Meniscal scaffolds: Early experience and review of the literature

The Knee 19 (2012) 760–765

Contents lists available at SciVerse ScienceDirect

The Knee

Meniscal scaffolds: Early experience and review of the literature S.J. Spencer ⁎, A. Saithna, M.R. Carmont, M.S. Dhillon, P. Thompson, T. Spalding University Hospital Coventry and Warwickshire NHS Trust

a r t i c l e

i n f o

Article history: Received 23 November 2011 Received in revised form 24 January 2012 Accepted 25 January 2012 Keywords: Meniscal scaffold Actifit Menaflex Meniscectomy Meniscal reconstruction

a b s t r a c t Introduction: Meniscal scaffold implants support the in-growth of new "meniscus like" tissue with the aim of alleviating post-meniscectomy knee pain and preventing further articular cartilage degeneration. Patients and methods: Twenty-three patients underwent meniscal scaffold implantation (14 medial, 9 lateral) with either the Menaflex (ReGen Biologics) (n = 12) or Actifit (Orteq) (n = 11) scaffolds. Minimum followup was 1 year with a mean of 24.1 months (18–27) for the Menaflex and 14.7 months (12–18) for the Actifit groups. Mean age at surgery was 35 years (17–47) with a mean Outerbridge grade of 1.9 in the affected compartment. Eight (36%) underwent concurrent osteotomy, ligament reconstruction or microfracture of the tibial plateau. KOOS, Lysholm, Tegner activity and IKDC scores were collected pre-operatively and at sixmonth interval post-surgery. Assessment of the reconstruction was obtained with MRI scanning and arthroscopy. One scaffold tore and was revised at 19 months post-operatively. Results: Twenty-one out of 23 (91.3%) had a significant improvement in knee scores when compared to presurgery levels at latest follow-up. Second-look arthroscopy in 14 at 1-year post-implantation showed variable amounts of regenerative tissue. There was no progression in chondral wear noted on repeat MRI scanning. Conclusion: Treatment with meniscal scaffold implants can provide good pain relief for the post-meniscectomy knee following partial meniscectomy. Longer follow-up is required to ascertain whether they also prevent the progressive chondral wear associated with a post-meniscectomy knee. © 2012 Elsevier B.V. All rights reserved.

1. Introduction The menisci have a key role in providing shock absorption, force transmission and load distribution across the knee joint. Furthermore they aid with joint stability, lubrication, congruence, nutrition and proprioception [1,2]. However arthroscopic meniscectomy remains the most commonly performed orthopaedic procedure in Europe and the US [3]. It is known that complete or partial meniscectomy predisposes the knee to degenerate joint disease [4–7] and therefore it would seem logical to try to preserve injured meniscal tissue by repair, reconstruction or replacement. While Meniscal Allograft Transplantation (MAT) is an option for complete meniscus replacement following total or near total meniscectomy [3,8], it is not appropriate following partial resection. In this situation meniscal scaffold implants offer an option for reconstructive surgery if the peripheral meniscal rim is intact and there is sufficient anterior and posterior horn tissue present for attachment. They avoid the theoretical risk of immune response or disease transmission from an allograft meniscus [9] and as they are simply cut to ⁎ Corresponding author at: Consultant Orthopaedic Surgeon, Southern General Hospital, 1345 Govan Road, Glasgow, G51 4TF, United Kingdom. Tel.: + 44 0141 232 7912; fax: + 44 0141 201 1155. E-mail address: [email protected] (S.J. Spencer). 0968-0160/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.knee.2012.01.006

