STRUCTURALLY NEW BIOPOLYMERS FROM ALPHA-L-AMINO ACIDS

在过去的五年里，几种结构上的新聚合物从 合成了氨基酸和二肽[假多(氨基酸)]。 在这些聚合物中，确定了酪氨酸衍生的聚碳酸酯 作为生物材料开发的有前途的候选者，因为他们已经 良好的工程性能，在生理条件下会降解， 并在植入后产生轻微的异物反应 动物模型。但是，有关物理力学的详细信息 性质、化学结构与聚合物的关系 性质、细胞-聚合物相互作用、表面性质、降解 降解产物的作用机理和毒理性质为 仍然下落不明。作为连接我们之前的合成阶段的桥梁 特定医疗植入物的研究和可能的开发，a 对酪氨酸衍生聚碳酸酯进行了为期三年的详细调查 建议。这项调查有五个主要目标： L。物理力学性能和热性能的测定， 包括与潜在的生物医学相关的工程特性 申请。 2.探索实施受控曲面的可行性 修改。现有酪氨酸衍生的悬垂链 聚碳酸酯将用于产生受控数量的 聚合物表面的游离羧酸基和氨基。 3.研究细胞与聚合物的相互作用，试图阐明 聚合物结构和表面化学之间可能的相关性，以及 生物反应。具有仔细表征表面和特性的器件 大块特性将用于体外细胞的附着和生长 炎症反应的研究和体内研究 气囊技术。 4.阐明了聚合物降解的速率和机理。基于 目前提议的退化机制，有四种可能的退化 产品已经确定。这些化合物将在纯净的 形式，并将作为模型化合物在进一步研究 降解机制。这些研究还将探索可能的 自催化效应和辅料的可能使用来修饰 聚合物降解率。 5.生物材料筛选试验。使用ASTM协议，聚合物和 将对其降解产物进行评估。生物材料筛选试验 包括评估硬组织和软组织的兼容性、细胞毒性 聚合物和聚合物降解产品，以及对 可灭菌性。 在成功完成这项研究计划后，将有可能 为了更好地评估酪氨酸衍生聚碳酸酯的潜在用途 作为医用植入材料。考虑到迫切需要提供 无处不在的医疗设备社区的新选择 POKY(乳酸)和聚乙醇酸，开发新的， 可降解植入材料已被公认为是一项重要的研究 挑战。

Over the last five years, several structurally new polymers derived from amino acids and dipeptides [pseudopoly(amino acids)] were synthesized. Among those polymers, the tyrosine-derived polycarbonates were identified as promising candidates for biomaterials development since they have favorable engineering properties, degrade under physiological conditions, and produce a mild foreign body response upon implantation in several animal models. However, detailed information about physicomechanical properties, correlations between chemical structure and polymer properties, cell-polymer interactions, surface properties, degradation mechanism and the toxicological properties of the degradation products is still missing. As a bridge between the previous synthetic phase of our studies and the possible development of specific medical implants, a three-year, detailed investigation of tyrosine-derived polycarbonates is proposed. This investigation has five main goals: l. Determination of the physicomechanical and thermal properties, including the engineering properties relevant to potential biomedical applications. 2. Exploration of the feasibility of performing controlled surface modifications. The existing pendent chains of tyrosine-derived polycarbonates will be used for the generation of controlled amounts of free carboxylic acid groups and amino groups on the polymer surface. 3. Study of the cell-polymer interactions in an attempt to elucidate possible correlations between polymer structure and surface chemistry, and the biological response. Devices with carefully characterized surface and bulk properties will be used in in vitro cell attachment and growth studies and in vivo investigations of the inflammatory response using the air-pouch technique. 4. Elucidation of the rate and mechanism of polymer degradation. Based on the currently proposed degradation mechanism, four likely degradation products have been identified. These compounds will be synthesized in pure form and will serve as model compounds in the further investigation of the degradation mechanism. These studies will also explore possible autocatalytic effects and the possible use of excipients to modify the polymer degradation rate. 5. Biomaterials screening assays. Using ASTM protocols, the polymer and its degradation products will be evaluated. Biomaterials screening tests include evaluations of hard and soft tissue compatibility, cytotoxicity of polymer and polymer degradation products, and an evaluation of sterilizability. Upon successful completion of this research program, it will be possible to better assess the potential utility of tyrosine-derived polycarbonates as medical implant materials. Considering the urgent need to provide the medical device community with new alternatives to the ubiquitous poky(lactic acid) and poly(glycolic acid), the development of new, degradable implant materials has been recognized as an important research challenge.