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(Rabbit Studies)Tj
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( )Tj
EMC
1.125 0 Td
[(Histologic evalua)-9.8 (tions were performed a)-9.8 (t 8,)37 ( 12 and 52 weeks.)37.1 ( Improved healing of experimental defects im)]TJ
39.573 0 Td
(-)Tj
-39.573 -1.2 Td
[(planted with autologous chondroc)20.2 (ytes was obser)-17.8 (ved compared to periosteal \037a)-9.7 (p alone a)-9.9 (t 8,)37 ( 12 and 52 weeks.)]TJ
/T1_0 1 Tf
-1.125 -1.762 Td
(Dog Study)Tj
/T1_1 1 Tf
T*
(\225)Tj
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( )Tj
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[(Histologic evalua)-9.8 (tions were performed a)-9.8 (t 6 and 12 weeks and 12 and 18 months.)37.3 ( )37 (Autologous chondroc)20.1 (ytes )]TJ
T*
[(sho)-10 (wed improved healing compared to both empty defects and to defects cover\
ed with periosteum alone a)-9 (t )]TJ
T*
[(6 and 12 weeks.)37.1 ( Ho)-9.9 (wever)74 (,)37 ( by the 12 and 18 month evalua)-9.7 (tions,)37 ( the repair tissue had deteriora)-9.7 (ted so tha)-9.9 (t no )]TJ
T*
[(advanta)-9.9 (ge of )37 (ACI over periosteum alone controls was demonstra)-9.5 (ted.)]TJ
-1.125 -1.492 Td
[(Beyond histologic variability of the defect site,)37.4 ( no adverse tissue reaction was identi\036ed in an)-9.6 (y animals in these )]TJ
T*
(studies.)Tj
/T1_0 1 Tf
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[(P)24 (ost-Appro)-10 (v)16.1 (al Studies)]TJ
/T1_1 1 Tf
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[(F)18 (ive additional large animal,)37.3 ( post-a)-10 (pproval studies were performed.)]TJ
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(Goat Studies )Tj
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(-)Tj
0 -1.2 TD
[(dia)-10 (tely after periosteal membrane placement.)37.4 ( Despite dif\036culty in post-opera)-9.7 (tive mana)-9.9 (gement of goa)-9.8 (ts and )]TJ
T*
[(resulting subchondral pla)-9.8 (te colla)-9.9 (pse in some animals in the 16-week studies,)37.3 ( results from all four studies )]TJ
T*
[(suggested tha)-9.9 (t chondroc)20.1 (ytes may contribute to histological repair of focal cartila)-9.5 (ge lesions.)37.1 ( In the only bila)-9.8 (teral )]TJ
T*
[(joint stud)-9.9 (y)55 (,)37 ( serious subchondral colla)-9.8 (pse and uniformly poor repair resulted in inconc)20.4 (lusive da)-10 (ta.)37.1 ( No safety )]TJ
T*
[(issues were identi\036ed in an)-9.8 (y of these studies.)]TJ
/T1_0 1 Tf
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(Horse Study )Tj
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(\225)Tj
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EMC
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[(The 8-week stud)-9.9 (y inc)20.1 (luded two experimental arms in order to model repair of cartila)-9.4 (ge lesions with or without )]TJ
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[(subchondral penetra)-9.8 (tion.)37 ( Both models exhibited destruction/dislodgement of the periosteal \037a)-9.4 (p; ho)-10 (wever)74.1 (,)37 ( )]TJ
T*
[(results suggested tha)-9.8 (t chondroc)20 (ytes may contribute to histologic repair in cartila)-9.5 (ge defects with subchondral )]TJ
T*
[(penetra)-9.9 (tion.)]TJ
-1.125 -1.492 Td
[(While the defects in all animal models exhibited highly variable repair \
tissue quality \(resulting in only modera)-9.1 (te )]TJ
T*
[(histologic scores\) the best repairs with implanted chondroc)20.5 (ytes produced hy)-9.9 (aline-like cartila)-9.8 (ge characterized )]TJ
T*
[(by ma)-9.9 (trix predomina)-9.9 (ting in type II colla)-9.8 (gen and saffranin-O or toluidine blue staining proteoglycan.)37.4 ( Chondroc)20.1 (yte )]TJ
T*
(labeling in one of the rabbit studies)Tj
4.664 0 0 4.664 114.4336 322.4921 Tm
(8)Tj
8 0 0 8 116.6723 319.8281 Tm
[( and in an independent stud)-9.8 (y in goa)-9.9 (ts by Dell\222Accio et al)]TJ
4.664 0 0 4.664 282.4846 322.4921 Tm
(10)Tj
8 0 0 8 286.962 319.8281 Tm
[( demonstra)-9.9 (ted )]TJ
-34.558 -1.2 Td
[(tha)-10 (t the hy)-9.9 (aline-like ma)-9.8 (trix in these defects was the product of the implanted autologous chondr\
oc)20.6 (ytes.)]TJ
/T1_0 1 Tf
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(14.)Tj
/Span<>> BDC
1.163 0 Td
( )Tj
EMC
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[(CLINIC)18 (AL STUDIES)]TJ
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(14.1)Tj
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( )Tj
EMC
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[(Pre-Appro)-10 (v)16 (al Studies)]TJ
/T1_1 1 Tf
-4.5 -1.492 Td
[(Clinical informa)-9.9 (tion regarding the use of autologous cultured chondroc)20.5 (ytes was obtained from 2 open-label,)37.3 ( ob)]TJ
(-)Tj
0 -1.2 TD
[(ser)-18 (va)-9.9 (tional studies consisting of a series of pa)-9.7 (tients trea)-9.8 (ted in Sweden and the Cartila)-9.8 (ge Repair Registr)-17.9 (y)55.1 (.)37 ( P)18 (a)-10 (tients )]TJ
T*
[(in the Swedish series received an autologous cultured chondroc)20.5 (yte product similar to Carticel)]TJ
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(\256)Tj
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(.)Tj
/T1_0 1 Tf
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(14.1.1)Tj
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( )Tj
