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- W3174105154 endingPage "101149" @default.
- W3174105154 startingPage "101149" @default.
- W3174105154 abstract "Effective design of biomaterials to aid regenerative repair of craniomaxillofacial (CMF) bone defects requires approaches that modulate the complex interplay between exogenously added progenitor cells and cells in the wound microenvironment, such as osteoblasts, osteoclasts, endothelial cells, and immune cells. We are exploring the role of the glycosaminoglycan (GAG) content in a class of mineralized collagen scaffolds recently shown to promote osteogenesis and healing of craniofacial bone defects. We previously showed that incorporating chondroitin-6-sulfate or heparin improved mineral deposition by seeded human mesenchymal stem cells (hMSCs). Here, we examine the effect of varying scaffold GAG content on hMSC behavior, and their ability to modulate osteoclastogenesis, vasculogenesis, and the immune response. We report the role of hMSC-conditioned media produced in scaffolds containing chondroitin-6-sulfate (CS6), chondroitin-4-sulfate (CS4), or heparin (Heparin) GAGs on endothelial tube formation and monocyte differentiation. Notably, endogenous production by hMSCs within Heparin scaffolds most significantly inhibits osteoclastogenesis via secreted osteoprotegerin (OPG), while the secretome generated by CS6 scaffolds reduced pro-inflammatory immune response and increased endothelial tube formation. All conditioned media down-regulated many pro- and anti-inflammatory cytokines, such as IL6, IL-1β, and CCL18 and CCL17 respectively. Together, these findings demonstrate that modifying mineralized collagen scaffold GAG content can both directly (hMSC activity) and indirectly (production of secreted factors) influence overall osteogenic potential and mineral biosynthesis as well as angiogenic potential and monocyte differentiation towards osteoclastic and macrophage lineages. Scaffold GAG content is therefore a powerful stimulus to modulate reciprocal signaling between multiple cell populations within the bone healing microenvironment." @default.
- W3174105154 created "2021-07-05" @default.
- W3174105154 creator A5018712181 @default.
- W3174105154 creator A5055024652 @default.
- W3174105154 creator A5070571498 @default.
- W3174105154 creator A5071677177 @default.
- W3174105154 date "2021-08-01" @default.
- W3174105154 modified "2023-10-13" @default.
- W3174105154 title "Glycosaminoglycan content of a mineralized collagen scaffold promotes mesenchymal stem cell secretion of factors to modulate angiogenesis and monocyte differentiation" @default.
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- W3174105154 doi "https://doi.org/10.1016/j.mtla.2021.101149" @default.
- W3174105154 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8336934" @default.
- W3174105154 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34368658" @default.