Medial Collateral Ligament Healing Research Articles

Lack of Consensus on the Management of Medial Collateral Ligament Tears in the Setting of Concomitant Anterior Cruciate Ligament Injury: A Critical Analysis.

» There is no clear agreement on the optimal timing or superior type of fixation for medial collateral ligament (MCL) tears in the setting of anterior cruciate ligament (ACL) injury.» Anatomic healing of medial knee structures is critical to maintain native knee kinematics, supported by biomechanical studies that demonstrate increased graft laxity and residual valgus rotational instability after ACL reconstruction (ACLR) alone in the setting of concomitant ACL/MCL injury.» Historically, most surgeons have favored treating acute combined ACL/MCL tears conservatively with MCL rehabilitation, followed by stress radiographs at 6 weeks after injury to assess for persistent valgus laxity before performing delayed ACLR to allow for full knee range of motion, and reduce the risk of postoperative stiffness and arthrofibrosis.» However, with the advancement of early mobilization and aggressive physical therapy protocols, acute surgical management of MCL tears in the setting of ACL injury can have benefits of avoiding residual laxity and further intra-articular damage, as well as earlier return to sport.» Residual valgus laxity from incomplete MCL healing at the time of ACLR should be addressed surgically, as this can lead to an increased risk of ACLR graft failure.» The treatment of combined ACL/MCL injuries requires an individualized approach, including athlete-specific factors such as level and position of play, timing of injury related to in-season play, contact vs. noncontact sport, and anticipated longevity, as well as consideration of the tear pattern, acuity of injury, tissue quality, and surgeon familiarity with the available techniques.

Utilizing mesenchymal stem cells to improve the healing process of the medial collateral ligament in the knee

The healing process of the medial collateral ligament (MCL) in the knee is often slow, resulting in adverse outcomes such as scar tissue formation, joint instability, limited range of motion, and an increased risk of re-injury. Consequently, novel therapeutic strategies are imperative to enhance MCL healing. Mesenchymal stem cells (MSCs) have emerged as a promising treatment modality due to their robust proliferative ability, reparative potential, and ability to differentiate into various cell types. Although preclinical studies have shown encouraging results for MSC-based approaches in MCL injuries, clinical studies in the orthopedic literature remain scarce. This review provides an overview of the MCL, conventional treatments for MCL injuries, and recent advances in MSC research for augmenting MCL healing. MSC-based approaches hold promise as a future therapeutic option to improve MCL healing. Nonetheless, further research is warranted to establish the effective ness and safety of this emerging treatment modality.

Treating Combined Anterior Cruciate Ligament and Medial Collateral Ligament Injuries Operatively in the Acute Setting Is Potentially Advantageous

Combined injury of the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) remains among the most common knee injury patterns in orthopaedics. Optimal treatment of grade III MCL injuries is still debated, especially when combined with ACL injury. Most patients with these severe injuries are treated conservatively for at least 6 weeks to allow for MCL healing, followed by delayed ACL reconstruction. Although acute treatment of the MCL was common in the 1970s, postoperative stiffness was frequently reported. Moreover, studies of such treatment failed to show clinical benefits of surgical over conservative treatment, and the MCL exhibited intrinsic healing capacity, leading to the consensus that all MCL injuries are treated conservatively. The current delayed treatment algorithm for ACL-MCL injuries has several disadvantages. First, MCL healing may be incomplete, resulting in residual valgus laxity that places the ACL graft at greater risk of failure. Second, delayed treatment lengthens the overall rehabilitation period, thereby prolonging the presence of atrophy and delaying return to preinjury activity levels. Third, the initial healing period leaves the knee unstable for longer and risks further intra-articular damage. Acute simultaneous surgical treatment of both ligaments has the potential to avoid these shortcomings. This article will review the evolution of treatment of ACL-MCL injuries and explain how it shifted toward the current treatment algorithm. We will (1) discuss why the consensus shifted, (2) discuss the shortcomings of the current treatment plan, (3) discuss the potential advantages of acute simultaneous treatment, and (4) present an overview of the available literature.