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(Swedish Series)Tj
/T1_1 1 Tf
-4.5 -1.492 Td
[(The series consists of 153 pa)-9.8 (tients who received autologous chondroc)20.4 (yte implanta)-9.9 (tion for various defects of the )]TJ
T*
[(knee.)37.1 ( P)18 (a)-10 (tients presented with cartila)-9.7 (ge defects of the femoral cond)-9.7 (yle,)37 ( pa)-10 (tella,)37.1 ( tibia,)37 ( a combina)-9.9 (tion of these,)37.1 ( or )]TJ
T*
[(osteochondritis dissecans,)37.2 ( with or without comorbidity such as anterior crucia)-9.6 (te ligament insuf\036cienc)20.2 (y requiring )]TJ
T*
(reconstruction.)Tj
0 -1.762 TD
[(F)20 (ollo)-10 (wing autologous chondroc)20.2 (yte implanta)-9.9 (tion,)37.1 ( pa)-10 (tients were follo)-9.8 (wed for various dura)-9.8 (tions.)37 ( Clinical follo)-9.9 (w-)]TJ
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[(up ranged from 1 week to 94 months; 86 pa)-9.6 (tients had a)-9.9 (t least 18 months of follo)-9.8 (w-up.)37.1 ( Most pa)-10 (tients had )]TJ
T*
[(arthroscopic evalua)-9.8 (tion; a subset had biopsy and histological evalua)-9.6 (tions.)37 ( )37 (All pa)-9.9 (tients were retrospectively )]TJ
T*
[(c)20 (lassi\036ed as ha)-9.9 (ving one of three c)20.2 (linical outcomes:)37.1 ( resumed all activities,)37.2 ( some improvement,)37.2 ( or no improvement.)37.2 ( )216 ( )]TJ
T*
[(Clinical outcomes were also reported for pa)-9.6 (tient subgroups inc)20.1 (luding:)37.1 ( 1\) 40 pa)-10 (tients with femoral cond)-9.8 (yle lesions,)37.1 ( )]TJ
T*
[(2\) 12 pa)-9.9 (tients with osteochondritis dissecans lesions and 3\) 22 pa)-9.6 (tients who failed a prior debridement.)]TJ
/T1_0 1 Tf
0 -1.762 TD
[(1\) Clinical Outcome - P)24.1 (atients with F)20.1 (emoral Condyle Lesions )]TJ
/T1_1 1 Tf
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[(A total of 78 of 153 pa)-9.8 (tients had femoral cond)-9.8 (yle lesions with or without co-morbidity)55.4 (.)37 ( P)18 (a)-10 (tients had one or more )]TJ
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(defects ranging in size from < 1-20 cm)Tj
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(2)Tj
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[(.)37 ( Of the pa)-9.9 (tients with femoral cond)-9.8 (yle lesions,)37.1 ( 40 were evaluable after a)-9.7 (t )]TJ
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[(least 18 months \(median = 25; range = 18 to 94 months\).)37.4 ( Clinical outcomes for the 40 pa)-9.7 (tients are summarized )]TJ
T*
(in )Tj
/T1_0 1 Tf
[(T)74 (able 5.)]TJ
58.461 65.933 Td
[(T)74 (able 5: P)24 (atient Response to T)74.2 (reatment)]TJ
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BT
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(Defect)Tj
-0.037 Tw 15.078 0 Td
(Resumed All )Tj
0 Tw T*
(Activities)Tj
6.547 1.2 Td
(Some )Tj
T*
(Improvement)Tj
6.86 1.2 Td
(No )Tj
T*
(Improvement)Tj
6.314 1.2 Td
[(T)74 (otal )]TJ
T*
[(P)18 (a)-10 (tients)]TJ
-34.799 -1.857 Td
[(F)24 (emoral )]TJ
T*
[(Cond)-10 (yle)]TJ
17.54 1.2 Td
(7)Tj
-0.86 -1.2 Td
(\(29%\))Tj
7.564 1.2 Td
(8)Tj
-0.86 -1.2 Td
(\(33%\))Tj
7.448 1.2 Td
(9)Tj
-0.86 -1.2 Td
(\(38%\))Tj
6.729 1.2 Td
(24)Tj
-36.699 -3.057 Td
[(F)24 (emoral Cond)-9.9 (yle plus other )]TJ
T*
[(Non-Cartila)-9.9 (ge Repair)]TJ
17.54 1.2 Td
(4)Tj
-0.86 -1.2 Td
(\(25%\))Tj
7.564 1.2 Td
(9)Tj
-0.86 -1.2 Td
(\(56%\))Tj
7.448 1.2 Td
(3)Tj
-0.86 -1.2 Td
(\(19%\))Tj
6.729 1.2 Td
(16)Tj
-36.699 -3.057 Td
[(T)74 (otal)]TJ
17.3 0 Td
(11)Tj
-0.62 -1.2 Td
(\(28%\))Tj
7.324 1.2 Td
(17)Tj
-0.62 -1.2 Td
(\(42%\))Tj
7.208 1.2 Td
(12)Tj
-0.62 -1.2 Td
(\(30%\))Tj
6.729 1.2 Td
(40)Tj
/T1_0 1 Tf
8 0 0 8 371.5 490.0364 Tm
[(2\) Clinical Outcome - P)24.1 (atients With Osteochondritis Dissecans Lesions)]TJ
/T1_1 1 Tf
0 -1.492 TD
[(Of the 12 pa)-9.9 (tients who received autologous cultured chondroc)20.4 (ytes for trea)-9.9 (tment of an osteochondritis lesion,)37.4 ( 6 of )]TJ
0 -1.2 TD
[(the 12 had )37.1 (\223resumed all activities\224,)37.2 ( 4 had )37 (\223some improvement\224)37.2 ( and 2 had )37.1 (\223no improvement\224)37.1 ( after the 18-month )]TJ
T*
[(\(median = 25; range = 18-94 months\) follo)-9.7 (w-up period.)]TJ
/T1_0 1 Tf
0 -1.785 TD
[(3\) Clinical Outcome - F)20.1 (ailed Earlier Procedures)]TJ
/T1_1 1 Tf
0 -1.492 TD
[(Debridement of the cartila)-9.7 (ge defect is often performed along with administra)-9.6 (tion of autologous cultured )]TJ
0 -1.2 TD
[(chondroc)20 (ytes.)37.1 ( )37 (T)74 (o help differentia)-9.8 (te the effects of the autologous cultured chondroc)20.4 (yte implanta)-9.9 (tion procedure )]TJ
T*
[(from those of debridement alone,)37.3 ( an analysis was performed on 22 pa)-9.7 (tients who had failed prior debridement )]TJ
T*
[(and had a follo)-9.9 (w-up period after autologous cultured chondroc)20.4 (yte implanta)-9.9 (tion which was a)-9.8 (t least as long as the )]TJ
T*
[(time period to failure of their initial debridement.)37.5 ( )37 (At the end of follo)-9.8 (w-up,)37 ( 5 of the 22 pa)-9.9 (tients had a functional )]TJ
T*
[(outcome ra)-9.9 (ting of )37.1 (\223resumed all activities\224,)37.2 ( 8 of the 22 pa)-9.9 (tients had a ra)-9.8 (ting of )37 (\223some improvement\224)37.2 ( and 9 of )]TJ
T*
[(the 22 pa)-9.9 (tients had a ra)-9.9 (ting of )37.1 (\223no improvement\224.)37.1 ( )37 (Thus,)37 ( 13 of the 22 pa)-9.8 (tients \(59%\) who had failed an earlier )]TJ