size at the time of surgery an “off the shelf” implant can be used with no need to wait for a size matched allograft to become available. There are two commercially available scaffold options for reconstruction of segmental meniscal defects: the Menaflex (ReGen Biologics, USA) formally the Collagen Meniscus Implant (CMI) and the Actifit (Orteq). Both act as scaffolds to induce vascular in-growth and consist of degradable porous material [10]. The Menaflex has been studied more extensively in preparation for FDA approval, with the Actifit in contrast only in clinical use for the last 3–4 years. The Menaflex consists of type I collagen derived from bovine Achilles tendon, with collagen fibres enriched with glucosamine-glycan to aid cellular in-growth. It is bio-resorbable, with most of the scaffold resorbed over 12–18 months. In October 2010, the United States Food and Drug Administration (USFDA) rescinded its clearance of the Menaflex following a re-evaluation of the scientific evidence on the grounds that it did not qualify for the 510(K) approval it had already received (intended for devices similar to products already on the market). The situation is currently under review. The Actifit is a biodegradable highly porous scaffold made from aliphatic polyurethane. The polymer consists of flexible segments made from polycaprolactone (80%) and stiff segments made from urethane (20%). It is strong and tough with good wear resistance characteristics and degrades slowly over time (around five years). It is broken down by hydrolysis into non-toxic components which are safely excreted or integrated in native tissue.

S.J. Spencer et al. / The Knee 19 (2012) 760–765

Much of the published literature on meniscal scaffold clinical use is from the surgeons who in some way have been involved in their design and/or development, with few independent studies to date. We present the first independent review of meniscal scaffold implant use in a UK centre with our early experience of their use in the treatment of the painful knee following partial meniscectomy. 2. Patients and methods Between March 2008 and June 2010, 24 patients underwent arthroscopic meniscal scaffold placement (13 Menaflex and 11 Actifit). There were five female and 19 male patients with a mean age at time of surgery of 35 years (17–47) (32 for the Menaflex group and 39 for the Actifit). Patients were considered for surgery if they had previously undergone partial meniscectomy more than 12 months earlier and if they had pain interfering with work, light sport or activities of daily living. Patients who had acute tears were not considered for reconstruction. Initially there was no restriction on grade of chondral wear at implantation but this evolved during the study period to Outerbridge [11] grade 0–3 accepted, grade 4 excluded. All knees were required to be stable with good axial alignment at the time of surgery or a concurrent ligament reconstruction/osteotomy was performed. KOOS, Lysholm, Tegner activity and IKDC scores [12–16] were all collected prospectively; preoperatively, and at 6, 12, 18 and 24 months post-operatively. Repeat arthroscopic assessment of the graft at one year was offered to all patients to assess healing and fitness to return to activity. Serial MRI scans were performed at 6, 12, 24 and 36 months postoperatively using a 3T magnet (GE HDx 3.0T, GE Medical Systems, Milwaukee, USA) scanner to provide sagittal proton density (PD), sagittal T2 gradient echo (GE), coronal and axial PDFS and volume GE sequences, including sagittal T2 mapping and PD CUBE when possible. Standard cartilage series were used and descriptive reports of the images were provided by a senior musculoskeletal radiologist (MD) to assess the volume, quality and differentiation of the scaffold and to determine whether there was any progression of chondral thinning. All data were collected prospectively with no cases lost to follow-up. One patient of the original 24 was excluded from the study. He was a 28 year old male currently awaiting further revision surgery following re-rupture of a revision ACL reconstruction performed at the time of meniscal implantation. Subsequent knee scores therefore were felt not to be an accurate reflection of the performance of the meniscal scaffold. Statistical analysis was performed with the Student's test using GraphPad software (California, USA). 2.1. Surgical technique and post-operative rehabilitation Routine knee arthroscopy is performed documenting chondral surface, state of the meniscus and confirming appropriate indications for scaffold insertion. Arthroscopic preparation of the meniscus is required to freshen up the edge back to vascular tissue. The segmental defect is shaped to create a 90° angle at the posterior and anterior ends using a combination of the appropriately angled punches. The rim is further freshened using the microfracture pick penetrating