Exosome-educated macrophages and exosomes differentially improve ligament healing.

Recently, our group used exosomes from mesenchymal stromal/stem cells (MSCs) to simulate an M2 macrophage phenotype, that is, exosome‐educated macrophages (EEMs). These EEMs, when delivered in vivo, accelerated healing in a mouse Achilles tendon injury model. For the current study, we first tested the ability of EEMs to reproduce the beneficial healing effects in a different rodent model, that is, a rat medial collateral ligament (MCL) injury model. We hypothesized that treatment with EEMs would reduce inflammation and accelerate ligament healing, similar to our previous tendon results. Second, because of the translational advantages of a cell‐free therapy, exosomes alone were also examined to promote MCL healing. We hypothesized that MSC‐derived exosomes could also alter ligament healing to reduce scar formation. Similar to our previous Achilles tendon results, EEMs improved mechanical properties in the healing ligament and reduced inflammation, as indicated via a decreased endogenous M1/M2 macrophage ratio. We also showed that exosomes improved ligament remodeling as indicated by changes in collagen production and organization, and reduced scar formation but without improved mechanical behavior in healing tissue. Overall, our findings suggest EEMs and MSC‐derived exosomes improve healing but via different mechanisms. EEMs and exosomes each have attractive characteristics as therapeutics. EEMs as a cell therapy are terminally differentiated and will not proliferate or differentiate. Alternatively, exosome therapy can be used as a cell free, shelf‐stable therapeutic to deliver biologically active components. Results herein further support using EEMs and/or exosomes to improve ligament healing by modulating inflammation and promoting more advantageous tissue remodeling.

Percutaneous Arthroscopic Assisted Knee Medial Collateral Ligament Repair

Medial collateral ligament (MCL) injuries are commonly encountered alongside anterior cruciate ligament injuries. Treatment modalities have ranged from conservative management to surgical repair, augmentation, and reconstruction. Various reports have reported residual valgus instability, especially in higher-grade injuries that have been treated conservatively. The MCL provides valgus stability but also is an element of anterior stability to the tibia in addition to the anterior cruciate ligament. In addition, meniscal “lift-off” and “floating” have been described as consequences after MCL injuries, and meniscal dysfunction has been shown to lead to accelerated joint degeneration; therefore, all efforts should be made to treat these injuries adequately. We describe a simple, minimally invasive technique that involves suturing the deep MCL to the medial joint capsule, allowing better MCL healing, causing less soft-tissue scarring, and preventing meniscal extrusion.

Treatment of Concomitant ACL and MCL Injuries: Spontaneous Healing of Complete ACL and MCL Tears.

The mainstay of treatment for anterior cruciate ligament (ACL) tear is considered to be surgery, especially when associated with medial collateral ligament (MCL) tears. We aimed to evaluate our hypothesis that some patients with concomitant ACL and MCL tears may develop spontaneous healing without surgical intervention. This study was conducted during 2013 to 2017. A total of 707 patient referred with combined ACL and MCL injuries. Patients were divided into three groups according to type of ACL and MCL management as follows: (1) group 1 as those who only had ACL reconstruction without any surgical treatment of MCL; (2) group 2 as those who had ACL reconstruction and MCL surgery (reconstruction, reefing, or both); (3) group 3 as those who showed spontaneous healing of ACL and MCL. Overall, 206 and 129 patients entered groups 1 and 2, respectively. Overall, 15 patients showed spontaneous healing of ACL and entered group 3. Skiing and soccer were the most common causes of injury within the third group, followed by traffic accidents (35.7%, 35.7% and 21.4%, respectively). All these were noncontact injuries within this groups. In group 3 only three patients had concomitant meniscal injury. Mean healing time for patient with spontaneous healing was 8.66 ± 3.41 months. All patients showed ACL tears at the proximal part of its attachment. During follow-up, all pivot shift, Lachman and MCL tests were either negative or one plus. All these individuals returned to previous physical activity. Among the total number of patients with skiing injuries presenting with concomitant ACL/MCL injuries (27 patients), five patients (18.5%) showed spontaneous healing. Valgus and external rotation injuries with dominancy of valgus force, apart from a MCL tear, may lead to proximal tear of ACL as well, and the inflammation from the torn MCL can potentiate and stimulate the healing process of ACL; thus, patient with this mechanism of injury is better followed before surgical intervention is planned as spontaneous healing may occur.