T*
[(debridement had outcomes tha)-9.7 (t were more fa)-9.9 (vorable and durable follo)-9.7 (wing autologous cultured chondroc)20.2 (yte )]TJ
T*
[(implanta)-9.9 (tion than their previous debridement without cells.)]TJ
/T1_0 1 Tf
0 -1.785 TD
(Histological Outcome)Tj
/T1_1 1 Tf
0 -1.492 TD
[(T)74 (wenty-two \(22\) pa)-9.9 (tients in the Swedish series had histological evalua)-9.5 (tion of biopsies from the implant site one )]TJ
0 -1.2 TD
[(or more years after their autologous chondroc)20.4 (yte implanta)-9.8 (tion.)37 ( F)18 (ifteen \(15\) of those pa)-9.8 (tients had defects of the )]TJ
T*
[(femoral cond)-9.9 (yle and 7 had defects of the pa)-9.7 (tella.)37.1 ( Six \(6\) of the 15 femoral cond)-9.8 (yle biopsies sho)-9.8 (wed hy)-10 (aline-like )]TJ
T*
[(cartila)-9.9 (ge,)37 ( 5 had a mixture of hy)-9.8 (aline and \036brocartila)-9.8 (ge,)37 ( and 4 had only \036brocartila)-9.8 (ge.)37.1 ( Of the 6 biopsies with hy)-9.8 (a)]TJ
(-)Tj
T*
[(line-like cartila)-9.8 (ge,)37 ( 2 had minimal to no surface irregularities and 4 had some surface irreg\
ularities \(e.g.,)37.7 ( \036ssures,)37.1 ( )]TJ
T*
[(\036brilla)-9.9 (tions,)37 ( etc.\).)]TJ
/T1_0 1 Tf
0 -1.492 TD
(Arthroscopic Outcome)Tj
/T1_1 1 Tf
T*
[(As an objective outcome evalua)-9.7 (tion,)37 ( 86 of the 153 pa)-9.8 (tients had a follo)-9.9 (w-up arthroscopy for investiga)-9.7 (tional pur)]TJ
40.518 0 Td
(-)Tj
-40.518 -1.2 Td
[(poses a)-9.9 (t 18 months or more post-implanta)-9.7 (tion.)37 ( In some cases,)37.1 ( the quality of repair obser)-17.7 (ved a)-9.9 (t arthroscopy was )]TJ
0 -1.2 TD
[(considered to be supportive of the c)20.3 (linical or functional outcomes.)37.3 ( )37 (A substantial number of pa)-9.8 (tients were noted a)-9.8 (t )]TJ
T*
[(arthroscopy to ha)-9.8 (ve tissue hypertrophy )]TJ
/T1_2 1 Tf
[([see )37 (Adverse Reactions \(6\)])]TJ
/T1_1 1 Tf
(.)Tj
/T1_0 1 Tf
0 -1.492 TD
(14.1.2)Tj
/Span<>> BDC
( )Tj
EMC
4.5 0 Td
[(Cartilage Repair Registr)-17.8 (y)]TJ
/T1_1 1 Tf
-4.5 -1.492 Td
[(The Cartila)-9.9 (ge Repair Registr)-17.8 (y \(CRR\) was established upon the introduction of Carticel)]TJ
4.664 0 0 4.664 621.9664 207.7604 Tm
(\256)Tj
8 0 0 8 625.6976 205.0964 Tm
( into orthopedic practice )Tj
-31.775 -1.2 Td
[(in March of 1995.)37.1 ( )37 (The CRR was designed to prospectively collect the c)20.4 (linical outcomes of Carticel and other )]TJ
0 -1.2 TD
[(cartila)-9.9 (ge repair trea)-9.9 (tments for chondral lesions in the knee.)37.4 ( Clinical da)-9.9 (ta were collected a)-9.8 (t baseline arthroscopy)55.1 (,)37 ( )]TJ
T*
[(implanta)-9.9 (tion,)37 ( inter)-17.9 (vals of 6 and 12 months,)37.2 ( and annually thereafter; adverse reaction da)-9.6 (ta were collected on an )]TJ
T*
[(ongoing basis through CRR adverse reaction collection and spontaneous re\
porting.)37.6 ( Inc)20.1 (lusion in the CRR was )]TJ
T*
[(based on a qualifying event tha)-9.7 (t was de\036ned as a knee arthroscopy in which a chondral lesion was ide\
nti\036ed )]TJ
T*
[(and a cartila)-9.9 (ge biopsy was har)-17.8 (vested.)37 ( P)18 (articipa)-9.9 (tion in the CRR was voluntar)-17.7 (y)54.9 (,)37.1 ( and not all pa)-9.9 (tients biopsied or )]TJ
T*
[(implanted were inc)20.1 (luded.)37.1 ( )37 (As of November 21,)37.1 ( 1997,)37 ( 891 pa)-9.9 (tients had been implanted worldwide,)37.3 ( and 644 of )]TJ
T*
[(these pa)-9.9 (tients were inc)20.1 (luded in the CRR.)37.1 ( Functional outcomes were based on responses to a modi\036ed version of\
)]TJ
T*
[(the Cincinna)-9.9 (ti Knee Ra)-9.9 (ting System.)]TJ
0 -1.492 TD
[(Da)-10 (ta from a subset of 191 US pa)-9.7 (tients in the CRR as of December 31,)37.3 ( 1996 who had undergone repair of lesions )]TJ
0 -1.2 TD
[(on the femoral cond)-9.8 (yle \(medial,)37.1 ( la)-10 (teral or trochlea\) were assessed to support licensure.)37.5 ( P)18 (a)-10 (tients were between )]TJ
T*
[(the a)-9.9 (ges of 15-57,)37 ( 66% \(126/191\) were male,)37.2 ( and 34% \(64/191\) were female and one pa)-9.6 (tient\222)55 (s gender was not )]TJ
T*
[(reported.)37.1 ( Of these 191 pa)-9.9 (tients,)37.1 ( 38 had a)-9.9 (t least 12 months of follo)-9.8 (w-up.)37 ( )37 (At stud)-9.9 (y baseline,)37.1 ( these 38 pa)-9.9 (tients\222 )]TJ
T*
[(mean ra)-9.9 (ting of overall condition was 3.2,)37.3 ( which is de\036ned as fair to poor:)37.2 ( limita)-9.9 (tions tha)-9.9 (t affect activities of daily )]TJ
T*
[(living-no sports possible.)37.2 ( )37 (At 12 month follo)-9.9 (w-up,)37.1 ( these pa)-10 (tients reported an overall condition score of 6.4 de\036ned )]TJ
T*
[(as good:)37.1 ( some limita)-9.9 (tion with sports but can participa)-9.7 (te if pa)-9.9 (tient compensa)-9.9 (tes.)37 ( )37 (Although these pa)-9.9 (tients were )]TJ
T*
[(ra)-10 (ted according to outcome measurements different from those used in the S\
wedish series,)37.8 ( the results were )]TJ
T*
(consistent with the Swedish experience.)Tj
/T1_0 1 Tf
44.938 71.221 Td
(14.2)Tj
/Span<>> BDC
( )Tj
EMC
4.5 0 Td
[( P)24 (ost-Appro)-9.9 (v)16 (al Studies)]TJ
/T1_1 1 Tf
-4.5 -1.2 Td
[(T)74 (wo post-a)-9.9 (pproval studies were conducted and completed as a condition of a)-9.5 (pproval for Carticel)]TJ
4.664 0 0 4.664 1015.8413 592.7921 Tm
(\256)Tj
8 0 0 8 1019.5724 590.1281 Tm
[(:)37 ( the Registr)-17.9 (y )]TJ
-36.072 -1.2 Td