761

into the vascular area to enable adequate bleeding into the scaffold. The anterior end is cut obliquely. The length of the defect is measured using a malleable ruler. Ten percent is added to the length prior to cutting the implant, allowing the implant to be fitted snugly in to place. Without this, on inserting the sutures, there is a tendency to compress the scaffold to the posterior end leaving a gap anteriorly. For insertion the portal on the affected side is widened to a size large enough to admit the surgeons little finger and the prepared implant is slid in to the joint using a small clamp or clip. Adequate leverage and opening of the affected compartment is required and sometimes needle release of the MCL is needed for medial compartment implantation. The implant is manipulated into place and fixed using a combination of devices depending on the surgeon's preference. Options include in-to-out or all inside suture systems [17,18]. Post-operative rehabilitation is necessarily slow to allow in-growth of tissue and healing of the scaffold to the rim. A hinged protective range of movement knee brace is used for eight weeks restricting bend to 30° for the first two weeks followed by gradual increase in bend to 90° by 6 weeks. Full flexion is achieved by 3 months. Weight bearing is restricted allowing gradual building to full weight bearing at 8–10 weeks with return to light sporting activities at 6 months, with unrestricted sport only allowed at 12 months. 3. Results In the Menaflex group there were seven medial and five lateral procedures with a mean follow-up of 24.1 months (18–27). With the Actifit scaffold there were seven medial and four lateral procedures with a mean follow-up of 14.7 months (12–18). Mean scaffold length for the entire series was 44.9 mm (35–68). The mean Outerbridge [10] grade was 1.9 (0–4) in the affected compartment and the mean number of prior operations 2.9 (1–7); indicating the long standing nature of knee problems within the group. Eight (36%) patients underwent additional procedures at the same sitting; three high tibial osteotomy, two distal femoral osteotomy, one revision ACL reconstruction, one LCL reconstruction and one having microfracture of the tibia chondral surface. Twenty-one out of 23 (91.3%) had improved knee scores at latest follow-up [mean 19.4 months (12–27)]. Compared to pre-surgery levels there was a significant improvement (all b0.05) in the mean Lysholm, IKDC and KOOS scores at 24 months for Menaflex (n= 9) and at 18 months for Actifit (n=5), (except for KOOS ADL (p =0.0572) and KOOS sport (p= 0.00793) for Actifit at 18 months), Table 1, (Figs. 1–3). The Tegner score had improved following surgery but did not reach a statistically significant level (Fig. 4). The remaining two out of 23 (8.7%) in whom scores were not improved at latest followup were as follows: one implant failure; a 25 year old female who was initially making good progress 19 months following Menaflex implant surgery and was exercising on a static bike when she developed sudden onset of knee pain. The meniscal repair had torn and was ultimately revised to an Actifit implant. One patient had an early improvement in scores which subsequently returned to the pre-surgery level; this patient had advanced arthritic changes noted at time of implant insertion surgery with grade 3 tibial and femoral chondral surface wear. Second-look arthroscopy was performed in 14 patients at mean 12.8 months. This showed variable amounts of regenerative tissue. For the Actifit patients, four out of five had >50% infill (Figs. 5 and 6), with one b50% (Fig. 9). In the patients treated with the Menaflex, five out of nine assessed had less than 50% infill (Fig. 8). Follow-up MRI was performed in all cases at a mean of 19 months post-surgery (range 6–36), Fig. 7. No progression of chondral wear following surgery was noted on subsequent scans. Mixed appearance of the tissue/scaffold construct was observed varying from good structural integrity (in-fill) to marked erosion. On the standard chondral sequences used there was correlation between the MRI features of implant

Table 1 Mean pre- and post-surgery knee scores with Menaflex at 24 months and Actifit at 18 months. Score

Menaflex pre-op (n = 11)

Menaflex 24 months (n = 9)

P value

95% CI

Actifit pre-op (n = 11)

Actifit 18 months (n = 5)

P value

95% CI

Lysholm Tegner activity IKDC KOOS pain KOOS symptoms KOOS ADL KOOS sport KOOS QOL

61.8 3.7 48.1 60.3 54.1 69.3 35 31.5

82.9 5.2 71.8 88.8 79.7 94 62.2 57

0.0028 0.0893 0.0022 0.0003 0.0011 0.0014 0.0017 0.0023

8.24 to 33.87 − 0.25 to 3.24 9.6675 to 37.7141 14.95 to 42.11 11.70 to 39.45 10.94 to 38.56 13.70 to 50.75 10.37 to 40.86

