Tissue Response to Fibro-Porous Biomaterials: Mechanical Studies Versus Surface Chemistry

实际上，目前所有的可植入医疗设备都受到一个重要的限制。 在植入后大约一个月内，身体会形成一个纤维软组织囊，并将其包围。 纤维囊的形成是对外来入侵者的自然防御。 对于生物机械装置，例如人造韧带、肌腱和心脏瓣膜，囊是有问题的，因为它阻止植入物有效地附着到天然组织结构。 因此，植入物与其周围环境在机械上不稳定。 此外，诸如用于随时间释放规定量的药物的植入物所需的生物化学通信受到胶囊的阻碍。 胶囊阻止有效扩散。 理想情况下，生物材料的设计应该改变，使植入物看起来自然，而不是外来的，这样纤维囊就不会首先形成。我们实验室的初步研究表明，如果构成植入物的聚合物纤维非常小，在软组织中的天然胶原纤维尺寸（0.5至3.0 mm）的量级，那么纤维囊就不会形成。 可能身体相信聚合物是一种天然结构，因此不会排斥它。如果以系统的科学方式进行验证，纤维尺寸（直径和间距）可以用于生物材料设计，以创建更有效的植入物。本研究的目的是系统地评估纤维直径和纤维间距对身体对纤维多孔材料的反应的影响。 因此，可以评估这些结构特征与传统上用于生物材料设计的化学特征的影响的比较，将新植入物的组织反应与具有不同表面化学的材料的组织反应进行比较。 因此，一种主要用于非生物医学行业的技术，称为静电纺丝，在这里得到了应用。 一旦制成，新材料将在皮肤模型中进行评估，以评估炎症反应和纤维囊厚度。本研究的意义在于应用创新的材料和制造方法来创建新的候选生物材料植入物。 通过系统分析，可能会创建消除纤维囊的设计。 这种方法可能会导致一种新的生物材料制造技术。 该项目还作为多学科研究的典范，将机械工程，聚合物化学和细胞生物学纳入创新设计方法。 该项目还包括一个重要的本科研究教育工作。 为一些本科生提供研究机会。 此外，创建和传播的材料，以有效的方法来指导本科生的研究教师包括在此补助金申请。

9905913SandersVirtually all current implantable medical devices suffer from an important limitation. Within approximately a month after implantation, the body makes and surrounds them with a capsule of fibrous soft tissue. Formation of the fibrous capsule is a natural defense against a foreign intruder. The capsule is problematic for biomechanical devices such as artificial ligaments, tendons, and heart valves because it prevents the implant from attaching effectively to the natural tissue structures. The implant is thus mechanically unstable with its surrounding environment. Further, biochemical communication such as needed for an implant intended to release a prescribed amount of a drug over time is hampered by the capsule. The capsule prevents effective diffusion. Ideally, biomaterial designs would be changed so that implants appear natural to the body, not foreign, so that the fibrous capsule does not form in the first place.Preliminary research from our laboratory indicates that if polymer fibers that make up implants are very small, on the order of natural collagen fiber dimensions in soft tissues (0.5 to 3.0 mm), then the fibrous capsule does not form. Possibly the body is convinced the polymer is a natural structure thus does not reject it. Potentially, if validated in a systematic scientific manner, fiber dimensions (diameter and spacing) could be utilized in biomaterial design to create more effective implants.The purpose of this research is to systematically evaluate the influence of fiber diameter and fiber spacing on the body's response to fibro-porous materials. So that a comparison of the influence of these architectural features with chemical features more traditionally used in biomaterial design can be assessed, tissue response to the new implants is compared with that for materials with different surface chemistries.No traditional biomaterials fabrication method exists for making materials with very small diameter fibers. Thus a technology used mainly in non-biomedical industries called electrospinning is pursued and applied here. Once fabricated, the new materials will be evaluated in a skin model so as to allow inflammatory response and fibrous capsule thickness to be assessed.The significance of this research is to apply an innovative material and fabrication method to create new candidate biomaterial implants. Potentially, through a systematic analysis, designs that eliminate the fibrous capsule will be created. The approach could lead to a new biomaterials fabrication technology. The project also serves as a model for multi-disciplinary research, incorporating mechanical engineering, polymer chemistry, and cell biology into an innovative design approach. The project also includes an important undergraduate research educational effort. Research opportunities for a number of undergraduates are provided. Further, creation and dissemination of material to faculty on effective approaches to advising of undergraduates in research is included within this grant application.