Histology and ultrastructure of a tissue-engineered collagen meniscus before and after implantation. Comparison of the collagen meniscus implant with partial meniscectomy. A prospective randomized trial. Tissue-engineered collagen meniscus implants: 5- to 6-year feasibility study results. One-year clinical and MR imaging outcome after partial meniscal replacement in stabilized knees using a collagen meniscus implant Arthroscopic collagen meniscus implant results at 6 to 8 years follow up Total meniscectomy in adolescents: a 40-year follow-up. Regeneration of Meniscal Cartilage with Use of a Collagen Scaffold. Analysis of Preliminary Data* Long-term follow-up of meniscectomy in athletes. A prospective longitudinal study. A Prospective Outcomes Study of Meniscal Allograft Transplantation Prospective Long-Term Outcomes of the Medial Collagen Meniscus Implant Versus Partial Medial Meniscectomy [Replacement of the meniscus with a collagen implant (CMI)]. A clinical study of collagen meniscus implants to restore the injured meniscus.
The collagen meniscus implant ( CMI ) is a tissue-engineering technique design ed to stimulate regeneration of meniscus-like tissue in cases of irreparable tears or previous meniscectomy .  CMI morphology was investigated before and after implantation by light microscopy , scanning electron microscopy ( SEM ) , and transmission electron microscopy ( TEM ) . In a case series biopsy specimens were harvested from four patients who underwent a second arthroscopic look 6 months after placement of the CMI . CMI sections appeared composed of parallel connective laminae of 10 - 30 microm , connected by smaller bundles ( 5 - 10 microm ) . This connective network formed lacunae with diameters between 40 and 60 microm . At greater magnification , the walls of the lacunae demonstrated tightly packed and r and omly distributed collagen fibrils , with diameters ranging from 73 to 439 nm . In the biopsy specimens , the lacunae were filled with connective tissue that contained newly formed vessels and fibroblast-like cells , presenting an abundant rough endoplasmic reticulum and several mitochondria . In the extracellular matrix , the collagen fibrils showed uniform diameters ( 126 nm + /- 32 nm ) . The original structure of CMI  was still recognizable , and no inflammatory cells were detected within the implant . The morphological findings of this case series demonstrate that CMI provides a three-dimensional scaffold suitable for colonization by precursor cells and vessels and leading to the formation of a fully functional tissue BACKGROUND Loss of meniscal tissue leads to increased pain and decreased clinical function and activity levels . We hypothesized that patients receiving a collagen meniscus implant would have better clinical outcomes than patients treated with partial medial meniscectomy alone . METHODS Three hundred and eleven patients with an irreparable injury of the medial meniscus or a previous partial medial meniscectomy , treated by a total of twenty-six surgeon-investigators at sixteen sites , were enrolled in the study . There were two study arms , one consisting of 157 patients who had had no prior surgery on the involved meniscus ( the " acute " arm of the study ) and one consisting of 154 patients who had had one , two , or three prior meniscal surgical procedures ( the " chronic " arm ) . Patients were r and omized either to receive the collagen meniscus implant or to serve as a control subject treated with a partial meniscectomy only . Patients underwent frequent clinical follow-up examinations over two years and completed vali date d outcomes question naires over seven years . The patients who had received a collagen meniscus implant were required by protocol to have second-look arthroscopy at one year to determine the amount of new tissue growth and to perform a biopsy to assess tissue quality . Reoperation and survival rates were determined . RESULTS In the acute group , seventy-five patients received a collagen meniscus implant and eighty-two were controls . In the chronic group , eighty-five patients received the implant and sixty-nine were controls . The mean duration of follow-up was fifty-nine months ( range , sixteen to ninety-two months ) . The 141 repeat arthroscopies done at one year showed that the collagen meniscus implants had result ed in significantly ( p = 0.001 ) increased meniscal tissue compared with that seen after the original index partial meniscectomy . The implant supported meniscus-like matrix production and integration as it was assimilated and resorbed . In the chronic group , the patients who had received an implant regained significantly more of their lost activity than did the controls ( p = 0.02 ) and they underwent significantly fewer non- protocol reoperations ( p = 0.04 ) . No differences were detected between the two treatment groups in the acute arm of the study . CONCLUSIONS New biomechanically competent meniscus-like tissue forms after placement of a collagen meniscus implant , and use of the implant appears safe . The collagen meniscus implant supports new tissue ingrowth that appears to be adequate to enhance meniscal function as evidence d by improved clinical outcomes in patients with a chronic meniscal injury . The collagen meniscus implant has the utility to be used to replace irreparable or lost meniscal tissue in patients with a chronic meniscal injury . The implant was not found to have any benefit for patients with an acute injury PURPOSE In this feasibility study , a 5- to 6-year clinical follow-up evaluation was conducted on 8 patients who had undergone reconstruction of 1 injured medial meniscus with a tissue-engineered collagen meniscus implant .  