Current Concepts in Natural History of Meniscal Injury and Future Options in Meniscus Healing: Orthobiologics



Fig. 26.1
Human lateral and medial meniscus



A430291_1_En_26_Fig2_HTML.jpg


Fig. 26.2
Meniscus cell type populations and their regional distribution




26.3 Biomechanical Function


As we mentioned before, the menisci perform various and important biomechanical functions. Their major role is to contribute in the transmission and distribution of the compressive loads during weight-bearing and increase the contact area between femur and tibia, reducing the stresses. Hence, the degenerative changes in meniscectomized knees which has been well established in literature [4, 23, 24]. In addition, the shock absorbing capacity of the menisci during dynamic loading has also been demonstrated in many studies. It has been shown that shock absorption in knees without menisci is approximately 20% lower than in the normal knee [2527]. Menisci serve also as secondary joint stabilizers, by limiting excess motion in all directions [3]. This is better demonstrated in clinical studies with ACL-deficient knees. Medial meniscectomy in knees without an intact ACL provides further anteroposterior and the rotational knee laxity [28, 29]. Besides, the most important structure resisting an anterior tibial force in the ACL-deficient knee is the posterior horn of the medial meniscus [29, 30]. The menisci provide joint lubrication and cartilage nutrition [31, 32] as well as the proprioception [3335].


26.4 Natural History of Meniscal Injuries


According to the recent literature, pathologic abnormalities are frequent in MR images in both osteoarthritic and normal knees [3639] and such tears could be either asymptomatic or lead to painful conditions when they are related with OA [40]. Moreover, the majority of the tears are located in the medial meniscus and seem to progress more than the lateral one as the injury becomes chronic [2]. Longitudinal meniscal tears are more frequently associated with a trauma history while horizontal, oblique or complex tears are often described as degenerative [37, 39, 41]. To date, our knowledge on how meniscal tears develop over time is poor, due to limited available data. Nevertheless, several studies demonstrated that patients suffering from meniscal tears have a progressive severity of these lesions over time [1, 2]. In middle-aged patients without OA, linear intrameniscal signal intensity on MR images of the medial compartment is unlikely to resolve and should be considered a risk factor for medial degenerative meniscal tear [1]. Moreover, any association between meniscal damage and frequent knee pain seems to be present because both are related to OA [1, 2, 42]. Thus, the necessity to better understand the natural history of meniscal injuries is apparent, as future research will provide the most appropriate treatment.


26.5 Classification of Meniscal Injuries


Several classification systems were proposed in the literature to describe meniscal tears based in their symptomatology, reparability, and type of injury. In this chapter, the International Classification introduced in 2007 will be presented [43]. This classification is based on morphologic characteristics of the tear at arthroscopy. Alternative anatomic findings have also been described [44].


26.5.1 International Classification of Meniscal Tears


The International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) Knee Committee developed a standardized international meniscal documentation system, based on morphological tear characteristics such as tear length, depth, pattern and location observed at arthroscopy [43]. Moreover, this classification system provides sufficient inter-observer reliability for pooling of data from international clinical trials designed to evaluate the outcomes of treatment for meniscal tears [45].


26.5.1.1 Tear Length


Tear length indicates the length of the meniscal tear that reaches the surface of the meniscus. It does not include contained tears (MRI grade II) that do not reach the surface of the meniscus.


26.5.1.2 Tear Depth


Tear depth mirrors the MRI classification of 0–3. A partial tear extends either through the superior or inferior surface of the meniscus, while a complete tear extends through both surfaces.


26.5.1.3 Location (Fig. 26.3)


The committee proposed a zone classification system to describe the location of the tears. Zone 1 includes tears at the menisco-synovial junction and tears with a rim width <3 mm. Zone 2 tears have a rim width of 3 to <5 mm. Zone 3 tears have a rim width >5 mm. These zones are equivalent to the red-red, red-white and white-white zone, respectively, which describes the vascular supply of the menisci. Nevertheless, vascular supply varies and cannot be evaluated arthroscopically. The meniscal tears can also be described according to their location in the anteroposterior plan as anterior, posterior or anterior and posterior tear [46]. Often a third mid body part is described [47].

