Mineralized nanofibrous scaffold promotes phenamil-induced osteoblastic differentiation while mitigating adipogenic differentiation
Yangxi Liu
Department of Biomedical Engineering, University of South Dakota, BioSNTR, Sioux Falls, South Dakota
Search for more papers by this authorJue Hu
Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Iowa, Iowa City, Iowa
Search for more papers by this authorCorresponding Author
Hongli Sun
Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Iowa, Iowa City, Iowa
Correspondence
Professor Hongli Sun, Ph. D., Iowa Institute for Oral Health Research Department of Oral and Maxillofacial Surgery, N405 DSB, College of Dentistry, 801 Newton Road, The University of Iowa, Iowa City, IA 52242.
Email: [email protected]
Search for more papers by this authorYangxi Liu
Department of Biomedical Engineering, University of South Dakota, BioSNTR, Sioux Falls, South Dakota
Search for more papers by this authorJue Hu
Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Iowa, Iowa City, Iowa
Search for more papers by this authorCorresponding Author
Hongli Sun
Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Iowa, Iowa City, Iowa
Correspondence
Professor Hongli Sun, Ph. D., Iowa Institute for Oral Health Research Department of Oral and Maxillofacial Surgery, N405 DSB, College of Dentistry, 801 Newton Road, The University of Iowa, Iowa City, IA 52242.
Email: [email protected]
Search for more papers by this authorAbstract
Large bone defects represent a significant unmet medical challenge. Cost effectiveness and better stability make small molecule organic compounds a more promising alternative compared with biomacromolecules, for example, growth factors/hormones, in regenerative medicine. However, one common challenge for the application of these small compounds is their side-effect issue. Phenamil is emerging as an intriguing small molecule to promote bone repair by strongly activating bone morphogenetic protein signaling pathway. In addition to osteogenesis, phenamil also induces significant adipogenesis based on some in vitro studies, which is a concern that impedes it from potential clinical applications. Besides the soluble chemical signals, cellular differentiation is heavily dependent on the microenvironments provided by the 3D scaffolds. Therefore, we developed a 3D nanofibrous biomimetic scaffold-based strategy to harness the phenamil-induced stem cell lineage differentiation. Based on the gene expression, alkaline phosphatase activity, and mineralization data, we indicated that bone-matrix mimicking mineralized-gelatin nanofibrous scaffold effectively improved phenamil-induced osteoblastic differentiation, while mitigating the adipogenic differentiation in vitro. In addition to normal culture conditions, we also indicated that mineralized matrix can significantly improve phenamil-induced osteoblastic differentiation in simulated inflammatory condition. In viewing of the crucial role of mineralized matrix, we developed an innovative and facile mineral deposition-based strategy to sustain release of phenamil from 3D scaffolds for efficient local bone regeneration. Overall, our study demonstrated that biomaterials played a crucial role in modulating small molecule drug phenamil-induced osteoblastic differentiation by providing a bone-matrix mimicking mineralized gelatin nanofibrous scaffolds.
CONFLICT OF INTEREST
The authors have declared that there is no conflict of interest.
Supporting Information
| Filename | Description |
|---|---|
| term3007-sup-0001_F1.pngPNG image, 1.1 MB |
Figure S1. Scanning electron microscopy (SEM) images of gelatin nanofibrous (GF) scaffold after at 300X (left) and 15000X (right) magnification, respectively. |
| term3007-sup-0002_F2.pngPNG image, 1.2 MB |
Figure S2. SEM images of MC3T3-E1 after 24 h cell culture GF (A-C) and HAGF (D-F) at 500X (A,D), 1000X (B,E) and 5000X (C,F) magnification, respectively. |
| term3007-sup-0003_F3.pngPNG image, 277.3 KB |
Figure S3. FTIR spectrum analysis showed similar chemical composition content of HAGF scaffold through either concentrated SBF deposition (blue) or two-step calcium phosphate deposition (red). |
| term3007-sup-0004_F4.pngPNG image, 70 KB |
Figure S4. ALP activity. ALP activity of MC3T3-E1 cultured on GF (blue) and HAGF (red) scaffold after 7 d cell culture (n = 3). *p < 0.05. |
| term3007-sup-0005_F5.pngPNG image, 78.3 KB |
Figure S5. Calcium content of blank scaffolds GF (blue) and HAGF (red) scaffold after 0, 7. and 28 d media culture in osteogenic medium (n = 3). *p < 0.05. Table on the right depicts the amount of microgram of calcium per scaffold. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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