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International Journal of Bioprinting 3D printed hydrogel for infected wound healing via PDT

group), and mice in different groups received implantation TEM image shows that MB@UiO-66(Ce)/PH dressings
at the wound sites with a different dose of MB@UiO- were spongy with porous interiors in the cross-section.
66(Ce)/PH on day 1. All hydrogel dressings were circular Figure 2C shows the compressive strain–stress curve of
in shape, with a diameter of 5 mm and a height of 0.5 mm. MB@UiO-66(Ce)/PH, the compressive strength of PH-1
Mice that were treated with only sterilized phosphate- hydrogel is ~45 kPa, while the compressive strength of
buffered saline were used as the CON group. the composite hydrogel significantly increased with the
Following surgery, mice were photographed at increase of NPs concentration (Figure 2D). Comparing the
predetermined time points (1, 3, 7, 10, and 14 days) and above hydrogels, Figure 2E and F shows that PH-1 hydrogel
sacrificed at either 7 or 14 days. The wound areas were possessed a relatively higher elongation (51%) and a higher
estimated using ImageJ software. The tissues at the infected tensile strength (2.6 kPa) compared with other groups. In
sites were dissected and fixed in a 4% formaldehyde summary, the tensile stress of the hydrogels increased with
solution for 24 h. Next, the tissues were embedded in the amount of the incorporated NPs.
molten paraffin for staining . Sections were stained 3.3. Effect of hydrogels on activity and proliferation
[46]
with hematoxylin and eosin (H&E) for H&E staining and of L929 cells
hematoxylin, acid fuchsin solution, and aniline blue for Early cell adhesion is an important factor in subsequent
Masson’s trichrome staining. biological behavior . The cytoskeletons of L929 cells
[47]
2.15. Statistical analysis were stained and observed after being cultured with
All data were presented as the mean ± standard deviation. different MB@UiO-66(Ce)/PH levels for 12 h. As shown
One-way analysis of variance (ANOVA) and t-test analyses in Figure 3A, L929 cells adhered and spread well with
were used to analyze the data for all groups. A p < 0.05 was polygonal structures on the surface of the hydrogels.
considered statistically significant. The cells in the five groups significantly increased with
time. Figure 3B shows that the hydrogel groups proliferated
3. Results and discussion slightly faster than the nonimplant group (CON) in
the early stage, but there was no significant difference
3.1. Preparation and characterization of at 7 days. This may be related to the porous structure of
MB@UiO-66(Ce) hydrogel, which facilitates cell proliferation. At the same
TEM images show MB@UiO-66(Ce) crystals with particle time, the hydrogel coating slows the UiO-66(Ce) release
sizes of ≈110 nm were successfully obtained. Figure S1 and thus reduces the toxicity of NPs. It is also shown that
shows that large, open mesopores were periodically UiO-66(Ce) loaded with MB can effectively reduce the
distributed throughout UiO-66(Ce), and MB was photosensitizer cytotoxicity in nearby cells. These results
successfully loaded on the NPs. TEM images further suggest that the hydrogel has good biocompatibility and no
confirmed that the NPs were well-dispersed, and the effect on the adhesion and proliferation of L929 cells.
ordered large mesopores were uniformly distributed across
the entire sample. The NP sizes were further examined by 3.4. Cytotoxicity of the hydrogels were detected by
dynamic laser scattering. Similar to the TEM observations, the CCK-8 test
the MB@UiO-66(Ce) particle size was mainly distributed L929 cells were incubated in the extracts for 3 days and
around 110.22 ± 11.85 nm, as shown in Figure S2. stained with the live/dead kit. Live cells were stained with
calcein AM (green fluorescence), whereas dead cells were
3.2. Preparation and characterization of stained with propidium iodide (red fluorescence). The
MB@UiO-66(Ce)/PH dressing live/dead assay showed that almost no red fluorescence
Photo-crosslinked hydrogel systems used for spots appeared in the whole group (Figure 3C). The
3D-bioprinting were obtained by mixing gelatin into comparatively high cellular activity within the extracts
SF and using riboflavin and SPS as crosslinking agents. indicated good biocompatibility of the gel materials.
Figure 2A shows the 3D-bioprinted dressings in a
hexagonal grid pattern. MB@UiO-66(Ce) was added to the 3.5. Cell migration
hydrogels in different proportions, and hydrogel dressings Cell migration is essential for promoting wound healing .
[48]
were constructed via bioprinting as hexagonal scaffolds To explore whether the hydrogels affected the migration of
with the dimensions of 7-mm radius, 2-mm height, and cells, we performed cell migration experiments. In different
1-mm grid. Figure 2B shows that the MB@UiO-66(Ce)/ groups, L929 cells migrated from the surrounding region
PH dressing had a rough surface for cell adhesion and a to the cell-free region after a 24-h culture. Figure 4A shows
1-mm grid formed by 3D bioprinting, which is consistent that cells in all groups gradually migrated to the scratched
with the designed grid pattern (Figure S3). Meanwhile, the area. In the early stage, the cell migration rate was the

Volume 9 Issue 5 (2023) 464 https://doi.org/10.18063/ijb.773