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Osteochondral regeneration with scaffold: in vivo study in sheep model

Description

Objectives Joints trauma and disease frequently involve structural damage to the entire osteochondral unit, composed by two different tissues: the articular cartilage surface and the underlying subchondral bone. A biomimetic resorbable scaffold has been developed for the treatment of symptomatic osteochondral lesions thanks to the presence of three distinct but integrated layers which make an organic mineral gradient. This study aimed at evaluating the performance of this osteochondral implant in an ovine trochlea defect model in terms of new cartilage and bone tissue formation.

Methods Bilateral critical-sized osteochondral defects (7 mm diameter and 5.5 mm depth) were created in the trochlear grooves of 22 skeletally mature sheep. The defects in one knee were filled with the scaffold (treatment group), whereas the contralateral defect was left empty (control group). One group of animals was sacrificed at 6 months and another one at a longer follow-up of 12 months. The osteochondral explants were subjected to gross analysis, micro-computed tomography (micro-CT), and ICRS II histological scoring to evaluate the quality of the osteochondral tissue repair.

Results Overall, significantly better results were documented when the osteochondral scaffold was implanted. The mean global ICRS II score at 6 months was 41% vs 30%, respectively, p=0.004, and at 12 months 54% vs 37%, respectively, p=0.002) (Figure 1). Histologically, a progressive higher overall improvement of the cartilage and bone tissue repair was seen at 6 and 12 months in the treatment group in terms of basal integration with subjacent bone, subchondral bone abnormalities, structural integrity with surrounding tissue, and amount of new bone formation. There was significant new trabecular bone growth across the entire bony defect area of the osteochondral defect with excellent filling of the bony defect area with new bone/marrow, in contrast to the control group defects where new bone growth was limited to the edges of the superficial portion of the bony defect area, with presence of fibrosis and sheets of adipose tissue within the center and deep portions. The micro-CT revealed a higher percentage of bone in the treatment group compared to controls both at 6 months (BV/TV 48.8±8.6% vs 37.4±9.5%, p<0.001) and 12 months (BV/TV 51.8±8.8% vs 42.1±12.6%, respectively; p=0.023).

Conclusions The osteochondral implant showed a significant effect in promoting new bone growth within the bony portion of the defect compared to control empty defects and a progression towards formation of cartilage-like tissue within the superficial layer of the defect. The ability to promote both cartilage and subchondral bone regeneration in this large animal model supports its potential for the treatment of the complex joint lesions involving the entire osteochondral unit.

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Authors

A D

Alessandro Di Martino

MD

Applied and Translational Research Center, IRCCS Istituto Ortopedico Rizzoli, Bologna

M S

Manuela Salerno

PhD

Applied and Translational Research Center, IRCCS Istituto Ortopedico Rizzoli, Bologna

E G

Elisabetta Galassi

Fin-Ceramica Faenza S.p.a., Faenza, Italy

L G

Laura Grillini

Fin-Ceramica Faenza S.p.a., Faenza, Italy

A D

Alessandro Dotti

Fin-Ceramica Faenza S.p.a., Faenza, Italy

G F

Giuseppe Filardo

MD, PhD, MBA, Prof

Applied and Translational Research Center, IRCCS Istituto Ortopedico Rizzoli, Bologna

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