Epiligament Tissue of the Medial Collateral Ligament in Rat Knee Joint: Ultrastructural Study

Georgiev, G; Iliev, Alexandar; Kotov, Georgi; Nedialkova, Violeta K; Kirkov, Vidin; Landzhov, Boycho

doi:10.7759/cureus.3812

Cited by 3 publications

(11 citation statements)

References 8 publications

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“…Similar ultrastructural characteristics of fibroblasts and fibrocytes, as reported above, were confirmed by Georgiev et al [ 8 ] in humans. They finally concluded due to the ultrastructural characteristics that fibroblasts might be involved in differentiation, phagocytosis, and collagen synthesis; the authors also hypothesized that single collagen fibers or those grouped in bundles may respond to ligament tension in different directions [ 8 , 21 ]. With the aim of obtaining more detailed knowledge of the MCL and ACL ELs and comparing it in rats, Iliev et al [ 32 ] found a statistically significant difference in the number of cells per mm 2 in the EL of the two ligaments, with a greater number in the MCL.…”

Section: Introductionmentioning

confidence: 99%

“…After extensive research on epiligament morphology of the MCL in rats and humans in both normal conditions and injury, as well as investigation of the same tissue in the ACL and comparison between these two commonly injured ligaments, a novel EL theory was proposed by Georgiev et al [6–8, 11, 12, 18–22].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to the ligament, the EL contains multiple cell types such as fibroblasts, fibrocytes, adipocytes, and blood vessels [6–8, 11, 12, 18–20, 33, 41]. Georgiev et al [21] presented the ultrastructural characteristics of these cells. Fibroblasts have been described as large and well formed; they display a very delicate chromatin structure with a prominent nucleolus.…”

Section: Introductionmentioning

confidence: 99%

“…It has been proposed that the EL has a role in ligament growth and healing and may control water and metabolite influx into the ligament [33, 40]. Several studies have pointed toward the EL as a donor of fibroblasts and other connective tissue cells, progenitor cells, and blood vessels, which migrate toward the body of the ligament via the endoligament and are crucial for ligament repair [6–8, 11, 12, 18–21, 41]. These studies clearly indicate that during early healing, EL tissue formed new granulation tissue after injury via the endoligament and thus is the main donor of cells and blood vessels for the repair process.…”

Section: Introductionmentioning

confidence: 99%

“…In the MCL and ACL, the immunohistochemical expression of the aforementioned collagen types was stronger in the EL than in the ligament proper and was greater in the EL of the MCL than in the ACL [32]. Fibroblasts are also responsible for the synthesis of matrix metalloproteinases (MMPs), decorin, fibronectin, and fibromodulin, which are involved not only in the degradation of the ligament after injury but also in subsequent cell proliferation and ligament remodeling [6–9, 11, 12, 18–22]. Georgiev et al [20] reported that the enzymatic activity of MMP‐2 and MMP‐9 was greater in the EL of the MCL than in the same structure of the ACL and speculated the important role of these enzymes in the normal function and difference in the healing potential of these ligaments.…”

Section: Introductionmentioning

confidence: 99%

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The novel epiligament theory: differences in healing failure between the medial collateral and anterior cruciate ligaments

et al. 2022

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According to current literature, 90% of knee ligament injuries involve the medial collateral ligament or the anterior cruciate ligament. In contrast to the medial collateral ligament, which regenerates relatively well, the anterior cruciate ligament demonstrates compromised healing. In the past, there were numerous studies in animal models that examined the healing process of these ligaments, and different explanations were established. Although the healing of these ligaments has been largely investigated and different theories exist, unanswered questions persist.Therefore, the aim of this article is 1) to review the different historical aspects of healing of the medial collateral ligament and present the theories for healing failure of the anterior cruciate ligament; 2) to examine the novel epiligament theory explaining the medial collateral ligament healing process and failure of anterior cruciate ligament healing; and 3) to discuss why the enveloping tissue microstructure of the aforementioned ligaments needs to be examined in future studies.We believe that knowledge of the novel epiligament theory will lead to a better understanding of the normal healing process for implementing optimal treatments, as well as a more holistic explanation for anterior cruciate ligament healing failure.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The novel epiligament theory: differences in healing failure between the medial collateral and anterior cruciate ligaments

et al. 2022

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Are There Any Differences in the Healing Capacity between the Medial Collateral Ligament’s (MCL) Proximal and Distal Parts in the Human Knee? Quantitative and Immunohistochemical Analysis of CD34, α-Smooth Muscle Actin (α-SMA), and Vascular Endothelial Growth Factor (VEGF) Expression Regarding the Epiligament (EL) Theory

