Correlating Material Properties to Osteoprotegerin Expression on Nanoparticulate Mineralized Collagen Glycosaminoglycan Scaffolds

• Published in: Advanced healthcare materials 2024-10, Vol.13 (26), p.e2401037-n/a
• Main Authors: Chen, Wei, Bedar, Meiwand, Zhou, Qi, Ren, Xiaoyan, Kang, Youngnam, Huang, Kelly X., Rubino, Grace, Kolliopoulos, Vasiliki, Moghadam, Shahrzad, Cascavita, Catherine T., Taylor, Jeremiah M., Chevalier, Jose M., Harley, Brendan A.C., Lee, Justine C.
• Format: Article
• Language: English
• Subjects: beta Catenin - metabolism; Biological activity; Biological properties; bone regeneration; Catenin; Cell differentiation; Cell Differentiation - drug effects; Cells, Cultured; Collagen; Collagen - chemistry; Differentiation (biology); Down-regulation; Glycosaminoglycans; Glycosaminoglycans - chemistry; Glycosaminoglycans - metabolism; Humans; Material properties; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mineralization; Nanoparticles; Nanoparticles - chemistry; nanoparticulate mineralized collagen glycosaminoglycan scaffolds; Osteoclastogenesis; Osteogenesis; Osteogenesis - drug effects; Osteoprogenitor cells; Osteoprotegerin; Osteoprotegerin - genetics; Osteoprotegerin - metabolism; phosphate; Phosphates - chemistry; Progenitor cells; Scaffolds; Sodium phosphate; Stem cells; Stiffness; Tissue Scaffolds - chemistry; Transcription Factors - metabolism; Transcriptional Coactivator with PDZ-Binding Motif Proteins; YAP-Signaling Proteins - metabolism; Yes-associated protein
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202401037

Precision material design directed by cell biological processes represents a frontier in developing clinically translatable regenerative technologies. While understanding cell‐material interactions on multipotent progenitor cells yields insights on target tissue differentiation, equally if not more important is the quantification of indirect multicellular interactions. In this work, the relationship of two material properties, phosphate content and stiffness, of a nanoparticulate mineralized collagen glycosaminoglycan scaffold (MC‐GAG) in the expression of an endogenous anti‐osteoclastogenic secreted protein, osteoprotegerin (OPG) by primary human mesenchymal stem cells (hMSCs) is evaluated. The phosphate content of MC‐GAG requires the type III sodium phosphate symporter PiT‐1/SLC20A1 for OPG expression, correlating with β‐catenin downregulation, but is independent of the effects of phosphate ion on osteogenic differentiation. Using three stiffness MC‐GAG variants that do not differ significantly by osteogenic differentiation, it is observed that the softest material elicited ≈1.6–2 times higher OPG expression than the stiffer materials. Knockdown of the mechanosensitive signaling axis of YAP, TAZ, β‐catenin and combinations thereof in hMSCs on MC‐GAG demonstrates that β‐catenin downregulation increases OPG expression by 1.5‐fold. Taken together, these data constitute a roadmap for material properties that can used to suppress osteoclast activation via osteoprotegerin expression separately from the anabolic processes of osteogenesis. The next generation in strategies for regenerative material design is one that evolves from stochastic to directed design via the integration of precision in modulating multicellular biological responses with precision in tuning of material properties. The current work defines the impact of two material properties in coordinating anabolic and catabolic aspects of bone homeostasis, providing a roadmap for future material modifications.