human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Long-term data on the clinical outcome and the fate of the meniscus allograft after transplantation are scarce . In this study we present the clinical , radiological and MRI outcome of the meniscus graft and the articular cartilage after  42 meniscus allograft transplantations in 41 patients with a minimum follow-up of 10 years . A total of 27 medial and 15 lateral meniscal allografts were transplanted . Eleven of the medial allograft procedures were associated with a high tibial osteotomy . The patients were evaluated clinical ly at the time of transplantation and at the final follow-up using the modified HSS scoring system . The knee injury and osteoarthritis outcome score ( KOOS ) was used as an evaluation tool for patient-related outcome at the final follow-up . Joint space width narrowing and Fairbank changes were radiological outcome parameters , which were available for 32 patients . Femoral and tibial cartilage degeneration , graft extrusion and signal intensity were scored on MRI scans obtained in 17 patients approximately 1 year after transplantation and at the final follow-up ( > 10 years ) . For statistical analysis the patients were divided into three groups : lateral meniscal allograft ( LMT ) , medial meniscal allograft transplantation with a high tibial osteotomy ( MMT+HTO ) and without ( MMT ) . The modified HSS score revealed a significant improvement in pain and function at the final follow-up for all groups . Further analysis also revealed that an MMT+HTO procedure result ed in a greater improvement at the final follow-up when compared to MMT . Nonetheless , the KOOS scores obtained at the final follow-up revealed the presence of substantial disability and symptoms , in addition to a reduced quality of life . Radiographical analysis revealed no further joint space narrowing in 13/32 knees ( 41 % ) . Fairbank changes remained stable in 9/32 knees ( 28 % ) . MRI analysis showed no progression of cartilage degeneration in 6/17 knees ( 35 % ) . An increased signal intensity of the allograft was present , as was partial graft extrusion in the majority of patients at the final follow-up . Seven cases had to be converted to a total knee arthroplasty during the follow-up ; the overall failure rate was 18 % . Long-term results after viable meniscus allograft transplantation are encouraging in terms of pain relief and improvement of function . Despite this significant improvement , substantial disability and symptoms were present in all investigated subgroups . Progression of further cartilage degeneration or joint space narrowing was absent in a considerable number of cases , indicating a potential chondroprotective effect . Level of evidence is therapeutic study , Level IV and retrospective analysis of prospect ively collected data Meniscal injuries in the vascularized peripheral part of the meniscus have a better healing potential than tears in the central avascular zone because meniscal healing principally depends on its vascular supply . Several biological strategies have been proposed to enhance healing of the avascular area of the meniscus : abrasion therapy , fibrin clot , organ culture , cell therapy , and applications of growth factors . However , data are too heterogeneous to achieve definitive conclusions on the use of these techniques for routine management of meniscal lesions . Although most pre clinical and clinical studies are very promising , they are still at an experimental stage . More prospect i ve r and omised controlled trials are needed to compare the different techniques for clinical results , applicability , and cost-effectiveness 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 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 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 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Long-term data on the clinical outcome and the fate of the meniscus allograft after transplantation are scarce . In this study we present the clinical , radiological and MRI outcome of the meniscus graft and the articular cartilage after  42 meniscus allograft transplantations in 41 patients with a minimum follow-up of 10 years . A total of 27 medial and 15 lateral meniscal allografts were transplanted . Eleven of the medial allograft procedures were associated with a high tibial osteotomy . The patients were evaluated clinical ly at the time of transplantation and at the final follow-up using the modified HSS scoring system . The knee injury and osteoarthritis outcome score ( KOOS ) was used as an evaluation tool for patient-related outcome at the final follow-up . Joint space width narrowing and Fairbank changes were radiological outcome parameters , which were available for 32 patients . Femoral and tibial cartilage degeneration , graft extrusion and signal intensity were scored on MRI scans obtained in 17 patients approximately 1 year after transplantation and at the final follow-up ( > 10 years ) . For statistical analysis the patients were divided into three groups : lateral meniscal allograft ( LMT ) , medial meniscal allograft transplantation with a high tibial osteotomy ( MMT+HTO ) and without ( MMT ) . The modified HSS score revealed a significant improvement in pain and function at the final follow-up for all groups . Further analysis also revealed that an MMT+HTO procedure result ed in a greater improvement at the final follow-up when compared to MMT . Nonetheless , the KOOS scores obtained at the final follow-up revealed the presence of substantial disability and symptoms , in addition to a reduced quality of life . Radiographical analysis revealed no further joint space narrowing in 13/32 knees ( 41 % ) . Fairbank changes remained stable in 9/32 knees ( 28 % ) . MRI analysis showed no progression of cartilage degeneration in 6/17 knees ( 35 % ) . An increased signal intensity of the allograft was present , as was partial graft extrusion in the majority of patients at the final follow-up . Seven cases had to be converted to a total knee arthroplasty during the follow-up ; the overall failure rate was 18 % . Long-term results after viable meniscus allograft transplantation are encouraging in terms of pain relief and improvement of function . Despite this significant improvement , substantial disability and symptoms were present in all investigated subgroups . Progression of further cartilage degeneration or joint space narrowing was absent in a considerable number of cases , indicating a potential chondroprotective effect . Level of evidence is therapeutic study , Level IV and retrospective analysis of prospect ively collected data Meniscal injuries in the vascularized peripheral part of the meniscus have a better healing potential than tears in the central avascular zone because meniscal healing principally depends on its vascular supply . Several biological strategies have been proposed to enhance healing of the avascular area of the meniscus : abrasion therapy , fibrin clot , organ culture , cell therapy , and applications of growth factors . However , data are too heterogeneous to achieve definitive conclusions on the use of these techniques for routine management of meniscal lesions . Although most pre clinical and clinical studies are very promising , they are still at an experimental stage . More prospect i ve r and omised controlled trials are needed to compare the different techniques for clinical results , applicability , and cost-effectiveness 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 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 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 
    Output:
    