A multilayer biomaterial for osteochondral regeneration shows superiority vs microfractures for the treatment of osteochondral lesions in a multicentre randomized trial at 2 years

Elizaveta Kon, Giuseppe Filardo, Mats Brittberg, Maurizio Busacca, Vincenzo Condello, Lars Engebretsen, Stefan Marlovits, Philipp Niemeyer, Patrik Platzer, Michael Posthumus, Peter Verdonk, Renè Verdonk, Jan Victor, Willem van der Merwe, Wojciech Widuchowski, Claudio Zorzi, Maurilio Marcacci, Elizaveta Kon, Giuseppe Filardo, Mats Brittberg, Maurizio Busacca, Vincenzo Condello, Lars Engebretsen, Stefan Marlovits, Philipp Niemeyer, Patrik Platzer, Michael Posthumus, Peter Verdonk, Renè Verdonk, Jan Victor, Willem van der Merwe, Wojciech Widuchowski, Claudio Zorzi, Maurilio Marcacci

Abstract

Purpose: The increasing awareness on the role of subchondral bone in the etiopathology of articular surface lesions led to the development of osteochondral scaffolds. While safety and promising results have been suggested, there are no trials proving the real potential of the osteochondral regenerative approach. Aim was to assess the benefit provided by a nanostructured collagen-hydroxyapatite (coll-HA) multilayer scaffold for the treatment of chondral and osteochondral knee lesions.

Methods: In this multicentre randomized controlled clinical trial, 100 patients affected by symptomatic chondral and osteochondral lesions were treated and evaluated for up to 2 years (51 study group and 49 control group). A biomimetic coll-HA scaffold was studied, and bone marrow stimulation (BMS) was used as reference intervention. Primary efficacy measurement was IKDC subjective score at 2 years. Secondary efficacy measurements were: KOOS, IKDC Knee Examination Form, Tegner and VAS Pain scores evaluated at 6, 12 and 24 months. Tissue regeneration was evaluated with MRI MOCART scoring system at 6, 12 and 24 months. An external independent agency was involved to ensure data correctness and objectiveness.

Results: A statistically significant improvement of all clinical scores was obtained from basal evaluation to 2-year follow-up in both groups, although no overall statistically significant differences were detected between the two treatments. Conversely, the subgroup of patients affected by deep osteochondral lesions (i.e. Outerbridge grade IV and OCD) showed a statistically significant better IKDC subjective outcome (+12.4 points, p = 0.036) in the coll-HA group. Statistically significant better results were also found for another challenging group: sport active patients (+16.0, p = 0.027). Severe adverse events related to treatment were documented only in three patients in the coll-HA group and in one in the BMS group. The MOCART score showed no statistical difference between the two groups.

Conclusions: This study highlighted the safety and potential of a biomimetic implant. While no statistically significant differences were found compared to BMS for chondral lesions, this procedure can be considered a suitable option for the treatment of osteochondral lesions.

Level of evidence: I.

Keywords: Bone marrow stimulation; Cartilage; Knee; Osteochondral; Scaffold.

Conflict of interest statement

Conflict of interest

E. Kon reports grants from Piramal, grants and personal fees from Finceramica, Zimmer-Biomet, Fidia, Green Bone, grants, personal fees and stock from Cartiheal. G. Filardo reports grants and personal fees from Finceramica, Zimmer-Biomet, Fidia, Green Bone, Cartiheal. M. Brittberg reports board membership of Episurf Medical, personal fees from Vericel, Össur, Smith&Nephew, Finceramica, stock from Neurovive, employment as editor in chief of Cartilage (Sage), honoraria from Hong Kong University, royalties from Elsevier and Sage. L. Engebretsen reports grants and personal fees from Arthrex, Inc, grants from Biomet, BJSM, Smith&Nephew, stock from iBalance. P. Niemeyer reports personal fees from Stryker, TiGenix. W. Van Der Merwe reports grants and personal fees from Arthrex, Inc, personal fees from Tornier. P. Verdonk reports personal fees and stock from Active Implants and Orteq Sports Medicine, grants from Cartiheal, personal fees from DePuy and Smith&Nephew. R. Verdonk reports Acad support. J. Victor reports board membership of BVOT/EKS, grants from Zimmer Biomet, De Puy, Stryker, Corin, royalties from Smith&Nephew. C. Zorzi reports personal fees and stock from Active Implants, grants from Pfizer. M. Marcacci reports grants from Finceramica, Zimmer-Biomet, Fidia, grants and personal fees from Green Bone, Cartiheal, Finceramica. M. Busacca, V. Condello, S. Marlovits, P. Platzer, M. Posthumus, W. Widuchowski declare that they have no conflict of interest.

Ethical approval

The study was performed in compliance with the protocol and in accordance with the Declaration of Helsinki, the International Conference of Harmonization Guidelines for Good Clinical Practice, standards from International Organization for Standardization (ISO) and valid international and national regulations. The study was approved by the local ethics committee and internal review board, and informed consent of all patients was obtained.

Figures

Fig. 1
Fig. 1
Flow chart: diagram of the patients eligible, randomized, ITT population and PP population
Fig. 2
Fig. 2
Osteochondral scaffold implantation for a traumatic focal medial femoral condyle lesion of 2 cm2 in a 30-year-old man
Fig. 3
Fig. 3
Change from baseline to 2-year follow-up of KOOS profile (black: coll-HA and grey: BMS)
Fig. 4
Fig. 4
Magnetic resonance imaging evaluation of a coll-HA implant in the medial femoral condyle, showing ongoing osteochondral remodelling at 6 months, 1 and 2 years of follow-up
Fig. 5
Fig. 5
Change from baseline to 2-year follow-up of IKDC Subjective Knee Evaluation score in deep osteochondral lesions subgroup (black: coll-HA and grey: BMS)
Fig. 6
Fig. 6
Change from baseline to 2-year follow-up of IKDC Subjective Knee Evaluation score in sport active patients’ subgroup (black: coll-HA and grey: BMS)
Fig. 7
Fig. 7
Change from baseline to 2-year follow-up of IKDC Subjective Knee Evaluation score in OCD subgroup (black: coll-HA and grey: BMS)

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