The regeneration of cartilage is challenging due to its low metabolic rate and avascular nature. An effective treatment for osteochondral defects remains a clinical challenge. Glycosaminoglycans such as heparan sulfate (HS) bind and enhance the activity of prochondrogenic growth factors and thus hold potential for targeted tissue regeneration without the requirement for exogenous growth factors. In this study, we examine the use of a cell- and growth factor-free HS-based technique for osteochondral repair in a rabbit model. The binding affinity between HS and several reparative proteins (TGF-β1, BMP-2, FGF-2, PDGF-BB, and VEGF165) was studied using surface plasmon resonance. Next, an HS-impregnated gel was implanted in a large osteochondral defect in the femoral trochlea of 19 New Zealand white rabbits to study the efficacy of the treatment. Over a 12-week period, HS showed significantly enhanced subchondral bone regeneration compared with a hydrogel control. Treatment with HS also resulted in an increased presence of hyaline cartilage in the chondral region. The use of HS in osteochondral defects appears to improve both subchondral and chondral tissue repair. Our data suggest that this effect is mediated by the ability of HS to promote endogenous growth factors.
Impact Statement
Repairing damaged joint cartilage remains a significant challenge. Treatment involving microfracture, tissue grafting, or cell therapy provides some benefit, but seldom regenerates lost articular cartilage. Providing a point-of-care solution that is cell and tissue free has the potential to transform orthopedic treatment for such cases. Glycosaminoglycans such as heparan sulfate (HS) are well suited for this purpose because they provide a matrix that enhances the prochondrogenic activities of growth factors normally found at sites of articular damage. In this study, we show the potential of a novel HS device, which is free of exogenous cells or growth factors, in regenerating osteochondral defects.
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