Histologically Confirmed Recellularization is a Key Factor that Affects Meniscal Healing in Immature and Mature Meniscal Tears

Yan, Wenqiang; Dai, Wenli; Cheng, Jin; Fan, Yunlong; Zhao, Fengyuan; Li, Yuwan; Maimaitimin, Maihemuti; Cao, Canhui; Shao, Zhenxing; Li, Qi; Liu, Zhenlong; Hu, Xiaoqing; Ao, Yingfang

doi:10.3389/fcell.2021.793820

Cited by 3 publications

(8 citation statements)

References 42 publications

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“…A previous study has demonstrated that apparent cell apoptosis was observed at the tear interface in an adult rabbit meniscal tear model. 35 In the present study, the apoptosis index around the tear interface was evaluated, showing that meniscal tears treated with hyaluronidase and TGF-β3 had the lowest apoptosis index compared with the control group. Moreover, the superior repair and integration of meniscal tears after hyaluronidase and TGF-β3 treatment decreased the degradation of cartilage in the MFC and MTP.…”

Section: Discussionmentioning

confidence: 75%

“…3,16 Second, cellularity decreases significantly with maturity. 35 Third, the mechanical property and intrinsic fiber arrangement are enhanced with maturity. For instance, with the maturity of the meniscus after birth, the size and density of collagen bundles increase significantly, and the deposition of the extracellular matrix including collagen and proteoglycans increases, thus enhancing mechanical properties.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the apoptosis index at the tear interface was evaluated using the TUNEL assay. 35 The slices stained with H&E and safranin O-Fast Green were captured using a digital slide scanner (NanoZoomer). The stained slices of collagen, aggrecan, SOX9, LOX, and LH2 were examined using a confocal microscope (Leica).…”

Section: Sample Collection and Processingmentioning

confidence: 99%

“…The American Journal of Sports Medicine 2023;51 (13):3509-3522 DOI: 10.1177/03635465231194028 Ó 2023 The Author(s) death zone at the tear site was observed in mature rabbits. 35 Differences in the recellularization process at the tear site between immature and mature specimens may be attributed to meniscal developmental characteristics. Compared with adult meniscal tissue, fetal meniscal tissue possesses more slender, immature collagen fibers and hypercellularity.…”

mentioning

confidence: 99%

“…Another study has confirmed a robust recellularization process at the meniscal tear edge in immature rabbits, while gradual enlargement of the cell death zone at the tear site was observed in mature rabbits. 35 Differences in the recellularization process at the tear site between immature and mature specimens may be attributed to meniscal developmental characteristics. Compared with adult meniscal tissue, fetal meniscal tissue possesses more slender, immature collagen fibers and hypercellularity.…”

mentioning

confidence: 99%

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Meniscal Fibrocartilage Repair Based on Developmental Characteristics: A Proof-of-Concept Study

Yan,

Zhu,

et al. 2023

Am J Sports Med

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Background: Unlike the adult meniscus, the fetal meniscus possesses robust healing capacity. The dense and stiff matrix of the adult meniscus provides a biophysical barrier for cell migration, which is not present in the fetal meniscus. Inspired by developmental characteristics, modifying the matrix of the adult meniscus into a fetal-like, loose and soft microenvironment holds opportunity to facilitate repair, especially in the avascular zone. Hypothesis: Modifying the dense and stiff matrix of the adult meniscus into a fetal-like, loose and soft microenvironment could enhance cell migration to the tear interface and subsequent robust healing capacity. Study Design: Controlled laboratory study. Methods: Fresh porcine menisci were treated with hyaluronidase or collagenase. The density and arrangement of collagen fibers were assessed. The degradation of proteoglycans and collagen was evaluated histologically. Cell migration within the meniscus or the infiltration of exogenous cells into the meniscus was examined. Dendritic silica nanoparticles with relatively large pores were used to encapsulate hyaluronidase for rapid release. Mesoporous silica nanoparticles with relatively small pores were used to encapsulate transforming growth factor–beta 3 (TGF-β3) for slow release. A total of 24 mature male rabbits were included. A longitudinal vertical tear (0.5 cm in length) was prepared in the avascular zone of the medial meniscus. The tear was repaired with suture, repaired with suture in addition to blank silica nanoparticles, or repaired with suture in addition to silica nanoparticles releasing hyaluronidase and TGF-β3. Animals were sacrificed at 12 months postoperatively. Meniscal repair was evaluated macroscopically and histologically. Results: The gaps between collagen bundles increased after hyaluronidase treatment, while collagenase treatment resulted in collagen disruption. Proteoglycans degraded after hyaluronidase treatment in a dose-dependent manner, but collagen integrity was maintained. Hyaluronidase treatment enhanced the migration and infiltration of cells within meniscal tissue. Last, the application of fibrin gel and the delivery system of silica nanoparticles encapsulating hyaluronidase and TGF-β3 enhanced meniscal repair responses in an orthotopic longitudinal vertical tear model. Conclusion: The gradient release of hyaluronidase and TGF-β3 removed biophysical barriers for cell migration, creating a fetal-like, loose and soft microenvironment, and enhanced the fibrochondrogenic phenotype of reparative cells, facilitating the synthesis of matrix and tissue integration. Clinical Relevance: Modifying the adult matrix into a fetal-like, loose and soft microenvironment via the local gradient release of hyaluronidase and TGF-β3 enhanced the healing capacity of the meniscus.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Sample Collection and Processingmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Meniscal Fibrocartilage Repair Based on Developmental Characteristics: A Proof-of-Concept Study

Yan,

Zhu,

et al. 2023

Am J Sports Med

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Finite element analysis of meniscus contact mechanical behavior based on kinematic simulation of abnormal gait

Zhao,

Xie,

Qiao

et al. 2024

Computer Methods in Biomechanics and Biomedical Engineering

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

Yan,

Wu,

Zhao

et al. 2023

Bioengineering

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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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Histologically Confirmed Recellularization is a Key Factor that Affects Meniscal Healing in Immature and Mature Meniscal Tears

Cited by 3 publications

References 42 publications

Meniscal Fibrocartilage Repair Based on Developmental Characteristics: A Proof-of-Concept Study

Meniscal Fibrocartilage Repair Based on Developmental Characteristics: A Proof-of-Concept Study

Finite element analysis of meniscus contact mechanical behavior based on kinematic simulation of abnormal gait

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

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