[(Based Stud)-9.9 (y \(RBS\) and the Stud)-9.9 (y of the )37.1 (T)74 (rea)-10 (tment of )37.1 (Articular Repair \(ST)55.1 (AR\).)]TJ
/T1_0 1 Tf
0 -1.492 TD
(14.2.1 )Tj
/Span<>> BDC
( )Tj
EMC
4.5 0 Td
[(Registr)-18 (y-Based Study \(RBS\))]TJ
/T1_1 1 Tf
-4.5 -1.493 Td
[(The RBS was a retrospective analysis of da)-9.6 (ta collected for a cohort of 97 US pa)-9.7 (tients trea)-9.9 (ted between March of )]TJ
0 -1.2 TD
[(1995 and March of 1997.)37.2 ( Of the 97 pa)-9.9 (tients enrolled,)37.1 ( 95% completed 1-year follo)-9.7 (w-up,)37 ( 80% completed 2-year )]TJ
0 -1.2 TD
[(follo)-10 (w-up and 74% completed 3-year follo)-9.6 (w-up.)37 ( Of these 97 pa)-9.9 (tients,)37.1 ( 44 were part of the subset of 191 US )]TJ
T*
[(pa)-10 (tients in the CRR described above.)37.3 ( )37 (A limita)-9.9 (tion of this stud)-9.9 (y is the lack of a control group.)37.3 ( P)18 (a)-10 (tients inc)20.1 (luded in )]TJ
0 -1.2 TD
[(this stud)-9.9 (y had a prior non-Carticel cartila)-9.7 (ge repair procedure \(e.g.,)37.2 ( debridement or marro)-9.8 (w stimula)-9.9 (tion procedure\) )]TJ
0 -1.2 TD
[(performed a)-9.9 (t the time of the index arthroscopy)55.4 (,)37 ( subsequently failed this procedure and went on to receive )]TJ
0 -1.2 TD
[(Carticel.)37.1 ( In the 5 years prior to the index arthroscopy for the stud)-9.5 (y)55 (,)37 ( this pa)-9.9 (tient popula)-9.9 (tion had received prior knee )]TJ
0 -1.2 TD
[(surgeries to inc)20.1 (lude:)37 ( 47% \(46/97\) of pa)-9.8 (tients had a)-9.9 (t least one debridement/la)-9.8 (va)-9.9 (ge of a cartila)-9.9 (ge defect,)37.1 ( 25% )]TJ
0 -1.2 TD
[(\(24/97\) of pa)-9.9 (tients had a bone marro)-9.8 (w stimula)-9.9 (tion procedure,)37.1 ( 31% \(30/97\) had a)-9.9 (t least one dia)-9.8 (gnostic arthros)]TJ
(-)Tj
0 -1.2 TD
[(copy)55 (,)37 ( 30% \(29/97\) had a)-9.9 (t least one meniscus repair/meniscectomy and 10% \(10/97\) of pa)-9.4 (tients had a ligament )]TJ
0 -1.2 TD
[(repair/reconstruction performed on the trea)-9.6 (ted knee.)]TJ
0 -1.492 TD
[(Using a modi\036ed Cincinna)-9.8 (ti Knee Ra)-9.9 (ting System a)-9.9 (t stud)-10 (y baseline,)37.1 ( this pa)-9.9 (tient popula)-9.9 (tion had a mean overall )]TJ
0 -1.2 TD
[(condition score of 3.1 de\036ned as fair to poor:)37.4 ( limita)-9.9 (tions tha)-9.9 (t affect activities of daily living-no sports possible.)37.4 ( )]TJ
0 -1.2 TD
[(P)18 (a)-10 (tients inc)20.1 (luded were between the a)-9.8 (ges of 16-56,)37.1 ( 69% \(67/97\) were male and 31% \(30/97\) were female.)37.4 ( F)20 (or )]TJ
0 -1.2 TD
[(the type of defect,)37.2 ( 62% \(60/97\) of the defects were acute while 37% \(36/97\) were chroni\
c.)37.5 ( Of the trea)-9.8 (ted defects,)37.1 ( )]TJ
0 -1.2 TD
[(75% \(73/97\) were trea)-9.8 (ted on the medial femoral cond)-9.7 (yle \(MFC\),)37 ( 26% \(25/97\) on the la)-9.8 (teral femoral cond)-9.8 (yle \(LFC\) )]TJ
0 -1.2 TD
[(and 19% \(18/97\) on the trochlea.)37.2 ( )37 (Adverse reactions collected during this stud)-9.6 (y are provided in )37.1 (Adverse Reactions )]TJ
0 -1.2 TD
(\(6\).)Tj
/T1_0 1 Tf
0 -1.785 TD
[(14.2.2 Study of the T)74.1 (reatment of Articular Repair \(ST)55.2 (AR\))]TJ
/T1_1 1 Tf
0 -1.492 TD
[(The ST)55 (AR stud)-9.9 (y was an open-label within pa)-9.8 (tient comparison of a prior non-Carticel \(index\) procedure to )]TJ
0 -1.2 TD
[(implanta)-9.9 (tion of Carticel for articular cartila)-9.7 (ge defects of the distal femur)74.3 (.)37 ( )37 (All pa)-9.9 (tients had experienced an )]TJ
0 -1.2 TD
[(inadequa)-9.9 (te response to a prior non-Carticel surgical trea)-9.6 (tment,)37.1 ( de\036ned as both:)37.1 ( a\) pa)-9.9 (tient and surgeon )]TJ
T*
[(a)-10 (greement tha)-9.9 (t the pa)-9.9 (tient\222)55.1 (s symptoms/function required surgical re-trea)-9.6 (tment of the defect and b\) the pa)-9.7 (tient\222)55 (s )]TJ
0 -1.2 TD
[(ra)-10 (ting of the overall condition of the knee was a score \035 5 using the M\
odi\036ed Cincinna)-9.3 (ti Knee Ra)-9.9 (ting System.)37.1 ( )]TJ
0 -1.2 TD
[(In this pa)-9.9 (tient popula)-9.9 (tion,)37 ( the median time to meet the failure criteria was 3.4 months for the pri\
or non-Carticel )]TJ
0 -1.2 TD
[(procedure and 90% of pa)-9.8 (tients failed within 10.3 months.)37.3 ( P)18 (a)-10 (tients who met these criteria were trea)-9.6 (ted with )]TJ
0 -1.2 TD
[(Carticel and assessed ever)-17.8 (y 6 months for up to 4 years.)]TJ
0 -1.492 TD
[(T)74 (rea)-10 (tment failure for Carticel was de\036ned as an)-9.6 (y of the follo)-9.8 (wing:)37 ( a\) the pa)-9.9 (tient underwent surgical retrea)-9.7 (tment )]TJ
0 -1.2 TD
[(tha)-10 (t viola)-9.9 (ted the subchondral bone or reimplanta)-9.7 (tion with Carticel for the same index defect,)37.5 ( b\) complete )]TJ
0 -1.2 TD
[(delamina)-9.9 (tion or removal of the graft,)37.3 ( or c\) the pa)-9.9 (tient\222)55 (s ra)-9.9 (ting of the overall condition of the knee using the )]TJ
0 -1.2 TD
[(Modi\036ed Cincinna)-9.9 (ti Knee Ra)-9.9 (ting System failed to improve from the baseline knee score over 3 consec\
utive )]TJ
0 -1.2 TD
[(6-month inter)-17.9 (vals.)]TJ
0 -1.492 TD
[(A total of 154 pa)-9.8 (tients were trea)-9.9 (ted with Carticel.)37.2 ( )37 (At the index surger)-17.9 (y required for stud)-9.8 (y entr)-17.9 (y)55 (,)37 ( pa)-10 (tients had one )]TJ
0 -1.2 TD
