(v) Meniscal allograft transplantation and meniscal scaffolds; where are we up to now?

MINI-SYMPOSIUM: SOFT TISSUE KNEE e CURRENT CONCEPTS

(v) Meniscal allograft transplantation and meniscal scaffolds; where are we up to now?

Meniscal function Menisci are found in all mammals, although there is variation their shape and attachments.1 The primary role of the menisci is to distribute load evenly across the knee. This is achieved by the concave upper surface and flat lower surface increasing the congruency of the tibio-femoral articulations. In the loaded knee, the lateral meniscus transmits 70% and the medial meniscus transmits 50% of the load through the respective compartments. Biomechanical studies have shown that meniscectomy decreases the tibio-femoral contact area by 50e75% and increases the peak contact pressure by 200e300%.2,3 The menisci have also been shown to facilitate joint lubrication, proprioception and secondary constraint for the knee.4

Nick A Smith Ben Parkinson Tim Spalding

Abstract Consequences of meniscal loss

The meniscus has an important function in protecting the joint surfaces within its compartment whilst facilitating joint lubrication and contributing to stability of the knee. It is now well recognized that meniscal loss leads to degenerative change. This paper details the options to reconstruct the meniscus. While the evidence is not conclusive for a chondroprotective effect, there is growing evidence that meniscal reconstruction gives significant functional and symptomatic improvement. Meniscal scaffolds are indicated for segmental loss of meniscal tissue, and provide a framework for regeneration of tissue. Two types are in current use, and medium-to long-term results indicate efficacy and durability, provided that strict indications are followed. Meniscal allograft transplantation has been around for over 30 years, with an evolution in technique from open surgery to arthroscopicassisted methods. Graft complications are low with advances in tissue bank provision and infection control. Analysis of patient-reported outcomes show maintenance of clinical benefit in the long-term, recognizing an early failure rate of approximately 10% in the first 18 months. Indications for transplantation are being extended as results improve, with combined surgery involving ligament reconstruction, osteotomy and cartilage repair. Meniscal scaffolds and meniscal allograft transplantation should no longer be considered ‘experimental’, and further research on evaluating the chondroprotective effect is awaited.

Meniscal tears are common injuries, with a yearly incidence of between 35 and 61 per 100,000 population.5,6 Historically, total menisectomy was a common procedure for a meniscal tear. As the importance of the menisci became better understood, there has been a shift towards meniscal preserving surgery whenever possible. The consequences of meniscectomy are well documented. Papalia et al. performed a systematic review looking at risk factors for osteoarthritis (OA) after the surgical management of meniscal tears in studies with a follow-up of 5e30 years.7 They identified 4642 patients in 32 studies, with a mean prevalence of knee OA of 53.5% (range 16e92.9%). When comparing radiological diagnoses of OA, the mean prevalence in the operated group was 39.5% compared to the contralateral (control) limb of 6.46%. They also found a higher incidence of OA following lateral compared to medial meniscectomy and in total compared to partial meniscectomy. Despite the trend change, more often than not it is not possible to preserve a torn meniscus. Even in those menisci that are repaired, approximately 20% will fail and require secondary meniscectomy.8 Currently, there is little evidence that acute prophylactic meniscal reconstruction is beneficial. Therefore, meniscal reconstruction should only be considered in symptomatic patients after a minimum of six months of appropriate rehabilitation following the meniscal loss. Figure 1 shows the decision making process for these patients. It is thought that symptoms are caused by an overloading (or abnormal loading) of the affected compartment, which can be corrected by meniscal reconstruction.3,9

Keywords meniscal allograft transplantation; meniscal scaffold; meniscectomy; meniscus

Meniscal scaffolds Meniscal scaffolds were introduced in the early nineties to combat the deleterious effects of partial meniscal deficiencies. The aim of a meniscal scaffold is to provide a structure that allows ingrowth of meniscus-like tissue. There are currently two scaffolds used in Europe:

Nick A Smith MSc MRCS BMBS BMedSci ST5 (SpR) CSRL, Clinical Sciences Building, Coventry, UK, University of Warwick. Conflicts of interest: none declared. Ben Parkinson FRACS (Ortho) MBBS Consultant, University Hospitals Coventry and Warwickshire, Secretary to Mr Tim Spalding, 5th Floor Orthopaedic Offices, University Hospitals Coventry and Warwickshire, Coventry, UK. Conflicts of interest: none declared.

