Patient-specific cartilage implants: development and surgical implantation

关节炎或损伤对关节软骨的损伤会导致严重的发病率，因为该组织几乎没有修复的潜力。一种方法是用工程化软骨重新修复受损区域。然而，由于只能从患者身上提取有限数量的细胞，该方法仅限于修复微小的局部缺陷。为了将潜在的治疗扩展到更大的、更具临床相关性的患者群体，需要开发大型结构。然而，大型植入物的令人困惑的问题是，需要考虑患者在病变部位的解剖结构，因为移植物匹配不足和关节表面修复不完善可能导致植入物过早失败。这项拟议的研究的目的是开发针对患者的工程化软骨植入物，适用于修复临床上大小的缺损。最近，我们开发了一种方法来创造大尺寸的软骨结构(&gt；3平方英尺。Cm)从一小群细胞(20,000英镑)，没有单独的细胞扩增阶段或支架。细胞在生物反应器中培养，可以诱导软骨组织广泛生长，这些软骨组织可以与缺损处的形状、曲率和厚度相匹配。为了在理想的位置和方向提供患者特定的植入物，我们将使用我们为软骨修复开发的计算机辅助外科策略。该项目将我们以前的工作成果转化为开发和手术植入特定患者的工程化软骨结构，以提供治疗与骨关节炎(OA)或创伤相关的大缺陷的前景，这些缺陷是目前可用的技术无法解决的。最终，使用这些新技术，患者将受益于通过适当的植入物匹配获得更好的临床结果，从而降低植入物失败的风险。我们预计我们的方法将修复由于骨性关节炎引起的退行性改变，并有可能推迟或消除关节置换手术的需要。

Damage to articular cartilage by arthritis or injury causes significant morbidity as the tissue has little potential for repair. One approach to resurface the damaged area with engineered cartilage. However, as only a limited number of cells can be extracted from a patient, the approach is restricted to the repair of small, localized defects. To extend potential treatment to a larger, more clinically relevant patient population, large-size constructs need to be developed. However, the confounding problem with large-sized implants is that the patient's anatomy at the lesion site needs to be taken into account as inadequate graft matching and imperfect restoration of the joint surface can lead to premature implant failure. The objective of this proposed study is to develop patient-specific engineered cartilage implants suitable for the repair of large, clinically-sized defects. Recently, we have developed an approach to create large-sized cartilage constructs (> 3 sq. cm) from a small population of cells (< 20,000) without a separate cell expansion phase or scaffold. The cells are cultivated in a bioreactor which elicits the extensive growth of cartilaginous tissue that can be matched to the shape, curvature and thickness of the defect site. To deliver the patient-specific implants at the desired location and orientation, we will use our computer-assisted surgical strategies developed for cartilage repair. This project translates the results from our previous work to develop and surgically implant, patient-specific engineered cartilage constructs to offer the prospect of treating large defects associated with osteoarthritis (OA) or trauma that cannot be addressed with currently available techniques. Ultimately, with these new technologies, patients will benefit from better clinical outcomes through proper implant matching resulting in a lower risk of implant failure. We expect that our methods will repair degenerative changes due to OA, and potentially delay or eliminate the need for joint replacement surgery