Influence of the site of injury on the spontaneous healing response in a rat model of total rupture of the anterior cruciate ligament

Kano, Takuma; Kokubun, Takanori; Murata, Kenji; Oka, Yuichiro; Ozone, Kaichi; Arakawa, Kohei; Morishita, Yuri; Takayanagi, Kunio; Kanemura, Naohiko

doi:10.1080/03008207.2021.1889529

Cited by 6 publications

(9 citation statements)

References 32 publications

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“…Different biomaterials including PLGA (poly(lactic-co-glycolic acid)) [ 16 , 17 , 18 , 19 ], PCL [ 16 , 17 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ], PUR (polyurethane) [ 21 ], and PEUUR2000 (poly(ester urethane urea) [ 20 ] were earlier tested for ligament as well as ligament-to-bone interface regeneration. In this study, PCL was selected as the material of construction for the model constructs because of its feasibility in terms of cost and ease of electrospinability.…”

Section: Introductionmentioning

confidence: 99%

Collagen Fibril Diameter Distribution of Sheep Anterior Cruciate Ligament

2023

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The anterior cruciate ligament (ACL) tissue is a soft tissue connecting the femur and tibia at the knee joint and demonstrates a limited capacity for self-regeneration due to its low vascularity. The currently available clinical procedures are unable to fully restore damaged ACL tissue, and tissue engineering can offer options with a potential of restoring the torn/ruptured ACL by using biomimetic constructs that are similar to native tissue in terms of structure, composition, and functions. However, a model substrate to understand how the ACL cells regenerate the injured tissue is still not available. In this study, it is hypothesized that the nanofiber-based model substrate with bimodal and unimodal fiber diameter distributions will mimic the diameter distribution of collagen fibrils seen in healthy and injured sheep ACL, respectively. The aims were to (i) create an ACL injury in a sheep ACL by applying extensional force to rupture the healthy ACL tissue, (ii) measure the collagen fibril diameter distributions of healthy and injured ACL, (iii) fabricate polycaprolactone (PCL) nanofiber-based model constructs using electrospinning with diameter distributions similar to healthy and injured ACL tissue, and (iv) measure mechanical properties of ACL tissue and PCL electrospun constructs. The results showed that the fiber diameter distributions of PCL electrospun constructs and those of the healthy and injured ACL tissues were similar. The novelty in this investigation is that the collagen fibril diameter distribution of healthy and injured sheep ACL tissues was reported for the first time. The study is significant because it aims to create a model construct to solve an important orthopedic-related clinical problem affecting millions of people globally. The model construct fabricated in this work is expected to have an important impact on ACL regeneration efforts.

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Section: Introductionmentioning

confidence: 99%

Collagen Fibril Diameter Distribution of Sheep Anterior Cruciate Ligament

2023

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“…1,10 A new model called the controlled abnormal movement (CAM) model controls abnormal tibial anterior translation after injury from outside the joint capsule in rodent studies and has reportedly achieved spontaneous healing. 11–14 In this model, the mechanical properties of the healed ACL, regardless of the injury site, were approximately 50% of those of a normal ligament. 11 This study showed the possibility of conservative treatment based on the assumption of spontaneous ACL healing in patients with ACL injuries.…”

Section: Introductionmentioning

confidence: 88%

“…However, in the ACLT model, an upward and backward regression of the injured ACL stump was observed. 11,13,14 These reports suggest that within 24 h after an ACL injury, the CAM–ACLT model shows a difference in the molecular mechanism underlying the healing response of the ACL parenchyma and the histological behavior of the injured ACL stump. Moreover, intra-articular tissues are involved in cross-linking between stumps after ACL injury.…”

Section: Introductionmentioning

confidence: 99%

The infrapatellar fat pad contributes to spontaneous healing after complete anterior cruciate ligament injury

Kano,

Minegish,

Terada

et al. 2023

Exp Biol Med (Maywood)