[(or more of the follo)-9.8 (wing inter)-17.9 (ventions:)37.1 ( 120 pa)-10 (tients \(78%\) had debridement,)37.3 ( 44 pa)-10 (tients \(29%\) had microfracture,)37.3 ( )]TJ
0 -1.2 TD
[(18 \(12%\) had subchondral drilling,)37.2 ( 10 \(6%\) had abrasion arthroplasty)55.3 (,)37 ( and 7 \(5%\) had an osteochondral autograft.)37.3 ( )]TJ
0 -1.2 TD
[(The mean lesion size was 4.6 \(\261 3.2,)37.3 ( SD\) cm)]TJ
4.664 0 0 4.664 863.8054 209.2722 Tm
(2)Tj
8 0 0 8 866.0441 206.6082 Tm
[(.)37 ( F)18 (ifty pa)-9.9 (tients \(32%\) had multiple lesions in the reference knee )]TJ
-16.881 -1.2 Td
[(and 29 pa)-9.9 (tients had Carticel implanted in more than one lesion.)37.4 ( Lesions tha)-9.9 (t were implanted were loca)-9.7 (ted on the )]TJ
T*
[(medial femoral cond)-9.8 (yle in 109 pa)-9.9 (tients,)37 ( la)-9.9 (teral femoral cond)-9.8 (yle in 32 pa)-9.9 (tients and trochlea in 46 pa)-9.8 (tients.)37.1 ( F)20 (orty )]TJ
T*
[(pa)-10 (tients \(26%\) had lesions which involved osteochondritis dissecans \(OC\
D\).)]TJ
0 -1.492 TD
[(Of the 154 pa)-9.9 (tients trea)-9.9 (ted with Carticel,)37.2 ( 28 pa)-10 (tients discontinued the stud)-9.8 (y early)55.1 (.)37 ( )37 (The numbers of pa)-9.9 (tients )]TJ
0 -1.2 TD
[(completing the 24 and 48 month follo)-9.7 (w-up visits are 136 and 115,)37.2 ( respectively)55.1 (.)37 ( )37 (The majority of Carticel pa)-9.7 (tients )]TJ
T*
[(\(N= 117\) did not meet failure criteria during the stud)-9.6 (y)55 (.)37 ( By the end of the stud)-9.8 (y)55 (,)37 ( a total of 37 pa)-9.8 (tients met the )]TJ
T*
[(trea)-9.9 (tment failure criteria.)37.2 ( Results for the 40 pa)-9.8 (tients with OCD lesions were comparable to the total stud)-9.5 (y )]TJ
T*
[(popula)-10 (tion as 34 \(85%\) did not meet the failure criteria for the stud)-9.4 (y and 6 \(15%\) failed trea)-9.8 (tment with Carticel.)37.2 ( )]TJ
/T1_0 1 Tf
T*
[(T)74 (able 6)]TJ
/T1_1 1 Tf
[( illustra)-9.9 (tes,)37 ( during each year of follo)-9.7 (w-up,)37 ( the number of pa)-9.8 (tients who failed Carticel by the surgical )]TJ
T*
[(criteria along with the number of pa)-9.7 (tients who failed by the Overall Modi\036ed Cincinna)-9.6 (ti scale criteria.)]TJ
/T1_0 1 Tf
7 0 0 7 754.1678 96.3282 Tm
[(T)74 (able 6: Categor)-17.9 (y and T)18.1 (iming of T)74 (reatment F)20.1 (ailure for P)24 (atients who Met T)74.1 (reatment F)20.1 (ailure Criteria \(N=37\))]TJ
ET
0 0 0 0.27 k
/GS2 gs
748.582 87.328 143.858 -16.568 re
892.44 87.328 30.187 -16.568 re
922.626 87.328 30.783 -16.568 re
953.409 87.328 32.797 -16.568 re
986.206 87.328 32.682 -16.568 re
1018.888 87.328 31.13 -16.568 re
f
/GS1 gs
q 1 0 0 1 748.0819 87.3281 cm
0 0 m
144.358 0 l
S
Q
q 1 0 0 1 748.5819 71.2603 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 892.4398 87.3281 cm
0 0 m
30.187 0 l
S
Q
q 1 0 0 1 892.4398 71.2603 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 922.6263 87.3281 cm
0 0 m
30.783 0 l
S
Q
q 1 0 0 1 922.6263 71.2603 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 953.4093 87.3281 cm
0 0 m
32.797 0 l
S
Q
q 1 0 0 1 953.4093 71.2603 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 986.2064 87.3281 cm
0 0 m
32.682 0 l
S
Q
q 1 0 0 1 986.2064 71.2603 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 1018.8881 87.3281 cm
0 0 m
31.63 0 l
S
Q
q 1 0 0 1 1018.8881 71.2603 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 1050.0181 71.2603 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 748.0819 70.7603 cm
0 0 m
144.358 0 l
S
Q
q 1 0 0 1 748.5819 58.2623 cm
0 0 m
0 11.998 l
S
Q
q 1 0 0 1 892.4398 70.7603 cm
0 0 m
30.187 0 l
S
Q
q 1 0 0 1 892.4398 58.2623 cm
0 0 m
0 11.998 l
S
Q
q 1 0 0 1 922.6263 70.7603 cm
0 0 m
30.783 0 l
S
Q
q 1 0 0 1 922.6263 58.2623 cm
0 0 m
0 11.998 l
S
Q
q 1 0 0 1 953.4093 70.7603 cm
0 0 m
32.797 0 l
S
Q
q 1 0 0 1 953.4093 58.2623 cm
0 0 m
0 11.998 l
S
Q
q 1 0 0 1 986.2064 70.7603 cm
0 0 m
32.682 0 l
S
Q
q 1 0 0 1 986.2064 58.2623 cm
0 0 m
0 11.998 l
S
Q
q 1 0 0 1 1018.8881 70.7603 cm
0 0 m
31.63 0 l
S
Q
q 1 0 0 1 1018.8881 58.2623 cm
0 0 m
0 11.998 l
S
Q
q 1 0 0 1 1050.0181 58.2623 cm
0 0 m
0 11.998 l
S
Q
q 1 0 0 1 748.0819 57.7623 cm
0 0 m
144.358 0 l
S
Q
q 1 0 0 1 748.5819 41.6945 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 892.4398 57.7623 cm
0 0 m
30.187 0 l
S
Q
q 1 0 0 1 892.4398 41.6945 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 922.6263 57.7623 cm
0 0 m
30.783 0 l
S
Q
q 1 0 0 1 922.6263 41.6945 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 953.4093 57.7623 cm
0 0 m
32.797 0 l
S
Q
q 1 0 0 1 953.4093 41.6945 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 986.2064 57.7623 cm
0 0 m
32.682 0 l
S
Q
q 1 0 0 1 986.2064 41.6945 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 1018.8881 57.7623 cm
0 0 m
31.63 0 l
S
Q
q 1 0 0 1 1018.8881 41.6945 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 1050.0181 41.6945 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 748.0819 41.1945 cm
0 0 m
144.358 0 l
S
Q
q 1 0 0 1 748.5819 25.1266 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 892.4398 41.1945 cm
0 0 m
30.187 0 l
S
Q
q 1 0 0 1 892.4398 25.1266 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 922.6263 41.1945 cm
0 0 m
30.783 0 l
S
Q
q 1 0 0 1 922.6263 25.1266 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 953.4093 41.1945 cm
0 0 m
32.797 0 l
S
Q
