Bone Marrow Stromal Cells Generate a Pro-Healing Inflammasome When Cultured on Titanium–Aluminum–Vanadium Surfaces with Microscale/Nanoscale Structural Features
The surface topography and chemistry of titanium–aluminum–vanadium (Ti6Al4V) implants play critical roles in the osteoblast differentiation of human bone marrow stromal cells (MSCs) and the creation of an osteogenic microenvironment. To assess the effects of a microscale/nanoscale (MN) topography, t...
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2025-01-01
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| author | David J. Cohen Christine M. Van Duyn Jingyao Deng Musaddiq K. Lodi Michelle B. Gallagher James T. Sugar Jeremy J. Rawlinson Preetam Ghosh Barbara D. Boyan Zvi Schwartz |
| author_facet | David J. Cohen Christine M. Van Duyn Jingyao Deng Musaddiq K. Lodi Michelle B. Gallagher James T. Sugar Jeremy J. Rawlinson Preetam Ghosh Barbara D. Boyan Zvi Schwartz |
| author_sort | David J. Cohen |
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| description | The surface topography and chemistry of titanium–aluminum–vanadium (Ti6Al4V) implants play critical roles in the osteoblast differentiation of human bone marrow stromal cells (MSCs) and the creation of an osteogenic microenvironment. To assess the effects of a microscale/nanoscale (MN) topography, this study compared the effects of MN-modified, anodized, and smooth Ti6Al4V surfaces on MSC response, and for the first time, directly contrasted MN-induced osteoblast differentiation with culture on tissue culture polystyrene (TCPS) in osteogenic medium (OM). Surface characterization revealed distinct differences in microroughness, composition, and topography among the Ti6Al4V substrates. MSCs on MN surfaces exhibited enhanced osteoblastic differentiation, evidenced by increased expression of RUNX2, SP7, BGLAP, BMP2, and BMPR1A (fold increases: 3.2, 1.8, 1.4, 1.3, and 1.2). The MN surface also induced a pro-healing inflammasome with upregulation of anti-inflammatory mediators (170–200% increase) and downregulation of pro-inflammatory factors (40–82% reduction). Integrin expression shifted towards osteoblast-associated integrins on MN surfaces. RNA-seq analysis revealed distinct gene expression profiles between MSCs on MN surfaces and those in OM, with only 199 shared genes out of over 1000 differentially expressed genes. Pathway analysis showed that MN surfaces promoted bone formation, maturation, and remodeling through non-canonical Wnt signaling, while OM stimulated endochondral bone development and mineralization via canonical Wnt3a signaling. These findings highlight the importance of Ti6Al4V surface properties in directing MSC differentiation and indicate that MN-modified surfaces act via signaling pathways that differ from OM culture methods, more accurately mimicking peri-implant osteogenesis in vivo. |
| format | Article |
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| institution | Kabale University |
| issn | 2313-7673 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Biomimetics |
| spelling | doaj-art-498a9c49614c453b90ea83713b7abe942025-01-24T13:24:47ZengMDPI AGBiomimetics2313-76732025-01-011016610.3390/biomimetics10010066Bone Marrow Stromal Cells Generate a Pro-Healing Inflammasome When Cultured on Titanium–Aluminum–Vanadium Surfaces with Microscale/Nanoscale Structural FeaturesDavid J. Cohen0Christine M. Van Duyn1Jingyao Deng2Musaddiq K. Lodi3Michelle B. Gallagher4James T. Sugar5Jeremy J. Rawlinson6Preetam Ghosh7Barbara D. Boyan8Zvi Schwartz9Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USADepartment of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USADepartment of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USAIntegrative Life Sciences, Virginia Commonwealth University, Richmond, VA 23284, USAMedtronic Spine, Memphis, TN 38132, USAMedtronic Spine, Memphis, TN 38132, USAMedtronic