Dynamic Fibrous Hydrogels for Stem Cell Homing and In Situ Bone Regeneration

A dynamic fibrous hydrogel (DFH) is developed by covalent crosslinking of gelatin with tea‐derived trichomes, which integrates the structural and compositional fidelity of native extracellular matrix with photothermal and oxidative responsiveness, introducing a novel “stem cell recruits stem cell” strategy that orchestrates co‐homing of endogenous and exogenous stem cells, and establishing a pioneering therapeutic paradigm for in situ tissue regeneration. Abstract Stem cell therapy holds great promise for enhancing bone regeneration, but its clinical outcomes are often hampered by ineffective cell homing and compromised paracrine activity in pathological oxidative microenvironments. Here, a dynamic fibrous hydrogel (DFH) is presented, fabricated by covalently crosslinking gelatin with tea‐derived trichomes (TH), which recapitulates the static and dynamic features of the native extracellular matrix (ECM) to enhance stem cell‐mediated bone repair. DFH features a robust, heterogeneous fibrous network that closely mimics the structural complexity and biochemical composition of the ECM, thereby creating a tailored niche for mesenchymal stem cell (MSC) delivery. Specifically, DFH exhibits potent photothermal responsiveness, enabling spatiotemporal regulation that boosts the paracrine secretion of SDF‐1 from encapsulated MSCs, thereby promoting stem cell migration. Furthermore, the polyphenol‐rich TH endows DFH with superior antioxidant capabilities, markedly improving MSC survival under oxidative stress. In murine cranial defects, MSC‐laden DFH (DFH@MSC) with photothermal stimulation enhances stem cell recruitment, promotes angiogenesis, and reduces inflammation, ultimately driving robust bone regeneration. By integrating ECM‐mimetic structural and compositional fidelity with spatiotemporal modulation, DFH introduces a novel “stem cell recruits stem cell” strategy that orchestrates the co‐homing of endogenous and exogenous stem cells, establishing a pioneering therapeutic paradigm for in situ tissue regeneration. A dynamic fibrous hydrogel (DFH) is developed by covalent crosslinking of gelatin with tea-derived trichomes, which integrates the structural and compositional fidelity of native extracellular matrix with photothermal and oxidative responsiveness, introducing a novel “stem cell recruits stem cell” strategy that orchestrates co-homing of endogenous and exogenous stem cells, and establishing a pioneering therapeutic paradigm for in situ tissue regeneration. Abstract Stem cell therapy holds great promise for enhancing bone regeneration, but its clinical outcomes are often hampered by ineffective cell homing and compromised paracrine activity in pathological oxidative microenvironments. Here, a dynamic fibrous hydrogel (DFH) is presented, fabricated by covalently crosslinking gelatin with tea-derived trichomes (TH), which recapitulates the static and dynamic features of the native extracellular matrix (ECM) to enhance stem cell-mediated bone repair. DFH features a robust, heterogeneous fibrous network that closely mimics the structural complexity and biochemical composition of the ECM, thereby creating a tailored niche for mesenchymal stem cell (MSC) delivery. Specifically, DFH exhibits potent photothermal responsiveness, enabling spatiotemporal regulation that boosts the paracrine secretion of SDF-1 from encapsulated MSCs, thereby promoting stem cell migration. Furthermore, the polyphenol-rich TH endows DFH with superior antioxidant capabilities, markedly improving MSC survival under oxidative stress. In murine cranial defects, MSC-laden DFH (DFH@MSC) with photothermal stimulation enhances stem cell recruitment, promotes angiogenesis, and reduces inflammation, ultimately driving robust bone regeneration. By integrating ECM-mimetic structural and compositional fidelity with spatiotemporal modulation, DFH introduces a novel “stem cell recruits stem cell” strategy that orchestrates the co-homing of endogenous and exogenous stem cells, establishing a pioneering therapeutic paradigm for in situ tissue regeneration. Advanced Science, EarlyView.