Tissue Engineering of Cartilage using Periosteum

描述（由申请人提供）：关节软骨是一种非常耐用的组织，覆盖在关节的关节骨表面，通过极大地减少骨骼之间的摩擦和分配压力来实现无痛运动。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，可能导致过早关节炎。关节炎是一个主要的健康问题，预计会随着人口老龄化而增加。因此，人们对修复或重建受损关节软骨的技术的发展非常感兴趣。一种成功的软骨修复方法对于受影响的患者数量和他们的生活质量来说意义重大。重要的是，在这个医疗费用不断上升的时代，成功的软骨修复将减少与关节置换术和多次手术相关的长期医疗费用。我们的长期目标是开发一种组织工程方法用于骨膜软骨修复。骨膜移植物有可能满足组织工程的三个要求（支架、细胞、生长因子），并且已经成功地用于修复受损关节软骨的生物表面修复。骨膜组织移植用于组织工程需要克服的主要障碍是骨膜的成软骨潜能随着患者年龄的增长而下降。我们假设骨膜下注射特定生长因子可以作为预处理“激活”骨膜用于关节软骨组织工程。从本质上讲，工程组织将在体内制备用于移植。在本提案中，我们计划研究骨膜下注射已知软骨生长因子的潜力，以增强(1)体内骨膜中软骨前体细胞的数量（目的1），(2)骨膜的体外软骨潜能（目的2）和(3)骨膜修复关节软骨缺陷的潜力（目的3）。除了关节软骨修复之外，这些研究还可能影响骨膜在其他领域的应用，如骨组织工程。此外，通过消除对细胞培养扩增设备和专业知识的需求，这种方法的成本应该大大降低，从而使软骨修复更容易在全球范围内实现。

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.