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Anterior cruciate ligament (ACL) injuries have a very low healing capacity but have recently been shown to heal spontaneously with conservative treatment. This study examined the mechanism of spontaneous ACL healing by focusing on the intra-articular tissues of the knee joint. Skeletally mature Wistar rats ( n = 70) were randomly assigned to two groups: the controlled abnormal movement (CAM) and anterior cruciate ligament transection (ACLT) groups. The ACL was completely transected at the mid-portion in both groups. Only the CAM group underwent extra-articular braking to control for abnormal tibial translation. The animals were allowed full cage activity until sacrifice for histological, and molecular biology analyses. The results showed that the behavior of the stump after ACL injury differed between models 12 h after injury. The femoral stump in the ACLT group retreated posteriorly and upwardly. Macrophage polarity analysis revealed that the stump immune response in the CAM group was more activated than that in the ACLT group 6 h after injury. Microarray analysis of the ACL parenchyma and infrapatellar fat pads suggested the involvement of nuclear factor kappa B (NF-κB) signaling. Real-time polymerase chain reaction (PCR) analysis showed that NF-κB gene expression in the infrapatellar fat pad was significantly increased in the CAM group than in the ACLT group. However, there was no difference in the gene expression levels in the ACL parenchyma between models. In conclusion, the healing response of the ACL was activated within 12 h of injury, resulting in differences in the healing response between the models. It has been suggested that infrapatellar fat pads are involved in the healing process and that angiogenesis and antiapoptotic effects through NF-κB signaling may contribute to this mechanism.

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“…We have previously reported anterior cruciate ligament (ACL) healing post traumatic injury and developed a knee instability animal model. In this study, we used this model to investigate OA progression [25][26][27]. Since this model provides external stability, joint instability by ACL injury can be controlled.…”

Section: Introductionmentioning

confidence: 99%

Biochemical reactions between intra-articular tissues and joint instability in a rat model of osteoarthritis

Murata

Kawabata

Kojima

et al. 2023

Preprint

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Aims: Joint instability is associated with various joint conditions including osteoarthritis (OA) and inflammation, and we have developed model which is determined to role of knee instability. Investigating cartilage maintenance factors such as hyaluronic acid (HA) and glycosaminoglycans (GAGs) can provide insights into the effect of the mechanical stress and the inhibitor used, with the following aims: 1) whether cartilage degeneration is inhibited in the new model, 2) whether combination TGF-β1 inhibition mitigates cartilage degeneration, and to determine the role of TGF-β1 in synovitis using fibroblasts. Main methods: We used this novel model to investigate inhibition of OA progression with a focus on HA and GAGs, which help maintain the cartilage and synovial membrane. In detail, mechanical tests, X-ray, histological, and protein and mRNA expression analyses were used to determine the role of joint stability using in vivo model or fibroblast from synovial membrane. Key findings: Joint stability mitigated cartilage degeneration loss, decreased osteophytes, increased the expression levels of HA and GAGs in the synovial membrane, and decreased the release of pro-inflammatory factors in rats. Moreover, injection of TGF-β1 inhibitor in an inflammatory synovial membrane promoted HA and GAGs expression. In synovial fibroblast cells, inhibition of TGF-β1 over expression significantly inhibited the downregulation of pro-inflammatory factors and promoted the upregulation of lubrification for cartilage. Significance: Our results suggest that joint instability is an independent mechanical factor for OA progression. The results provide novel insights into the association between OA and joint instability, which has significant human sciences implications.

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Influence of the site of injury on the spontaneous healing response in a rat model of total rupture of the anterior cruciate ligament

Cited by 6 publications

References 32 publications

Collagen Fibril Diameter Distribution of Sheep Anterior Cruciate Ligament

Collagen Fibril Diameter Distribution of Sheep Anterior Cruciate Ligament

The infrapatellar fat pad contributes to spontaneous healing after complete anterior cruciate ligament injury

Biochemical reactions between intra-articular tissues and joint instability in a rat model of osteoarthritis

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