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 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- 
    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 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- 
    Output:
    