Natural fish swim bladder-derived MPN-nanofibrous biomimetic system exhibit ECM-responsive signal regulation and promote robust tendon–bone healing

Abstract Enhanced tendon‒bone healing is of critically importance for achieving optimal postoperative recovery following a rotator cuff tendon tear (rotator cuff tears, RCTs). Although RCTs patch-augmented scaffolds demonstrate clinical potential, there is a paucity of reports on biodegradable scaff...

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Main Authors: Lei Shi, Peng Zhou, Cong Ye, Jie Sun, Hongdong Ma, Ran Tao, Peng Zhang, Fei Han
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-025-03580-y
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author Lei Shi
Peng Zhou
Cong Ye
Jie Sun
Hongdong Ma
Ran Tao
Peng Zhang
Fei Han
author_facet Lei Shi
Peng Zhou
Cong Ye
Jie Sun
Hongdong Ma
Ran Tao
Peng Zhang
Fei Han
author_sort Lei Shi
collection DOAJ
description Abstract Enhanced tendon‒bone healing is of critically importance for achieving optimal postoperative recovery following a rotator cuff tendon tear (rotator cuff tears, RCTs). Although RCTs patch-augmented scaffolds demonstrate clinical potential, there is a paucity of reports on biodegradable scaffolds that effectively integrate high strength and bioactivity. Inspired by the composition and aligned nanofibrous structure of the natural fish bladder matrix (fish swim bladder, FSB), we employed a gallium (Ga)‒tannic acid (TA) metal‒polyphenol network (MPN)-modified decellularized fish bladder matrix (GaPP@FSB) as a novel biomaterial to address this problem. Ga-TA MPN represents a “two birds with one stone” modification strategy that allows GaPP@FSB to demonstrate commendable mechanical strength alongside multiple biological activities, including antibacterial, antioxidant, anti-inflammatory and osteogenic differentiation promotion. Furthermore, GaPP@FSB regulates the focal adhesion-based mechanical signal transduction pathway in tendon stem/progenitor cells (TSPCs), thereby activating the α5β1/Akt/PI3K pathway to induce tenogenic differentiation. Additionally, this scaffold exhibits remarkable anti-inflammatory and antibacterial activities. In a rat RCTs model, GaPP@FSB promoted regeneration at the tendon‒bone interface while restoring both rotator cuff biomechanics and joint movement function. Consequently, this biomaterial derived from natural FSB has outstanding biosafety and biological activity, making it a highly promising candidate for clinical applications in both tendon repair and the restoration of the tendon‒bone interface. Graphical abstract
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institution Kabale University
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spelling doaj-art-99d3987b5f4a47f89f83dcb8355b96df2025-08-20T04:01:41ZengBMCJournal of Nanobiotechnology1477-31552025-07-0123112410.1186/s12951-025-03580-yNatural fish swim bladder-derived MPN-nanofibrous biomimetic system exhibit ECM-responsive signal regulation and promote robust tendon–bone healingLei Shi0Peng Zhou1Cong Ye2Jie Sun3Hongdong Ma4Ran Tao5Peng Zhang6Fei Han7Department of Orthopaedics, Affiliated Hospital of Nantong University, Medical School of Nantong UniversityDepartment of Orthopaedics, The 941th Hospital of Joint Logistic Support Force of Chinese People’s Liberation ArmyDepartment of Orthopaedics, Affiliated Hospital of Nantong University, Medical School of Nantong UniversityHand Surgery Research Center, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong UniversityDepartment of Orthopaedics, Affiliated Hospital of Nantong University, Medical School of Nantong UniversityDepartment of Orthopaedics, Affiliated Hospital of Nantong University, Medical School of Nantong UniversityDepartment of Sports Medicine, Huashan Hospital, Fudan UniversityDepartment of Orthopaedics, Affiliated Hospital of Nantong University, Medical School of Nantong UniversityAbstract Enhanced tendon‒bone healing is of critically importance for achieving optimal postoperative recovery following a rotator cuff tendon tear (rotator cuff tears, RCTs). Although RCTs patch-augmented scaffolds demonstrate clinical potential, there is a paucity of reports on biodegradable scaffolds that effectively integrate high strength and bioactivity. Inspired by the composition and aligned nanofibrous structure of the natural fish bladder matrix (fish swim bladder, FSB), we employed a gallium (Ga)‒tannic acid (TA) metal‒polyphenol network (MPN)-modified decellularized fish bladder matrix (GaPP@FSB) as a novel biomaterial to address this problem. Ga-TA MPN represents a “two birds with one stone” modification strategy that allows GaPP@FSB to demonstrate commendable mechanical strength alongside multiple biological activities, including antibacterial, antioxidant, anti-inflammatory and osteogenic differentiation promotion. Furthermore, GaPP@FSB regulates the focal adhesion-based mechanical signal transduction pathway in tendon stem/progenitor cells (TSPCs), thereby activating the α5β1/Akt/PI3K pathway to induce tenogenic differentiation. Additionally, this scaffold exhibits remarkable anti-inflammatory and antibacterial activities. In a rat RCTs model, GaPP@FSB promoted regeneration at the tendon‒bone interface while restoring both rotator cuff biomechanics and joint movement function. Consequently, this biomaterial derived from natural FSB has outstanding biosafety and biological activity, making it a highly promising candidate for clinical applications in both tendon repair and the restoration of the tendon‒bone interface. Graphical abstracthttps://doi.org/10.1186/s12951-025-03580-yFish swim bladderRotator cuff tearsTendon–bone healingMetal‒polyphenol networkECM-responsive signalling
spellingShingle Lei Shi
Peng Zhou
Cong Ye
Jie Sun
Hongdong Ma
Ran Tao
Peng Zhang
Fei Han
Natural fish swim bladder-derived MPN-nanofibrous biomimetic system exhibit ECM-responsive signal regulation and promote robust tendon–bone healing
Journal of Nanobiotechnology
Fish swim bladder
Rotator cuff tears
Tendon–bone healing
Metal‒polyphenol network
ECM-responsive signalling
title Natural fish swim bladder-derived MPN-nanofibrous biomimetic system exhibit ECM-responsive signal regulation and promote robust tendon–bone healing
title_full Natural fish swim bladder-derived MPN-nanofibrous biomimetic system exhibit ECM-responsive signal regulation and promote robust tendon–bone healing
title_fullStr Natural fish swim bladder-derived MPN-nanofibrous biomimetic system exhibit ECM-responsive signal regulation and promote robust tendon–bone healing
title_full_unstemmed Natural fish swim bladder-derived MPN-nanofibrous biomimetic system exhibit ECM-responsive signal regulation and promote robust tendon–bone healing
title_short Natural fish swim bladder-derived MPN-nanofibrous biomimetic system exhibit ECM-responsive signal regulation and promote robust tendon–bone healing
title_sort natural fish swim bladder derived mpn nanofibrous biomimetic system exhibit ecm responsive signal regulation and promote robust tendon bone healing
topic Fish swim bladder
Rotator cuff tears
Tendon–bone healing
Metal‒polyphenol network
ECM-responsive signalling
url https://doi.org/10.1186/s12951-025-03580-y
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