The marriage of immunomodulatory, angiogenic, and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scaffold for military medicine
Abstract Background Most bone-related injuries to grassroots troops are caused by training or accidental injuries. To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops, it is imperative to develop new strategies and scaffolds to pro...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Military Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40779-023-00469-5 |
| _version_ | 1797752749719289856 |
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| author | Ping Wu Lin Shen Hui-Fan Liu Xiang-Hui Zou Juan Zhao Yu Huang Yu-Fan Zhu Zhao-Yu Li Chao Xu Li-Hua Luo Zhi-Qiang Luo Min-Hao Wu Lin Cai Xiao-Kun Li Zhou-Guang Wang |
| author_facet | Ping Wu Lin Shen Hui-Fan Liu Xiang-Hui Zou Juan Zhao Yu Huang Yu-Fan Zhu Zhao-Yu Li Chao Xu Li-Hua Luo Zhi-Qiang Luo Min-Hao Wu Lin Cai Xiao-Kun Li Zhou-Guang Wang |
| author_sort | Ping Wu |
| collection | DOAJ |
| description | Abstract Background Most bone-related injuries to grassroots troops are caused by training or accidental injuries. To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops, it is imperative to develop new strategies and scaffolds to promote bone regeneration. Methods In this study, a porous piezoelectric hydrogel bone scaffold was fabricated by incorporating polydopamine (PDA)-modified ceramic hydroxyapatite (PDA-hydroxyapatite, PHA) and PDA-modified barium titanate (PDA-BaTiO3, PBT) nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. The physical and chemical properties of the Cs/Gel/PHA scaffold with 0–10 wt% PBT were analyzed. Cell and animal experiments were performed to characterize the immunomodulatory, angiogenic, and osteogenic capabilities of the piezoelectric hydrogel scaffold in vitro and in vivo. Results The incorporation of BaTiO3 into the scaffold improved its mechanical properties and increased self-generated electricity. Due to their endogenous piezoelectric stimulation and bioactive constituents, the as-prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory, angiogenic, and osteogenic capabilities; they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration, tube formation, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) and facilitated the migration, osteo-differentiation, and extracellular matrix (ECM) mineralization of MC3T3-E1 cells. The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model. The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis, and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization. Conclusion The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation, angiogenesis, and osteogenesis functions may be used as a substitute in periosteum injuries, thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat effectiveness in grassroots troops. |
| first_indexed | 2024-03-12T17:08:59Z |
| format | Article |
| id | doaj.art-29fc57eae9fc4b92914f2011c0b2eb7b |
| institution | Directory Open Access Journal |
| issn | 2054-9369 |
| language | English |
| last_indexed | 2024-03-12T17:08:59Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Military Medical Research |
| spelling | doaj.art-29fc57eae9fc4b92914f2011c0b2eb7b2023-08-06T11:10:15ZengBMCMilitary Medical Research2054-93692023-07-0110112210.1186/s40779-023-00469-5The marriage of immunomodulatory, angiogenic, and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scaffold for military medicinePing Wu0Lin Shen1Hui-Fan Liu2Xiang-Hui Zou3Juan Zhao4Yu Huang5Yu-Fan Zhu6Zhao-Yu Li7Chao Xu8Li-Hua Luo9Zhi-Qiang Luo10Min-Hao Wu11Lin Cai12Xiao-Kun Li13Zhou-Guang Wang14Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical UniversityKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical UniversityDepartment of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan UniversityNational Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and TechnologyKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical UniversityKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical UniversityDepartment of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan UniversityDepartment of Overseas Education College, Jimei UniversityNational Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and TechnologySchool and Hospital of Stomatology, Wenzhou Medical UniversityNational Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and TechnologyDepartment of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan UniversityDepartment of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan UniversityOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical UniversityKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical UniversityAbstract Background Most bone-related injuries to grassroots troops are caused by training or accidental injuries. To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops, it is imperative to develop new strategies and scaffolds to promote bone regeneration. Methods In this study, a porous piezoelectric hydrogel bone scaffold was fabricated by incorporating polydopamine (PDA)-modified ceramic hydroxyapatite (PDA-hydroxyapatite, PHA) and PDA-modified barium titanate (PDA-BaTiO3, PBT) nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. The physical and chemical properties of the Cs/Gel/PHA scaffold with 0–10 wt% PBT were analyzed. Cell and animal experiments were performed to characterize the immunomodulatory, angiogenic, and osteogenic capabilities of the piezoelectric hydrogel scaffold in vitro and in vivo. Results The incorporation of BaTiO3 into the scaffold improved its mechanical properties and increased self-generated electricity. Due to their endogenous piezoelectric stimulation and bioactive constituents, the as-prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory, angiogenic, and osteogenic capabilities; they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration, tube formation, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) and facilitated the migration, osteo-differentiation, and extracellular matrix (ECM) mineralization of MC3T3-E1 cells. The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model. The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis, and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization. Conclusion The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation, angiogenesis, and osteogenesis functions may be used as a substitute in periosteum injuries, thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat effectiveness in grassroots troops.https://doi.org/10.1186/s40779-023-00469-5Piezoelectric hydrogelTissue engineering scaffoldImmunomodulationAngiogenesisOsteogenic differentiation |
| spellingShingle | Ping Wu Lin Shen Hui-Fan Liu Xiang-Hui Zou Juan Zhao Yu Huang Yu-Fan Zhu Zhao-Yu Li Chao Xu Li-Hua Luo Zhi-Qiang Luo Min-Hao Wu Lin Cai Xiao-Kun Li Zhou-Guang Wang The marriage of immunomodulatory, angiogenic, and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scaffold for military medicine Military Medical Research Piezoelectric hydrogel Tissue engineering scaffold Immunomodulation Angiogenesis Osteogenic differentiation |
| title | The marriage of immunomodulatory, angiogenic, and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scaffold for military medicine |
| title_full | The marriage of immunomodulatory, angiogenic, and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scaffold for military medicine |
| title_fullStr | The marriage of immunomodulatory, angiogenic, and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scaffold for military medicine |
| title_full_unstemmed | The marriage of immunomodulatory, angiogenic, and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scaffold for military medicine |
| title_short | The marriage of immunomodulatory, angiogenic, and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scaffold for military medicine |
| title_sort | marriage of immunomodulatory angiogenic and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scaffold for military medicine |
| topic | Piezoelectric hydrogel Tissue engineering scaffold Immunomodulation Angiogenesis Osteogenic differentiation |
| url | https://doi.org/10.1186/s40779-023-00469-5 |
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