Collagen Meniscus Implant (CMIÒ) The Collagen Meniscus Implant (Ivy Sports Medicine GmbH, Gr€afelfing, Germany) was the first meniscal scaffold used for the treatment of partial meniscal deficiency. It was known as the CMI and has also been called Menaflex, before recently reverting to its original name of Collagen Meniscal Implant. It consists of

Tim Spalding FRCS Orth MBBS Consultant, University Hospitals Coventry and Warwickshire, 5th Floor Orthopaedic Offices, University Hospitals Coventry and Warwickshire, Coventry, UK. Conflicts of interest: none declared.

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Please cite this article in press as: Smith NA, et al., (v) Meniscal allograft transplantation and meniscal scaffolds; where are we up to now?, Orthopaedics and Trauma (2014), http://dx.doi.org/10.1016/j.mporth.2014.12.003

MINI-SYMPOSIUM: SOFT TISSUE KNEE e CURRENT CONCEPTS

Symptomatic meniscal deficient knee?

Intact anterior and posterior attachments AND Intact meniscal rim?

No

raft Meniscal allograft n transplantation

Yes

Ligament instability? Malalignment? Cartilage ICRS grade 3b or worse?

Meniscal scaffold

Yes

Additional surgery (staged or simultaneous) Ligament reconstruction Osteotomy Articular cartilage procedure Figure 1 Flow diagram for meniscal reconstruction decision making.

must be intact anterior and posterior horns, to allow stable fixation of the implant to host tissue. Sufficient meniscus should be missing to be considered as the cause of symptoms and to justify further resection to the vascular meniscal rim. Effectively, this means that scaffolds are indicated if a third or less of the meniscal width remains. The meniscal rim should be intact to support the hoop stress of the meniscus as the implant does not have circumferential continuity. If the meniscal rim is deficient or is extruded outside the joint margin then the implant is contraindicated, as it will not provide the required support. The articular surfaces should be International Cartilage Repair Society (ICRS) Grade 2 or less. ICRS Grade 3a, where the chondral loss is more than 50% thickness, may be suitable if the area is relatively small. However, if the surface is worn to the calcified layer (ICRS 3b) or there are bare bone surfaces exposed, it is likely to be too abrasive to the scaffold and compromise regeneration potential. Implantation can be combined with cartilage repair procedures but the result of such combination is unclear.

purified bovine type I collagen (Achilles tendon) and a small amount of glycosaminoglycan, forming a defined stable matrix scaffold. As it is the oldest scaffold, there are significantly more studies assessing its safety, chondral effects and efficacy. Biopsies have shown that it is extensively reabsorbed by 12e18 months and replaced by fibrocartilaginous tissue.10 Actifit Actifit (Orteq, London, UK) is a synthetic scaffold consisting of 80% biodegradable polyester (poly-caprolactone) and 20% polyurethane (Figure 2). The polyester portion is designed to provide elasticity and control degradation, whilst the polyurethane is designed to provide mechanical strength. This makes the Actifit stiffer than the Collagen Meniscus Implant, with easier handling characteristics for insertion. It was extensively tested in animal models before introduction and clinical use.11 Indications Meniscal scaffolds are indicated in patients who have persistent symptoms of activity-related pain or swelling following partial meniscectomy. Patients should have had symptoms for at least six months before considering reconstruction, with the level of symptoms including pain interfering with work, light sport or activities of daily living. There is no supportive evidence at present for reconstruction at the time of initial partial menisectomy.12 As scaffolds are for partial meniscal defects or segmental loss, specific criteria need to be met at the time of surgery. There