56.5 3.8 42.1 56.7 52.5 66.8 37.3 27.8

86.6 4.4 74 85.6 87.6 93 66 61.4

0.0088 0.4451 0.0013 0.022 0.0041 0.0572 0.0793 0.0005

8.89 to 51.40 − 1.08 to 2.34 15.0003 to 48.9057 4.83 to 52.92 13.14 to 56.97 − 0.92 to 53.28 − 3.83 to 61.28 17.65 to 49.51

762

S.J. Spencer et al. / The Knee 19 (2012) 760–765

Lysholm

100

A

KOOS-CMI

100

80

80

Symptoms

60 40

CMI

60

Pain

ACTIFIT

40

ADL's

20

Sport

20 0 Preop

6m

12m

18m

24m

QOL

0 Preop

Fig. 1. Lysholm score Menaflex and Actifit implants.

6m

B integrity/structure and macroscopic findings at second-look arthroscopy. The MRI findings do not suggest differentiation into fibrocartilage but rather demonstrate an oedema-like signal within the implant which so far persists in our cohort to mean 19 months post surgery.

12m

18m

24m

KOOS-ACTIFIT

100

Symptoms

80

Pain 60 ADL's 40

4. Discussion

Sport

We have presented our early prospective experience and the first independent review from a UK centre of 23 patients undergoing reconstruction of either the lateral or medial meniscus. Twenty-one out of 23 patients (91.3%) had improved clinical scores at last follow-up, mean 19.4 months (12–27) following meniscal scaffold implant surgery. While MRI and second-look arthroscopy demonstrated good correlation with meniscal implant state showing variable amounts of regenerated tissue, there was no progression of chondral wear or complication directly related to the implant seen on MRI scans. There are relatively few studies looking at the clinical results of reconstruction of meniscal deficits using meniscal scaffolds [9,19–23]. In terms of symptomatic relief, our early results are encouraging. It has however yet to be seen in the longer term whether the treatment with scaffolds can restore the meniscal function well enough to improve joint load transmission and prevent further articular cartilage degeneration. A comprehensive review of the literature was performed. Given its longer length of clinical use more has been published on the Menaflex then on the Actifit scaffold. 4.1. Menaflex Steadman et al. report on eight patients at mean 5.8 years follow-up with their phase II feasibility study [9]. Mean Lysholm and Tegner Activity Scores were significantly improved at latest follow-up. MRI demonstrated no degeneration in the chondral surfaces and progressive maturity of the implant. At second-look arthroscopy the authors reported 69% filling of the defect with regenerate tissue. Zaffagnini et al. also presented on eight Menaflex patients at mean 6.8 years, where four were pain free [22]. On MRI the implant had a normal signal but was of reduced size in two and the articular cartilage showed no

20 QOL 0 Preop

6m

12m

18m

Fig. 3. Indivdual components of KOOS score detailed.a. Menaflex b. Actifit.

deterioration in six. The authors concluded that the implant ‘may have helped reduce the deterioration of the knee joint’. Bulgeroni et al. [23] presented mean 5 year results in 28 Menaflex patients. Lysholm and Tegner scores showed significant improvement and were unchanged between 2 and 5 years post-surgery. Radiographic evaluation showed no deterioration at 5 years and MRI signal intensity progressively decreased at 2 and 5 years. The authors concluded that the regenerate tissue matures over time. A prospective multicentre randomised control trial (RCT) compared treatment with either insertion of the medial Menaflex or with partial meniscectomy for 311 patients, 157 with acute tears and 154 with chronic injuries having had one or more previous meniscal operations [20]. Second-look arthroscopy was performed at 1 year and mean follow-up was 5 years. In all groups the Lysholm score had significantly improved from the pre-operative level to 6 years but there was no difference in scores noted between the groups. There was a difference identified in reoperation rate; 9.5% in the Menaflex group versus 22.7% in the meniscectomy alone group. The “Tegner index” was developed by the study group as a measure of lost activity due to an injury regained from the treatment intervention. On this score a significant difference was observed, the Menaflex patients gained in activity while the meniscectomy group reduced activity over the study period. Most recently

Tegner 10 9

IKDC

100

8 7

80

6 5

60 40

CMI

4

ACTIFIT

3

CMI ACTIFIT

2

20

1 0

0 Preop

6m

12m

18m

24m

Fig. 2. IKDC score Menaflex and Actifit implants.