A comparative study of the epiligament of the medial collateral and the anterior cruciate ligament in the human knee. Immunohistochemical analysis of collagen type I and V and procollagen type III

BackgroundRecent reports in rat models have shown that fibroblasts in the epiligament, an enveloping tissue of the ligament, are not static cells and play an important role during the early ligament healing of isolated grade III injury of the collateral ligaments of the knee. Fibroblasts produce collagen types I, III and V and infiltrate within the ligament body via the endoligament. In addition, similarities have been reported between the structure of the epiligament of the medial collateral ligament and anterior cruciate ligament of the knee in rat and in human. In line with the ascribed role of the epiligament tissue and the synthesis of these collagens and their role in ligament healing, the aim of this study was to determine their presence in the normal epiligament of the aforementioned ligaments in humans, to compare their differential expression and to present a novel hypothesis about the failure of healing of the anterior cruciate ligament in contrast to the medial collateral ligament. Materials and methodsWe used samples from the mid-substance of the medial collateral and the anterior cruciate ligament of the knee joint, acquired from 12 fresh knee joints. Routine histological analysis was performed through hematoxylin and eosin stain, Mallory’s trichrome stain and Van Gieson’s stain. The immunohistochemical analysis was conducted using monoclonal antibodies against collagen type I and V and procollagen type III. The number of cells in the epiligament, endoligament and the ligament tissue was assessed quantitatively through a computerized system for image analysis NIS-Elements Advanced Research and Statistica software. ResultsOur observations revealed certain differences in the morphology of the epiligament, as well as variations in the expression of the investigated molecules. Expression of collagen type I was mostly low-positive (1+) in the epiligament and positive (2+) in the ligament tissue of both ligaments. Expression of procollagen type III was mostly positive (2+) in the epiligament and ligament tissue of the medial collateral ligament, low-positive (1+) in the epiligament and negative (0) in ligament tissue of the anterior cruciate ligament. Expression of collagen type V was predominantly low-positive (1+) in the epiligament and negative (0) in the ligament tissue of both ligaments. The immunoreactivity for all three molecules was always higher in the epiligament of the medial collateral ligament than that of the anterior cruciate ligament. ConclusionsThe results of our study illustrate for the first time that fibroblasts in the human epiligament are indeed responsible for the synthesis of the main types of collagen participating in the early ligament healing, thus corresponding to previous data of the medial collateral ligament healing in animal models. The differences between the epiligament of the investigated ligaments could add a novel explanation for the failed anterior cruciate ligament healing.

The effect of healing in the medial collateral ligament of human knee joint: A three-dimensional finite element analysis.

The medial collateral ligament (MCL) is one of the main ligaments that provide knee joint with major restraints against valgus, internal, and external torque loads. The MCL injury most frequently occurs near its femoral attachment but can be healed spontaneously. Hence, the usual clinical treatment for MCL injury is conservative therapy with early controlled rehabilitation motion. However, the effect of the variations in the healing conditions of the MCL portion (i.e. near the femoral insertion) is still unclear. In this study, finite element tibiofemoral joint models with three different MCL healing conditions were analyzed under six kinds of joint loads, such as 10 and 20 N·m valgus tibial torques, 5 and 10 N·m internal tibial torques, and 5 and 10 N·m external tibial torques. The three healing conditions corresponded to the early, medium, and final (i.e. healthy) stages of the healing period, respectively. It was found that different MCL healing conditions greatly affected the main joint kinematics under valgus tibial torques, but neither the reaction force nor stress results of the MCL. The peak strain values in the MCL healing portion changed greatly under all the six loads. Moreover, all the joint kinematics, strain results, and reaction force of the MCL at the medium stage were similar to those in the healthy joint, that is, at the final healing stage. These imply that the partially healed MCL might be enough for providing the restraints for knee joints and would not lead to some high strains occurring in the MCL.

