– Written by Peter Verdonk, Belgium and Francesco Perdisa, Italy

Meniscectomy is one of the most common procedures in orthopaedic surgery, capable of returning the knee to satisfactory functionality when a meniscal tear occurrs¹. However over the years, several concerns have arisen about its detrimental effects on the joint status in the medium- to long-term. In fact it is nowadays acknowledged that loss of meniscal tissue permanently alters knee biomechanics and homeostasis, with secondary degenerative changes to the articular cartilage and higher risk of developing symptomatic osteoarthritis (OA)². Hence, meniscus repair and substitution have gained significant interest.

Unfortunately, the effectiveness of meniscal repair strictly relies on the tissue quality and defect location with respect to the vascular supply; tears in the vascularised ‘red’ peripheral zone are more likely to heal, whereas the more common lesions in the avascular ‘white’ area have a poor chance of healing³. Meniscectomy is unavoidable in over 90% of cases.

In recent decades, meniscus substitution strategies have been developed to replace symptomatic loss of meniscal tissue. Meniscal allograft transplantation (MAT) and meniscus prostheses are suitable to replace a complete or subtotal loss of meniscal substance, while scaffolds have been developed for segmental meniscus defects.

Whereas MAT is a well-established procedure, with extensive literature highlighting the results in very long-term follow-up, the role and indication of repair, scaffolds and prosthesis remain more controversial. All these options are now available in order to save or replace damaged meniscal tissue, with the goal of providing early pain relief, healing of the damaged or absent tissue and prevention of secondary joint degeneration in the long term.

However, their effectiveness in terms of clinical improvement, as well as long-term chondroprotection can still be improved.

This narrative review aims to highlight the current state of the art in advancements in meniscal surgery.

REPAIR PROCEDURES

When surgically approaching an injured meniscus, the possibility of a repair should always be considered and several options are today available for the surgeon, from open to minimally invasive procedures.

Despite the fact that meniscal repair has become more common in recent times, the indications still remain controversial. Dehaven et al first stated the best indication for surgical repair was a tear within 2 mm of the peripheral junction⁴. Later Beaufils et al extended this cut-off to 4 mm for arthroscopic repair, provided that the tear is located into the red-red zone⁵.

Different techniques can be applied in order to perform a meniscal repair. Inside-out techniques allow most meniscal tear types and locations to be repaired with high precision. However, more recent arthroscopic all-inside techniques are now widespread due to the minor morbidity and shorter surgical time, together with comparable success rates. However, outside-in repair remains the preferred procedure for anterior horn tears⁶.

Regardless of the technique used, current repair techniques provide stability to the tear, with a 60 % complete healing rate⁷. Meniscal repair has been shown to be associated with relatively higher complications and reoperation rates (up to 22% mean at 10 years) compared to meniscectomy in the short term. While in the long term, patients showed better outcomes and less activity limitations when a repair was performed⁸.

Recent advances

Improved diagnostic tools and a thorough knowledge of biomechanics have recently drawn the attention of clinicians to particular patterns of meniscal lesions that have been misdiagnosed or underestimated in the past⁹.

First described by Strobel et al in 1988, ramp lesions involve the posteromedial menisco-capsular or menisco-synovial junction and have been reported in 9 to 40% of ACL tears, but they have been historically under-recognised during standard arthroscopy and using MRI⁹. Some authors consider these tears to have a high probability of healing, being in the red-red zone, whereas others highlighted the need for a surgical stabilisation due to the high mechanical stress the area is subject to. Thus, several techniques have been proposed for the arthroscopic repair of these lesions, either outside-in or inside-out, requiring an additional postero-medial portal, with satisfactory results being reported up to mid-term follow-up. However, nowadays the use of all-inside procedures is becoming the gold standard for the treatment of ramp lesions thanks to progress in specific surgical devices⁹.

Another clinical entity that recently came to attention is the meniscus root lesion. It consists of a radial tear of the meniscal root, with partial or complete avulsion within 9 to 10 mm from the tibial footprint¹⁰. This entity was first described in 1935 due to concomitant bone avulsion at the tibial plateau visible on X-ray, though the first modern description was in 1991¹¹. These tears can occur in either meniscus, but in 70% of the cases they are located at the posterior medial root and can be due to both traumatic or degenerative conditions¹¹. Biomechanically, the effects of posterior medial or lateral root tears have been compared to that of a total meniscectomy¹⁰, with a high risk of secondary cartilage and subchondral bone conditions¹¹ on the medial side and residual increased rotational instability on the lateral side. Currently, arthroscopic repair is the main indication for many of these lesions, depending on their type. The surgery can performed all-inside, inside-out or outside-in for partial avulsion or those close to an intact root, whereas transosseous techniques are preferred for complete root tear reinsertion¹¹. Care should be given in case of concomitant or previous ligament reconstruction in order to avoid tunnel conflicts, otherwise the use of suture anchors has also been described to overcome this issue.

