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地塞米松洗脱细胞接种构建体在软骨修复临床前犬模型中的评估

Evaluation of Dexamethasone-Eluting Cell-Seeded Constructs in a Preclinical Canine Model of Cartilage Repair.

作者信息

Lee Andy J, Gangi Lianna R, Hu Yizhong Jenny, Dinescu Andreea T, Guo X Edward, Bozynski Chantelle C, Kuroki Keiichi, Stoker Aaron M, Marra Kacey G, Ateshian Gerard A, Cook James L, Hung Clark T

机构信息

Department of Biomedical Engineering, Columbia University, New York, New York, USA.

Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri, USA.

出版信息

Tissue Eng Part A. 2025 Feb;31(3-4):208-218. doi: 10.1089/ten.tea.2024.0244. Epub 2024 Nov 28.

Abstract

In this 12-month long, preclinical large animal study using a canine model, we report that engineered osteochondral grafts (comprised of allogeneic chondrocyte-seeded hydrogels with the capacity for sustained release of the corticosteroid dexamethasone [DEX], cultured to functional mechanical properties, and incorporated over porous titanium bases), can successfully repair damaged cartilage. DEX release from within engineered cartilage was hypothesized to improve initial cartilage repair by modulating the local inflammatory environment, which was also associated with suppressed degenerative changes exhibited by menisci and synovium. We note that not all histological and clinical outcomes at an intermediary time point of three months paralleled 12-month outcomes, which emphasizes the importance of studies in valid preclinical models that incorporate clinically relevant follow-up durations. Together, our study demonstrates that engineered cartilage fabricated under the conditions reported herein can repair full-thickness cartilage defects and promote synovial joint health and function.

摘要

在这项为期12个月、使用犬类模型的临床前大型动物研究中,我们报告称,工程化骨软骨移植物(由接种同种异体软骨细胞的水凝胶组成,具有持续释放皮质类固醇地塞米松[DEX]的能力,培养至具有功能力学性能,并整合在多孔钛基上)能够成功修复受损软骨。从工程化软骨中释放的DEX被认为可通过调节局部炎症环境来改善初始软骨修复,这也与半月板和滑膜所表现出的退行性变化受到抑制有关。我们注意到,在三个月的中间时间点,并非所有组织学和临床结果都与12个月时的结果一致,这强调了在纳入临床相关随访时长的有效临床前模型中进行研究的重要性。总之,我们的研究表明,在此处报告的条件下制造的工程化软骨能够修复全层软骨缺损,并促进滑膜关节的健康和功能。

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Biocompatibility of titanium from the viewpoint of its surface.从表面角度看钛的生物相容性。
Sci Technol Adv Mater. 2022 Aug 15;23(1):457-472. doi: 10.1080/14686996.2022.2106156. eCollection 2022.

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