The hypothesis was that these patients would show significant clinical improvement over their preoperative status and would have maintained their status determined at the 2-year follow-up evaluation . TYPE OF STUDY Prospect i ve longitudinal feasibility study follow-up evaluation . METHODS Eight patients underwent arthroscopic placement of a collagen meniscus implant by a single surgeon to reconstruct and restore the irreparably damaged medial meniscus of 1 knee . All patients returned for clinical , radiographic , magnetic resonance imaging , and arthroscopic examinations an average of 5.8 years ( range , 5.5 - 6.3 y ) after collagen meniscus implant placement .  RESULTS Lysholm scores improved significantly ( P = .045 ) from 75 preoperatively to 88 at most recent follow-up evaluation . Average Tegner activity scores improved significantly ( P = .001 ) from 3 to 6 . Patient self- assessment improved significantly ( P = .046 ) from 2.4 to 1.9 ( 1 = normal , 4 = severely abnormal ) . Pain scores improved from 23 to 11 ( 0 = no pain , 100 = worst pain ) . Imaging studies confirmed that the chondral surfaces of the medial compartment had not degenerated further since the placement of the implant 5.8 years earlier . Relook arthroscopy with direct measurement of the newly generated tissue revealed 69 % defect filling . Histologic assessment of tissue biopsy specimens from 3 patients showed the presence of fibrocartilage with a uniform extracellular matrix . CONCLUSIONS The meniscus-like tissue that developed after collagen meniscus implant placement has maintained its structure and functioned without negative effects for more than 5 years . The hypothesis was affirmed that these patients were improved significantly compared with their preoperative status and unchanged compared with 2-year evaluations . LEVEL OF EVIDENCE Level IV Purpose The purpose of the study was to evaluate the clinical and radiological outcomes after medial/lateral collagen meniscus substitution ( CMI ) at 12 months postoperatively . Methods Sixty-seven patients ( m : f = 47:20 , mean age 36 ± 10 years ) underwent arthroscopic CMI after previous subtotal medial ( n = 55 ) or lateral meniscectomy ( n = 12 ) due to persistent joint line pain ( n = 25 ) or to prophylactic reasons ( n = 42 ) . Clinical follow-up consisted of IKDC score , Tegner score , Lysholm score , and visual analog scale for pain and satisfaction ( preinjury , preoperatively , and 12 months postoperatively ; follow-up rate 90 % ) . MRI scans were analyzed according to the Genovese criteria . Results Nineteen patients ( 29 % ) showed a normal ( A ) , 35 nearly normal ( B ) , 5 abnormal ( C ) , and 1 patient severely abnormal total IKDC score ( D ) . The median Tegner preinjury score was 7 ( range 2–10 ) and at follow-up 6 ( range 2–10 ) . The mean Lysholm score before surgery was 68 ± 20 and 93 ± 9 at follow-up . Preoperatively , the mean VAS pain was 4.4 ± 3.1 and 2.0 ± 1.0 at follow-up . Clinical failure of the CMI occurred in 3 patients ( n = 1 infection , n = 1 failure of the implant , n = 1 chronic synovitis ) . On MRI , the CMI was completely resorbed in 3 patients ( 5 % ) , partially resorbed in 55 ( 92 % ) , and entirely preserved in 3 ( 5 % ) patients . In 5 patients ( 8 % ) the CMI was isointense , in 54 ( 90 % ) slightly and 1 ( 2 % ) highly hyperintense . 43 ( 72 % ) patients showed an extrusion of the CMI implant of more than 3 mm . Conclusions Significant pain relief and functional improvement throughout all scores at 1 year was noted . The CMI undergoes significant remodeling , degradation , resorption , and extrusion in most of the patients . No difference in outcomes between the medial and lateral CMI was observed . Level of evidence Prospect i ve therapeutic study , Level IV Meniscal substitution is a fundamental procedure to prevent osteoarthritis of the knee after massive meniscectomy . Stone , Steadman and Rodkey have developed a bioreadsorbable collagen matrix ( CMI ) which acts as a scaffold to restore the original medial meniscal . The objective of this study was to prospect ively evaluate the results of CMI implantation at a follow up from a minimum of 6 to a maximum of 8 years . Eight patients ( mean age 25 ) were evaluated at a final observation point from 6 to 8 years after CMI implantation . Inclusion