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Surgical technique Although both scaffolds are different in construction, the surgical techniques are identical. First, the meniscus is prepared by trimming the remaining tissue to give a rectangular defect within the healthy meniscal tissue (Figure 3a). The vascularized outer zone of the meniscus should be reached, leaving a bleeding meniscal rim to allow tissue ingrowth and cell colonization of the scaffold. It is crucial that the outer 2 mm of the meniscal rim is

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MINI-SYMPOSIUM: SOFT TISSUE KNEE e CURRENT CONCEPTS

c). Fixation is achieved using a combination of different meniscal repair methods, depending on the surgeon’s experience (Figure 3d). Usually, all-inside suture systems are used, inserted from the ipsilateral portal for the posterior horn and the opposite portal for the anterior sutures, to ensure perpendicular access. For best capture of the meniscal tissue, sutures are inserted in a horizontal configuration. Post-operatively, patients follow a strict program involving a graduated return to flexion and weight-bearing over an 8-week period, as detailed by guidelines for each product. By 3 months patients should have full flexion and be walking on the flat without the knee swelling. Running and impact joint loading activities are avoided for 6 months, before building up to full pivoting activities at 9 months at the earliest. Full maturity of the implant develops over an 18e24-month period. Clinical outcomes There are more studies that have assessed the efficacy of Collagen Meniscus Implant than the Actifit, because the CMI has been in use for longer. A recent systematic review found a total of 624 patients across 15 studies (two RCTs and 13 case series) that had been assessed after receiving scaffolds.13 Of these 15 studies, 12 had used Collagen Meniscus Implants, two had used the Actifit and one study had compared both scaffolds. The mean age at the time of surgery was 37 years (range 16e67) across all studies. They found that 13 studies concluded that meniscal scaffolds resulted in improved outcomes for patients. They also found that the failure rate was 10.25%, and a severe implantrelated complication rate was observed in 5.25%. They also found that histological analysis of Collagen Meniscus Implant

Figure 2 Medial and lateral Actifit scaffolds. Legend. Photo courtesy of Orteq Sports Medicine.

not compromised, as a complete radial defect in the meniscus causes a loss in the circumferential collagen fibres and is a contraindication to scaffold reconstruction. The length of the defect is measured and the implant is cut (10% oversized) and manipulated into place through an enlarged portal (Figure 3b and

Figure 3 Meniscal scaffold technique arthroscopy pictures. (a). Meniscal defect prepared. (b). Meniscal defect measured. (c). Meniscal scaffold inserted. (d). Meniscal scaffold sutured in place.

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Please cite this article in press as: Smith NA, et al., (v) Meniscal allograft transplantation and meniscal scaffolds; where are we up to now?, Orthopaedics and Trauma (2014), http://dx.doi.org/10.1016/j.mporth.2014.12.003

MINI-SYMPOSIUM: SOFT TISSUE KNEE e CURRENT CONCEPTS

chondral loss (Outerbidge IV or ICRS 3b or 3c), but recently surgeons have accepted a higher failure rate in such patients and have combined transplantation with articular cartilage repair techniques. It is the authors’ experience that patients with severe chondral loss can still benefit from meniscal allograft transplantation, but have a higher risk of graft failure. The upper age limit for meniscal allograft transplantation is usually 50e55 years of age, although most case series usually only define their patients’ ages as ‘young’.20

scaffolds showed new ‘meniscus-like’ tissue had formed, with extensive reabsorption of the scaffold. However, the two studies that did not show improvements were both RCTs. One RCT was on a selected cohort with varus alignment, comparing high tibial osteotomy (HTO) alone to HTO plus Collagen Meniscus Implant.14 The numbers in this study were small and there was a high drop-out rate in the comparator group. The second RCT had 311 participants and had two participant groups: chronic meniscal deficiency (prior partial meniscectomy) and acute meniscal deficiency (no previous surgery).12 The follow-up was 7 years, and they found that the chronic group treated with Collagen Meniscus Implants had improved outcomes compared to partial meniscectomy, but the acute group did not. In 2012 the National Institute for Health and Care Excellence (NICE) published guidelines on partial meniscal replacement using a biodegradable scaffold (NICE guideline IPG430). They noted that there were no safety concerns over scaffolds but that the evidence for meniscal scaffolds was limited in quantity. They therefore advised that further research was required and that surgeons should only undertake the procedure with special permissions.