Georgiev,

Yordanov,

Gaydarski

et al. 2024

Biomedicines

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The human knee is a complex joint that comprises several ligaments, including the medial collateral ligament (MCL). The MCL provides stability to the knee and helps prevent its excessive inward movement. The MCL also has a thin layer of connective tissue known as the epiligament (EL), which adheres to the ligament. This unique feature has drawn attention in the field of ligament healing research, as it may have implications for the recovery process of MCL injuries. According to the EL theory, ligament regeneration relies heavily on the provision of cells, blood vessels, and molecules. The present study sought to compare the expression of vascular endothelial growth factor (VEGF), CD34, and α-smooth muscle actin (α-SMA) in healthy knees’ proximal and distal MCL segments to better understand how these proteins affect ligament healing. By improving the EL theory, the current results could lead to more effective treatments for ligament injury. To conduct the present analysis, monoclonal antibodies were used against CD34, α-SMA, and VEGF to examine samples from 12 fresh knee joints’ midsubstance MCLs. We identified a higher cell density in the EL than in the ligament connective tissue, with higher cell counts in the distal than in the proximal EL part. CD34 immunostaining was weak or absent in blood vessels and the EL, while α-SMA immunostaining was strongest in smooth muscle cells and the EL superficial layer. VEGF expression was mainly in the blood vessels’ tunica media. The distal part showed more SMA-positive microscopy fields and higher cell density than the proximal part (4735 vs. 2680 cells/mm2). Our study identified CD34, α-SMA, and VEGF expression in the MCL EL, highlighting their critical role in ligament healing. Differences in α-SMA expression and cell numbers between the ligament’s proximal and distal parts may explain different healing capacities, supporting the validity of the EL theory in ligament recovery.

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The Epiligament: Structure, Postnatal Development and Role in Ligament Healing

Stamenov

Yordanova

Dimitrov

et al. 2019

Cureus

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While much is known about the ligament, the precise morphology and function of the thin layer of connective tissue lining its surface, termed the epiligament, have not been fully studied yet. Herein, we aimed at reviewing the recent findings on the structural and functional significance of the epiligament in both animal models and human tissue. The epiligament is made up of various connective tissue cells such as fibroblasts, fibrocytes, mast cells, and adipocytes and contains a number of neurovascular bundles. Arrangement of collagen fibers in the epiligament is rather chaotic, in multiple directions, which allows for greater mobility and resistance to stress. Differences in the collagen content and types of enzymes of the group of matrix metalloproteinases between the epiligament and the underlying ligament tissue have been reported and are reviewed herein. While the ligament tissue mainly contains collagen type I, the epiligament is also rich in collagen types III and V. As suggested by a number of studies, the epiligament plays a key role in ligament repair as a donor of cells and matrix metalloproteinases, particularly matrix metalloproteinase-2 and 9, which are essential for scar tissue remodeling. In conclusion, future studies will likely reveal additional functional aspects of the epiligament, which may allow scientists to devise more suitable treatment strategies for damaged ligaments in a world where injuries resulting from sports activities or daily routine have long merited their due attention.

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Epiligament Tissue of the Medial Collateral Ligament in Rat Knee Joint: Ultrastructural Study

Cited by 3 publications

References 8 publications

The novel epiligament theory: differences in healing failure between the medial collateral and anterior cruciate ligaments

The novel epiligament theory: differences in healing failure between the medial collateral and anterior cruciate ligaments

The Epiligament: Structure, Postnatal Development and Role in Ligament Healing

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