Pre Inj Preop

6m

12m

18m

24m

Fig. 4. Tegner activity score Menaflex and Actifit implants.

S.J. Spencer et al. / The Knee 19 (2012) 760–765

763

The goals of meniscal scaffold surgery are twofold; to treat postmeniscectomy knee pain and to re-establish near normal knee load transmission in an attempt to prevent further articular cartilage degeneration. With regard to the first goal of pain relief following surgery, the majority 21 out of 23 (91.3%) of our patients’ knee scores were improved at latest follow-up (mean 19.4 months), a finding in agreement with all the published studies to date [9,20–23]. It is worth noting however, in all but one of these studies, the lack of a control group for comparison. In the RCT comparing Menaflex insertion with partial meniscectomy alone, no difference was found when the implant was used in the acute setting [20], and all treatment groups displayed improved knee score. A difference was reported however, on a single scoring parameter, the Tegner Index, when chronic tears were treated. The Menaflex group increased in their activity while those treated with meniscectomy decreased. This was interpreted by the authors as to mean that patients reduce activity after meniscectomy in order to maintain low pain levels. Satisfactory implant integrity is important for the second goal; restoring meniscal function. Our second-look arthroscopic analysis of the Menaflex has been mixed, ranging from good infill in some to an almost absent eroded implant in others. Implant erosion seemed more likely to occur in those with worse chondral wear at time of surgery and perhaps this was due to an abrasive effect of the joint on the implant. In contrast the Actifit appears to be performing more consistently on second-look arthroscopy with good in-growth and retention of the implant. In keeping with this, the literature varies on second-look arthroscopy of the Menaflex; Rodkey et al. report on

Fig. 5. 22-year old male, insertion of 68 mm medial Actifit implant; a. Pre-implantation; b. implant in place; c. second-look arthroscopy of showing greater than 50% infill new meniscal type tissue from periphery by 5 months.

Zaffagnini et al. published their minimum 10 year follow-up cohort study comparing 17 patients undergoing medial Menaflex implantation with 16 receiving meniscectomy alone [22]. Lysholm, VAS pain, IKDC, Tegner activity level score and SF 36 were recorded, and for imaging outcomes bilateral weight bearing radiographs and MRI were used. Similar numbers of acute and chronic injuries were in each group. Results showed a significantly lower VAS pain score, higher objective IKDC, Tegner index and SF-36 in the Menaflex group. Perhaps most interesting was the finding of significantly less medial joint space narrowing in the Menaflex group suggesting that meniscal scaffolds may have a chondroprotective function. 4.2. Actifit Clinically studied in a ‘proof of principle’ multicentre study and results are now published at 1 year [21]. The study consisted of 52 patients, 34 medial and 18 lateral, with mean age 30.5 (18–50) and with stable knees or made stable within 12 weeks. Chondral surface wear was limited to ICRS grade 1 or 2. Patients with more than three surgeries on the involved meniscus were excluded as were those with a BMI > 35. Tissue in-growth was assessed at 3 months by dynamic contrast-enhanced MRI (DCE-MRI) and by second-look arthroscopy at 12 months during which a biopsy of the inner free edge of the scaffold was taken. Tissue in growth was demonstrated at 3 months on DCE-MRI in 35 out of 43 (81.4%) patients and all but one of the second-look arthroscopies.

Fig. 6. b, c and d. 45 year old male undergoing medial meniscus reconstruction using Actifit implant, a. Pre-implant b. 45 mm implant in place, c Second-look arthroscopy at 10 months showing good infill of meniscal type tissue (near 100%).

