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The dynamic balance between hypoxia and oxidative stress constitutes the oxygen‐related microenvironment in injured tissues. Due to variability, oxygen homeostasis is usually not a therapeutic target for injured tissues. It is found that when administered intravenously, mesenchymal stem cells (MSCs) and in vitro induced apoptotic vesicles (ApoVs) exhibit similar apoptotic markers in the wound microenvironment where hypoxia and oxidative stress co‐existed, but MSCs exhibited better effects in promoting angiogenesis and wound healing. The derivation pathway of ApoVs by inducing hypoxia or oxidative stress in MSCs to simulate oxygen homeostasis in injured tissues is improved. Two types of oxygen‐related environmental stressed ApoVs are identified that directly target endothelial cells (ECs) for the accurate regulation of vascularization. Compared to normoxic and hypoxic ones, oxidatively stressed ApoVs (Oxi‐ApoVs) showed the strongest tube formation capacity. Different oxygen‐stressed ApoVs deliver similar miRNAs, which leads to the broad upregulation of EC phosphokinase activity. Finally, local delivery of Oxi‐ApoVs‐loaded hydrogel microspheres promotes wound healing. Oxi‐ApoV‐loaded microspheres achieve controlled ApoV release, targeting ECs by reducing the consumption of inflammatory cells and adapting to the proliferative phase of wound healing. Thus, the biogenerated apoptotic vesicles responding to oxygen‐related environmental stress can target ECs to promote vascularization. [ABSTRACT FROM AUTHOR]

Macrophage immunotherapy is an emerging treatment strategy that modulates the immune system to promote wound healing. The functionality and regeneration of tissue depend on spatially and temporally regulating the biophysical and biochemical microenvironmental with poorly understood mechanisms. Biomaterials are carefully crafted to display and deliver macrophage regulatory signals in a precise and near‐physiological way, serving as powerful artificial microenvironments in which to explore and direct the fate of macrophages. The review starts with discussing the classification and function of macrophages, and then introduces the polarization of macrophages in different microenvironments of conventional wounds and chronic wounds. Recent advances in biomaterials that balance the phenotypes of macrophages in wound healing are emphasized. Finally, looking ahead, the potential ability of biomaterial scaffolds to modulate immune signaling to produce an environment conducive to regeneration is discussed. [ABSTRACT FROM AUTHOR]

In this study, injectable charge and receptor "cytokine reservoir" hydrogel for cytokine management during tissue repair. Hydrogel system consists of oxidized glucomannan aldehyde and levodopa-grafted ε-polylysine. The "cytokine reservoir" hydrogel actively recruited macrophages through electrostatic forces and regulated macrophages by mimicking "receptor-ligand" interactions to alter cytokine production patterns. [Display omitted] • A charge and receptor "cytokine reservoir" hydrogel system was developed. • The effect of electric charge on macrophage was expounded. • Functions of crosslinking bonds were explored in modulus. • Decreased inflammation promotes angiogenesis and collagen deposition. • The system was optimized for inflammation regulation and wound healing. Collecting and utilizing various cytokines released by trauma and implantable materials for stimulating the body in producing a robust immune-inflammatory response would be a promising method. Therefore, an injectable "cytokine reservoir" hydrogel for cytokine management during tissue repair was developed by combining a dual network hydrogel of oxidized glucomannan aldehyde (KGM-CHO) and levodopa-grafted ε-polylysine (EPL-DOPA). The "cytokine reservoir" hydrogel actively recruited macrophages through electrostatic forces and regulated macrophages by mimicking "receptor-ligand" interactions to alter cytokine production patterns. Meanwhile, the dual network hydrogels recruited and stored cytokines by "charge" force then released them according to the degradation of hydrogels, leading to the change of cytokine release pattern. In conclusion, this study provided a unique insight in designing the cytokine management-based tissue engineering strategies for tissue repair. [ABSTRACT FROM AUTHOR]