Knee Joint Resurfacing with Anatomic Tissue Engineered Osteochondral Implants

摘要 关节软骨排列在关节的骨性表面，有效地传递产生的高应力。 与日常生活活动有关。然而，对这种组织的破坏非常普遍，美国约9%的人。 30岁及以上患有髋关节或膝关节骨关节炎(OA)的人群。这对许多人产生了不利影响 患有这种疾病的退伍军人，限制了他们进行许多日常生活活动的能力，降低了他们的 总体生活质量。不幸的是，对于受损的患者来说，可行的治疗选择很少。 关节软骨，大多数最终是用金属和塑料假体进行关节置换，这很容易 最终需要进行翻修手术。为了满足这种临床需求，我们开发了新型水凝胶。 促进间充质干细胞(MSCs)向软骨细胞分化，并为其提供支持 软骨样组织细胞外基质沉积和功能成熟的环境 并在我们尤卡坦小型猪的大型动物模型中进行软骨修复。此外，我们最近展示了 活的、工程化的软骨结构可以形成模仿复合体的解剖结构 原始关节曲面的几何图形。我们还开发了一种技术，使永久骨骼 活体种植体与现有骨的固定和体内结合。在这项提案中，我们利用了这一点 解决生物关节表面重新铺设的“圣杯”问题的进展：更换大部分承重物 关节软骨面。我们的实验将以尤卡坦小型猪的股骨髁为模型， 成功将通过复杂和临床相关的结果衡量标准进行评估。一旦在此进行验证 在临床前环境下，这项技术可以直接转化为人体临床试验，并推广到其他 身体的关节。最终，这项工作有朝一日可能会消除用金属和 这将有助于预防和缓解退伍军人群体以及整个社会中的严重影响。

Abstract Articular cartilage lines the boney surfaces of joints and efficiently transmits the high stresses that originate with activities of daily living. However, damage to this tissue is extremely prevalent, with ~9% of the U.S. population aged 30 and older having osteoarthritis (OA) of the hip or knee. This adversely impacts the many Veterans with this condition, limiting their ability to carry out many activities of daily living and lowering their overall quality of life. Unfortunately, there are very few viable treatment options for patients with damaged articular cartilage, and most culminate in joint replacement with metal and plastic prostheses, which are prone to wear and ultimately require revision surgery. To address this clinical need, we developed novel hydrogels that promote the chondrogenic differentiation of mesenchymal stem cells (MSCs) and provide a supportive environment for extracellular matrix deposition and functional maturation of a cartilage-like tissue, both in vitro and in our Yucatan minipig large animal model of cartilage repair. Moreover, we recently demonstrated that living, engineered cartilage constructs can be formed into anatomic structures that mimic the complex geometries of native joint surfaces. We have also developed technology that enables the permanent boney fixation and in vivo integration of the living implant with existing bone. In this proposal, we capitalize on this progress to address the `holy grail' of biologic joint resurfacing: replacement of the majority of a load-bearing articular cartilage surface. Our experiment will use the femoral condyle of the Yucatan minipig as a model, and success will be assessed via sophisticated and clinically relevant outcome measures. Once validated in this pre-clinical setting, this technology may be directly translated into human clinical trials, and extended to other joints in the body. Ultimately, this work may one day eliminate the need for joint replacement with metal and plastic and alleviate the serious implications of OA in the Veteran population, as well as society as a whole.