q 1 0 0 1 953.4093 25.1266 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 986.2064 41.1945 cm
0 0 m
32.682 0 l
S
Q
q 1 0 0 1 986.2064 25.1266 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 1018.8881 41.1945 cm
0 0 m
31.63 0 l
S
Q
q 1 0 0 1 1018.8881 25.1266 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 1050.0181 25.1266 cm
0 0 m
0 15.568 l
S
Q
q 1 0 0 1 748.0819 24.6266 cm
0 0 m
144.358 0 l
S
Q
q 1 0 0 1 892.4398 24.6266 cm
0 0 m
30.187 0 l
S
Q
q 1 0 0 1 922.6263 24.6266 cm
0 0 m
30.783 0 l
S
Q
q 1 0 0 1 953.4093 24.6266 cm
0 0 m
32.797 0 l
S
Q
q 1 0 0 1 986.2064 24.6266 cm
0 0 m
32.682 0 l
S
Q
q 1 0 0 1 1018.8881 24.6266 cm
0 0 m
31.63 0 l
S
Q
BT
0 0 0 1 k
/GS0 gs
/T1_1 1 Tf
-0.037 Tw 7 0 0 7 896.4398 78.3302 Tm
[(1 Y)75 (ear)]TJ
4.312 0 Td
[(2 Y)75 (ears)]TJ
4.398 0 Td
[(3 Y)75 (ears)]TJ
4.685 0 Td
[(4 Y)75 (ears)]TJ
0 Tw 4.669 0 Td
[(T)74 (otal)]TJ
-38.615 -2.367 Td
[(P)18 (a)-10 (tients who F)20.1 (ailed During the Inter)-17.8 (val)]TJ
20.551 0 Td
(14)Tj
4.312 0 Td
(11)Tj
4.398 0 Td
(11)Tj
4.685 0 Td
(1)Tj
4.669 0 Td
(37)Tj
-37.329 -1.857 Td
[(Surger)-17.9 (y criteria)]TJ
19.265 0 Td
(0)Tj
4.312 0 Td
(5)Tj
4.398 0 Td
(5)Tj
4.685 0 Td
(1)Tj
4.669 0 Td
(11)Tj
-37.329 -2.367 Td
[(Overall Modi\036ed Cincinna)-9.8 (ti Scale criteria)]TJ
19.265 0 Td
(14)Tj
4.312 0 Td
(6)Tj
4.398 0 Td
(6)Tj
4.685 0 Td
(0)Tj
4.669 0 Td
(26)Tj
8 0 0 8 1091.5 599.7281 Tm
[(The Overall Modi\036ed Cincinna)-9.8 (ti mean baseline score for the pa)-9.7 (tient popula)-9.9 (tion as a whole was 3.26,)37.2 ( poor:)37.1 ( )]TJ
T*
[(signi\036cant limita)-9.9 (tions tha)-9.9 (t affect activities of daily living,)37.3 ( to fair:)37.1 ( modera)-9.9 (te limita)-9.9 (tions tha)-9.9 (t affect activities of daily )]TJ
T*
[(living,)37 ( no sports possible.)37.2 ( )37 (At 48 months,)37.1 ( the mean score was 6.39,)37.2 ( good:)37 ( some limita)-9.9 (tions with sports but can )]TJ
T*
[(participa)-9.9 (te/compensa)-9.9 (te.)37 ( )37 (The improvement was sta)-9.8 (tistically signi\036cant.)37.2 ( )]TJ
/T1_0 1 Tf
[(T)74 (able 7)]TJ
/T1_1 1 Tf
[( sho)-9.9 (ws the improvement in the )]TJ
T*
[(Overall Modi\036ed Cincinna)-9.8 (ti score over time.)]TJ
/T1_0 1 Tf
7 0 0 7 1148.1134 547.0481 Tm
[(T)74 (able 7: Mean Overall Modi\037ed Cincinnati Score at Baseline and Follow-\
up Visits)]TJ
ET
/GS1 gs
q 1 0 0 1 1099.2655 540.2081 cm
0 0 m
143.3 0 l
S
Q
q 1 0 0 1 1099.7655 518.9 cm
0 0 m
0 20.808 l
S
Q
q 1 0 0 1 1242.5656 540.2081 cm
0 0 m
38.703 0 l
S
Q
q 1 0 0 1 1242.5656 518.9 cm
0 0 m
0 20.808 l
S
Q
q 1 0 0 1 1281.2683 540.2081 cm
0 0 m
35.576 0 l
S
Q
q 1 0 0 1 1281.2683 518.9 cm
0 0 m
0 20.808 l
S
Q
q 1 0 0 1 1316.8445 540.2081 cm
0 0 m
34.985 0 l
S
Q
q 1 0 0 1 1316.8445 518.9 cm
0 0 m
0 20.808 l
S
Q
q 1 0 0 1 1351.8291 540.2081 cm
0 0 m
34.246 0 l
S
Q
q 1 0 0 1 1351.8291 518.9 cm
0 0 m
0 20.808 l
S
Q
q 1 0 0 1 1386.0753 540.2081 cm
0 0 m
34.259 0 l
S
Q
q 1 0 0 1 1386.0753 518.9 cm
0 0 m
0 20.808 l
S
Q
q 1 0 0 1 1419.8345 518.9 cm
0 0 m
0 20.808 l
S
Q
q 1 0 0 1 1099.2655 518.4 cm
0 0 m
143.3 0 l
S
Q
q 1 0 0 1 1099.7655 489.1021 cm
0 0 m
0 28.798 l
S
Q
q 1 0 0 1 1242.5656 518.4 cm
0 0 m
38.703 0 l
S
Q
q 1 0 0 1 1242.5656 489.1021 cm
0 0 m
0 28.798 l
S
Q
q 1 0 0 1 1281.2683 518.4 cm
0 0 m
35.576 0 l
S
Q
q 1 0 0 1 1281.2683 489.1021 cm
0 0 m
0 28.798 l
S
Q
q 1 0 0 1 1316.8445 518.4 cm
0 0 m
34.985 0 l
S
Q
q 1 0 0 1 1316.8445 489.1021 cm
0 0 m
0 28.798 l
S
Q
q 1 0 0 1 1351.8291 518.4 cm
0 0 m
34.246 0 l
S
Q
q 1 0 0 1 1351.8291 489.1021 cm
0 0 m
0 28.798 l
S
Q
q 1 0 0 1 1386.0753 518.4 cm
0 0 m
34.259 0 l
S
Q
q 1 0 0 1 1386.0753 489.1021 cm
0 0 m
0 28.798 l
S
Q
q 1 0 0 1 1419.8345 489.1021 cm
0 0 m
0 28.798 l
S
Q
q 1 0 0 1 1099.2655 488.6021 cm
0 0 m
143.3 0 l
S
Q
q 1 0 0 1 1242.5656 488.6021 cm
0 0 m
38.703 0 l
S
Q
q 1 0 0 1 1281.2683 488.6021 cm
0 0 m
35.576 0 l
S
Q
q 1 0 0 1 1316.8445 488.6021 cm
0 0 m
34.985 0 l
S
Q
q 1 0 0 1 1351.8291 488.6021 cm
0 0 m
34.246 0 l
S
Q
q 1 0 0 1 1386.0753 488.6021 cm
0 0 m
34.259 0 l
S
Q
BT
/GS0 gs
/T1_1 1 Tf
7 0 0 7 1165.7896 531.2101 Tm
(Visit)Tj
12.168 0 Td
(Baseline )Tj
0.266 -1.2 Td
(N=154)Tj
4.837 1.2 Td
(Month 12 )Tj
0.468 -1.2 Td
(N=146)Tj
4.572 1.2 Td
(Month 24 )Tj
0.468 -1.2 Td
(N=131)Tj
4.477 1.2 Td
(Month 36 )Tj
0.468 -1.2 Td
(N=104)Tj
4.389 1.2 Td
(Month 48 )Tj
0.468 -1.2 Td
(N=101)Tj
-41.443 -1.915 Td
[(Overall Modi\036ed Cincinna)-9.8 (ti Score)]TJ
4.081 0 0 4.081 1189.3596 511.733 Tm
(1 )Tj
7 0 0 7 1103.7654 501.002 Tm
(Mean \(SD\))Tj
21.753 1.2 Td
(3.26)Tj
-0.241 -1.2 Td
(\(1.02\))Tj
5.547 1.2 Td
(5.58 )Tj
-0.241 -1.2 Td
(\(1.99\))Tj
5.281 1.2 Td
(5.92 )Tj
-0.241 -1.2 Td
(\(2.08\))Tj
5.186 1.2 Td
(5.87 )Tj
-0.241 -1.2 Td
(\(2.19\))Tj
5.099 1.2 Td
(6.39 )Tj
-0.241 -1.2 Td
(\(2.31\))Tj
4.081 0 0 4.081 1100.4999 481.5331 Tm
(1)Tj
7 0 0 7 1102.4587 479.2021 Tm
[(Scores are for pa)-9.8 (tients who returned for follo)-9.7 (w-up.)37 ( P)18 (a)-10 (tients who failed by score criteria are inc)20.4 (luded and pa)-10 (tients who failed )]TJ
-0.28 -1.2 Td
[(by surgical criteria are exc)20.2 (luded from the scores for timepoints after the failure criteria were met\
.)]TJ
8 0 0 8 1091.4999 456.7021 Tm
[(In addition to the change over time in activity level as measured with t\
he Overall Modi\036ed Cincinna)-9.1 (ti Scale,)37 ( there )]TJ
T*