Medial collateral ligament healing after posttraumatic radial head arthroplasty: A retrospective study of 33 cases with a mean follow-up of 73 months

Comminuted radial head fractures are usually associated with destabilizing lesions of the elbow. The radial head prosthesis (RHP) is a therapeutic alternative when fracture fixation is impossible, as it restores one of the elbow's secondary stabilizers. The aim of this study was to assess healing of the medial collateral ligament (MCL) after implantation of a RHP. All patients implanted with a RHP during the 2003–2012 period were eligible for follow-up ultrasound evaluation of MCL healing. A clinical evaluation with standardized tests (DASH and MEPS) was performed and the patients asked to evaluate their elbow's stability during the same follow-up visit. Out of the 33 eligible patients, 20 were included with a mean follow-up of 73 months. The MCL had been torn in 15 of these 20 patients; the MCL appeared healed on the ultrasound images in 13 patients. The elbow was considered subjectively stable in 19 patients. The mean DASH score was 21.4 (±16.67) and the mean MEPS was 84.7 (±13.9); these scores were 17.19 (±14.0) and 88.3 (±10.9) for patients with a healed MCL, versus 32.5 (±10.6) and 70 (±0.0) for patients with a non-healed MCL. Our findings suggest that a torn MCL can heal after RHP implantation, even without surgical ligament repair or reattachment.

Primed Mesenchymal Stem Cells Alter and Improve Rat Medial Collateral Ligament Healing.

Cell therapy with mesenchymal stem cells (MSCs) can improve tissue healing. It is possible, however, that priming MSCs prior to implantation can further enhance their therapeutic benefit. This study was then performed to test whether priming MSCs to be more anti-inflammatory would enhance healing in a rat ligament model, i.e. a medial collateral ligament (MCL). MSCs were primed for 48 h using polyinosinic acid and polycytidylic acid (Poly (I:C)) at a concentration of 1 μg/ml. Rat MCLs were surgically transected and administered 1 × 10(6) cells in a carrier solution at the time of injury. A series of healing metrics were analyzed at days 4 and 14 post-injury in the ligaments that received primed MSCs, unprimed MSCs, or no cells (controls). Applying primed MSCs beneficially altered healing by affecting endothelialization, type 2 macrophage presence, apoptosis, procollagen 1α, and IL-1Ra levels. When analyzing MSC localization, both primed and unprimed MSCs co-localized with endothelial cells and pericytes suggesting a supportive role in angiogenesis. Priming MSCs prior to implantation altered key ligament healing events, resulted in a more anti-inflammatory environment, and improved healing.

Acceleration of healing of the medial collateral ligament of the knee by local administration of synthetic microRNA-210 in a rat model

BackgroundInjury to the medial collateral ligament (MCL) of the knee joint is the most common ligament injury of the knee. Ligament healing generally takes a long time. Micro-ribonucleic acid (miRNA) is one of the noncoding RNAs and plays a crucial role in physiological function; miRNA (miR)-210 is known as a potent factor of angiogenesis, which is an important initiator of ligament healing. The purpose of this study is to examine the effect of local injection of double-stranded (ds) miR-210 on the healing of the MCL of rat knee joint. MethodsMCLs of Sprague-Dawley rats were cut transversely. After the fascia and skin were sutured, dsmiR-210 or control dsRNA was injected into the injured site of MCL. At 2 weeks and 4 weeks, histological analysis and immunofluorescence staining of vascular endothelial growth factor, isolectin B4, collagen type 1, and Ki67 as well as a mechanical test were performed. Analysis of complementary deoxyribonucleic acid (cDNA) microarray data was performed at 1 week. ResultsHistological analysis showed that parallel fibres in the injured site were organised at 2 weeks and became thicker at 4 weeks in the miR-210-treated group, whereas the injured site in controls was filled with loose fibrous tissues and was thinner than that in the miR-210-treated group. The number of blood vessels in the miR-210-treated group was significantly higher than that in controls (p < 0.05), and vascular endothelial growth factor, Ki67, and collagen type 1 in the miR-210-treated group were intensely expressed in the repaired site as compared to the control group. The mechanical test indicated that the ultimate failure load in the miR-210-treated group was significantly higher than that in the control group at 2 weeks. The cDNA microarray analysis showed significant upregulation of genes related to cell proliferation and cell differentiation, and genes involved in negative regulation of apoptosis. ConclusionThis study showed that local injection of dsmiR-210 could accelerate MCL healing in rat, which is likely due to stimulation of angiogenesis at the healing site.