A430291_1_En_26_Fig3_HTML.gif


Fig. 26.3
Different meniscal zones


26.5.1.4 Tear Pattern (Fig. 26.4)


The meniscal tears could be described in different types as follows:

A430291_1_En_26_Fig4_HTML.gif


Fig. 26.4
Types of meniscal tears


Longitudinal-Vertical Tear (Fig. 26.5a, b)

The longitudinal-vertical tear may be located anywhere along the meniscus. The extension of this tear may result in a bucket-handle tear.

A430291_1_En_26_Fig5_HTML.gif


Fig. 26.5
Arthroscopic view of meniscal tears. (a) Longitudinal, (b) bucket handle, (c) horizontal and (d) radial


Horizontal Tear (Fig. 26.5c)

The horizontal tear begins at the inner margin of the meniscus and extends towards the capsule.


Radial Tear (Fig. 26.5d)

The radial tear also begins at the inner margin and extends towards the capsule. This type is typically located at the junction of the middle and posterior third of the lateral meniscus. These tears may extend completely through the meniscal rim, transecting the meniscus.


Flap Tear

A flap tear may be either vertical or horizontal. The vertical flap tear extends through both the inferior and superior surfaces of the meniscus. In addition, the horizontal flap is an extension of the horizontal tear. Either the inferior or superior surface of the meniscus may remain intact in a horizontal flap tear.


Complex Tear

This term describes complex patterns that demonstrate tearing in several planes.


Discoid Meniscus

The discoid meniscus is a congenital variance that most of the time occurs laterally. In 1974, Watanabe [48], the father of the modern arthroscopy, classified this abnormality into three types. The incomplete discoid type is larger than a normal meniscus and has normal attachments. The complete discoid type covers the entire tibial plateau, but also maintains normal attachment. Finally, the third type of discoid meniscus lacks a posterior capsular attachment and is more often symptomatic than the other two types. Recently, Ahn et al. proposed two novel classification systems, one based on the morphological arthroscopic findings and the other based on preoperative MRI results [49, 50]. In the first, there are three types in terms of peripheral rim stability and tear site: menisco-capsular junction anterior horn type, menisco-capsular junction posterior horn type and posterolateral corner loss type. These three types require different arthroscopic techniques for repair. MRI classifies four types of discoid meniscus based on meniscal displacement secondary to a peripheral vertical tear. No shift, the peripheral portion of the discoid meniscus is not separated from the capsule, and the entire meniscus is not displaced. Anteromedially shift, the periphery of the posterior horn is detached from the capsule, and the entire meniscus is displaced anteriorly or anteromedially.

Posteromedial shift, the periphery of the anterior horn is detached from the capsule and the entire discoid meniscus is displaced posteriorly or posteromedially. Central shift, the periphery of the posterolateral portion is torn or lost, and the entire discoid meniscus is displaced centrally towards the intercondylar notch. This classification system provides more information to surgeons in choosing the appropriate treatment methods, acknowledging that the final decision regarding procedure is made during arthroscopy after thorough analysis of the tear.


26.5.2 Traumatic Lesions


By definition, traumatic tears arise as a result of a specific knee injury and may be isolated or associated with ligament or cartilage lesions. Ligament repair provides meniscal as well as cartilage integrity over time [51]. Traumatic tears generally occur in younger active patients following twisting movements with the knee in leger flexion. Two pathological conditions could be described, traumatic tears in stable or in ACL-deficient knee.


26.5.3 Degenerative Lesions (Fig. 26.6)


On the contrary, degenerative meniscal tears are slow developing lesions in older degenerative menisci and they have a more complex multifactorial pathogenesis than the traumatic meniscal tears. The prevalence of such tears in the general population increases with increasing age, ranging from 16% in knees of 50- to 59-year-old women to over 50% in the knees of men aged 70–90 years [37]. In knees with osteoarthritis, a prevalence of meniscus tear of over 90% has been reported [5254].