[(were similar and consistent changes in knee symptoms and function as mea\
sured with the Knee Injur)-17.2 (y and Os)]TJ
(-)Tj
T*
[(teoarthritis Outcome Score \(KOOS\),)37.3 ( a measure of knee-speci\036c symptoms and function consisting of the fo\
llo)-9.4 (wing )]TJ
T*
[(\036ve subscales:)37.1 ( pain,)37 ( symptoms,)37.1 ( sports and recrea)-9.8 (tion,)37 ( knee-rela)-9.9 (ted quality of life,)37.2 ( and activities of daily living.)37.2 ( )37 (At )]TJ
T*
(12 months post-Carticel)Tj
4.664 0 0 4.664 1162.8503 420.9661 Tm
(\256)Tj
8 0 0 8 1166.5815 418.3021 Tm
[( implant,)37.1 ( the mean improvement from baseline for the pa)-9.5 (tient popula)-9.9 (tion as a whole in )]TJ
-9.385 -1.2 Td
[(each subscale was as follo)-9.8 (ws:)37 ( pain 19 \(N = 146\),)37.1 ( symptoms 15 \(N = 147\),)37.2 ( sports and recrea)-9.8 (tion 17 \(N = 129\),)37.1 ( )]TJ
T*
[(knee-rela)-9.9 (ted quality of life 18 \(N = 147\),)37.3 ( and activities of daily living 18 \(N = 145\).)37.3 ( )37 (At 48 months post-Carticel )]TJ
T*
[(implant,)37.1 ( the mean improvement from baseline was as follo)-9.5 (ws:)36.9 ( pain 24 \(N = 100\),)37.2 ( symptoms 19 \(N = 101\),)37.1 ( sports )]TJ
T*
[(and recrea)-9.9 (tion 31 \(N = 86\),)37.1 ( knee-rela)-9.9 (ted quality of life 32 \(N = 101\),)37.3 ( and activities of daily living 23 \(N = 99\).)37.3 ( )]TJ
0 -1.492 TD
[(Adverse reactions collected during this stud)-9.7 (y are provided in )37.2 (Adverse Reactions \(6\).)]TJ
/T1_0 1 Tf
3.097 Tw 0 -1.785 TD
(15.)Tj
/Span<>> BDC
1.163 0 Td
( )Tj
EMC
(REFERENCES)Tj
/T1_1 1 Tf
-0.037 Tc 0.037 Tw -0.6 -1.492 Td
[(1)-37 (.)]TJ
/Span<>> BDC
( )Tj
EMC
0 Tc 0 Tw 1.687 0 Td
[(Knutsen G,)37.1 ( Engebretsen L,)37.1 ( Ludvigsen )37 (T)92 (,)37 ( )]TJ
/T1_2 1 Tf
(et al.)Tj
/T1_1 1 Tf
[( )37 (Autologous chondroc)20.1 (yte implanta)-9.8 (tion compared with microf)]TJ
(-)Tj
0 -1.2 TD
[(racture in the knee.)37.2 ( )]TJ
/T1_2 1 Tf
(J Bone Joint Surg,)Tj
/T1_1 1 Tf
( 2004; 86A:455-464.)Tj
-0.037 Tc 0.037 Tw -1.687 -1.2 Td
[(2)-37 (.)]TJ
/Span<>> BDC
( )Tj
EMC
0 Tc 0 Tw 1.687 0 Td
[(Bentley G,)37.1 ( Biant LC,)37.1 ( Carrington R)-19.9 (WJ,)37 ( )]TJ
/T1_2 1 Tf
(et al.)Tj
/T1_1 1 Tf
[( )37 (A prospective,)37.1 ( randomized comparison of autologous chon)]TJ
(-)Tj
T*
[(droc)20 (yte implanta)-9.9 (tion versus mosaicplasty for osteochondral defects in the knee.)37.6 ( )]TJ
/T1_2 1 Tf
[(J Bone Joint Surg Br)74.2 (.)]TJ
/T1_1 1 Tf
( )Tj
T*
(2003;85-B:223-230.)Tj
-0.037 Tc 0.037 Tw -1.687 -1.2 Td
[(3)-37 (.)]TJ
/Span<>> BDC
( )Tj
EMC
0 Tc 0 Tw 1.687 0 Td
[(Brittberg M,)37.1 ( Lindahl )37 (A,)37 ( Nilsson )37.1 (A,)37 ( )]TJ
/T1_2 1 Tf
(et al.)Tj
/T1_1 1 Tf
[( )37.1 (T)73.9 (rea)-9.9 (tment of deep cartila)-9.8 (ge defects in the knee with autologous )]TJ
T*
[(chondroc)20 (yte transplanta)-9.8 (tion.)37 ( )]TJ
/T1_2 1 Tf
(N Engl J Med.)Tj
/T1_1 1 Tf
( 1994;331:889-895.)Tj
-0.037 Tc 0.037 Tw -1.687 -1.2 Td
[(4)-37 (.)]TJ
/Span<>> BDC
( )Tj
EMC
0 Tc 0 Tw 1.687 0 Td
[(P)18 (eterson L,)37 ( Minas )37.1 (T)92.1 (,)37 ( Brittberg M,)37 ( )]TJ
/T1_2 1 Tf
(et al.)Tj
/T1_1 1 Tf
[( )37.1 (T)74 (wo- to 9-year outcome after autologous chondroc)20.1 (yte transplanta)-9.9 (tion )]TJ
T*
[(of the knee.)37.1 ( )]TJ
/T1_2 1 Tf
(Clin Orthop.)Tj
/T1_1 1 Tf
( 2000;1\(374\):212-234.)Tj
-0.037 Tc 0.037 Tw -1.687 -1.2 Td
[(5)-37 (.)]TJ
/Span<>> BDC
( )Tj
EMC
0 Tc 0 Tw 1.687 0 Td
[(P)18 (eterson L,)37.1 ( Brittberg M,)37.1 ( Kiviranta I,)37.1 ( )]TJ
/T1_2 1 Tf
(et al.)Tj
/T1_1 1 Tf
[( )37 (Autologous chondroc)20.1 (yte transplanta)-9.9 (tion.)37.1 ( Biomechanics and long-)]TJ
T*
[(term durability)55.1 (.)37 ( )]TJ
/T1_2 1 Tf
[(Am J Sports Med.)37.2 ( )]TJ
/T1_1 1 Tf
(2002;30:2-12.)Tj
-0.037 Tc 0.037 Tw -1.687 -1.2 Td
[(6)-37 (.)]TJ
/Span<>> BDC
( )Tj
EMC
0 Tc 0 Tw 1.687 0 Td
[(P)18 (eterson L,)37.1 ( Menche D,)37.1 ( Grande D,)37 ( )]TJ
/T1_2 1 Tf
(et al.)Tj
/T1_1 1 Tf
[( Chondroc)20.1 (yte transplanta)-9.9 (tion-an experimental model in the rabbit.)37.4 ( )]TJ
T*
[(T)74 (ransactions from the 30)]TJ
4.664 0 0 4.664 1183.2024 229.2061 Tm
(th)Tj
8 0 0 8 1186.5697 226.5421 Tm
[( )37 (Annual Orthopedic Research Society)55.2 (,)37.1 ( )36.9 (Atlanta,)37.1 ( F)24 (ebruar)-17.9 (y 7-9,)37 ( 1984.)37 ( P)18 (ala)-9.9 (tine,)37 ( )]TJ
-9.634 -1.2 Td
[(III.:Orthopedic Research Society)55.2 (,)37.1 ( 1984:218.)37 ( )37 (Abstract.)]TJ
-0.037 Tc 0.037 Tw -1.687 -1.2 Td
[(7)-37 (.)]TJ
/Span<>> BDC
( )Tj
EMC
0 Tc 0 Tw 1.687 0 Td
[(Grande DA,)37.1 ( Pitman MI,)37.1 ( P)18 (eterson L,)37.1 ( )]TJ
/T1_2 1 Tf
(et al.)Tj
/T1_1 1 Tf
[( )37 (The repair of experimentally produced defects in rabbit articular )]TJ
T*
[(cartila)-9.9 (ge by autologous chondroc)20.2 (yte transplanta)-9.9 (tion.)37 ( )]TJ
/T1_2 1 Tf
[(J Orthop Res.)37.1 ( )]TJ
/T1_1 1 Tf
(1989;7\(2\):208-18.)Tj
-0.037 Tc 0.037 Tw -1.687 -1.2 Td
[(8)-37 (.)]TJ
/Span<>> BDC
( )Tj
EMC
0 Tc 0 Tw 1.687 0 Td
[(Brittberg M,)37.1 ( Nilsson )37 (A,)37 ( Lindahl )37.1 (A,)37 ( )]TJ
/T1_2 1 Tf
(et al.)Tj
/T1_1 1 Tf
[( Rabbit articular cartila)-9.7 (ge defects trea)-9.9 (ted with autologous cultured )]TJ
T*
[(chondroc)20 (ytes.)37.1 ( )]TJ
/T1_2 1 Tf
[(Clin Orthop Rela)-9.9 (t Res.)]TJ
/T1_1 1 Tf
( 1996 May;\(326\):270-83.)Tj
-0.037 Tc 0.037 Tw -1.687 -1.2 Td
[(9)-37 (.)]TJ
/Span<>> BDC
( )Tj
EMC
0 Tc 0 Tw 1.687 0 Td