criteria were an irreparable meniscal tear or a previous meniscectomy involving the medial meniscus . Follow up evaluation included Cincinnati Knee Rating Scale ( CKRS ) , IKDC , subjective evaluation and X-ray and MRI control . There were no complications related to the device . All patients were able to return to day activities without limitations 3 months after surgery . Both subjective CKRS score and objective IKDC score showed improvement in all cases except one patient with an ACL re-injury . In two cases scores were slightly worse from 2 years after surgery to the final observation point . The other five cases obtained maximum score at final follow-up . In four cases the absence of pain remained until the final observation point , while in four cases a low entity of pain was described at long term follow-up . MRI showed in five cases mixoid degeneration signal , two had normal signal with reduced size , while one patient had no recognizable implant . Six patients had preserved cartilage and articular space , with no changes respect to pre-op control . Arthroscopic second look evaluation has been performed in three cases , revealing in two cases the presence of the implant , although with a reduced size respect to the original one , while in one case the CMI was almost disappeared . Our small series of eight patients prospect ively followed from 6 to 8 years of follow-up has shown highly satisfactory results . Although the aspect of the implant was mostly abnormal , the implant may have helped reduce the deterioration of the knee joint at final observation time We continued a prospect i ve longitudinal follow-up study of 53 remaining patients who underwent open total meniscectomy as adolescents and who at that time had no other intra-articular pathology of the knee . Their clinical , radiological and patient-reported outcomes are described at a mean follow-up of 40 years ( 33 to 50 ) . The cohort of patients who had undergone radiological evaluation previously after 30 years were invited for clinical examination , radiological evaluation and review using two patient-reported outcome measures . A total of seven patients ( 13.2 % ) had already undergone total knee replacement at the time of follow-up . A significant difference was observed between the operated and non-operated knee in terms of range of movement and osteoarthritis of the tibiofemoral joint , indicating a greater than fourfold relative risk of osteoarthritis at 40 years post-operatively . All patients were symptomatic as defined by the Knee Injury and Osteoarthritis Outcome Score . This study represents the longest follow-up to date and it can be concluded that meniscectomy leads to symptomatic osteoarthritis of the knee later in life , with a result ant 132-fold increase in the rate of total knee replacement in comparison to their geographical and age-matched peers A collagen scaffold was design ed for use as a template for the regeneration of meniscal cartilage and was tested in ten patients in an initial , Food and Drug Administration-approved , clinical feasibility trial . The goal of the study was to evaluate the implantability and safety of the scaffold as well as its ability to support tissue ingrowth . The study was based on the findings of in vitro and in vivo investigations in dogs that had demonstrated cellular ingrowth and tissue regeneration through the scaffold . Nine patients remained in the study for at least thirty-six months , and one patient voluntarily withdrew after three months for personal reasons . The collagen scaffold was found to be implantable and to be safe over the three-year period . Histologically , it supported regeneration of tissue in meniscal defects of various sizes . No adverse immunological reactions were noted on sequential serological testing . On second-look arthroscopy , performed either three or six months after implantation , gross and histological evaluation revealed newly formed tissue replacing the implant as it was resorbed . At thirty-six months , the nine patients reported a decrease in the symptoms . According to a scale that assigned 1 point for strenuous activity and 5 points for an inability to perform sports activity , the average score was 1.5 points before the injury , 3.0 points after the injury and before the operation , and 2.4 points at six months postoperatively , 2.2 points at twelve months , 2.0 points at twenty-four months , and 1.9 points at thirty-six months . According to a scale that assigned 0 points for no pain and 3 points for severe pain , the average pain score was 2.2 points preoperatively and 0.6 point thirty-six months postoperatively . One patient , who had had a repair of a bucket-h and le tear of the medial meniscus and augmentation with the collagen scaffold , had retearing of the cartilage nineteen months after implantation . Another patient had débridement because of an irregular area of regeneration at the scaffold-meniscus interface twenty-one months after implantation . Magnetic resonance