While the optimal treatment of these tears is still debated, most authors report good clinical outcomes after root tear repair. However, Chung et al – in a recent meta-analysis¹² – pointed out that medial meniscal root repair, besides the clinical benefit, did not improve meniscal extrusion, nor stopped the progression of OA.

Augmentation techniques

The structural healing rate after meniscus repair has been shown to be relatively low (50 to 80%), but it improves when the repair is performed in conjunction with ACL reconstruction, probably due to growth factors (GFs) and cytokines coming into the articular space from the ACL bone tunnels. For this reason, different biologic methods have been developed in order to increase the presence of growth factors and cytokines.

Bone perforations in the notch area or vascular access channels can be created to produce intra-articular bleeding, mechanical methods such as trephination and abrasion aim at increase the vascularity at the repair site, whereas other methods involve direct growth factor delivery on-site, such as the application of synovial flaps, fibrin clots or the use of mesenchymal stem cells (MSCs)¹³.

GF-based strategies aim to enhance the limited regenerative potential related to the vascularisation pattern of the meniscus by providing angiogenic stimuli. Even though vascular endothelial growth factor is the main angiogenic GF, it is not capable of improving meniscal healing alone and a combination of GFs might be more effective¹⁴.

Platelet-rich plasma (PRP) contains a high number of proteins, cytokines and different GFs. Moreover, it can be easily obtained by a sample of autologous peripheral blood through minimal manipulation. Besides different formulations and activation methods, it can be applied as a liquid product or as a gel when it is treated with activating agents¹⁵. Unfortunately, few clinical data from low-level studies are available on PRP use for meniscal repair to date. A comparative study by Griffin et al failed to observe any benefit of PRP administration after meniscal repair, both in terms of clinical outcomes or failure rate¹⁶. Conversely, PRP administration at the end of open meniscal repair improved clinical outcomes at 24 months follow-up in a case-control study¹⁷.

MSCs can be harvested from various autologous sources (bone marrow, adipose tissue, muscle and synovium)^18,19. The rationale of using MSCs for meniscal treatment is to provide both cell precursors and their signalling activity on-site. Preclinical studies showed MSCs favour the repair of meniscal defects in the avascular zone, forming a meniscal-like tissue with extracellular matrix²⁰. Moreover, MSCs showed the ability to differentiate into meniscal fibrochondrocytes after intra-articular injection in animal models²⁰.

Nevertheless, very limited clinical evidence is available; Vangsness et al performed a randomised controlled trial reporting better improvement in pain than controls at 12 and 24 months after a single intra-articular injection of allogeneic bone marrow-derived MSCs following partial medial meniscectomy. They also found that a medium cell-dose correlated with better meniscal regeneration at MRI²¹. Pak et al investigated the safety of adipose-derived MSCs administration, with no major issues. However, they reported only a single case where injecting MSCs combined with PRP was effective for a grade II tear of the medial meniscus^22,23. Combining preclinical and preliminary clinical findings, the use of MSCs shows promising results in promoting meniscal repair or post-meniscectomy regeneration, even though there is limited clinical literature due to several translational issues still to be overcome.

REPLACEMENT

Meniscus allograft transplantation

MAT was first introduced in 1984, with the ideal indication of treating symptomatic subtotal or total meniscectomies in young to middle-aged patients, with proven clinical efficacy in the long term – even in combination with other knee procedures (ACL reconstruction, osteotomy, cartilage repair).

The re-operation rate after MAT is however relatively high, with as many as 30 to 46% of patients requiring subsequent surgery²⁵. However, it has been highlighted that most of the re-operated patients undergo surgical debridement only. Concerning functional outcomes, 76% of the patients returned to light low-impact sports in a series by Noyes et al²⁶ and most authors raise concerns against the application of MAT in active athletes²⁷.

The graft has abnormal MRI appearance in more than 75% of cases, but this feature seems not to correlate with any clinical parameter. With regard to OA progression, up to 58% of the patients showed stable features on X-ray evaluation, while a slight-to-moderate worsening was observed in the remaining ones between 5 and 15 years of follow-up. Overall survival rates after MAT were reported as 93.5% at 3 years and 95% at 5 years and 80% at 10 years in different studies²⁸.

This time-dependent trend suggest meniscus allograft might represent an effective but temporary solution for post-meniscectomy pain.

Scaffolds

Meniscus scaffolds are three-dimensional biocompatible structures, capable of supporting meniscus-like fibrocartilagineous tissue regeneration in segmental meniscus defects. Two constructs for meniscal replacement are available on the market: the first is made of bovine collagen (collagen meniscus implant: CMI®, Ivy Sports Medicine GmbH, Gräfelfing, Germany), the second more recent one, consists of a synthetic polyurethane-based material (Actifit® orteq Sports Medicine, UK)²⁹.

