Anti-Apoptosis Therapy for Meniscal Avascular Zone Repair: A Proof-of-Concept Study in a Lapine Model

In the present study, 24 rabbits were firstly used to evaluate the apoptosis index and matrix degeneration after untreated adult meniscal tears. Vertical tears (0.25 cm in length) were prepared in the avascular zone of the anterior horn. Specimens were harvested at 1, 3, 6, 12 weeks postoperatively....

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Main Authors: Wenqiang Yan, Yue Wu, Fengyuan Zhao, Ruilan Dai, Yunan Zhou, Dingge Liu, Jin Cheng, Xiaoqing Hu, Yingfang Ao
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Bioengineering
Subjects:
Online Access:https://www.mdpi.com/2306-5354/10/12/1422
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author Wenqiang Yan
Yue Wu
Fengyuan Zhao
Ruilan Dai
Yunan Zhou
Dingge Liu
Jin Cheng
Xiaoqing Hu
Yingfang Ao
author_facet Wenqiang Yan
Yue Wu
Fengyuan Zhao
Ruilan Dai
Yunan Zhou
Dingge Liu
Jin Cheng
Xiaoqing Hu
Yingfang Ao
author_sort Wenqiang Yan
collection DOAJ
description In the present study, 24 rabbits were firstly used to evaluate the apoptosis index and matrix degeneration after untreated adult meniscal tears. Vertical tears (0.25 cm in length) were prepared in the avascular zone of the anterior horn. Specimens were harvested at 1, 3, 6, 12 weeks postoperatively. The apoptosis index around tear sites stayed at a high level throughout the whole follow-up period. The depletion of glycosaminoglycans (GAG) and aggrecan at the tear site was observed, while the deposition of COL I and COL II was not affected, even at the last follow-up of 12 weeks after operation. The expression of SOX9 decreased significantly; no cellularity was observed at the wound interface at all timepoints. Secondly, another 20 rabbits were included to evaluate the effects of anti-apoptosis therapy on rescuing meniscal cells and enhancing meniscus repair. Longitudinal vertical tears (0.5 cm in length) were made in the meniscal avascular body. Tears were repaired by the inside-out suture technique, or repaired with sutures in addition to fibrin gel and blank silica nanoparticles, or silica nanoparticles encapsulating apoptosis inhibitors (z-vad-fmk). Samples were harvested at 12 months postoperatively. We found the locally administered z-vad-fmk agent at the wound interface significantly alleviated meniscal cell apoptosis and matrix degradation, and enhanced meniscal repair in the avascular zone at 12 months after operation. Thus, local administration of caspase inhibitors (z-vad-fmk) is a promising therapeutic strategy for alleviating meniscal cell loss and enhancing meniscal repair after adult meniscal tears in the avascular zone.
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spelling doaj.art-83ce468a31d6482b967268b57fc12bbd2023-12-22T13:54:13ZengMDPI AGBioengineering2306-53542023-12-011012142210.3390/bioengineering10121422Anti-Apoptosis Therapy for Meniscal Avascular Zone Repair: A Proof-of-Concept Study in a Lapine ModelWenqiang Yan0Yue Wu1Fengyuan Zhao2Ruilan Dai3Yunan Zhou4Dingge Liu5Jin Cheng6Xiaoqing Hu7Yingfang Ao8Department of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, ChinaDepartment of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, ChinaDepartment of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, ChinaDepartment of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, ChinaDepartment of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, ChinaDepartment of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, ChinaDepartment of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, ChinaDepartment of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, ChinaDepartment of Sports Medicine, Peking University Third Hospital, Institute of Sports Medicine of Peking University, Beijing 100191, ChinaIn the present study, 24 rabbits were firstly used to evaluate the apoptosis index and matrix degeneration after untreated adult meniscal tears. Vertical tears (0.25 cm in length) were prepared in the avascular zone of the anterior horn. Specimens were harvested at 1, 3, 6, 12 weeks postoperatively. The apoptosis index around tear sites stayed at a high level throughout the whole follow-up period. The depletion of glycosaminoglycans (GAG) and aggrecan at the tear site was observed, while the deposition of COL I and COL II was not affected, even at the last follow-up of 12 weeks after operation. The expression of SOX9 decreased significantly; no cellularity was observed at the wound interface at all timepoints. Secondly, another 20 rabbits were included to evaluate the effects of anti-apoptosis therapy on rescuing meniscal cells and enhancing meniscus repair. Longitudinal vertical tears (0.5 cm in length) were made in the meniscal avascular body. Tears were repaired by the inside-out suture technique, or repaired with sutures in addition to fibrin gel and blank silica nanoparticles, or silica nanoparticles encapsulating apoptosis inhibitors (z-vad-fmk). Samples were harvested at 12 months postoperatively. We found the locally administered z-vad-fmk agent at the wound interface significantly alleviated meniscal cell apoptosis and matrix degradation, and enhanced meniscal repair in the avascular zone at 12 months after operation. Thus, local administration of caspase inhibitors (z-vad-fmk) is a promising therapeutic strategy for alleviating meniscal cell loss and enhancing meniscal repair after adult meniscal tears in the avascular zone.https://www.mdpi.com/2306-5354/10/12/1422meniscal tearapoptosismeniscal repaircaspases inhibitorz-vad-fmk
spellingShingle Wenqiang Yan
Yue Wu
Fengyuan Zhao
Ruilan Dai
Yunan Zhou
Dingge Liu
Jin Cheng
Xiaoqing Hu
Yingfang Ao
Anti-Apoptosis Therapy for Meniscal Avascular Zone Repair: A Proof-of-Concept Study in a Lapine Model
Bioengineering
meniscal tear
apoptosis
meniscal repair
caspases inhibitor
z-vad-fmk
title Anti-Apoptosis Therapy for Meniscal Avascular Zone Repair: A Proof-of-Concept Study in a Lapine Model
title_full Anti-Apoptosis Therapy for Meniscal Avascular Zone Repair: A Proof-of-Concept Study in a Lapine Model
title_fullStr Anti-Apoptosis Therapy for Meniscal Avascular Zone Repair: A Proof-of-Concept Study in a Lapine Model
title_full_unstemmed Anti-Apoptosis Therapy for Meniscal Avascular Zone Repair: A Proof-of-Concept Study in a Lapine Model
title_short Anti-Apoptosis Therapy for Meniscal Avascular Zone Repair: A Proof-of-Concept Study in a Lapine Model
title_sort anti apoptosis therapy for meniscal avascular zone repair a proof of concept study in a lapine model
topic meniscal tear
apoptosis
meniscal repair
caspases inhibitor
z-vad-fmk
url https://www.mdpi.com/2306-5354/10/12/1422
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