A430291_1_En_26_Fig6_HTML.gif


Fig. 26.6
Degenerative lateral meniscus


26.5.4 Meniscal Lesions in Children


Traumatic meniscal injuries in children are uncommon despite the constantly increasing incidence due to the higher number of sports activities. They could be either isolated or combined with ligament lesions. Most frequently, they are associated with congenital abnormalities such as the discoid or the hypermobile meniscus. Meniscal repair is recommended in children and should be considered first because of the higher potential healing compared to adults.


26.6 Management of Meniscal Injuries


Nowadays, numerous treatment options are available to manage meniscal injuries, varying from conservative treatment and meniscectomy to repair and replacement. The treatment of choice is based on the type of meniscal tear as well as on the healing potential of the index meniscus. Degenerative tears have a high prevalence in patients with early or moderate OA [55]. Most of the time, such tears are asymptomatic and a conservative treatment is indicated [56]. Nevertheless, non-operative treatment is converted to surgery in 0–30% of patients [5760]. In the case of suspected symptomatic tears, arthroscopic partial meniscectomy (Fig. 26.7) is usually performed even if there is still no evidence for its superiority compared to the conservative treatment [57, 58]. No arthroscopic surgery should be proposed for a degenerative meniscus lesion with advanced osteoarthritis on weight-bearing radiographs. As the vascular supply is fundamental to the success of meniscal repair, injuries located in the avascular zone of the meniscus have a poor prognosis of healing and therefore a partial meniscectomy is indicated [61]. However, the first goal is always to preserve as much viable tissue as possible. Meniscal repair should be the first surgical option in young patients with traumatic meniscal tears. Commonly arthroscopic management is performed and it can be divided into three groups: the inside-out technique, the outside-in technique and the all-inside (Fig. 26.8) technique all with similar failure rates [62]. Meniscectomy is acceptable only in cases of an irreparable lesion as it leads to structural degradation of the knee [4]. In the case of extensive destruction and loss of the meniscus after a meniscectomy among young patients who complain of pain on the ipsilateral compartment, a meniscal replacement procedure could be discussed. It is generally agreed that alignment and stability of the knee should be normal or corrected at the time of the surgery [63]. Allografts and meniscal scaffold are two current options to treat these sequelae, with encouraging results in a well selected patient population [6367].

A430291_1_En_26_Fig7_HTML.gif


Fig. 26.7
Partial meniscectomy for unrepairable longitudinal meniscal tear


A430291_1_En_26_Fig8_HTML.gif


Fig. 26.8
Meniscal suture with all-inside technique


26.7 Orthobiologics in Meniscus Healing


Regenerative medicine encourages natural healing in tissue reconstruction by generating conditions which promote tissue rebuilding. Current trends propose novel technologies in the field of meniscal surgery. A principal role is played by the biological augmentation which represents one of the most advanced strategies to promote tissue regeneration [68]. As a matter of fact, orthobiologics may be described as the clinical application of biologically delivered materials engineered to promote the repair or regeneration of musculoskeletal tissue [69]. This biological technology was widely used for soft tissue and cartilage injuries and it was one of the first successful procedures of tissue engineering in orthopaedics, i.e. the combination of cells, grown factors and scaffolds. Nowadays, biological applications are more and more commonplace as a treatment option for meniscal injuries in order to avoid meniscal tissue loss, to enhance meniscus healing and promote regeneration. Thus, several methods have been proposed to reach this target such as platelet-rich plasma (PRP), growth factors, stem cells, fibrin clot and gene therapy.


