Advanced phosphocreatine-grafted chitosan hydrogel promote wound healing by macrophage modulation
Background: The repair of wounds usually caused by trauma or other chronic diseases remained challenging in clinics due to the potential risk of inflammation and inadequate tissue regenerative properties. Among them, the behaviour of immune cells, such as macrophages, is critical in tissue repair.Ma...
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Frontiers Media S.A.
2023-05-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1199939/full |
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author | Weibei Sheng Haotian Qin Tiehua Wang Jin Zhao Chongzhou Fang Peng Zhang Peng Liu Anjaneyulu Udduttula Hui Zeng Yingqi Chen |
author_facet | Weibei Sheng Haotian Qin Tiehua Wang Jin Zhao Chongzhou Fang Peng Zhang Peng Liu Anjaneyulu Udduttula Hui Zeng Yingqi Chen |
author_sort | Weibei Sheng |
collection | DOAJ |
description | Background: The repair of wounds usually caused by trauma or other chronic diseases remained challenging in clinics due to the potential risk of inflammation and inadequate tissue regenerative properties. Among them, the behaviour of immune cells, such as macrophages, is critical in tissue repair.Materials and methods: In this study, a water-soluble phosphocreatine-grafted methacryloyl chitosan (CSMP) was synthesized with a one-step lyophilization method, followed by the fabrication of CSMP hydrogel with a photocrosslinked method. The microstructure, water absorption and mechanical properties for the hydrogels were investigated. Then, the macrophages were co-cultured with hydrogels and the pro-inflammatory factors and polarization markers for these macrophages were detected through real-time quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), and flow cytometry methods. Finally, the CSMP hydrogel was implanted in a wound defect area in mice to test its ability to promote wound healing.Results: The lyophilized CSMP hydrogel had a porous structure with pores ranging in size from 200 to 400 μm, which was larger than the CSM hydrogel’s. The lyophilized CSMP hydrogel possessed a higher water absorption rate compared with the CSM hydrogel. The compressive stress and modulus of these hydrogels were increased in the initial 7 days immersion and then gradually decreased during the in vitro immersion in PBS solution up to 21 days; the CSMP hydrogel showed a higher value in these parameters versus the CSM hydrogel. The CSMP hydrogel inhibited the expression of inflammatory factors such as interleukin-1β (IL-1β), IL-6, IL-12, and tumor necrosis factor-α (TNF-α) in an in vitro study cocultured with pro-inflammatory factors in pre-treated bone marrow-derived macrophages (BMM). The mRNA sequencing results showed that the CSMP hydrogel might inhibit the macrophages’ M1 type polarization through the NF-κB signaling pathway. Furthermore, when compared to the control group, the CSMP hydrogel promoted more skin area repair in the mouse wound defect area, and inflammatory factors such as IL-1β, IL-6, and TNF-α were lower in the repaired tissue for the CSMP group.Conclusion: This phosphate-grafted chitosan hydrogel showed great promise for wound healing through regulating the macrophage’s phenotype via the NF-κB signaling pathway. |
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language | English |
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spelling | doaj.art-8928339649ad4e26808a4879a6ec7ee52023-05-12T06:07:18ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-05-011110.3389/fbioe.2023.11999391199939Advanced phosphocreatine-grafted chitosan hydrogel promote wound healing by macrophage modulationWeibei Sheng0Haotian Qin1Tiehua Wang2Jin Zhao3Chongzhou Fang4Peng Zhang5Peng Liu6Anjaneyulu Udduttula7Hui Zeng8Yingqi Chen9Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Emergency, Shenzhen People’s Hospital, Shenzhen, ChinaDepartment of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, ChinaCentral Laboratory, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, ChinaCentre of Biomaterials, Cellular & Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore, IndiaDepartment of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, ChinaBackground: The repair of wounds usually caused by trauma or other chronic diseases remained challenging in clinics due to the potential risk of inflammation and inadequate tissue regenerative properties. Among them, the behaviour of immune cells, such as macrophages, is critical in tissue repair.Materials and methods: In this study, a water-soluble phosphocreatine-grafted methacryloyl chitosan (CSMP) was synthesized with a one-step lyophilization method, followed by the fabrication of CSMP hydrogel with a photocrosslinked method. The microstructure, water absorption and mechanical properties for the hydrogels were investigated. Then, the macrophages were co-cultured with hydrogels and the pro-inflammatory factors and polarization markers for these macrophages were detected through real-time quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), and flow cytometry methods. Finally, the CSMP hydrogel was implanted in a wound defect area in mice to test its ability to promote wound healing.Results: The lyophilized CSMP hydrogel had a porous structure with pores ranging in size from 200 to 400 μm, which was larger than the CSM hydrogel’s. The lyophilized CSMP hydrogel possessed a higher water absorption rate compared with the CSM hydrogel. The compressive stress and modulus of these hydrogels were increased in the initial 7 days immersion and then gradually decreased during the in vitro immersion in PBS solution up to 21 days; the CSMP hydrogel showed a higher value in these parameters versus the CSM hydrogel. The CSMP hydrogel inhibited the expression of inflammatory factors such as interleukin-1β (IL-1β), IL-6, IL-12, and tumor necrosis factor-α (TNF-α) in an in vitro study cocultured with pro-inflammatory factors in pre-treated bone marrow-derived macrophages (BMM). The mRNA sequencing results showed that the CSMP hydrogel might inhibit the macrophages’ M1 type polarization through the NF-κB signaling pathway. Furthermore, when compared to the control group, the CSMP hydrogel promoted more skin area repair in the mouse wound defect area, and inflammatory factors such as IL-1β, IL-6, and TNF-α were lower in the repaired tissue for the CSMP group.Conclusion: This phosphate-grafted chitosan hydrogel showed great promise for wound healing through regulating the macrophage’s phenotype via the NF-κB signaling pathway.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1199939/fullphosphocreatine-grafted chitosan hydrogelwound healingmacrophage modulationNF-κB signaling pathwaytissue engineering |
spellingShingle | Weibei Sheng Haotian Qin Tiehua Wang Jin Zhao Chongzhou Fang Peng Zhang Peng Liu Anjaneyulu Udduttula Hui Zeng Yingqi Chen Advanced phosphocreatine-grafted chitosan hydrogel promote wound healing by macrophage modulation Frontiers in Bioengineering and Biotechnology phosphocreatine-grafted chitosan hydrogel wound healing macrophage modulation NF-κB signaling pathway tissue engineering |
title | Advanced phosphocreatine-grafted chitosan hydrogel promote wound healing by macrophage modulation |
title_full | Advanced phosphocreatine-grafted chitosan hydrogel promote wound healing by macrophage modulation |
title_fullStr | Advanced phosphocreatine-grafted chitosan hydrogel promote wound healing by macrophage modulation |
title_full_unstemmed | Advanced phosphocreatine-grafted chitosan hydrogel promote wound healing by macrophage modulation |
title_short | Advanced phosphocreatine-grafted chitosan hydrogel promote wound healing by macrophage modulation |
title_sort | advanced phosphocreatine grafted chitosan hydrogel promote wound healing by macrophage modulation |
topic | phosphocreatine-grafted chitosan hydrogel wound healing macrophage modulation NF-κB signaling pathway tissue engineering |
url | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1199939/full |
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