Monocytes Seeded on Engineered Hypertrophic Cartilage Do Not Enhance Endochondral Ossification Capacity

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Orthopedic Research

Background:

• Engineered hypertrophic cartilage (HC) is a promising bone substitute material.
• HC's osteoinductive potential relies on extracellular matrix factors.
• Devitalized HC has limited osteoinductivity, necessitating strategies for enhancement.

Purpose of the Study:

• To investigate if seeding HC with monocytes committed to osteoclastogenesis enhances remodeling and bone formation.
• To assess the impact of monocyte seeding on devitalized HC's osteoinductivity.
• To evaluate the effect of monocyte-primed HC on cellular chemotaxis and bone regeneration.

Main Methods:

• Engineered living or devitalized HC from human mesenchymal stromal cells (MSCs).
• Seeded HC with human monocytes in the presence of M-CSF and RANK-L for in vitro culture or ectopic implantation in nude mice.
• Assessed in vitro resorption, glycosaminoglycan content, and cell chemotaxis.
• Evaluated in vivo remodeling, cell invasion, and bone formation capacity.

Main Results:

• Monocyte seeding induced in vitro resorption of devitalized HC, increasing factor release but decreasing glycosaminoglycans.
• Supernatants from monocyte-seeded devitalized HC enhanced monocyte chemotaxis in vitro but not MSCs or endothelial cells.
• In vivo, monocyte seeding did not significantly improve HC remodeling or invasion by osteoclasts, endothelial cells, or MSCs.
• In vitro priming of HC by monocytes did not enhance bone-forming capacity.

Conclusions:

• Seeding engineered hypertrophic cartilage with monocytes does not enhance its bone-forming capacity, despite in vitro evidence of resorption.
• The strategy is ineffective for improving remodeling and osteoinductivity of devitalized HC in vivo.
• Further research is needed to develop effective strategies for enhancing engineered HC remodeling and bone regeneration.