Platelet-rich plasma did not improve early healing of medial collateral ligament in rats.

The medial collateral ligament (MCL) is the most frequently injured ligament of the knee. Platelet-rich plasma (PRP) is a relatively new treatment option developed to enhance the healing response after injury to different tissue types. This study aimed at investigating whether the addition of PRP to MCL tears in rats would alter healing both biomechanically and histologically. Bilateral full-thickness tears of the MCL were surgically induced in the knees of 32 rats. Right ligament was saturated with PRP (n = 32, study group), and the left ligament was saturated with saline (n = 32, control group). The animals were killed 3 weeks later and the surgical sites were evaluated by gross inspection, biomechanically and histologically. There was no gross difference in the mass of granulation tissue, load to failure, stiffness and displacement between the study and control groups. Histological examination by means of maturity score revealed no significant differences between the study and control groups. The addition of PRP to a healing MCL did not improve any of the outcome measures in this model.

Physical examination and imaging of medial collateral ligament and posteromedial corner of the knee.

The medial collateral ligament (MCL) is the most commonly injured knee ligament. Most will heal well with nonoperative treatment. However, not all medial knee injuries are the same. A detailed physical examination can help determine the severity of the medial-sided injury. When combined with advanced imaging, the examination will delineate damage to associated medial knee structures, including the location of MCL damage, posteromedial capsule injuries, and combined cruciate injuries. Failure to recognize MCL injuries that may be prone to chronic laxity can lead to significant disability, joint damage, and failure of concomitant cruciate ligament reconstructions. Magnetic resonance imaging is the mainstay of diagnostic imaging, with coronal sequences allowing full assessment of the MCL complex. Tangential views aid in the diagnosis of concomitant injuries. Stress radiography can play a role in evaluating MCL healing and subtle chronic laxity. Ultrasonography is also gaining acceptance as a means to assess MCL injuries. Use of a detailed examination and advanced imaging will allow optimal treatment of medial knee injuries and improve clinical outcomes.

Surgical menopause initiates molecular changes that do not result in mechanical changes in normal and healing ligaments.

ObjectivesLigaments which heal spontaneously have a healing process that is similar to skin wound healing. Menopause impairs skin wound healing and may likewise impair ligament healing. Our purpose in this study was to investigate the effect of surgical menopause on ligament healing in a rabbit medial collateral ligament model.MethodsSurgical menopause was induced with ovariohysterectomy surgery in adult female rabbits. Ligament injury was created by making a surgical gap in the midsubstance of the medial collateral ligament. Ligaments were allowed to heal for six or 14 weeks in the presence or absence of oestrogen before being compared with uninjured ligaments. Molecular assessment examined the messenger ribonucleic acid levels for collagens, proteoglycans, proteinases, hormone receptors, growth factors and inflammatory mediators. Mechanical assessments examined ligament laxity, total creep strain and failure stress.ResultsSurgical menopause in normal medial collateral ligaments initiated molecular changes in all the categories evaluated. In early healing medial collateral ligaments, surgical menopause resulted in downregulation of specific collagens, proteinases and inflammatory mediators at 6 weeks of healing, and proteoglycans, growth factors and hormone receptors at 14 weeks of healing. Surgical menopause did not produce mechanical changes in normal or early healing medial collateral ligaments. With or without surgical menopause, healing ligaments exhibited increased total creep strain and decreased failure stress compared with uninjured ligaments.ConclusionsSurgical menopause did not affect the mechanical properties of normal or early healing medial collateral ligaments in a rabbit model. The results in this preclinical model suggest that menopause may result in no further impairment to the ligament healing process. Cite this article: Bone Joint Res 2015;4:38–44

Histological characteristics of ligament healing after bio-enhanced repair of the transected goat ACL.

