Visible light-cured tissue engineering polymers filled with bioactive glass

描述（由申请人提供）：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），以适应各种应用的机械性能。这项建议有两个具体目标。1)以可见光固化聚合物为基质，生物活性玻璃为填充物，研制生物相容性良好的组织工程支架。2)评估未填充和生物活性玻璃填充聚合物支架的生物相容性。增强的生物相容性将通过三个基本机制实现：聚合物设计，光活化系统的性质，并通过将生物活性玻璃（BAG）的聚合物。我们将利用聚乙二醇（PEG）和聚乳酸（PLA）合成可生物降解的甲基丙烯酸酯单体。通过改变PEG-PLA甲基丙烯酸酯化单体中PEG重复单元的数量，我们将系统地控制相邻乳酸酯基团之间的链段长度。因此，将控制每单位体积降解的聚合物释放的酸性副产物的量，并因此控制支架的生物相容性。这种设计将间接控制聚合物的亲水性和交联密度，从而控制酸性产物的释放速率。通过在聚合物中加入BAG，酸性降解产物将在释放时被中和。我们还将使用可见光光引发剂体系沿着可聚合共引发剂。后者将结合在聚合物网络内，使可聚合性最小化。可见光，即更深的穿透，将可能导致更均匀的固化TEM比目前使用的UV活化。这将使TEM中的残留单体最小化，从而增强生物相容性。TEM中残留单体的量不能直接测量，但可以通过测量固化TEM的转化度（DC）和努普硬度（KHN）来间接测定。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或没有BAG的TEM固化样品周围溶液的pH值来评估聚合物设计和BAG对酸度的影响。基于可见光的光引发系统可以深入穿透生物组织，这将提供一种固化支架穿过介入结构的方法，皮肤和肌肉这将是在组织和器官修复中应用微创手术的关键，最大限度地减少对周围组织的损伤，并减少恢复时间及其相关费用。 项目叙述：该项目旨在开发具有增强生物相容性的改进的组织工程复合材料，以及为广泛应用定制机械性能的灵活性。一种基于可见光的光引发系统，其深入穿透生物组织，将提供一种固化穿过介入结构的生物活性玻璃增强聚合物支架的方法，皮肤和肌肉这对于在组织和器官修复中使用微创手术，最大限度地减少对周围组织的损伤，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.