Surgical technique In the early days of meniscal allograft transplantation, surgeons used an open approach with detachment of the affected compartment’s collateral ligament or use of a joint distractor.21 This has been largely superceded by arthroscopically-assisted or allarthroscopic techniques.20 The meniscus is fixed at the roots (anterior and posterior horns) as well as rim fixation to the capsule peripherally using a combination of meniscal repair techniques. There are two main methods of meniscal root fixation: bone bridge/plug techniques and suture fixation through bone tunnels. The bone bridge/plug fixation is the more common technique, with a recent systematic review showing that over two thirds of transplants had a bony fixation.20 The perceived advantages of a bone fixation are a slight improvement in contact mechanics in biomechanical studies and less meniscal extrusion. However, no differences in patient-reported outcome measures (PROMs) or pull-out strength have been shown.22 Potential advantages of an all-suture technique without bone plugs are that it is a more minimally invasive and less complicated technique. It may also have histological advantages, as significantly higher cellular viability and collagen organization was found on biopsy of grafts secured by an all suture technique compared to bone plug fixation.23 Ultimately, there is no clear consensus about which technique is superior, and it is likely that the techniques are comparable as long as the roots are fixed securely in the appropriate position. The authors favour an arthroscopic all-suture technique via bone tunnels. This involves dissecting the meniscus off the donor tibial plateau and preparing each end with non-absorbable sutures. The sutures are then led through bone tunnels in the prepared meniscal root insertion sites (Figure 4). The graft is passed into the knee through a working portal and fixed in place with multiple stacked vertical mattress sutures using a combination of all-inside devices and inside-out sutures tied over the capsule, as per standard meniscal repair techniques. The sutures for the anterior and posterior roots are tied over a bone bridge on the proximal tibia. Figure 5 (a, b and c) shows a lateral compartment before and after allograft insertion and at 1 year post-operatively.

Meniscal allograft transplantation Meniscal allograft transplantation began to emerge in the 1980’s, with the implantation of medial meniscal allografts in dogs.15 This showed for the first time that a completely detached meniscus could be implanted successfully. They also showed that the preservation technique was important; the tissue culture preservation group did considerably better than the gluteraldehyde group. In 1989, Milachowski, Weismeier and Wirth reported a series of meniscal transplantations in 30 sheep, and then in 22 patients.16 This group performed the first human meniscal allograft transplantation in May 1984, although they were originally performed for protection of anterior cruciate ligament (ACL) reconstructions. Since the first reported human meniscal transplantation, there have been thousands of transplants performed worldwide. In 2003 it was estimated that over 4000 transplantations had been performed in the USA alone.17 In a consensus meeting amongst Danish surgeons, it was estimated that the yearly need for meniscal allograft transplantations in Denmark was between 10 and 50 (population of 5 million).18 Although not directly comparable, extrapolating these figures would give a yearly need for between 126 and 630 meniscal transplants in the UK and between 628 and 3139 in the USA. Indications The prime indication for meniscal allograft transplantation is to treat a symptomatic compartment of the knee with a history of a (sub)total meniscectomy. The classical symptom is compartmental pain with activity, although swelling can also be a feature. Malalignment, ligament instability and chondral deficiency should be corrected concomitantly. Worse outcomes have been reported without these corrections.19 The acceptable degree of chondral loss is controversial, but the presence of full thickness chondral loss results in a poor local mechanical environment for the meniscal transplant to survive. Traditionally, meniscal transplantation was contraindicated in the presence of

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Biomechanical studies A number of biomechanical studies have been performed comparing the load sharing ability of meniscal allografts with the native meniscus, as well as a knee with no meniscus. In 1997, Paletta et al. used young human cadaveric knees to test the total contact area and peak contact pressure changes following meniscectomy and then after subsequent allograft transplantation.24 They found that the total contact area decreased by 45e50% following meniscectomy and then increased by 42