BackgroundRecently, healing of a ruptured anterior cruciate ligament (ACL) is reconsidered. In a previous study, we have shown that the transected ACL can heal after treatment with the triple X locking suture alone or combined with small intestine submucosa (SIS). The first research question of this study was whether the healing ACLs in both groups show histological characteristics that are typical for ligament healing. Secondly, did the combined treatment with SIS lead to improved histological healing, in terms of the morphology of the fibrous synovial layer, the extracellular matrix (ECM), collagen fiber orientation, cellularity, ratio of myofibroblasts, and collagen type 3 staining. The hypothesis was that SIS enhances the healing by the scaffolding effect, endogenous growth factors, and chemoattractants.MethodsIn the Suture group, the left ACL was transected and sutured with the triple X locking suture repair technique. In the Suture-SIS group, the left ACL underwent the same procedure with the addition of SIS. The right ACL served as internal control. Standard histology and immunostaining of α-smooth muscle actin (SMA) and collagen type 3 were used.ResultsMicroscopy showed that the fibrous synovial layer around the ACL was reestablished in both groups. The collagen fibers in the Suture-SIS group stained denser, were more compactly arranged, and the ECM contained fewer voids and fat vacuoles. Neovasculature running between the collagen fibers was observed in both experimental groups. Collagen type 3 stained less in the Suture-SIS group. The cellularity in the Suture group, Suture-SIS group and Control was 1265 ± 1034 per mm2, 954 ± 378 per mm2, 254 ± 92, respectively; 49%, 26% and 20% of the cells stain positive for α-SMA, respectively.ConclusionThe healing ACL in both treated groups showed histological characteristics which are comparable to the spontaneously healing medial collateral ligament and showed that the ACL has a similar intrinsic healing response. Though, no definitive conclusions on the beneficial effects of the SIS scaffold on the healing process can be made.

Anterior cruciate ligament and medial collateral ligament injuries.

The diagnosis and treatment of combined anterior cruciate ligament (ACL) and medial collateral ligament (MCL) injuries have evolved over the past 30 years. A detailed physical examination along with careful review of the magnetic resonance imaging and stress radiographs will guide decision making. Early ACL reconstruction and acute MCL repair are recommended when there is increased medial joint space opening with valgus stress in extension, a significant meniscotibial deep MCL injury (high-riding medial meniscus), or a displaced tibial-sided superficial MCL avulsion (stener lesion of the knee). Delayed ACL reconstruction to allow for MCL healing is advised when increased valgus laxity is present only at 30 degrees of flexion and not at 0 degree. However, at the time of ACL surgery, medial stability has to be re-assessed after the reconstruction is completed. In patients with neutral alignment in the chronic setting, graft reconstruction of both the ACL and MCL is recommended.

Enhanced Medial Collateral Ligament Healing Using Mesenchymal Stem Cells: Dosage Effects on Cellular Response and Cytokine Profile