26.7.1 Platelet-Rich Plasma and Growth Factors (Fig. 26.9)


Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline [70], generally obtained after centrifugation of peripheral blood. Its use is gaining increased attention in many clinical applications as an autologous regenerative technology. It is based on the delivery of a pool of growth factors and cytokines with tissue healing potential [7173]. The growth factors also promote chondrogenesis and the maintenance of the phenotype of the chondrocyte could be useful in the treatment of injured cartilage or meniscus [74]. Among them, the following interesting factors have recently been identified: transforming growth factor-β1 (TGFβ1), platelet-derived growth factor bb (PDGF bb), insulin growth factor-I (IGF-I), fibroblast growth factor 2 (FGF2) and bone morphogenic protein-6. Nevertheless, the use of PRP is still highly controversial and faces regulatory constraints [75]. Although it has been widely used in a sports medicine setting aiming to enhance tissue healing [71, 76], in the case of meniscus, only a few clinical studies investigate its effect. Griffin et al. [77] analysed whether PRP augmentation at the time of meniscal repair decreases the likelihood of subsequent meniscectomy and also if PRP influences functional, clinical and patient-reported outcomes. At a minimum follow-up of 2 years, they reported similar results for both groups regarding all outcomes. On the other hand, Pujol et al. [78] reported slightly improved clinical outcomes and higher rates of meniscal healing after biological augmentation with PRP compared to a standard open meniscal repair.

A430291_1_En_26_Fig9_HTML.gif


Fig. 26.9
Platelet-rich plasma. The three layers include red blood cells in the bottom, platelet-rich plasma in the middle and platelet-poor plasma on the top


26.7.2 Mesenchymal Stem Cells


Mesenchymal stem cells (MSCs) hold great promise in regenerative medicine. They are defined as multipotent cells derived from various human tissues, including bone marrow, adipose tissue, peripheral blood and synovium. By definition, stem cells have been characterized by their ability to self-renew and due to their developmental plasticity are able to differentiate into specific therapeutic cell types. To date many experimental, preclinical and clinical studies have been established in various clinical fields such as cartilage, tendon and meniscus [79, 80]. Regarding the latter, it is also known that the molecules secreted by MSCs form a regenerative micro-environment which promotes healing [81, 82]. Matsukura et al. [83] found high levels of mesenchymal stem cells in the synovium fluid after meniscus injury compared to normal knee joints, suggesting that they may play a role in endogenous meniscal regeneration, either as direct repair cells or as a source for secretion of bioactive modulators. Regarding this potential, the exogenous application of mesenchymal stem cells could be an intriguing novel strategy in meniscal intrinsic repair. Over the last decade, there have been several animal studies investigating the effect of MSCs with encouraging results. Zellner et al. [81] reported the efficacy of mesenchymal stem cells in the repair of meniscal defects in the avascular zone. Similar results were detected by Horie et al. [84] that reported a significantly higher meniscal regeneration in a rabbit model of partial meniscectomy after implantation of synovial tissue-derived mesenchymal stem cells. They also reported that synovial mesenchymal stem cells differentiated into cells resembling meniscal fibrochondrocytes. Desando et al. [85] investigated the intra-articular adipose-derived stromal cell injection in the healing process of the menisci in an experimental rabbit model. They concluded that these cells promoted cartilage and meniscal repair and were able to attenuate inflammatory events in synovial membrane and to inhibit OA progression. However, clinical studies that have focused on using MSCs for meniscal repair are currently limited. Centeno et al. [86], in a case study, determined if isolated and expanded human autologous mesenchymal stem cells could effectively regenerate cartilage and meniscal tissue when percutaneously injected into knees. At 24 weeks post-injection, they found statistically significant cartilage and meniscus growth on MRI, as well as increased range of motion and decreased pain. Equally, Pak et al. [87], in another case study, reported the repair of a grade II meniscal tear following a percutaneous injection of autologous ASCs along with PRP, hyaluronic acid, and CaCl2. Vangsness et al. [88], in a randomized, double-blind, controlled study, investigated the safety of the intra-articular injection of human mesenchymal stem cells into the knee, the ability of mesenchymal stem cells to promote meniscus regeneration following partial meniscectomy, and the effects of mesenchymal stem cells on osteoarthritic changes in the knee. They reported evidence of meniscus regeneration and an improvement in knee pain. These results support the study of human mesenchymal stem cells for knee-tissue regeneration and protective effects. In conclusion, the use of mesenchymal stem cells seems to stimulate the regeneration of meniscal tissue and appears to be a promising approach to treat meniscal tears and defects in order to restore as much native meniscal tissue as possible. However, these regenerative technologies still need to be optimized [89].


