Visible light-cured tissue engineering polymers filled with bioactive glass

描述(申请人提供)：拟议研究的长期目标是开发具有增强的生物相容性和灵活性的组织工程材料(TEM)，以适应广泛应用的机械特性。这项提议有两个具体目标。1)研制一种生物相容的组织工程支架材料。2)评价未填充和生物活性玻璃填充聚合物支架的生物相容性。生物相容性的增强将通过三个基本机制实现：聚合物设计，光激活系统的性质，以及在聚合物中加入生物活性玻璃(BAG)。我们将以聚乙二醇聚乳酸为原料合成可生物降解的甲基丙烯酸酯单体。通过改变聚乙二醇聚乳酸甲基丙烯酸酯单体中的聚乙二醇单元数，我们将系统地控制相邻乳酸基团之间的链段长度。因此，每单位体积降解的聚合物释放的酸性副产物的量将被控制，从而支架的生物相容性将被控制。这种设计将间接控制聚合物的亲水性和交联度，从而控制酸性产品的释放速度。通过在聚合物中加入袋子，酸性降解产物在释放时将被中和。我们还将使用可见光-光引发剂系统以及可聚合的共引发剂。后者将结合在聚合物网络内，使可浸出性降至最低。可见光，即更深的穿透性，可能会导致比目前使用的紫外线激活更均匀地固化的透射电子显微镜。这将使透射电子显微镜中残留的单体最小化，从而提高生物相容性。透射电子显微镜中残留单体的量不能直接测量，但可以通过测量固化后的透射电子显微镜的转化率(DC)和诺氏硬度(KHN)来间接确定。我们将测量和比较各种TEM的DC和KHN。我们还将通过测量和比较有无袋子的TEMS固化样品周围溶液的pH值来评估聚合物设计和袋子对酸度的影响。一种基于可见光的光引发系统可以深入到生物组织中，这将提供一种跨越中间结构(如皮肤和肌肉)的支架固化方法。这将是在组织和器官修复中应用侵入性较小的手术、将对周围组织的损害降至最低以及缩短恢复时间和相关费用的关键。 项目简介：该项目致力于开发具有增强生物相容性的改进组织工程复合材料，以及为广泛应用量身定做机械性能的灵活性。一种基于可见光的光引发系统可以深入到生物组织中，这将提供一种在中间结构(如皮肤和肌肉)上固化生物活性玻璃增强聚合物支架的方法。这对于在组织和器官修复中使用侵入性较小的手术，将对周围组织的损害降至最低，并减少恢复时间及其相关费用至关重要。

DESCRIPTION (provided by applicant): The long-term goals of the proposed research are to develop tissue-engineering materials (TEM) with enhanced biocompatibility, and flexibility to tailor mechanical properties for a wide range of applications. There are two specific aims for this proposal. 1) To develop a biocompatible tissue-engineering scaffold based on visible light-cured polymer that is filled with bioactive glass. 2) To assess the biocompatibility of unfilled and bioactive glass-filled polymer scaffolds. Enhanced biocompatibility will be attained via three basic mechanisms: polymer design, nature of the photo-activation system, and by incorporating bioactive glass (BAG) in the polymer. We will synthesize biodegradable methacrylated monomers using Polyethylene glycol (PEG) and polylactic acid (PLA). By changing the number of PEG repeat units in the PEG-PLA methacrylated monomer, we will systematically control the length of the chain segment between adjacent lactate groups. Consequently, the amount of acidic by-products released per unit volume of the polymer that degrades, and therefore the biocompatibility of the scaffold, will be controlled. This design will indirectly control hydrophilicity and cross-link density of the polymer, and thus the rate of release of acidic products. By adding BAG in the polymer the acidic degradation products will be neutralized as they are released. We will also use a visible light-photoinitiator system along with a polymerizable coinitiator. The latter will be bound within the polymer network, minimizing leachability. Visible light, that is deeper penetrating, will potentially cause a more uniformly cured TEM than currently used UV activation. This will minimize residual monomer in the TEM, and thus enhance biocompatibility. The amount of residual monomers in the TEM cannot be directly measured but can be indirectly determined by measuring degree of conversion (DC) and Knoop hardness (KHN) of the cured TEM. We will measure and compare DC and KHN of the various TEMs. We will also evaluate the effects of polymer design and BAG on acidity by measuring and comparing the pH of solutions surrounding cured samples of TEMs with or without BAG. A photoinitiating system based on visible light that penetrates deep into biological tissues will provide a means of curing scaffolds across intervening structures, e.g., skin and muscles. This will be key to applying less invasive surgery in tissue and organ repair, minimizing damage to surrounding tissues, and reducing recovery time and its associated expenses. PROJECT NARRATIVE: This project seeks to develop improved tissue engineered composite materials with enhanced biocompatibility, and the flexibility to tailor mechanical properties for a wide range of applications. A photo-initiating system based on visible light that penetrates deep into biological tissues will provide a means of curing bioactive glass-reinforced polymer scaffolds across intervening structures, e.g., skin and muscles. This will be crucial to the use of less invasive surgery in tissue and organ repair, minimizing damage to surrounding tissues, and reducing recovery time and its associated expenses.