Electrospun Collagen Type II: Cartilage Feasibilty

描述(由申请人提供)： 骨关节炎，又称退行性关节疾病，是最常见的关节炎类型之一，其特征是或与关节软骨细胞外基质(ECM)的破坏有关。关节软骨细胞外基质的这种恶化会导致骨外露和随后的骨与骨之间的摩擦和相关的炎症，导致关节疼痛和运动丧失。根据关节炎基金会的数据，仅在美国，估计就有2100万人受到骨性关节炎的影响，其中高达80%的人报告说运动或活动有一定的限制。这给美国经济每年造成的直接开支和工资/生产损失估计高达650亿美元。胶原蛋白是在所有组织中发现的天然支架，已被广泛探索用作组织工程支架，但成功有限。在这项可行性研究中，将研究II型胶原的电纺丝和随后的软骨细胞种植在软骨组织工程中的潜在应用(专利正在申请中)。电纺II型胶原的初步研究表明，II型胶原可以电纺形成直径在110 nm到1.8微米之间的纤维组成的无纺布纤维垫。初步的软骨细胞种植表明，电纺的II型胶原支架支持细胞生长，并易于渗透。此外，现建议进行详细的可行性研究。具体目标1是从牛关节软骨中提取II型胶原的初步加工，包括胶原蛋白的提取和纯化。具体目标2将是电自旋随机取向的II型胶原的各种结构，并创造出不同的物理和机械特性。具体目标3将通过对块状材料的拉伸测试以及测量纤维直径、孔尺寸、支架渗透性和孔隙率来表征电纺II型胶原结构(干燥和水合)的生物力学/结构特性。具体目标4将评估II型胶原的组成和整体结构特性(纤维直径和孔径)在最佳细胞种植和与II型胶原相互作用2、4和6周后对软骨细胞反应和整体组织发育的影响。

DESCRIPTION (provided by applicant): Osteoarthritis (OA), also known as degenerative joint disease, is one of the most common types of arthritis and is characterized, or associated, with the breakdown of the extracellular matrix (ECM) of articular cartilage. This deterioration of the articular cartilage ECM leads to bone exposure and subsequent bone-on-bone rubbing and associated inflammation that causes pain and loss of movement in the joint. According to the Arthritis Foundation, OA affects an estimated 21 million people in the United States alone with up to 80% of those individuals reporting some limitation in movement or activity. This costs the United Sates economy an estimated $65 billion per year in direct expenses and lost wages/production. Collagen is the natural scaffolding found in all tissues and has been explored extensively for use as a tissue-engineering scaffold with limited success. In this feasibility study, the electrospinning of collagen type II and subsequent chondrocyte seeding will be investigated for potential use in cartilage tissue engineering (Patents Pending). A preliminary of study electrospun collagen type II demonstrated that collagen type II could be electrospun to form non-woven fibrous mats composed of fibers that ranged from 110 nm to 1.8 microns in diameter. The preliminary chondrocyte seeding demonstrated that electrospun collagen type II scaffolds support cell growth and are readily infiltrated. Furthermore, detailed, feasibility studies are now proposed herein. Specific Aim 1 will be collagen type II preliminary processing from bovine articular cartilage including extraction of collagen and purification. Specific Aim 2 will be to electrospin various structures of randomly orientated collagen type II and create a diversity of physical and mechanical characteristics. Specific Aim 3 will characterize the biomechanical/structural properties of the electrospun collagen type II constructs (dry and hydrated) by tensile testing of the bulk material as well as measuring fiber diameter, pore dimensions, scaffold permeability and porosity. Specific Aim 4 will evaluate the collagen type II composition and overall structural properties (fiber diameter and pore size) on the chondrocytes response and overall tissue development after optimum cell seeding and 2, 4 and 6 week interactions with the collagen type II.