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of treatment to help heal infected diabetic wounds.
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In addition, Labiba K El-Khordagui et al. fabricated a bilayer hydrogel scaffold

via the hyaluronic acid/CS (HA/CS) ink (Figure 2B). The scaffold contained an upper
dense planar hydrogel layer and the antibacterial/regenerative nanofiber layer by

combining with PLLA nanofiber microspheres, which could promote diabetic wound

healing. Compared with traditional hydrogels, this hydrogel has achieved a leap from

passive dressings to actively regulated precision treatment platforms through digital

extrusion printing technology. It not only replicates the bionic bilayer structure of the

skin, but also creates a customizable multi-level pore network by embedding drug-

loaded nanofiber microspheres, thus structurally far exceeding the uniform random

pores of traditional hydrogels. Meanwhile, this design enables ZNP and DDAB to be

efficiently loaded, evenly distributed and continuously released, ultimately achieving a

synergistic effect of powerful antibacterial properties, regulation of the inflammatory

microenvironment, and significant acceleration of tissue regeneration. It has achieved

an ultra-high healing rate of 95% in diabetic infection wound models, which is difficult

for traditional hydrogels to reach.
Although physical cross-linking method offered the unique advantages, it also

presented notable drawbacks. For example, inadequate control over cross-linking

uniformity could lead to hydrogels with compromised mechanical properties, reduced

strength, and diminished stability. During in vivo applications, the rapid degradation

rate of certain materials may render them unsuitable for scenarios demanding high

mechanical strength or prolonged implantation periods. This accelerated degradation

can compromise the hydrogel’s structural integrity over time, thereby adversely

affecting the overall therapeutic outcome.

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