Kops, N. | Search bioRxiv

bioRxiv2023

Incorporating strontium enriched amorphous calcium phosphate granules in collagen/collagen-magnesium-hydroxyapatite osteochondral scaffold improves subchondral bone repair

To date, osteochondral defect repair with a collagen/collagen-magnesium-hydroxyapatite (Col/Col-Mg-HAp) scaffold has demonstrated good clinical results. However, subchondral bone repair has been suboptimal, potentially leading to damage to the regenerated overlying neocartilage. This study aimed at improving the bone repair potential of this scaffold by incorporating strontium (Sr) ion enriched amorphous calcium phosphate (Sr-ACP) granules (100-150 {micro}m). Sr concentration of Sr-ACP was determined with ICP-MS at 2.49 {+/-} 0.04 wt.%. Then 30 wt.% ACP or Sr-ACP granules were integrated into the scaffold prototypes. The ACP or Sr-ACP granules were well distributed and embedded in the collagenic matrix demonstrated by micro-CT and scanning electron microscopy/energy dispersive x-ray spectrometry. Good cytocompatibility of ACP/Sr-ACP granules and ACP/Sr-ACP enriched scaffolds was confirmed in in vitro cytotoxicity assays. An overall promising early tissue response and good biocompatibility of both ACP and Sr-ACP enriched scaffolds were demonstrated in a subcutaneous mouse model. In a goat osteochondral defect model, significantly more bone observed at 6 months with the treatment of Sr-ACP enriched scaffolds compared to scaffold only in particular in the weight-bearing femoral condyle subchondral bone defect. Overall, the incorporation of osteogenic Sr-ACP granules in Col/Col-Mg-HAp scaffolds showed to be a feasible and promising strategy to improve subchondral bone repair.

bioengineering↗

bioRxiv2022

Pharmacologic inhibition of EPHA2 decreases inflammation and pathological endochondral ossification in osteoarthritis

Low-grade inflammation and pathological endochondral ossification are processes underlying the progression of osteoarthritis, the most prevalent joint disease worldwide. In this study, data mining on publicly available transcriptomic datasets revealed EPHA2, a receptor tyrosine kinase associated with cancer, to be associated with both inflammation and endochondral ossification in osteoarthritis. A computational model of cellular signaling networks in chondrocytes predicted that in silico activation of EPHA2 in healthy chondrocytes increases inflammatory mediators and triggers hypertrophic differentiation, the phenotypic switch characteristic of endochondral ossification. We then evaluated the effect of inhibition of EPHA2 in cultured human chondrocytes isolated from individuals with osteoarthritis and demonstrated that inhibition of EPHA2 indeed reduced inflammation and hypertrophy. Additionally, systemic subcutaneous administration of the EPHA2 inhibitor ALW-II-41-27 attenuated joint degeneration in a mouse osteoarthritic model, reducing local inflammation and pathological endochondral ossification. Collectively, we demonstrate that pharmacological inhibition of EPHA2 with ALW-II-41-27 is a promising disease-modifying treatment that paves the way for a novel drug discovery pipeline for osteoarthritis.

pharmacology and toxicology↗