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McDermott el al. reported a human cadaveric study comparing the native knee with an all suture allograft fixation, a bone plug fixation and meniscectomy.3 They found that both the bone plug technique (p ¼ 0.0029) and the all suture technique (p ¼ 0.0199) of allograft fixation significantly reduced peak contact pressures compared to menisectomy. They also found that the peak contact pressures of the knees with meniscal allografts (either technique) were not significantly different to the native knee. These results support the hypothesis that a meniscal allograft functions in a similar way to a native meniscus. However, there are limitations to the application of these cadaveric results to patients, and in living patients the meniscus is subject to a different immunological, biochemical and biomechanical environment. Clinical outcomes Despite the fact that meniscal allograft transplantation has been performed for over 30 years now, there have been no RCTs. Therefore, the best estimate of efficacy comes from pooled results of case series. A recent systematic review reported that the mean weighted Lysholm score (score 0 to 100, with 100 being the best) improved from 56 pre-operatively to 83 at final follow-up, with a mean follow-up of 5.1 years.20 Other PROMs also showed similar levels of improvement, including Tegner and International Knee Documentation Committee (IKDC) subjective knee scores.

Figure 4 Meniscal allograft with its prepared meniscal root sutures coming through the bone tunnels, prior to insertion in the knee.

e65% after allograft transplantation (compared with meniscectomy scores) at all knee flexion angles. They also found that peak contact pressures increased by 235e335% following meniscectomy, and were decreased by 55e65% after allograft transplantation (compared with meniscectomy scores) at all knee flexion angles. The improvements following transplantation did not, however, reach the level of the native knee. More recently,

Figure 5 Lateral meniscal transplantation arthroscopy pictures. (a). Lateral compartment before the allograft insertion. (b). Intra-operative picture after the allograft insertion. (c). One year post-operative arthroscopic picture of the same knee.

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Further controversies, including graft preservation methods and meniscal root fixation techniques, should also be addressed with prospective comparative studies.

Allowing a return to full sporting activities following meniscal allograft transplantation is controversial. Cycling and then running is generally permitted at 3e6 months post-operatively, whilst return to pivoting sports is usually not recommended. Some patients will return to high-risk activities, and they simply need to be counselled extensively about the associated long-term risks of this.20 Pooled complication rates for isolated meniscal transplantation have ranged from 6 to 11%, although this is likely to significantly underestimate the true complication rate, as followup in some studies did not appear to be comprehensive.19,25 One recently published large study (200 patients) found a 32% reoperation rate following meniscal allograft transplantation, with the majority of cases being just a simple debridement.26 The average graft survival time has been reported to be between 10 and 16 years.27e29 Disease transmission and immune rejection are possible complications of meniscal allograft transplantation, although these are extremely rare. There has only been one reported case of possible rejection reported in the literature.30

