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.

Conditioned medium (CM) contains variety of factors secreted by cells, which directly regulate cellular processes, showing tremendous potential in regenerative medicine. Here, for the first time, we proposed a novel regenerative therapy mediated by biodegradable micro-nano electrospun fibers loaded with highly active conditioned medium of adipose-derived stem cells (ADSC-CM). ADSC-CM was successfully loaded into the nanofibers with biological protection and controllable sustained-release properties by emulsion electrospinning and protein freeze-drying technologies. In vitro , ADSC-CM released by the fibers accelerated the migration rate of fibroblasts; inhibited the over proliferation of fibroblasts by inducing apoptosis and damaging cell membrane; in addition, ADSC-CM inhibited the transformation of fibroblasts into myofibroblasts and suppressed excessive production of extracellular matrix (ECM). In vivo , the application of CM-biomaterials significantly accelerated wound closure and improved regeneration outcome, showing superior pro-regenerative performance. This study pioneered the application of CM-biomaterials in regenerative medicine, and confirmed the practicability and significant biological effects of this innovative biomaterials.

Exudate management is critical to improve chronic wound healing. Herein, inspired by a Janus‐structured lotus leaf with asymmetric wettability, a Janus electrospun short fiber scaffold is fabricated via electrospinning technologies and short fiber modeling. This scaffold is composed of hydrophilic 2D curcumin‐loaded electrospun fiber and hydrophobic 3D short fiber via layer‐by‐layer assembly and electrostatic interactions which can aggregate the wound exudate by pumping from the hydrophobic layer to the hydrophilic via multiple contact points between hydrophilic and hydrophobic fibers, and simultaneously trigger the cascade release of curcumin in the upper 2D electrospun fiber. The 3D short fiber with high porosity and hydrophobicity can quickly aggregate exudate within 30 s after compounding with hydrophilic 2D electrospun fiber via a spontaneous pump. In vitro experiments show that Janus electrospun short fiber has good biocompatibility, and the cascade release of curcumin can significantly promote the proliferation and migration of fibroblasts. In vivo experiments show that it can trigger cascade release of curcumin by aggregating wound exudate, so as to accelerate wound healing process and promote collagen deposition and vascularization. Hence, this unique biometric Janus scaffold provides an alternative for chronic wound healing.