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micle-dense structure. The damage of skin barrier and poor vascularization in diabetic

patients increase the risk of bacterial infection, in which local hyperglycemia also

creates a fertile environment for bacterial proliferation. 83,84 This interplay between
hypoxia and infection transforms diabetic wounds into a complex inflammatory state

that impedes the healing process. 85,86 Recent advances in hydrogel wound dressings

have yielded improved mechanical barrier function, histocompatibility, and

antimicrobial properties, making them a promising option for diabetic wound care. This

microenvironment regulation strategy can avoid direct interference with host cell

behavior, especially in the high-risk environment of chronic wound infection. Jiajing

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Zhou et al. designed a lichen-inspired 3D bioprinted bioderived hydrogel (BBH) with
a customizable structure to accelerate the healing of chronic diabetic wounds. BHs

exhibited powerful properties both in vitro and in vivo, including enhanced dissolved

oxygen production of microalgae and effective anti-infection of probiotics. Peng Li et

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al. proposed a 3D-printable antibacterial porous flexible hydrogel electrode (APFE)
that combined electrical stimulation therapy targeting infected diabetic wound healing.

APFE revealed excellent cell activity, and the antibacterial rate of methicillin-resistant
staphylococcus aureus (MRSA) and Escherichia coli (E. coli) reached 85.71% and

93.65%, respectively.

Collectively, these innovative strategies orchestrated a multifaceted therapeutic

outcome in diabetic wounds, concurrently addressing oxidative stress via ROS

scavenging, inhibiting inflammation, and promoting tissue repair through macrophage

phenotype modulation.

3.2. Regulation of cellular behavior

3D printing technology plays a significant role in regulating cell behavior. It can

guide the directional migration, proliferation and differentiation of cells by constructing

scaffolds with bionic multi-level channels, customized mechanical properties and

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heterogeneous structures . The multi-nozzle system can also precisely target the
immunomodulatory factors and growth factors to different regions of the scaffold, and

collaboratively regulate the polarization of macrophages to the M2 type to alleviate

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