Conclusion The deleterious long-term consequences of menisectomy are now well known. It is evident from the low baseline PROMs that patients undergoing meniscal reconstruction have a significant disease burden, especially when considering their young age. Meniscal reconstruction techniques have been shown to provide significant symptomatic benefit to patients, but we must wait for more methodologically sound studies to be able to definitively answer and quantify the long-term chondroprotective benefits. A REFERENCES 1 Messner K, Gao J. The menisci of the knee joint. Anatomical and functional characteristics, and a rationale for clinical treatment. J Anat 1998; 193(Pt 2): 161e78. 2 Baratz M, Fu F, Mengato R. Meniscal tears: the effect of meniscectomy and of repair on intraarticular contact areas and stress in the human knee. Am J Sports Med 1986; 14: 270e4. 3 McDermott I, Lie D, Edwards A, Bull A, Amis A. The effects of lateral meniscal allograft transplantation techniques on tibio-femoral contact pressures. Knee Surg Sports Traumatol Arthrosc 2008; 16: 553e60. 4 Levy IM, Torzilli PA, Gould JD, Warren RF. The effect of lateral meniscectomy on motion of the knee. J Bone Joint Surg Am 1989; 71: 401e6. 5 Baker BE, Peckham AC, Pupparo F, Sanborn JC. Review of meniscal injury and associated sports. Am J Sports Med 1985; 13: 1e4. 6 Jameson SS, Dowen D, James P, Serrano-Pedraza I, Reed MR, Deehan DJ. The burden of arthroscopy of the knee: a contemporary analysis of data from the English NHS. J Bone Joint Surg Br 2011; 93: 1327e33. 7 Papalia R, Del Buono A, Osti L, Denaro V, Maffulli N. Meniscectomy as a risk factor for knee osteoarthritis: a systematic review. Br Med Bull 2011; 99: 89e106. 8 Nepple JJ, Dunn WR, Wright RW. Meniscal repair outcomes at greater than five years: a systematic literature review and meta-analysis. J Bone Joint Surg Am 2012; 94: 2222e7. 9 Waller C, Hayes D, Block JE, London NJ. Unload it: the key to the treatment of knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2011; 19: 1823e9. 10 Grassi A, Zaffagnini S, Marcheggiani Muccioli GM, Benzi A, Marcacci M. Clinical outcomes and complications of a collagen meniscus implant: a systematic review. Int Orthop 2014; 38: 1945e53. 11 Tienen TG, Heijkants RG, Buma P, De Groot JH, Pennings AJ, Veth RP. A porous polymer scaffold for meniscal lesion repairea study in dogs. Biomaterials 2003; 24: 2541e8. 12 Rodkey WG, DeHaven KE, Montgomery 3rd WH, et al. Comparison of the collagen meniscus implant with partial meniscectomy. A prospective randomized trial. J Bone Joint Surg Am 2008; 90: 1413e26. 13 Papalia R, Franceschi F, Diaz Balzani L, D’Adamio S, Maffulli N, Denaro V. Scaffolds for partial meniscal replacement: an updated systematic review. Br Med Bull 2013; 107: 19e40.

Graft type There are a number of graft preservation techniques, of which fresh frozen and cryopreserved are most common. Lyophilized and irradiated grafts have historically been used but these techniques have been shown to cause graft shrinkage.22 Cryopreservation is done in the hope of maintaining the integrity of the allograft with some viable cells; however, it has not been shown to be definitively better than other techniques.31 Cryopreservation also requires strict thawing protocols, which are difficult to achieve in the operating theatre. There has therefore been a trend change towards using fresh frozen allografts.20

Chondroprotection There is currently little definitive evidence to show that meniscal allograft transplantation is chondroprotective in humans. Although there are a number of animal model studies that have shown encouraging results in RCTs, similar studies have not been performed in humans to-date. Sekiya et al. compared joint space changes following meniscal allograft transplantation to the contralateral limb, finding no significant differences between the groups,32 but other studies have shown joint space loss following surgery. It is scientifically plausible that meniscal allograft transplantation is chondroprotective, but without definitive evidence this cannot be a claimed benefit. It is therefore for this reason that meniscal allograft transplantation is not indicated as a prophylactic treatment for asymptomatic meniscal deficiency.

Future research The two fundamental research questions are whether meniscal reconstruction improves PROMs and whether it is chondroprotective, when compared to a control treatment strategy. There are currently no meniscal allograft transplantation RCTs that provide definitive evidence for its efficacy, although case series have consistently shown a sustained improvement in PROMs in the short and medium term. The authors are currently undertaking a pilot RCT using articular cartilage volume changes as the primary outcome measure, with the hope of beginning to determine whether meniscal allograft transplantation is chondroprotective.

