Liquid cartilage for arthroscopy

项目摘要 这个多PI提案是组织工程师和整形外科医生之间的合作， 软骨填充物，称为软骨凝胶，这将是有效的修复凿和局灶性缺损的膝盖， 关节镜手术软骨凝胶是使用广泛传代的同种异体肋骨软骨细胞形成的， 保留了它们形成在表型上类似于关节软骨的机械坚固的新软骨的能力 (e.g.,产生胶原II和润滑素，缺乏胶原I和X）。初步数据显示， 在移植物培养中以及在体内16周后在小型猪膝关节中填充凿痕缺陷。我们还开发了 小型猪的关节镜技术。在这个建议中，我们将表明，除了凿痕缺陷， 当关节镜下施用时，软骨凝胶也将有效地愈合局灶性缺损。这将是 实现了两个目标。在目标1中，我们将检查软骨凝胶1），以表明除了20 × 1 mm的凿痕缺陷外， 软骨凝胶能够填充直径5mm的局灶性缺损。在外植体培养（目标1，阶段I），和2）找到 关节镜下软骨凝胶仍保留在骨凿和局灶性缺损中的最大关节内压力（目的 1，第二阶段）。在目标2中，我们将确定软骨凝胶是否能愈合骨凿和局灶性关节软骨缺损。 小型猪使用关节镜。因为软骨凝胶是根据外科医生的调查设计的， 是基于严谨的科学证明其形成软骨的能力，成功完成这一建议 将允许使用关节镜来治疗软骨缺损。

PROJECT SUMMARY This multi-PI proposal is a collaboration among tissue engineers and an orthopaedic surgeon to develop a liquid cartilage filler, called chondrogel, that would be efficacious in repairing gouge and focal defects of the knee using an arthroscopy approach. Chondrogel is formed using extensively passaged, allogeneic rib chondrocytes that have retained their ability to form mechanically robust neocartilage that is phenotypically akin to articular cartilage (e.g., production of collagen II and lubricin, absence of collagen I and X). Preliminary data show that chondrogel fills gouge defects in explant culture and also in vivo after 16wks in the minipig knee. We have also developed arthroscopic techniques for the minipig. In this proposal, we will show that, in addition to gouge defects, chondrogel will be effective in healing focal defects as well when administered arthroscopically. This will be achieved in two aims. In Aim 1, we will examine chondrogel 1) to show that, in addition to 20x1mm gouge defects, chondrogel is capable of filling focal defects 5mm in dia. in explant culture (Aim 1, Phase I), and 2) to find the maximum arthroscopic intraarticular pressure where chondrogel is still retained in gouge and focal defects (Aim 1, Phase II). In Aim 2, we will determine if chondrogel heals gouge and focal articular cartilage defects in the minipig using arthroscopy. Because chondrogel has been designed based on surgeon surveys and because it is based on rigorous science demonstrating its ability to form cartilage, successful completion of this proposal would allow the use of arthroscopy to treat cartilage defects.