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enabled hydrogels to combine multifunctional components with spatially controlled

structures, thereby simultaneously targeting interrelated pathological barriers at the

molecular, cellular and tissue levels. 3D printed hydrogels could overcome these
obstacles through multi-level mechanism interventions. (1) Dynamic

microenvironment regulation could be achieved by regulating water and O2

permeability, reactive oxygen species clearance, and infection control. (2) Targeted cell

behavior regulation to restore fibroblast migration, macrophage polarization, and ECM

remodeling. (3) Accelerate angiogenesis and tissue regeneration through continuous

growth factor delivery and dynamic ECM remodeling.

3.1. Regulation of microenvironment

Microenvironment was important for the biological behavior of cells, affecting the

adhesion, migration, differentiation, proliferation and intercellular communication

between cells, and ECM or biomaterial surface. As a finely regulated “command

center”, the microenvironment guided cells to complete a series of life activities through

a variety of signaling molecules and physical and chemical factors. In addition, the

chemical composition, size, microstructure of biomaterials, and the geometry of cells
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themselves also influenced the microenvironment. In diabetic wound repair, hydrogel
exhibited fine regulate the water content of the wound, promoted O2 permeability,

removed ROS in time, reduced oxidative stress response, and provided a new

therapeutic strategy for diabetic chronic wound healing.

Hydrogel for treating diabetic wounds must be able to absorb a large amount of

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wound exudates and maintain a moist microenvironment. A moist wound
microenvironment enhanced cell survival, sustains growth factor release, and

significantly accelerated the healing process by optimizing key healing processes,

including re-epithelialization, angiogenesis, and ECM remodeling. 65 3D printing

technology, especially the extruding-based bioprinting strategy, has achieved multi-

level precise control of the macroscopic structure and microscopic pores of hydrogel

scaffolds by precisely programming the rheological properties, printing parameters and

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model structure of hydrogel inks. This control ability enables researchers to design

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