The indication involves a segmental symptomatic loss of meniscus tissue, with intact anterior and posterior attachments, and intact rim over the entire circumference in order to allow a stable implant fixation.

The surgical technique is similar for both the devices, involving the arthroscopic resection of the damaged tissue and subsequent implantation of a custom-sized, porous material, which is finally sutured to the meniscal rim and capsule using standard inside-out or all-inside sutures²⁹. Both the implants available for clinical use, either based on collagen or a polyurethane, showed promising short-term clinical results and stable satisfactory outcomes up to mid- or long-term evaluation. However, the MRI appearance at follow-up raised several concerns in both cases, showing the implants were reduced in size, with a hyperintense signal in most cases. On the other hand, the clinical significance of these findings is still unclear²⁹.

These scaffolds for meniscal replacement have shown to provide pain relief and symptoms improvement for the treatment of painful segmental meniscal defects. Several limitations emerged in terms of quality of the regenerated tissue and also about the hypothesised chondroprotective action³⁰. Longer term studies are necessary to fully understand the potential of these implants for wider use. Even though augmentation strategies are under investigation, several translational issues currently limit their clinical use.

Prosthesis

To this purpose, a new implant was recently conceived in order to fulfil the need for treatment of chronic middle-aged patients with a medial post-meniscectomy syndrome. NUsurface® (Active Implants Corp., Memphis, TN, USA) is a non-anatomically shaped artificial meniscus composed of reinforced polycarbonate-urethane, solely designed for medial meniscus replacement. Preliminary in-vitro experiments confirmed the ability of load distribution under static loading. A subsequent preliminary trial in a meniscectomised sheep model showed good materials properties but mild cartilage degeneration after the implantation of this device³¹.

The only report on a clinical pilot study showed close-to-normal kinematic properties in the knees of three patients after implantation³², but more extensive clinical trials are currently ongoing (trial number: NCT01712191).

CONCLUSIONS

The meniscus is a crucial player in knee homeostasis and its preservation is now considered necessary to obtain satisfactory clinical results, above all in the long-term follow-up to avoid the future onset of arthritis. Nevertheless, repair procedures result in variable outcomes. Several strategies to enhance the healing potential of the meniscus have been proposed, via the delivery of ‘factors’ or ‘agents’ to promote tissue healing, particularly in the avascular zone of the meniscus, so that many more patients might benefit from procedures aimed at the preservation of meniscal tissue. Even when a repair is impossible or failed, different innovative options are now available in order to replace damaged or lost meniscal tissue, with the aim of allowing satisfactory clinical improvement to patients and delaying the need for knee arthroplasty. However, the role of any of these procedures in terms of chondroprotection is questionable and overall long-term outcomes can still be improved.

Peter Verdonk M.D., Ph.D.

Orthopaedic Surgeon, Knee Specialist

Knee Surgery & Sports Traumatology

Antwerp Orthopaedic Centre

Antwerp University Hospital

Antwerp, Belgium

Francesco Perdisa M.D.