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14 Linke RD, Ulmer M, Imhoff AB. [Replacement of the meniscus with a collagen implant (CMI)]. Oper Orthop Traumatol 2006; 18: 453e62. 15 Canham W, Stanish W. A study of the biological behavior of the meniscus as a transplant in the medial compartment of a dog’s knee. Am J Sports Med 1986; 14: 376e9. 16 Milachowski KA, Weismeier K, Wirth CJ. Homologous meniscus transplantation. Experimental and clinical results. Int Orthop 1989; 13: 1e11. 17 Sgaglione NA, Steadman JR, Shaffer B, Miller MD, Fu FH. Current concepts in meniscus surgery: resection to replacement. Arthroscopy 2003; 19(suppl 1): 161e88. 18 Backer M, Buhl A, Jakobsen B, et al. Consensus declaration regarding meniscus transplantation. Consensus Conference on Meniscal Transplantation in Denmark. Bispebjerg, Copenhagen, Denmark: Copenhagen University Hospital, 1998. 19 Rosso F, Bisicchia S, Bonasia DE, Amendola A. Meniscal allograft transplantation: a systematic review. Am J Sports Med 2014 [Epub ahead of print]. 20 Smith NA, MacKay N, Costa M, Spalding T. Meniscal allograft transplantation in a symptomatic meniscal deficient knee: a systematic review. Knee Surg Sports Traumatol Arthrosc 2014 [Epub ahead of print]. 21 Cameron JC, Saha S. Meniscal allograft transplantation for unicompartmental arthritis of the knee. Clin Orthop Relat Res 1997; 337: 164e71. 22 Samitier G, Alentorn-Geli E, Taylor DC, et al. Meniscal allograft transplantation. Part 1: systematic review of graft biology, graft shrinkage, graft extrusion, graft sizing, and graft fixation. Knee Surg Sports Traumatol Arthrosc 2014 [Epub ahead of print]. 23 Rodeo SA, Seneviratne A, Suzuki K, Felker K, Wickiewicz TL, Warren RF. Histological analysis of human meniscal allografts. A preliminary report. J Bone Joint Surg Am 2000; 82-A: 1071e82. 24 Paletta Jr GA, Manning T, Snell E, Parker R, Bergfeld J. The effect of allograft meniscal replacement on intraarticular contact area and pressures in the human knee. A biomechanical study. Am J Sports Med 1997; 25: 692e8.

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25 Elattar M, Dhollander A, Verdonk R, Almqvist K, Verdonk P. Twenty-six years of meniscal allograft transplantation: is it still experimental? A meta-analysis of 44 trials. Knee Surg Sports Traumatol Arthrosc 2011; 19: 147e57. 26 McCormick F, Harris JD, Abrams GD, et al. Survival and reoperation rates after meniscal allograft transplantation: analysis of failures for 172 consecutive transplants at a minimum 2-year follow-up. Am J Sports Med 2014; 42: 892e7. 27 Stone KR, Adelson WS, Pelsis JR, Walgenbach AW, Turek TJ. Longterm survival of concurrent meniscus allograft transplantation and repair of the articular cartilage: a prospective two- to 12-year followup report. J Bone Joint Surg Br 2010; 92: 941e8. 28 van der Wal RJP, Thomassen BJW, van Arkel ERA. Long-term clinical outcome of open meniscal allograft transplantation. Am J Sports Med 2009; 37: 2134e9. 29 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: 715e24. 30 Hamlet W, Liu SH, Yang R. Destruction of a cryopreserved meniscal allograft: a case for acute rejection. Arthroscopy 1997; 13: 517e21. 31 McDermott ID. What tissue bankers should know about the use of allograft meniscus in orthopaedics. Cell Tissue Bank 2010; 11: 75e85. 32 Sekiya JK, Giffin JR, Irrgang JJ, Fu FH, Harner CD. Clinical outcomes after combined meniscal allograft transplantation and anterior cruciate ligament reconstruction. Am J Sports Med 2003; 31: 896e906.

Acknowledgements This paper was supported by Arthritis Research UK (grant number 20149).

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Please cite this article in press as: Smith NA, et al., (v) Meniscal allograft transplantation and meniscal scaffolds; where are we up to now?, Orthopaedics and Trauma (2014), http://dx.doi.org/10.1016/j.mporth.2014.12.003