imaging scans demonstrated progressive maturation of the signal within the regenerated meniscus at three , six , twelve , and thirty-six months . These findings suggest that regeneration of meniscal cartilage through a collagen scaffold is possible . Additional studies are needed to determine long-term efficacy We report the results of a prospect i ve longitudinal study of 147 athletes who had had a meniscectomy for an isolated meniscus injury . The patients were review ed in detail after median periods of 4.5 years and 14.5 years and the results analysed . The frequency of complaints related to the operation increased from 53 % at 4.5 years to 67 % at 14.5 years , while demonstrable knee instability increased from 10 % to 36 % . The incidence of radiographic changes of degeneration rose from 40 % to 89 % and at late review 8 % of patients had definite osteoarthritis by the criteria of Ahlbäck ( 1968 ) . In consequence 46 % had given up or reduced their sporting activity , and 6.5 % had changed their occupation . Radiographic deterioration started after the 4.5-year review in 49 % of the patients and was more frequent after lateral than medial meniscectomy Background : Symptomatic early-onset chondromalacia often develops after a meniscectomy in the affected knee compartment . The role of meniscal transplantation in reducing pain and improving function in patients with prior ipsilateral meniscectomy is still being defined . Hypothesis : Patients with symptomatic early-onset chondromalacia of the knee after ipsilateral meniscectomy  will have improved clinical outcomes after meniscal transplantation . Study Design : Case series ; Level of evidence , 4 . Methods : All patients who underwent meniscal allograft transplantation between July 2003 and December 2006 were prospect ively followed . The indications for surgery were unicompartmental knee pain and postactivity effusions after total or near-total meniscectomy in patients with closed physes .  High-field magnetic resonance imaging ( 1.5-T or 3-T magnets ) was used to assess the articular cartilage of the affected compartment . The meniscal transplantations were performed with an arthroscopically assisted technique . Modified Cincinnati knee and International Knee Documentation Committee ( IKDC ) subjective and IKDC objective outcome scores were obtained on all patients preoperatively and postoperatively to evaluate patients ’ outcomes . Results : Forty patients with an average age of 25 years and a body mass index of 25.4 were included . After an average final follow-up of 2.5 years , IKDC subjective scores increased significantly from 54.5 to 72.0 ( P < .001 ) . Modified Cincinnati knee scores increased from 55.2 to 75.3 ( P < .001 ) . The preoperative IKDC objective scores measuring effusion improved significantly from 6 A ( normal ) , 29 B ( nearly normal ) , and 5 C ( abnormal ) , when compared with the postoperative scores of 33 A ( normal ) and 1 B ( nearly normal ) ( P < .01 ) . Five patients sustained tears of their meniscal transplants and underwent partial meniscectomies of the transplant graft . Conclusion : The results confirm that meniscal transplantation significantly reduces pain , decreases activity-related effusions , and improves function in patients with prior meniscectomy ; however , the long-term chondroprotective effects remain unknown Background : Loss of meniscal tissue can be responsible for increased pain and decreased function . Hypothesis : At a minimum 10-year follow-up , patients receiving a medial collagen meniscus implant ( MCMI ) would show better clinical , radiological , and magnetic resonance imaging ( MRI ) outcomes than patients treated with partial medial meniscectomy ( PMM ) . Study Design : Cohort study ; Level of evidence 2 . Methods : Thirty-three nonconsecutive patients ( men ; mean age , 40 years ) with meniscal injuries were enrolled in the study to receive MCMI or to serve as a control patient treated with PMM . The choice of treatment was decided by the patient . All patients were clinical ly evaluated at time 0 and at 5 years and a minimum of 10 years after surgery ( mean follow-up , 133 months ) by Lysholm , visual analog scale ( VAS ) for pain , objective International Knee Documentation Committee ( IKDC ) knee form , and Tegner activity level scores . The SF-36 score was performed preoperatively and at final follow-up . Bilateral weightbearing radiographs were completed before the index surgery and at final follow-up . Minimum 10-year follow-up MRI images were compared with preoperative MRI images by means of the Yulish score . The Genovese score was also used to evalute MCMI MRI survivorship . Results : The MCMI group , compared with the PMM one , showed significantly lower VAS for pain ( 1.2 ± 0.9 vs 3.3 ± 1.8 ; P = .004 ) and higher objective IKDC ( 7A and 10B for MCMI , 4B and 12C for PMM ; P = .0001 ) , Teger index ( 75 ± 27.5 vs 50 ± 11.67 ; P = .026 ) , and SF-36 ( 53.9 ± 4.0 vs 44.1 ± 9.2 ; P = .026 for Physical Health Index ; 54.7 ± 3.8 vs 