A heparan sulfate device for the regeneration of osteochondral defects

• Main Authors: Lee, Jonathan H., Luo, Xiaoman, Ren, Xiafei, Tan, Tuan Chun, Smith, Raymond A. A., Swaminathan, Kunchithapadam, Sekar, Sakthivel, Bhakoo, Kishore, Nurcombe, Victor, Hui, James H., Cool, Simon M.
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2021
• Subjects: Science::Medicine; Osteochondral Defect; Heparan Sulfate
• Online Access: https://hdl.handle.net/10356/151236
• Institution: Nanyang Technological University

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.