26.7.3 Fibrin Clot


The fibrin clot has also been evaluated during the last 20 years. It seems to act as a chemotactic and mitogenic stimulus for reparative cells and to provide a scaffolding for the reparative process [32]. Several clinical studies reported good results especially for meniscal repair in the avascular zone. Henning et al. [90] described that in isolated meniscal tears the injection of an exogenous fibrin clot decreases the failure rate of meniscal repair from 41% to 8%. Van Trommel et al. [91], in a small series of five patients, used fibrin clot to enhance meniscal repair for complete radial tears in the avascular popliteal zone of the lateral meniscus. They noted that all menisci were fully healed without further signs of degeneration in second look arthroscopy. Similarly, Ra et al. [92] reported successful meniscal repair using fibrin clots in complete radial tears evaluated with MRI and second look arthroscopy. Equally, Kamimura et al. [93] found that meniscal repair of degenerative horizontal cleavage tears using fibrin clots resulted in improved clinical subjective scores, and reached a healing rate of 70% in follow-up arthroscopy. Some disadvantages of this technique are the demanding placement and the difficult preservation of the clot in the meniscal tear.


26.7.4 Gene Therapy


Gene therapy is an interesting approach that aims to provide meniscal healing through local growth factor delivery. Using ex vivo and in vivo strategies, genes have been transferred successfully to, and expressed within, numerous tissues of the musculoskeletal system, including the meniscus [94]. Various vectors have been used such as retroviral, adenoviral and adeno-associated and each of them presents peculiar characteristics [95, 96]. To date, despite several in vitro studies [9799], only a few preclinical studies have been performed on gene therapy as a treatment in meniscal injuries. Goto et al. [100] infected a monolayer culture of human and canine meniscal cells with retroviruses carrying either a human TGFβ1 cDNA or marker genes. They reported an increased synthesis of collagen and proteoglycans to the addition of TGFβ1 compared with the control group. Zhang et al. [101] investigated whether the introduction of human insulin-like growth factor 1 (hIGF-1) gene could improve the repair of full-thickness meniscal defects in the avascular zone of the anterior horn. They reported that repaired meniscal defects were filled with white tissue similar to that in normal meniscal fibrocartilage. To our knowledge, clinical trials using therapeutic gene transfer have not yet been performed. Nevertheless, we believe that the rapid evolution in this particular research area will soon provide surgeons with new treatment options.


26.7.5 Meniscal Scaffolds and Tissue Engineering


Meniscal scaffolds (Fig. 26.10) are natural or synthetic structures composed of biomaterials designed to hold physical and/or mechanical properties comparable to the native meniscus. Hence, they should provide the following important characteristics: optimal mechanical strength, biocompatibility, porosity, safe degradation and ease of use in surgical practice. Recently, meniscal replacement involving synthetic scaffolds has been proposed as an option for symptomatic knees following partial meniscectomy with the aim of improving symptoms while also potentially reducing degradation. On the one hand, the cell-free meniscal scaffolds are only used in a very selective group of patients and despite promising results, none of them has currently demonstrated regeneration of a functional, long-lasting meniscal tissue. On the other hand, biological augmentation with cells or autologous growth factors might represent a viable and effective option to improve the overall regenerative potential of meniscal scaffolds as tissue engineering, which applies the principles of biology and engineering to the development of functional substitutes for damaged tissue [102]. Although the term has been applied to a multitude of biological strategies in previous literature, it correctly refers to the addition of cells or growth factors to a scaffold with the aim of host target tissue regeneration [103].
Jul 31, 2017 | Posted by in ORTHOPEDIC | Comments Off on Current Concepts in Natural History of Meniscal Injury and Future Options in Meniscus Healing: Orthobiologics

Full access? Get Clinical Tree

Get Clinical Tree app for offline access