进行化学和形态学表征，并对模板与表面结合的选择性进行量化。在具体目标2中，将使用目标1中开发的方法来检验以下假设：印有细胞表面分子的涂层可以控制细胞行为。将使用两种功能评估，受体活化和随后的细胞反应。在印迹有BMPR-IA的表面的情况下，成骨细胞分化将被刺激，最终导致矿化的细胞外基质的形成。通过促进所需的细胞活性，生物特异性生物材料可以控制细胞-生物材料界面处的初始事件。

DESCRIPTION (provided by applicant): Ideally, implants should be designed with the ability to induce specific biological responses by promoting recognition of the biomaterial by particular proteins and/or cells, thereby promoting desired cell and tissue behavior. In the case of bone-contacting materials, this would mean that immediately following implantation the devices would be recognized by cells of the osteoblastic lineage, and the cells subsequently would be induced to form bone on or in close proximity to the surface. This could avoid fibrous encapsulation that often walls off implants and could lead to better integration into the surrounding bone. The overall goal of this project is to develop surface modification strategies to create biomaterials that are selective for particular cell surface molecules. It is hypothesized that these biospecific surfaces can induce desirable biomolecular and cellular events at the tissue-implant interface. The approach to be investigated involves imprinting surfaces with selective recognition sites having a specific shape and with a defined arrangement of functional groups. In Specific Aim 1, versatile formulations will be developed for creating adherent molecularly imprinted coatings on orthopedic and dental biomaterials. Alkoxysilanes with ionic, polar, and hydrophobic terminal functional groups will be used to enhance noncovalent assembly of monomers and result in greater complementarity between imprinted surface and template biomolecule. Peptides mimicking the ligand-binding region of bone morphogenetic receptor IA (BMPR-IA) will be imprinted. The coatings will be chemically and morphologically characterized, and the selectivity of template binding to the surfaces will be quantified. In Specific Aim 2, the methodology developed in Aim 1 will be used to test the hypothesis that coatings imprinted with cell surface molecules can control cell behavior. Two functional assessments, receptor activation and subsequent cell responses, will be used. In the case of surfaces imprinted with BMPR-IA, osteoblastic differentiation will be stimulated, ultimately leading to formation of a mineralized extracellular matrix. By promoting desired cell activities, biospecific biomaterials can control initial events at the cell-biomaterial interface.