Allogenic Bioengineered Cartilage Achieves Hyaline Cartilage Repair in a Large Animal Model: A Promising Step Forward

Background: Chondrocyte-based cell therapy remains a promising method for cartilage repair, despite limitations faced during the last 30 years.Purpose/Hypothesis: This work presents hyaline-like bioengineered beads from donor chondrocytes as a novel treatment option for cartilage lesions. It was hypothesized that the implanted cartilage minigrafts would be able to treat cartilage lesions by complete fusion among themselves and by integration with surrounding tissue. No tissue rejection was expected because of cartilage's reported immunological privilege.Study Design: Controlled laboratory study.Methods: Allogenic cartilage beads with hyaline characteristics were produced from frozen chondrocytes of a minipig donor. A total of 8 G & ouml;ttingen minipigs underwent the implantation of bioengineered cartilage beads into 8 to 10 mm-diameter full-thickness chondral lesions (3 lesions/knee). Animals were sacrificed at 6 weeks (n = 2) and 6 months (n = 6) after implantation. The safety and efficacy of implantation were assessed by macroscopic and histological analyses as well as by magnetic resonance imaging.Results: No signs of acute or chronic rejection were observed in any study animals upon implantation. For 6 minipigs at 6 months, magnetic resonance imaging results showed better coverage of the grafted lesions compared with empty (control) lesions. When the cartilage beads were maintained in the lesion, complete integration of the minigrafts with surrounding subchondral bone and native cartilage was observed. Repair tissue in grafted lesions maintained hyaline-like quality and showed evidence of a chondral zonal arrangement at 6 months' follow-up. Additionally, grafted lesions (n = 17) had better macroscopic repair scores than empty lesions (n = 7) (mean inverse Goebel score, 4.24 and 5.57, respectively). Graft-filled lesions showed only a slight superiority in histological repair scores (mean Bern score, 5.76 and 5.43, respectively).Conclusion: Allogenic cartilage beads hold potential as an advanced therapy medicinal product for treating cartilage lesions in 1-step surgery with established safety and efficacy.Clinical Relevance: This successful preclinical study highlights allogenic cartilage beads as a promising method for cartilage repair. Moreover, using donor chondrocytes may allow reduced patient morbidity and 1-step surgery. Hence, this advanced therapy medicinal product is suitable for treating large lesions and older patients and is currently being evaluated in a phase I/IIa clinical trial. Chondrocyte-based cell therapy remains a promising method for cartilage repair, despite limitations faced during the last 30 years.This work presents hyaline-like bioengineered beads from donor chondrocytes as a novel treatment option for cartilage lesions. It was hypothesized that the implanted cartilage minigrafts would be able to treat cartilage lesions by complete fusion among themselves and by integration with surrounding tissue. No tissue rejection was expected because of cartilage's reported immunological privilege.Controlled laboratory study.Allogenic cartilage beads with hyaline characteristics were produced from frozen chondrocytes of a minipig donor. A total of 8 Göttingen minipigs underwent the implantation of bioengineered cartilage beads into 8 to 10 mm-diameter full-thickness chondral lesions (3 lesions/knee). Animals were sacrificed at 6 weeks (n = 2) and 6 months (n = 6) after implantation. The safety and efficacy of implantation were assessed by macroscopic and histological analyses as well as by magnetic resonance imaging.No signs of acute or chronic rejection were observed in any study animals upon implantation. For 6 minipigs at 6 months, magnetic resonance imaging results showed better coverage of the grafted lesions compared with empty (control) lesions. When the cartilage beads were maintained in the lesion, complete integration of the minigrafts with surrounding subchondral bone and native cartilage was observed. Repair tissue in grafted lesions maintained hyaline-like quality and showed evidence of a chondral zonal arrangement at 6 months' follow-up. Additionally, grafted lesions (n = 17) had better macroscopic repair scores than empty lesions (n = 7) (mean inverse Goebel score, 4.24 and 5.57, respectively). Graft-filled lesions showed only a slight superiority in histological repair scores (mean Bern score, 5.76 and 5.43, respectively).Allogenic cartilage beads hold potential as an advanced therapy medicinal product for treating cartilage lesions in 1-step surgery with established safety and efficacy.This successful preclinical study highlights allogenic cartilage beads as a promising method for cartilage repair. Moreover, using donor chondrocytes may allow reduced patient morbidity and 1-step surgery. Hence, this advanced therapy medicinal product is suitable for treating large lesions and older patients and is currently being evaluated in a phase I/IIa clinical trial.

Vanarix
Ctr Biomed Imaging
Geneva Univ Hosp
Hirslanden Clin La Colline
Veterinärmedizinische Universität Wien
University of Geneva