764

S.J. Spencer et al. / The Knee 19 (2012) 760–765

A

B

C

at minimum 10 years following implant surgery [22]. Despite its limitations, this study is the first to show the potential joint preserving benefit of scaffold use when compared to simple meniscectomy. Further work is required in this area with larger numbers randomised to treatment and observed over a longer time period before an answer to the true chondroprotective role of meniscal scaffolds can be found. One of the major limitations of our study is that there is no control group for comparison. It could be argued that the pain relief observed might have occurred with meniscectomy alone. It is worth bearing in mind however that this was a group of patients who had already had multiple previous meniscectomies with ongoing pain at time of scaffold implantation in which it could be argued that a further meniscectomy alone is less likely to be effective. Another limitation was that eight patients (36%) underwent an additional procedure at the same time as insertion of the meniscal scaffold in order to correct the recognised poor mechanical aspects of the joint. We acknowledge that the additional procedure may have had an influence on outcome scores following surgery. This does however represent a typical case mix undergoing this type of surgery and is similar or even slightly lower than that of other published series, with 41% requiring additional surgery in Bulgheroni's study [23].

D

Fig. 7. (Same patient as Fig. 6). MRI scans, medial Actifit, pre-op and 14-month images.a. Pre-op MRI Sagittal T2 GE (Gradient Echo) image (1.5 T − TR/TE = 676/18).b. 14 months post-op MRI Sagittal PD (Proton Density) image, showing maintainence of structural integrity but note the uniform oedema-like signal of the Actifit implant compared to the native meniscus (3.0 T − TR/TE = 1280/23).c. Pre-op MRI Coronal PD FS (Fat Suppressed) image (1.5 T - TR/TE = 2400/13).d. 14 months post-op Coronal PD FS image (3.0 T – TR/TE = 1560/23).

141 patients at a year, with stable supple tissue, no failures due to lack of healing to the rim and increase in meniscal tissue compared to index partial meniscectomy [20], (from 37% of meniscus to 73%). Zaffagnini et al. [22] however looked at three out of eight patients, with the implant present in two but reduced in size and in one it had almost disappeared. Biopsy of the new tissue generated following treatment with the Menaflex scaffold has shown the presence of fibrocartilage with a uniform extra cellular matrix and a collagenous nature to the tissue [9]. With the Actifit implant at time of secondlook arthroscopy 43 out of 44 (97.7%) showed integration of the implant at 12 months [21]. All (44) specimens of tissue from the centre of the inner free edge of the new meniscus biopsied during the second look were reported as showing “fully vital material” [21]. Analysis showed immature tissue with meniscus like characteristics, and type I collagen present (but no type II). It is not known yet whether this meniscus like tissue can reestablish load transmission well enough to prevent further chondral wear. To date, no progression has been shown based on an assessment of chondral surface grade either at second-look arthroscopy [9], on repeat MRI scanning [23] or on plain radiographs [23]. These studies are encouraging; however they are all limited by the lack of a control group for comparison and relative short length of followup. Zaffagnini et al. have recently reported a cohort of 17 Menaflex patients with significant reduction (when compared to meniscectomy alone) in medial compartment wear seen on plain radiographs

Fig. 8. Menaflex implant—a. pre-op; b. at implantation; c. disappointing appearance at 2.5 years with marked implant erosion.

S.J. Spencer et al. / The Knee 19 (2012) 760–765

765

References

Fig. 9. Actifit implant—46 year old female, lateral implant, right knee a. Measuring up for 32 mm implant at time of insertion, b. 1 year second-look arthroscopy, intact implant but disappointing infill, b50%.

5. Conclusion Meniscal reconstruction with synthetic implants acting as a scaffold appear to provide good symptomatic improvement for postmeniscectomy pain, and this is in agreement with work already published in this field. It is hoped that with time it will be possible to show the real benefit that meniscal reconstruction could have over meniscectomy alone in preventing further chondral wear.

Acknowledgements The authors of this paper would like to acknowledge the work of Hayley Standell in collection of data for this study.