43.8 ± 6.5 ; P = .004 for Mental Health Index ) scores . Radiographic evaluation showed significantly less medial joint space narrowing in the MCMI group than in the PMM group ( 0.48 ± 0.63 mm vs 2.13 ± 0.79 mm ; P = .0003 ) . No significant differences between groups were reported regarding Lysholm ( P = .062 ) and Yulish ( P = .122 ) scores . Genovese score remained constant between 5 and 10 years after surgery ( P = .5 ) . The MRI evaluation of the MCMI patients revealed 11 cases of myxoid degeneration signal : 4 had a normal signal with reduced size , and 2 had no recognizable implant . Conclusion : Pain , activity level , and radiological outcomes are significantly improved with use of the MCMI at a minimum 10-year follow-up compared with PMM alone . R and omized controlled trials on a larger population are necessary to confirm MCMI benefits at long term OBJECTIVE Replacement of an almost completely absent medial meniscus with a collagen implant ( CMI ) , reconstruction of form and function of the medial meniscus , delay of the development of arthrosis deformans . INDICATIONS Subtotal degenerative or traumatic loss of the medial meniscus , stable meniscal periphery , stable anterior and posterior meniscal insertions , joint with stable ligaments . CONTRAINDICATIONS Complete loss of the medial meniscus . Untreated knee ligament instability . Extreme varus deformity . Extensive cartilaginous damage , i.e. , levels IV and VI as described by Bauer and Jackson . Advanced unicompartmental or generalized arthrosis . Replacement of the lateral meniscus . SURGICAL TECHNIQUE St and ard anterior arthroscopy portals . Resection of the medial meniscus leaving a complete and stable outer rim . Revitalization of the periphery to promote healing . Measurement of defect size . Insertion and fixation of the CMI with nonresorbable suture material in inside-out technique . POSTOPERATIVE MANAGEMENT Postoperative knee brace with limited motion in extension/ flexion of 0/0/60 degrees until week 4 , 0/0/90 degrees until week 6 . Continuous passive motion within the limits of motion from the 1st postoperative day , actively assisted physiotherapy . No weight bearing for 6 weeks , then increased weight bearing for 2 weeks until full weight bearing is achieved . Cycling can commence from 3 months postoperatively . Full sporting activity after 6 months . RESULTS 60 patients ( 19 - 68 years , average 41.6 years ) with subtotal loss of the medial meniscus and varus morphotype were treated from January 2001 to May 2004 as part of a prospect i ve , r and omized , arthroscopically controlled study . The sample consisted of 30 patients with high tibial valgus osteotomy combined with implantation of a CMI , and 30 patients with valgization correction osteotomy only . The CMI had to be removed from one patient because of a dislocation . Evaluation on the Lysholm Score , IKDC ( International Knee Documentation Committee ) , and subjective pain data revealed only slight , nonsignificant differences for 39 patients after 24 months ( CMI and correction n = 23 ; correction only n = 16 ) . The chondroprotective effect of the CMI in the long term remains to be seen The meniscus performs critical functions within the knee , and its loss frequently leads to osteoarthritis and irreversible joint damage . Because prosthetic replacement of the meniscus has proven ineffective , the authors used tissue engineering techniques to develop a resorbable collagen scaffold ( collagen meniscus implant ) that supports ingrowth of new tissue and eventual regeneration of the lost meniscus . Eight patients underwent arthroscopic placement the collagen meniscus implant to reconstruct and restore the irreparably damaged medial meniscus of one knee . Seven patients had one or more prior meniscectomies , and one patient had an acute meniscus injury . Patients were observed with frequent clinical , serologic , radiographic , and magnetic resonance imaging examinations for at least 24 months ( range , 24 - 32 months ) . All patients underwent relook arthroscopy and biopsy of the implant regenerated tissue at either 6 or 12 months after implantation . All patients improved clinical ly from preoperatively to 1 and 2 years postoperatively based on pain , Lysholm scores , Tegner activity scale , and self assessment . Relook arthroscopy revealed tissue regeneration in all patients with apparent preservation of the joint surfaces based on visual observations . Histologic analysis confirmed new fibrocartilage matrix formation . Radiographs confirmed no progression of degenerative joint disease . The collagen meniscus implant is implantable , biocompatible , resorbable , and supports new tissue regeneration as it is resorbed . This tissue seems to function similar to meniscus tissue by protecting the chondral surfaces
PURPOSE The purpose of this study was to evaluate the clinical and structural outcomes after resorbable collagen meniscus scaffold implantation through a systematic review of the published literature .