Characterized Chondrocyte Implantation Results in Better Structural Repair When Treating Symptomatic Cartilage Defects of the Knee in a Randomized Controlled Trial Versus Microfracture

doi:10.1177/0363546507311095

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Characterized Chondrocyte Implantation Results in Better Structural Repair When Treating Symptomatic Cartilage Defects of the Knee in a Randomized Controlled Trial Versus Microfracture

Daniel B. F. Saris, MD, PhD^a^,*, Johan Vanlauwe, MD^b, Jan Victor, MD^c, Miroslav Haspl, MD, PhD^d, Michael Bohnsack, MD^e, Yves Fortems, MD^f, Bruno Vandekerckhove, MD^g, K. Frederik Almqvist, MD, PhD^h, Toon Claes, MDⁱ, Frank Handelberg, MD^j, Koen Lagae, MD^k, Jan van der Bauwhede, MD^l, Hilde Vandenneucker, MD^b, K. Gie Auw Yang, MD, PhD^a, Mislav Jelic, MD, PhD^d, Rene Verdonk, MD, PhD^h, Nancy Veulemans, Ir^m, Johan Bellemans, MD, PhD^b and Frank P. Luyten, MD, PhDⁿ

From the ^a Department of Orthopedics, University Medical Center Utrecht, Utrecht, the Netherlands, ^b Department Orthopedics, University Hospitals Leuven, Leuven, Belgium, ^c Department of Orthopedics, AZ St Lucas Brugge, Brugge, Belgium, ^d Department of Orthopaedic Surgery, School of Medicine, University of Zagreb, Zagreb, Croatia, ^e Department of Orthopedic Surgery, Hannover Medical School, Hannover, Germany, ^f Department of Orthopedics, AZ St Jozef, Malle, Belgium, ^g Department of Orthopedics, AZ St Jan Brugge, Brugge, Belgium, ^h Department of Orthopedics, Ghent University Hospital, Ghent, Belgium, ⁱ Department of Orthopedics, AZ St Elisabeth, Herentals, Belgium, ^j Department of Orthopedics, Universitair Ziekenhuis Brussel, Brussels, Belgium, ^k SPM Monica, Antwerp, Belgium, ^l Department of Orthopedics, AZ Groeninge, Kortrijk, Belgium, ^m Clinical Affairs, TiGenix NV, Leuven, Belgium, and ⁿ Division of Rheumatology, Department of Musculoskeletal Sciences, University Hospitals, Katholieke Universiteit Leuven, Leuven, Belgium

^* Address correspondence to Daniel B. F. Saris, MD, PhD, PO Box 85500, 3508 GA Utrecht, the Netherlands (e-mail: d.saris{at}umcutrecht.nl).

Background: As the natural healing capacity of damaged articularcartilage is poor, joint surface injuries are a prime targetfor regenerative medicine. Characterized chondrocyte implantationuses an autologous cartilage cell therapy product that has beenoptimized for its biological potency to form stable cartilagetissue in vivo.

Purpose: To determine whether, in symptomatic cartilage defectsof the femoral condyle, structural regeneration with characterizedchondrocyte implantation is superior to repair with microfracture.

Study Design: Randomized controlled trial; Level of evidence,1.

Methods: Characterized chondrocyte implantation was comparedwith microfracture in patients with single grade III to IV symptomaticcartilage defects of the femoral condyles in a multicenter trial.Patients aged 18 to 50 years were randomized to characterizedchondrocyte implantation (n = 57) or microfracture (n = 61).Structural repair was blindly assessed in biopsy specimens takenat 1 year using (1) computerized histomorphometry and (2) evaluationof overall histological components of structural repair. Clinicaloutcome was measured using the self administered Knee injuryand Osteoarthritis Outcome Score. Adverse events were recordedthroughout the study.

Results: Characterized chondrocyte implantation resulted inbetter structural repair, as assessed by histomorphometry (P= .003) and overall histologic evaluation (P = .012). Aspectsof structural repair relating to chondrocyte phenotype and tissuestructure were superior with characterized chondrocyte implantation.Clinical outcome as measured by the Knee injury and OsteoarthritisOutcome Score at 12 to 18 months after characterized chondrocyteimplantation was comparable with microfracture at this stage.Both treatment groups had a similar mean baseline overall Kneeinjury and Osteoarthritis Outcome Score (56.30 ± 13.61and 59.53 ± 14.95 for microfracture and characterizedchondrocyte implantation, respectively), which increased inboth groups to 70.56 ± 12.39 and 72.63 ± 15.55at 6 months, 73.26 ± 14.66 and 73.10 ± 16.01 at12 months, and 74.73 ± 17.01 and 75.04 ± 14.50at 18 months, respectively. Both techniques were generally welltolerated; the incidence of adverse events after characterizedchondrocyte implantation was not markedly increased comparedwith that for microfracture.

Conclusion: One year after treatment, characterized chondrocyteimplantation was associated with a tissue regenerate that wassuperior to that after microfracture. Short-term clinical outcomewas similar for both treatments. The superior structural outcomemay result in improved long-term clinical benefit with characterizedchondrocyte implantation. Long-term follow-up is needed to confirmthese findings.

Key Words: chondrocyte • chondral • regenerative medicine • autologous chondrocyte implantation (ACI) • characterized chondrocyte implantation (CCI) • cell therapy product • microfracture • cartilage repair

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