STRUCTURALLY NEW BIOPOLYMERS FROM ALPHA-L-AMINO ACIDS

来自α-L-氨基酸的结构新颖的生物聚合物

• 批准号: 2179831
• 负责人: Joachim B. Kohn
• 金额: $ 19.86万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2179831
• 关键词: biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; carbonates; diamines; flow cytometry; infrared spectrometry; laboratory rat; leukocyte activation /transformation; osteoblasts; physiologic bone resorption; polymers; scanning electron microscopy; tissue /cell culture; tyrosine

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.

在过去的五年里，几种结构新颖的聚合物衍生自 合成了氨基酸和二肽[假聚（氨基酸）]。 在这些聚合物中，鉴定了酪氨酸衍生的聚碳酸酯 作为生物材料发展的有前途的候选者，因为它们 有利的工程性质，在生理条件下降解， 并在几个植入后产生轻微的异物反应 动物模型然而，关于物理力学的详细信息 性能，化学结构与聚合物之间的相关性 性质，细胞-聚合物相互作用，表面性质，降解 机制和降解产物的毒理学性质是 仍然失踪。作为我们的前一个合成阶段之间的桥梁 研究和可能开发的具体医疗植入物， 对酪氨酸衍生的聚碳酸酯进行了为期三年的详细研究， 提出了这项调查有五个主要目标： L.物理机械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， 应用. 2.实施控制面的可行性探讨 修改.现有的酪氨酸衍生的侧链 聚碳酸酯将用于产生受控量的 聚合物表面上的游离羧酸基团和氨基。 3.细胞-聚合物相互作用的研究， 聚合物结构和表面化学之间可能的相关性，以及 生物反应。具有仔细表征的表面和 体特性将用于体外细胞附着和生长 研究和体内调查的炎症反应， 气囊技术 4.阐明聚合物降解的速率和机理。基于 目前提出的退化机制，四个可能的退化 产品已被确认。这些化合物将以纯 形式，并将作为模型化合物在进一步的研究， 降解机理这些研究还将探索 自催化作用和可能使用的赋形剂，以改变 聚合物降解速率 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价。生物材料筛选试验 包括评价硬组织和软组织相容性、 聚合物和聚合物降解产物，以及 灭菌性 在成功完成这项研究计划后， 为了更好地评估酪氨酸衍生的聚碳酸酯的潜在效用 作为医用植入材料。考虑到迫切需要提供 医疗器械社区，为无处不在的 poky（乳酸）和聚（乙醇酸），开发新的， 可降解植入材料已被公认为一个重要的研究 挑战.