Mesenchymal stem cells (MSCs) have potential therapeutic applications for musculoskeletal injuries due to their ability to differentiate into several tissue cell types and modulate immune and inflammatory responses. These immune-modulatory properties were examined in vivo during early stage rat medial collateral ligament healing. Two different cell doses (low dose 1 × 10(6) or high dose 4 × 10(6) MSCs) were administered at the time of injury and compared with normal ligament healing at days 5 and 14 post-injury. At both times, the high dose MSC group demonstrated a significant decrease in M2 macrophages compared to controls. At day 14, fewer M1 macrophages were detected in the low dose group compared to the high dose group. These results, along with significant changes in procollagen I, proliferating cells, and endothelialization suggest that MSCs can alter the cellular response during healing in a dose-dependent manner. The higher dose ligaments also had increased expression of several pro-inflammatory cytokines at day 5 (IL-1β, IFNγ, IL-2) and increased expression of IL-12 at day 14. Mechanical testing at day 14 revealed increased failure strength and stiffness in low dose ligaments compared to controls. Based on these improved mechanical properties, MSCs enhanced functional healing when applied at a lower dose. Different doses of MSCs uniquely affected the cellular response and cytokine expression in healing ligaments. Interestingly, the lower dose of cells proved to be most effective in improving functional properties.

Cellular senescence occurring in the rabbit medial collateral ligament during healing

Medial collateral ligament (MCL) healing proceeds in a temporally ordered fashion after injury. Despite the critical roles of fibroblasts during ligament repair, the phenotypic features of these healing fibroblasts have not been well characterized. Here, we show that healing MCL fibroblasts obtained from rabbits at 3-week postinjury exhibited higher rates of senescent phenotypes and produced higher levels of TGF-β1, collagens, α-SMA, and matrix metalloproteinases (MMPs), than the corresponding fibroblasts from sham-operated MCLs. Mechanical stretch further enhanced the cellular senescence and the expression of TGF-β1, collagens, α-SMA, and MMPs in both sham and healing MCL fibroblasts. In addition to MCL fibroblasts at 3-week postinjury, the increased cellular senescence was also detected in healing MCL fibroblasts obtained at 4- and 6-week postinjury. Most importantly, the association between the cellular senescence and ligament healing was confirmed in tissue sections by the senescence-associated β-galactosidase (SA-β-gal) staining. Using a recombinant TGF-β1 and a neutralizing antibody, we found that those phenotypic changes, such as cellular senescence and the expression of collagens and MMPs, in MCL fibroblasts under mechanical loading conditions were regulated through TGF-β1. Taken together, our results propose that cellular senescence and turnover of extracellular matrixes regulated by TGF-β1 in MCL fibroblasts are critical for ligament healing.

The effects of plasma rich in growth factors (PRGF-Endoret) on healing of medial collateral ligament of the knee

Platelet-rich plasma (PRP) has been increasingly used in sports-related injuries for therapeutic applications. However, there are numerous manufacturing procedures and treatment protocols of PRP use, which make difficult to assess its real efficacy for tissue healing. This study addressed to evaluate the therapeutic effects of locally delivered plasma rich in growth factors (PRGF-Endoret) on the early healing of medial collateral ligament (MCL) in rabbit knees. Thirty-one Japanese white rabbits were subjected to a mop-end tear in the MCL of the left knee. PRGF-Endoret was prepared using Anitua's technique. Two groups were set up. In 17 knees, prepared 1.0ml of PRGF-Endoret after clotting was applied on the tear site, while in 14 knees the tear site was untreated serving as a control. Quantitative aspects of PRGF-Endoret, the concentration of platelets, leukocytes and erythrocytes and therapeutic growth factors such as PDGF-BB and TGF-β1 were measured. Rabbits were sacrificed at 3 and 6weeks after the operation and histological and biomechanical evaluation were performed. No leukocytes were measured and certain amount of growth factors such as PDGF-BB and TGF-β1 were confirmed in the PRGF-Endoret. PRGF-Endoret stimulated proliferation of fibroblasts and neovascularization, and induced statistically better structural properties in repaired MCL. Our findings provide evidence that local administration of PRGF-Endoret promotes early steps in ligament healing and the repair of structural properties in a rabbit model. PRGF-Endoret would be a useful product in clinical treatment of ligament injuries.

Paper # 83: The Effects of Autologous Platelet-Rich Plasma on Healing of Medial Collateral Ligament of the Knee: Biomechanical and Histological Study in Rabbits

Paper # 83: The Effects of Autologous Platelet-Rich Plasma on Healing of Medial Collateral Ligament of the Knee: Biomechanical and Histological Study in Rabbits