ELECTROSPINNING ARTIFICIAL LIGAMENTS AND TENDONS FOR POTENTIAL PROSTHESES

描述（由申请人提供）：在美国，每年发生超过800，000例韧带、肌腱和关节囊损伤。虽然骨关节炎是治疗韧带和肌腱损伤的替代方法，但由于天然组织的血管化有限，它并不总是成功的。作为这个问题的一种选择，移植物和假体被用来重建这些组织。前交叉韧带（ACL）是一种关节内韧带，有助于膝关节的运动学和稳定性，通常在运动员和从事高要求活动的人中撕裂或断裂。ACL重建的方法包括使用自体移植物、同种异体移植物和假体，但这些选择存在缺点。尽管有这些缺点，美国医生在2006年估计进行了20万例重建手术。为了克服目前治疗韧带和肌腱损伤（如ACL撕裂）的局限性，本提案的长期研究目标是开发模拟这些人体组织特性的人工韧带和肌腱。由于选择用于执行该项目的材料的机械性能与目前可用的假体中使用的材料的机械性能形成显著对比，因此我们期望开发具有增强性能和更接近天然组织的人工韧带和肌腱。为了实现长期的研究目标，提出了三个具体目标：1）选择聚合物和二级结构对静电纺丝聚合物纳米纤维（EPN）性能的影响的调查，2）将碳纳米颗粒掺入到EPN中以提高其机械性能，3）细胞接种以评估生物相容性。这些研究将研究生物相容性聚氨酯的静电纺丝条件，以获得微米和纳米纤维，这些纤维将组装成特定的二级结构，以类似于韧带和肌腱。这些组件将被广泛表征，使我们能够设计目标应用程序。此外，碳纳米管和碳纳米纤维将被纳入EPN中，以增强所形成的组件的机械性能。最后，对成纤维细胞在组件上的接种和增殖的研究将检查生物相容性以及使用拟议结构作为人工韧带和肌腱的潜力。该项目将研究某些合成聚合物可以电纺成微米和纳米纤维并组装成特定的二级结构的假设，这些二级结构将具有类似于天然韧带和肌腱的机械性能。此外，我们假设这些二级结构的机械性能将通过掺入碳纳米颗粒而增强。该项目具有创新性，因为它通过静电纺丝结合使用某些聚氨酯（未针对拟议应用进行探索）来设计假体。除了所提出的材料和技术的独特组合外，目标假体韧带和肌腱可能上级目前使用的材料。 公共卫生相关性：在美国，每年有超过80万例韧带、肌腱和关节囊受伤，很多这样的损伤需要修复手术该项目的目标是为潜在的假肢开发人工韧带和肌腱，这可能会影响公众健康。

DESCRIPTION (provided by applicant): Over 800,000 injuries to ligaments, tendons and the joint capsule occur every year in the U.S.A. While suturing is an alternative to treat ligaments' and tendons' injuries, it is not always successful because of the natural tissues' limited vascularization. As an option to this problem, grafts and prostheses are used to reconstruct these tissues. The Anterior Cruciate Ligament (ACL), an intra-articular ligament that contributes to the kinematics and stability of the knee, is commonly torn or ruptured in athletes and people practicing demanding activities. The approaches to ACL reconstruction include the use of autografts, allografts and prostheses, but these choices present shortcomings. In spite of these drawbacks, U.S. doctors performed an estimated 200,000 reconstructive surgeries in 2006. To overcome current limitations on treating ligament and tendon injuries like a torn ACL, the long term research objective of this proposal is to develop artificial ligaments and tendons that will mimic the properties of these human tissues. Since the mechanical properties of the materials selected to perform this project contrast significantly with those of the materials used in currently available prostheses, we expect to develop artificial ligaments and tendons with enhanced properties and closer resemblance to natural tissues. To achieve the long term research objective, three specific aims are proposed: 1) selection of polymers and investigation of the effect that secondary structures have on the properties of electrospun polymer nanofibers (EPN), 2) incorporation of carbon nanoparticles to the EPN to enhance their mechanical properties and 3) cell seeding to assess biological compatibility. These studies will investigate the electrospinning conditions of biocompatible polyurethanes to obtain micro- and nanofibers, which will be assembled into specific secondary structures to resemble ligaments and tendons. These assemblies will be extensively characterized, allowing us to design the targeted applications. Furthermore, carbon nanotubes and carbon nanofibers will be incorporated into the EPN to enhance the mechanical properties of the assemblies formed. Finally, studies on fibroblasts seeding and proliferation on the assemblies will examine the biological compatibility and potential for using the proposed structures as artificial ligaments and tendons. This project will investigate the hypothesis that certain synthetic polymers can be electrospun into micro- and nanofibers and assembled into specific secondary structures, which will possess mechanical properties similar to natural ligaments and tendons. Furthermore, we hypothesize that the mechanical properties of these secondary structures will be enhanced by incorporation of carbon nanoparticles. This project is innovative because it combines the use of certain polyurethanes (not explored for the proposed applications) through electrospinning to design prostheses. In addition to the unique combination of materials and technique proposed, the prosthetic ligaments and tendons targeted are potentially superior to the materials currently in use. PUBLIC HEALTH RELEVANCE: More than 800,000 injuries to ligaments, tendons and the joint capsule occur every year in the U.S.A., and many of these injuries require reconstructive surgery. The objective of this project is to develop artificial ligaments and tendons for potential prostheses, which could impact the public health.