ELECTROSTATIC SURFACE OPTIMIZATION FOR OSSEOINTEGRATION

用于骨整合的静电表面优化

• 批准号: 6171196
• 负责人: MICHELE S MARCOLONGO
• 金额: $ 7.5万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6171196
• 关键词: atomic force microscopy; biomaterial development /preparation; biomaterial evaluation; biomaterial interface interaction; biomaterials; cell adhesion; conformation; fibronectins; fluorimetry; ionic bond; molecular film; osteoblasts; surface property; tissue /cell culture; tissue engineering; titanium

Debilitating degenerative joint diseases are routinely treated by joint replacements to allow restoration of relatively pain-free motion to the affected joint. Fracture healing and bony fusion (for example, in the treatment of degenerative disease) can be facilitated by the use of synthetic bone grafts or tissue engineered scaffolds. The success of each of these surgical interventions is dependent on the ability of bone tissue to integrate with the surface of the implant biomaterial. In order to achieve osseointegration, the bone forming cell (the osteoblast) must first adhere to the biomaterial surface; the osteoblast/biomaterial interaction must then be conducive to the elaboration of a bone-specific extracellular matrix (ECM) which will undergo mineralization and remodeling to form an integrated bone/biomaterial interface. A handful of synthetic biomaterials, termed bioactive materials, will elicit osseointegration; these are calcium phosphate ceramics (including hydroxyapatite) and bioactive glasses. In contrast, the more commonly used bone implant materials, titanium alloy (Ti6A14V) and cobalt chromium alloy, will not support osteoblast adhesion and direct bone bonding in vivo, instead the resulting interface consists predominantly of fibrous tissue. From many experiments it is clear that material properties affecting osseointegration include surface charge, chemistry, and topography, although the specific parameters that facilitate osseointegration are presently poorly understood. Once the specific surface properties which encourage osteoblast attachment are determined, it would then be possible to engineer the surface of any compatible material to make that material bioactive or bone bonding. We suggest that a dominant mechanism in cellular attachment to a biomaterial surface is electrostatic in nature, with the electrostatic characteristics of the surface encouraging the adsorption of specific ECM proteins (in particular, fibronectin, an important serum protein involved in cell adhesion) to facilitate initial attachment of osteoblasts to the biomaterial surface. While evidence of the importance of electrostatic interactions has been documented, the relative contributions of surface charge, charge distribution, and charge density on cellular attachment and protein adsorption are presently not understood. Previous studies have been limited in this regard as they have not uncoupled the electrostatics from functionality and surface energy due to surface chemistry. In this work, we propose a unique model to elucidate the effect of electrostatics on osteoblast adhesion and protein adsorption. We hypothesize that negatively charged surfaces will promote osteoblast attachment and spreading, while positively charged surfaces will inhibit cellular attachment and we expect that osteoblasts will exhibit differential adhesion on surfaces whose charge distribution and charge density has been patterned at varying subcellular dimensions. Further, we hypothesize that the quantity of fibronectin adsorbed to differently charged surfaces will not differ, but the conformation of the fibronectin on those charged surfaces will.

使人衰弱的退行性关节疾病通常通过关节治疗来治疗 更换以允许恢复相对无痛的运动 受影响的关节。 骨折愈合和骨融合（例如，在 退行性疾病的治疗）可以通过使用来促进 合成骨移植物或组织工程支架。 的成功 这些手术干预中的每一项都取决于骨骼的能力 组织与植入物生物材料的表面整合。 为了实现骨整合，骨形成细胞（ 成骨细胞）必须首先粘附到生物材料表面；这 成骨细胞/生物材料的相互作用必须有利于 详细阐述骨特异性细胞外基质（ECM） 经过矿化和重塑，形成一个完整的 骨/生物材料界面。 一些合成生物材料，称为 生物活性材料，将引发骨整合；这些是钙 磷酸盐陶瓷（包括羟基磷灰石）和生物活性玻璃。 相比之下，更常用的骨植入材料，钛 合金（Ti6A14V）和钴铬合金，不会支持成骨细胞 体内粘附和直接骨结合，而不是由此产生的 界面主要由纤维组织组成。 来自许多 实验清楚地表明材料特性影响 骨整合包括表面电荷、化学和地形， 尽管促进骨整合的具体参数是 目前了解甚少。 一旦特定的表面特性 鼓励成骨细胞附着确定后， 可以对任何兼容材料的表面进行设计，以使其 材料生物活性或骨粘合。 我们认为细胞附着的主要机制是 生物材料表面本质上是静电的，静电 表面特性促进特定物质的吸附 ECM 蛋白（特别是纤连蛋白，一种重要的血清蛋白 参与细胞粘附）以促进初始附着 成骨细胞附着在生物材料表面。 虽然证据表明 静电相互作用的重要性已被记录， 表面电荷、电荷分布和的相对贡献 细胞附着和蛋白质吸附的电荷密度是 目前不明白。 之前的研究仅限于这方面 认为它们没有将静电与功能分离 和由于表面化学而产生的表面能。 在这项工作中，我们建议 阐明静电对成骨细胞影响的独特模型 粘附和蛋白质吸附。 我们假设带负电 表面将促进成骨细胞附着和扩散，同时 带正电的表面会抑制细胞附着，我们 期望成骨细胞在表面上表现出不同的粘附力 其电荷分布和电荷密度已被图案化 不同的亚细胞尺寸。 此外，我们假设 吸附到不同电荷表面的纤连蛋白的数量将 没有区别，但带电的纤连蛋白的构象不同 表面会。