Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell–Macrophage Interaction
Abstract Regenerating nonthrombotic and compliant artery, especially in the aging body, remains a major surgical challenge, mainly owing to the inadequate knowledge of the major cell sources contributing to arterial regeneration and insufficient bioactivity of delivered peptides in grafts. Ultrathin...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-04-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.201903307 |
| _version_ | 1818322269426941952 |
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| author | Wanli Chen Sansan Jia Xinchi Zhang Siqian Zhang Huan Liu Xin Yang Cun Zhang Wei Wu |
| author_facet | Wanli Chen Sansan Jia Xinchi Zhang Siqian Zhang Huan Liu Xin Yang Cun Zhang Wei Wu |
| author_sort | Wanli Chen |
| collection | DOAJ |
| description | Abstract Regenerating nonthrombotic and compliant artery, especially in the aging body, remains a major surgical challenge, mainly owing to the inadequate knowledge of the major cell sources contributing to arterial regeneration and insufficient bioactivity of delivered peptides in grafts. Ultrathin nanofibrous sheaths stented with biodegrading elastomer present opening channels and reduced material residue, enabling fast cell recruitment and host remodeling, while incorporating peptides offering developmental cues are challenging. In this study, a recombinant human thymosin β4 dimer (DTβ4) that contains two complete Tβ4 molecules is produced. The adult perivascular adipose is found as the dominant source of vascular progenitors which, when stimulated by the DTβ4‐loaded nanofibrous sheath, enables 100% patency rates, near‐complete structural as well as adequate functional regeneration of artery, and effectively ameliorates aging‐induced defective regeneration. As compared with Tβ4, DTβ4 exhibits durable regenerative activity including recruiting more progenitors for endothelial cells and smooth muscle cells, when incorporated into the ultrathin polycaprolactone sheath. Moreover, the DTβ4‐loaded interface promotes smooth muscle cells differentiation, mainly through promoting M2 macrophage polarization and chemokines. Incorporating artificial DTβ4 into ultrathin sheaths of fast degrading vascular grafts creates an effective interface for sufficient muscular remodeling thus offering a robust tool for vessel replacement. |
| first_indexed | 2024-12-13T10:54:07Z |
| format | Article |
| id | doaj.art-2ab7df7f1e294deb8c394aa23c7ea738 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-13T10:54:07Z |
| publishDate | 2020-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-2ab7df7f1e294deb8c394aa23c7ea7382022-12-21T23:49:39ZengWileyAdvanced Science2198-38442020-04-0178n/an/a10.1002/advs.201903307Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell–Macrophage InteractionWanli Chen0Sansan Jia1Xinchi Zhang2Siqian Zhang3Huan Liu4Xin Yang5Cun Zhang6Wei Wu7State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology Department of Oral & Maxillofacial Surgery School of Stomatology the Fourth Military Medical University Xi'an Shaanxi ChinaState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology Department of Oral & Maxillofacial Surgery School of Stomatology the Fourth Military Medical University Xi'an Shaanxi ChinaState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology Department of Oral & Maxillofacial Surgery School of Stomatology the Fourth Military Medical University Xi'an Shaanxi ChinaState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology Department of Oral & Maxillofacial Surgery School of Stomatology the Fourth Military Medical University Xi'an Shaanxi ChinaDepartment of Pathophysiology Institute of Basic Medical Science Xi'an Medical University Xi'an ChinaState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology Department of Oral & Maxillofacial Surgery School of Stomatology the Fourth Military Medical University Xi'an Shaanxi ChinaState Key Laboratory of Cancer Biology Biotechnology Center School of Pharmacy the Fourth Military Medical University Xi'an ChinaState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology Department of Oral & Maxillofacial Surgery School of Stomatology the Fourth Military Medical University Xi'an Shaanxi ChinaAbstract Regenerating nonthrombotic and compliant artery, especially in the aging body, remains a major surgical challenge, mainly owing to the inadequate knowledge of the major cell sources contributing to arterial regeneration and insufficient bioactivity of delivered peptides in grafts. Ultrathin nanofibrous sheaths stented with biodegrading elastomer present opening channels and reduced material residue, enabling fast cell recruitment and host remodeling, while incorporating peptides offering developmental cues are challenging. In this study, a recombinant human thymosin β4 dimer (DTβ4) that contains two complete Tβ4 molecules is produced. The adult perivascular adipose is found as the dominant source of vascular progenitors which, when stimulated by the DTβ4‐loaded nanofibrous sheath, enables 100% patency rates, near‐complete structural as well as adequate functional regeneration of artery, and effectively ameliorates aging‐induced defective regeneration. As compared with Tβ4, DTβ4 exhibits durable regenerative activity including recruiting more progenitors for endothelial cells and smooth muscle cells, when incorporated into the ultrathin polycaprolactone sheath. Moreover, the DTβ4‐loaded interface promotes smooth muscle cells differentiation, mainly through promoting M2 macrophage polarization and chemokines. Incorporating artificial DTβ4 into ultrathin sheaths of fast degrading vascular grafts creates an effective interface for sufficient muscular remodeling thus offering a robust tool for vessel replacement.https://doi.org/10.1002/advs.201903307agingarterial regenerationbiodegradable graftsdimeric thymosin‐β4M2 macrophages |
| spellingShingle | Wanli Chen Sansan Jia Xinchi Zhang Siqian Zhang Huan Liu Xin Yang Cun Zhang Wei Wu Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell–Macrophage Interaction Advanced Science aging arterial regeneration biodegradable grafts dimeric thymosin‐β4 M2 macrophages |
| title | Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell–Macrophage Interaction |
| title_full | Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell–Macrophage Interaction |
| title_fullStr | Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell–Macrophage Interaction |
| title_full_unstemmed | Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell–Macrophage Interaction |
| title_short | Dimeric Thymosin β4 Loaded Nanofibrous Interface Enhanced Regeneration of Muscular Artery in Aging Body through Modulating Perivascular Adipose Stem Cell–Macrophage Interaction |
| title_sort | dimeric thymosin β4 loaded nanofibrous interface enhanced regeneration of muscular artery in aging body through modulating perivascular adipose stem cell macrophage interaction |
| topic | aging arterial regeneration biodegradable grafts dimeric thymosin‐β4 M2 macrophages |
| url | https://doi.org/10.1002/advs.201903307 |
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