Spine, Memphis, TN 38132, USADepartment of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, USADepartment of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USADepartment of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, USAThe surface topography and chemistry of titanium–aluminum–vanadium (Ti6Al4V) implants play critical roles in the osteoblast differentiation of human bone marrow stromal cells (MSCs) and the creation of an osteogenic microenvironment. To assess the effects of a microscale/nanoscale (MN) topography, this study compared the effects of MN-modified, anodized, and smooth Ti6Al4V surfaces on MSC response, and for the first time, directly contrasted MN-induced osteoblast differentiation with culture on tissue culture polystyrene (TCPS) in osteogenic medium (OM). Surface characterization revealed distinct differences in microroughness, composition, and topography among the Ti6Al4V substrates. MSCs on MN surfaces exhibited enhanced osteoblastic differentiation, evidenced by increased expression of RUNX2, SP7, BGLAP, BMP2, and BMPR1A (fold increases: 3.2, 1.8, 1.4, 1.3, and 1.2). The MN surface also induced a pro-healing inflammasome with upregulation of anti-inflammatory mediators (170–200% increase) and downregulation of pro-inflammatory factors (40–82% reduction). Integrin expression shifted towards osteoblast-associated integrins on MN surfaces. RNA-seq analysis revealed distinct gene expression profiles between MSCs on MN surfaces and those in OM, with only 199 shared genes out of over 1000 differentially expressed genes. Pathway analysis showed that MN surfaces promoted bone formation, maturation, and remodeling through non-canonical Wnt signaling, while OM stimulated endochondral bone development and mineralization via canonical Wnt3a signaling. These findings highlight the importance of Ti6Al4V surface properties in directing MSC differentiation and indicate that MN-modified surfaces act via signaling pathways that differ from OM culture methods, more accurately mimicking peri-implant osteogenesis in vivo.https://www.mdpi.com/2313-7673/10/1/66biomimetic Ti6Al4V surface topographyRNA-seqosteogenic mediaMSCspathway analysis |
| spellingShingle | David J. Cohen Christine M. Van Duyn Jingyao Deng Musaddiq K. Lodi Michelle B. Gallagher James T. Sugar Jeremy J. Rawlinson Preetam Ghosh Barbara D. Boyan Zvi Schwartz Bone Marrow Stromal Cells Generate a Pro-Healing Inflammasome When Cultured on Titanium–Aluminum–Vanadium Surfaces with Microscale/Nanoscale Structural Features Biomimetics biomimetic Ti6Al4V surface topography RNA-seq osteogenic media MSCs pathway analysis |
| title | Bone Marrow Stromal Cells Generate a Pro-Healing Inflammasome When Cultured on Titanium–Aluminum–Vanadium Surfaces with Microscale/Nanoscale Structural Features |
| title_full | Bone Marrow Stromal Cells Generate a Pro-Healing Inflammasome When Cultured on Titanium–Aluminum–Vanadium Surfaces with Microscale/Nanoscale Structural Features |
| title_fullStr | Bone Marrow Stromal Cells Generate a Pro-Healing Inflammasome When Cultured on Titanium–Aluminum–Vanadium Surfaces with Microscale/Nanoscale Structural Features |
| title_full_unstemmed | Bone Marrow Stromal Cells Generate a Pro-Healing Inflammasome When Cultured on Titanium–Aluminum–Vanadium Surfaces with Microscale/Nanoscale Structural Features |
| title_short | Bone Marrow Stromal Cells Generate a Pro-Healing Inflammasome When Cultured on Titanium–Aluminum–Vanadium Surfaces with Microscale/Nanoscale Structural Features |
| title_sort | bone marrow stromal cells generate a pro healing inflammasome when cultured on titanium aluminum vanadium surfaces with microscale nanoscale structural features |
| topic | biomimetic Ti6Al4V surface topography RNA-seq osteogenic media MSCs pathway analysis |
| url | https://www.mdpi.com/2313-7673/10/1/66 |
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