[(Breinan H,)37.1 ( Minas )37 (T)92 (,)37 ( Barone L,)37.1 ( )]TJ
/T1_2 1 Tf
[(et al.)37.1 ( )]TJ
/T1_1 1 Tf
[(Histological evalua)-9.9 (tion of the course of healing of canine articular carti)]TJ
39.036 0 Td
(-)Tj
-39.036 -1.2 Td
[(la)-10 (ge defects trea)-9.8 (ted with cultured autologous chondroc)20.3 (ytes.)37 ( )]TJ
/T1_2 1 Tf
[(T)18 (iss Engin)]TJ
/T1_1 1 Tf
( 1998; 4\(1\):101-14.)Tj
-1.687 -1.2 Td
(10.)Tj
/Span<>> BDC
1.163 0 Td
( )Tj
EMC
-0.001 Tw 0.525 0 Td
[(Dell\222Accio F)111 (,)37 ( )37 (V)17.9 (anlauwe J,)37.1 ( Bellemans,)37.1 ( )]TJ
/T1_2 1 Tf
(et al.)Tj
/T1_1 1 Tf
[( Expanded phenotypically stable chondroc)20.1 (ytes persist in the repair )]TJ
0 Tw T*
[(tissue and contribute to cartila)-9.7 (ge ma)-10 (trix forma)-9.8 (tion and structural integra)-9.8 (tion in a goa)-9.9 (t model of autologous )]TJ
T*
[(chondroc)20 (yte implanta)-9.8 (tion.)37 ( )]TJ
/T1_2 1 Tf
(Journal of Orthopaedic Research)Tj
/T1_1 1 Tf
[( 21 2003; 21:)37.1 ( 123\226131.)]TJ
/T1_0 1 Tf
-2.25 -1.492 Td
(16.)Tj
/Span<>> BDC
1.163 0 Td
( )Tj
EMC
3.337 0 Td
(HOW SUPPLIED/STORAGE AND HANDLING)Tj
-4.5 -1.785 Td
(16.1)Tj
/Span<>> BDC
( )Tj
EMC
4.5 0 Td
(How Supplied)Tj
/T1_1 1 Tf
-4.5 -1.492 Td
[(The Carticel product,)37.2 ( NDC 69866-1025-1,)37 ( consists of viable,)37.2 ( autologous cells packa)-9.8 (ged and labeled for im)]TJ
(-)Tj
T*
[(planta)-9.9 (tion within speci\036ed time limits.)37.2 ( Each vial contains a)-9.8 (pproxima)-9.9 (tely 12 million autologous cells for a single )]TJ
T*
[(implanta)-9.9 (tion procedure.)]TJ
0 -1.492 TD
[(The shipping vials containing chondroc)20.2 (ytes are accompanied by a technical da)-9.6 (ta sheet with detailed speci\036ca)]TJ
(-)Tj
0 -1.2 TD
[(tions for the processed cells.)37.3 ( )36.9 (The vial\(s\) of cells is placed within secondar)-17.6 (y packa)-9.9 (ging ca)-10 (pable of maintaining the )]TJ
T*
[(a)-10 (ppropria)-9.9 (te stora)-9.9 (ge tempera)-9.9 (ture and cell viability for up to 72 hours.)]TJ
/T1_0 1 Tf
45.115 69.711 Td
(16.2)Tj
/Span<>> BDC
( )Tj
EMC
4.5 0 Td
(Storage and Handling)Tj
/T1_1 1 Tf
-4.5 -1.492 Td
(The Carticel)Tj
4.664 0 0 4.664 1487.6672 590.4521 Tm
(\256 )Tj
8 0 0 8 1492.5177 587.7881 Tm
[(transport box should be held a)-9.8 (t room tempera)-9.8 (ture and remain c)20.2 (losed until the time of implanta)-9.9 (tion )]TJ
-5.012 -1.2 Td
[(to ensure proper stora)-9.8 (ge conditions for the cells.)]TJ
/T1_0 1 Tf
0 -2.055 TD
[(Do Not Refrigerate,)37.1 ( Freeze,)37.1 ( or Incubate the Carticel Shipping Container or its Contents.)37.3 ( )]TJ
0 -1.492 TD
(Do Not Sterilize.)Tj
T*
[(If the Vial is Damaged or Sterility has been Compromised,)37.4 ( Do Not Use.)]TJ
0 -1.785 TD
(17.)Tj
/Span<>> BDC
1.163 0 Td
( )Tj
EMC
3.337 0 Td
[(P)54 (A)55 (TIENT COUNSELING INFORMA)55.1 (TION)]TJ
/T1_1 1 Tf
-4.5 -1.492 Td
[(P)18 (a)-10 (tients receiving autologous cultured chondroc)20.4 (ytes for trea)-9.9 (tment of an articular cartila)-9.7 (ge defect should receive )]TJ
0 -1.2 TD
[(the follo)-9.9 (wing informa)-9.9 (tion and instructions.)]TJ
1.125 -1.492 Td
(\225)Tj
/Span<>> BDC
( )Tj
EMC
1.125 0 Td
[(Physical activity should be resumed according to the rehabilita)-9.5 (tion plan recommended by the physician.)37.3 ( )]TJ
T*
[(Generally)55.1 (,)37 ( protected weight bearing is recommended for the \036rst 6 to 8 weeks fo\
llo)-9.3 (wing implanta)-9.9 (tion.)37 ( )37 (The )]TJ
T*
[(pa)-10 (tient should receive speci\036c instructions on crutch use,)37.4 ( ambula)-9.9 (tion and weight bearing advancement on )]TJ
T*
[(the trea)-9.9 (ted limb.)]TJ
-1.125 -1.2 Td
(\225)Tj
/Span<>> BDC
( )Tj
EMC
1.125 0 Td
[(If pain starts to develop as the next level of activity is increased,)37.6 ( decrease activity to the former level until )]TJ
T*
(the pain resolves.)Tj
-1.125 -1.2 Td
(\225)Tj
/Span<>> BDC
( )Tj
EMC
1.125 0 Td
[(If exercise causes pain and/or s)-9.7 (welling,)37 ( reduce the amount of physical activity)55.3 (.)]TJ
-1.125 -1.2 Td
(\225)Tj
/Span<>> BDC
( )Tj
EMC
1.125 0 Td
(Swelling should be controlled using ice packs.)Tj
-1.125 -1.2 Td
(\225)Tj
/Span<>> BDC
( )Tj
EMC
1.125 0 Td
[(P)18 (a)-10 (tient adherence to the prescribed rehabilita)-9.6 (tion program is important and activity a)-9.6 (t variance from the )]TJ
T*
[(rehabilita)-9.9 (tion program may compromise c)20.3 (linical bene\036t from Carticel.)]TJ
-1.125 -1.2 Td
(\225)Tj
/Span<>> BDC
( )Tj
EMC
1.125 0 Td
[(At an)-10 (ytime during the rehabilita)-9.7 (tion process or after)74.2 (,)37 ( if sharp pain with locking or s)-9.8 (welling is experienced,)37.2 ( )]TJ
T*
(contact the physician for medical advice.)Tj
15.294 -2.4 Td
[(V)18 (ericel Corpora)-9.9 (tion )]TJ
0.433 -1.492 Td
(64 Sidney Street)Tj
-3.107 -1.492 Td
[(Cambridge,)37.1 ( MA 02139-4136 USA )]TJ
-2.046 -1.492 Td
[(T)74 (elephone:)37.1 ( 800-453-6948 or 617-588-5566)]TJ
4.604 -1.492 Td
[(F)20 (ax:)37 ( 844-333-2847)]TJ
-17.427 -3.548 Td
(Carticel)Tj
4.664 0 0 4.664 1474.7875 291.8321 Tm
(\256)Tj
8 0 0 8 1478.5186 289.1681 Tm
[( is a Registered )37.1 (T)74 (rademark of )37.2 (V)18 (ericel Corpora)-9.9 (tion.)]TJ
36.413 -1.2 Td
(65001)Tj
-1.635 -1.2 Td
(Revision M)Tj
0.877 -1.2 Td
(11/2015)Tj
-177.054 -31.778 Td
(7)Tj
45.205 0 Td
(8)Tj
44.875 0 Td
(9)Tj
44.583 0 Td
(10)Tj
45.115 0 Td
(11)Tj
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