Tissue Engineering of Cartilage using Periosteum

描述（由申请人提供）：关节软骨是非常耐用的组织，覆盖我们关节中的关节骨表面，并通过大大减少骨之间的摩擦和分布应力来允许无痛运动。不幸的是，当软骨因受伤或疾病而受损时，它的愈合能力有限，并可能导致过早的关节炎。关节炎是一个主要的健康问题，预计随着人口老龄化而增加。因此，对修复或重建受损关节软骨的技术的开发有相当大的兴趣。一个成功的软骨修复方法的影响将是巨大的，在受影响的患者数量和他们的生活质量。重要的是，在这个医疗保健成本不断上升的时代，成功的软骨修复将降低与关节置换及其多次翻修相关的医疗保健的长期成本。我们的长期目标是开发一种利用骨膜修复软骨的组织工程方法。骨膜移植物有可能有助于组织工程的三个要求（支架，细胞，生长因子）中的每一个，并已成功地用于修复受损关节软骨的生物表面重建。利用骨膜组织移植物进行组织工程的主要障碍是随着患者年龄的增加，骨膜的软骨形成潜力下降。我们推测，骨膜下注射特定的生长因子可以作为一种预处理，以“激活”骨膜的关节软骨组织工程。本质上，工程组织将在体内制备用于移植。在这个提议中，我们计划检查骨膜下注射已知的软骨形成生长因子的潜力，以增强（1）体内骨膜中软骨形成前体细胞的数量（目标1），（2）骨膜的体外软骨形成潜力（目标2）和（3）骨膜修复关节软骨缺损的潜力（目标3）。除了关节软骨修复，这些研究有可能影响骨膜在其他应用中的应用，如骨组织工程。此外，通过消除对细胞培养扩增设施和专业知识的需求，这种方法的成本应该大大降低，从而使软骨修复在全球范围内更容易获得。

DESCRIPTION (provided by applicant): Articular cartilage is the remarkably durable tissue that covers the articulating bone surfaces in our joints and permits pain-free movement by greatly reducing friction between bones and distributing stress. Unfortunately, when cartilage is damaged due to injury or disease, it has a limited capacity to heal and can lead to premature arthritis. Arthritis is a major health issue that is predicted to increase as our population ages. As such, there is considerable interest in the development of techniques to repair or reconstruct damaged articular cartilage. The implications of a successful method for cartilage repair would be great in terms of the number of patients affected and their quality of life. Importantly, in this era of escalating health care costs, successful cartilage repair would decrease the long-term costs of health care related to joint replacement and multiple revisions thereof. Our long-term objective is to develop a tissue engineering approach for cartilage repair using periosteum. Periosteal grafts have the potential to contribute to each of the three requirements for tissue engineering (scaffold, cells, growth factors), and have been used successfully in biological resurfacing for the repair of damaged articular cartilage. The principle obstacle to overcome for the use of periosteal tissue grafts for tissue engineering is the declining chondrogenic potential of periosteum with increasing age of the patient. We hypothesize that subperiosteal injection of specific growth factors can be used as a pretreatlnent to "activate" periosteum for articular cartilage tissue engineering. In essence, the engineered tissue will be prepared in vivo for transplantation. In this proposal, we plan to examine the potential for subperiosteal injection of known chondrogenic growth factors to enhance (1) the number of chondrogenic precursor cells in periosteum in vivo (Aim 1), (2) the in vitro chondrogenic potential of periosteum (Aim 2) and (3) the potential of periosteum to repair articular cartilage defects (Aim 3). Beyond articular cartilage repair, these studies have the potential to impact the use of periosteum for other applications such as tissue engineering of bone. In addition, by eliminating the need for cell culture expansion facilities and expertise, the cost of this approach should be considerably less thereby making cartilage repair more globally accessible.