Speaker
Description
"Introduction
An osteochondral scaffold with a superficial collagen layer for cartilage replacement and a collagen/Magnesium-hydroxyapatite (Mg-HA) layer for bone replacement has demonstrated good clinical results in osteochondral defects [1]. However, subchondral bone repair remained suboptimal, with a long maturation time. In this study, we first confirmed the role of Mg-HA into the collagen-based scaffold on bone repair in vivo, and second, we investigated the added benefit of adding Bone Morphogenetic Protein 2 (BMP-2) or Platelet-Derived Growth Factor-BB (PDGF-BB) to the scaffold and studied their release kinetics in vitro as well as the effect on the bone repair in an osteochondral defect in vivo.
Methodology
Osteochondral defects were created in bovine osteochondral biopsies, filled with scaffolds and implanted subcutaneously in 12-week-old athymic mice for 4 weeks. To confirm the effect of the Mg-HA, osteochondral defects were filled with scaffolds consisting either of collagen-only or collagen/Mg-HA. To study the effect of BMP-2 or PDGF-BB on the bone repair capacity of the scaffold, 4μg BMP-2 or 100ng or 2μg PDGF-BB was loaded into the layered scaffold. The percentage of the defect filled with repair tissue was quantified on safranin-O staining. To investigate inflammation in the defects, immunohistochemistry for myeloperoxidase (MPO), and immunohistochemical stainings for F4/80, iNOS, and CD206 were performed to evaluate the infiltration of neutrophils and M1/M2 macrophages in the defects. To evaluate the release kinetics of BMP-2 and PDGF-BB from the separate layers of the scaffold, the different layers were soaked in BMP-2 or PDGF-BB and their release over time in vitro was measured by ELISA.
Results
More repair tissue was observed in defects filled with collagen/Mg-HA compared to collagen-only, confirming the positive effect of Mg-HA on bone repair. More M1 and M2 macrophages were found in the defects loaded with collagen/Mg-HA scaffolds, indicating that a stronger initial inflammatory response triggered by Mg-HA accelerated the tissue repair in the early phase. The majority of PDGF-BB was burst released from both scaffold layers, whereas BMP-2 was bound and largely retained for 2 weeks in vitro. The collagen/Mg-HA layer retained more growth factors than the collagen-only layer. In vivo addition of both growth factors decreased pro-inflammation and increased tissue repair after 4 weeks, although statistical significance was not reached.
Conclusion
Incorporation of Mg-HA in the collagen scaffold favors tissue repair by a stronger initial inflammatory response. Loading BMP-2 or PDGF-BB into the scaffold might be promising to further accelerate bone repair and is further being investigated in a goat model.
Reference
1. Di Martino, A. et al., Cell-Free Biomimetic Osteochondral Scaffold for the Treatment of Knee Lesions: Clinical and Imaging Results at 10-Year Follow-up. Am J Sports Med. 49(10), 2645-2650 (2021)."
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