A fraction of the OA patient population is affected by post-traumatic osteoarthritis (PTOA) following acute joint injuries. Stopping or reversing the progression of PTOA following joint injury could improve long-term functional outcomes, reduced disability, and medical costs. To more effectively treat articular cartilage injury, we have developed a novel cell-based therapy that involves the pre-targeting of apoptotic chondrocytes and the delivery of healthy, metabolically active chondrocytes using click chemistry. Specifically, a pre-targeting agent was prepared via conjugating apoptotic binding peptide (ApoPep-1) and trans-cyclooctene (TCO) onto polyethylene glycol (PEG) polymer carrier. The pre-targeting agent would be introduced to injured areas of articular cartilage, leading to the accumulation of TCO groups on the injured areas from actively binding to apoptotic chondrocytes. Subsequently, methyltetrazine (Tz)-bearing chondrocytes would be immobilized on the surface of TCO-coated injured cartilage via Tz-TCO click chemistry reaction. Using an ex vivo human cartilage explant PTOA model, the effectiveness of this new approach was evaluated. Our studies show that this novel approach (Tz-TCO click chemistry) significantly enhanced the immobilization of healthy and metabolically active chondrocytes to the areas of apoptotic chondrocytes. Histological analyses demonstrated that this treatment regimen would significantly reduce the area of cartilage degeneration and enhance ECM regeneration. The results support that Tz-TCO click chemistry-mediated cell delivery approach has great potential in clinical applications for targeting and treatment of cartilage injury.

中文翻译：

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用于软骨再生的基于点击化学的预靶向细胞递送

在急性关节损伤后，一小部分 OA 患者会受到创伤后骨关节炎 (PTOA) 的影响。停止或逆转关节损伤后 PTOA 的进展可以改善长期功能结果、减少残疾和医疗费用。为了更有效地治疗关节软骨损伤，我们开发了一种新的基于细胞的疗法，该疗法包括预靶向凋亡软骨细胞和使用点击化学递送健康、代谢活跃的软骨细胞。具体而言，通过将凋亡结合肽（ApoPep-1）和反式环辛烯（TCO）缀合到聚乙二醇（PEG）聚合物载体上来制备预靶向剂。预靶向剂将被引入关节软骨的受伤区域，导致 TCO 基团在受伤区域的积累，从而与凋亡的软骨细胞主动结合。随后，携带甲基四嗪 (Tz) 的软骨细胞将通过 Tz-TCO 点击化学反应固定在 TCO 包被的受损软骨表面。使用离体人类软骨外植体 PTOA 模型，评估了这种新方法的有效性。我们的研究表明，这种新方法（Tz-TCO 点击化学）显着增强了健康和代谢活跃的软骨细胞在凋亡软骨细胞区域的固定。组织学分析表明，这种治疗方案将显着减少软骨退化面积并增强 ECM 再生。