NAno-BIotechnology Laboratory – 1st Clinic

Rizzoli Orthopaedic Institute

Bologna, Italy

Contact: Peter.Verdonk@aspetar.com

References

1. Lyman S, Hidaka C, Valdez AS, Hetsroni I, Pan TJ, Do H et al. Risk factors for meniscectomy after meniscal repair. Am J Sports Med 2013; 41:2772-2778.
2. Heijink A, Gomoll AH, Madry H, Drobnic M, Filardo G, Espregueira-Mendes J et al. Biomechanical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 2012; 20:423-435.
3. Longo UG, Campi S, Romeo G, Spiezia F, Maffulli N, Denaro V. Biological strategies to enhance healing of the avascular area of the meniscus. Stem Cells Int 2012;2012:528359.
4. DeHaven KE, Sebastianelli WJ. Open meniscus repair. Indications, technique, and results. Clin Sports Med 1990; 9:577-587.
5. Beaufils P. [Meniscal lesions]. Rev Prat 1998; 48:1773-1779.
6. Goodwillie AD, Myers K, Sgaglione NA. Current strategies and approaches to meniscal repair. J Knee Surg 2014; 27:423-434.
7. Paxton ES, Stock MV, Brophy RH. Meniscal repair versus partial meniscectomy: a systematic review comparing reoperation rates and clinical outcomes. Arthroscopy 2011; 27:1275-1288.
8. Xu C, Zhao J. A meta-analysis comparing meniscal repair with meniscectomy in the treatment of meniscal tears: the more meniscus, the better outcome? Knee Surg Sports Traumatol Arthrosc 2015; 23:164-170.
9. Chahla J, Dean CS, Moatshe G, Mitchell JJ, Cram TR, Yacuzzi C et al. Meniscal ramp lesions: anatomy, incidence, diagnosis, and treatment. Orthop J Sports Med 2016; 4:2325967116657815 [Epub].
10. Allaire R, Muriuki M, Gilbertson L, Harner C D. Biomechanical consequences of a tear of the posterior root of the medial meniscus. Similar to total meniscectomy. J Bone Joint Surg Am 2008; 90:1922-1931.
11. LaPrade RF, Matheny LM, Moulton SG, James EW, Dean CS. Posterior meniscal root repairs: outcomes of an anatomic transtibial pull-out technique. Am J Sports Med 2017l; 45:884-891.
12. Chung KS, Ha JK, Ra HJ, Kim JG. A meta-analysis of clinical and radiographic outcomes of posterior horn medial meniscus root repairs. Knee Surg Sports Traumatol Arthrosc 2016; 24:1455-1468.
13. Moran CJ, Busilacchi A, Lee CA, Athanasiou KA, Verdonk PC. Biological augmentation and tissue engineering approaches in meniscus surgery. Arthroscopy 2015; 31:944-955.
14. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004; 25:581-611.
15. Eppley BL, Woodell JE, Higgins J Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg 2004; 114:1502-1508.
16. Griffin JW, Hadeed MM, Werner BC, Diduch DR, Carson EW, Miller MD. Platelet-rich plasma in meniscal repair: does augmentation improve surgical outcomes? Clin Orthop Relat Res 2015; 473:1665-1672.
17. Pujol N, Salle De Chou E, Boisrenoult P, Beaufils P. Platelet-rich plasma for open meniscal repair in young patients: any benefit? Knee Surg Sports Traumatol Arthrosc 2015; 23:51-58.
18. Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell 2011; 9:11-15.
19. Filardo G, Madry H, Jelic M, Roffi A, Cucchiarini M, Kon E. Mesenchymal stem cells for the treatment of cartilage lesions: from preclinical findings to clinical application in orthopaedics. Knee Surg Sports Traumatol Arthrosc 2013; 21:1717-1729.
20. Korpershoek JV, de Windt TS, Hagmeijer MH, Vonk LA, Saris DB. Cell-based meniscus repair and regeneration: at the brink of clinical translation?: A systematic review of preclinical studies. Orthop J Sports Med 2017; 5:2325967117690131 [Epub].
21. Vangsness CT Jr, Farr J II, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am 2014; 96:90-98.
22. Pak J, Chang JJ, Lee JH, Lee SH. Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints. BMC Musculoskelet Disord 2013; 14:337.
23. Pak J, Lee JH, Lee SH. Regenerative repair of damaged meniscus with autologous adipose tissue-derived stem cells. Biomed Res Int 2014; 2014:436029.
24. Verdonk R, Van Daele P, Claus B, Vandenabeele K, Desmet P, Verbruggen G et at. [Viable meniscus transplantation]. Orthopade 1994; 23:153-159.
25. Verdonk R, Volpi P, Verdonk P, Van der Bracht H, Van Laer M, Almqvist KF et al. Indications and limits of meniscal allografts. Injury 2013; 44(suppl 1):S21-S27.
26. Noyes FR, Barber-Westin SD. Long-term survivorship and function of meniscus transplantation. Am J Sports Med 2016; 44:2330-2338.
27. Rosso F, Bisicchia S, Bonasia DE, Amendola A. Meniscal allograft transplantation: a systematic review. Am J Sports Med 2015; 43:998-1007.
28. Verdonk PC, Demurie A, Almqvist KF, Veys EM, Verbruggen G, Verdonk R. Transplantation of viable meniscal allograft. Survivorship analysis and clinical outcome of one hundred cases. J Bone Joint Surg Am 2005; 87:715-724.
29. Filardo G, Andriolo L, Kon E, de Caro F, Marcacci M. Meniscal scaffolds: results and indications. A systematic literature review. Int Orthop 2015; 39:35-46.
30. Zaffagnini S, Grassi A, Marcheggiani Muccioli GM, Bonanzinga T, Nitri M, Raggi F et al. MRI evaluation of a collagen meniscus implant: a systematic review. Knee Surg Sports Traumatol Arthrosc 2015; 23:3228-3237.
31. Zur G, Linder-Ganz E, Elsner JJ, Shani J, Brenner O, Agar G et al. Chondroprotective effects of a polycarbonate-urethane meniscal implant: histopathological results in a sheep model. Knee Surg Sports Traumatol Arthrosc 2011; 19:255-263.
32. De Coninck T, Elsner JJ, Linder-Ganz E, Cromheecke M, Shemesh M, Huysse W et al. In-vivo evaluation of the kinematic behavior of an artificial medial meniscus implant: a pilot study using open-MRI. Clin Biomech (Bristol, Avon) 2014; 29:898-905.