[1] Shoemaker SC, Markolf KL. The role of the meniscus in the anterior-posterior stability of the loaded anterior cruciate-deficient knee. Effects of partial versus total excision. J Bone Joint Surg Am 1986;68:71–9. [2] Walker PS, Erkiuan MJ. The role of the menisci in force transmission across the knee. Clin Orthop Relat Res 1975;109:184–92. [3] Verdonk PCM, Van Laer MEE, Verdonk R. Meniscus replacement: from allograft to tissue engineering. Sports Orthop Traumatol 2008;24(2):78–82. [4] Higuchi H, Kimura M, Shirakura K, Terauhci M, Takagishi K. Factors affecting long-term results after arthroscopic partial meniscectomy. Clin Orthop Relat Res 2000;337:161–8. [5] Rockborn P, Gillquist J. Outcome of arthroscopic meniscectomy: a 13-year physical and radiographic follow-up of 43 patients under 23 years of age. Acta Orthop Scand 1995;66(2):113–7. [6] Fauno P, Nielson AB. Arthroscopic partial meniscectomy: a long-term follow-up. Arthroscopy 1992;8(3):345–9. [7] Hede A, Larsen E, Sandberg H. Partial versus total meniscectomy: a prospective, randomized study with long-term follow-up. J Bone Joint Surg Br 1992;74(1):118–21. [8] ElAttar M, Dhollander A, Verdonk R, Almqvist KF, Verdonk P. Twenty-six years of meniscal alolograft transplantation: is it still experimental? A meta-analysis of 44 trials. Knee Surg Sports Traumatol Arthrosc 2011;19:147–57. [9] Steadman JR, Rodkey WG. Tissue-engineered collagen meniscus implants: 5- to 6-year feasibility study results. Arthroscopy 2005;21(5):515–25. [10] Van Tienen TG, Hannink G, Buma P. Meniscal replacement using synthetic materials. Clin Sports Med 2009;28:143–56. [11] Outerbridge RE. The aetiology of chondromalacia patellae. J Bone Joint Surg Br 1961;43:752–7. [12] Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and Osteoarthritis Outcome Score (KOOS)—development of a self-administered outcome measure. J Orthop Sports Phys Ther 1998;28:88–96. [13] Lysholm J, Gillquist J. Evaluation of knee ligament surgery results with special emphasis on use of a scoring scale. Am J Sports Med 1982;10:150–4. [14] Tegner Y, Lysholm J. Rating systems in the evaluation of knee ligament injuries. Clin Orthop Relat Res 1985;198:43–9. [15] Briggs KK, Kocher MS, Rodkey WG, Steadman JR. Reliability, validity, and responsiveness of the Lysholm knee score and Tegner activity scale for patients with meniscal injury of the knee. J Bone Joint Surg Am 2006;88:698–705. [16] Irrgang JJ, Anderson AF, Boland AL, Harner CD, Kurosaka M, Neyret P, et al. Development and validation of the international knee documentation committee subjective knee form. Am J Sports Med 2001;29:600–13. [17] Orteq website. Available online at: www.orteq.com Accessed June 2011. [18] Collagen Meniscal Implant website. Available online at: www.ivysportsmed.com/ for-surgeons/surgical-technique.aspx Accessed October 2011. [19] Stone KR, Steadman JR, Rodkey WG, Li ST. Regeneration of meniscal cartilage with use of a collagen scaffold. Analysis of preliminary data. J Bone Joint Surg Am 1997 Dec;79(12):1770–7. [20] Rodkey WG, DeHaven KE, Montgomery WH, Baker CL, Beck CL, Hormel SE, et al. Comparison of the Collagen Meniscus Implant with partial meniscectomy—a prospective randomized trial. J Bone Joint Surg Am 2008;79:1413–26. [21] Verdonk R, Verdonk P, Huysse W, Forsyth R, Heinrichs E. Tissue ingrowth after implantation of a novel, biodegradable polyurethane scaffold for treatment of partial meniscal lesions. Am J Sports Med 2011;39(4):774–82. [22] Zaffagnini S, Muccioli GMM, Lopomo N, Bruni D, Giordano G, Ravazzolo G, et al. Prospective long-term outcomes of the medial Collagen Meniscus Implant versus partial medial meniscectomy: a minimum 10-year follow-up study. Am J Sports Med 2011;39(5):977–85. [23] Bulgheroni P, Murena L, Ratti C, Bulgheroni E, Ronga M, Cherubino P. Follow-up of collagen meniscal implant patients: clinical, radiological, and magnetic resonance imaging results at 5 years. Knee 2010;17:224–9.