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. 2022 May 1;11(1):10.
doi: 10.1186/s13619-022-00113-y.

Fabrication of SA/Gel/C scaffold with 3D bioprinting to generate micro-nano porosity structure for skin wound healing: a detailed animal in vivo study

Changmei Niu #  1 , Liyang Wang #  1   2 , Dongdong Ji  3 , Mingjun Ren  4 , Dongxu Ke  1 , Qiang Fu  5   6 , Kaile Zhang  5   6 , Xi Yang  7
Affiliations

Fabrication of SA/Gel/C scaffold with 3D bioprinting to generate micro-nano porosity structure for skin wound healing: a detailed animal in vivo study

Changmei Niu et al. Cell Regen. .

Abstract

Bioprinting has exhibited remarkable promises for the fabrication of functional skin substitutes. However, there are some significant challenges for the treatment of full-thickness skin defects in clinical practice. It is necessary to determine bioinks with suitable mechanical properties and desirable biocompatibilities. Additionally, the key for printing skin is to design the skin structure optimally, enabling the function of the skin. In this study, the full-thickness skin scaffolds were prepared with a gradient pore structure constructing the dense layer, epidermis, and dermis by different ratios of bioinks. We hypothesized that the dense layer protects the wound surface and maintains a moist environment on the wound surface. By developing a suitable hydrogel bioink formulation (sodium alginate/gelatin/collagen), to simulate the physiological structure of the skin via 3D printing, the proportion of hydrogels was optimized corresponding to each layer. These results reveal that the scaffold has interconnected macroscopic channels, and sodium alginate/gelatin/collagen scaffolds accelerated wound healing, reduced skin wound contraction, and re-epithelialization in vivo. It is expected to provide a rapid and economical production method of skin scaffolds for future clinical applications.

Keywords: 3D bioprinting; Hydrogel; Skin scaffold; Skin tissue engineering.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Printing test of hydrogel bioink. A The preparation of four different bioinks (Gel 1, Gel 2, Gel 3, and Gel 4, respectively). Gelatinization was occurred through the physical crosslinking at laboratory temperature. B The multilayer skin scaffold for printing. C The lines of the scaffold were observed under an optical microscope
Fig. 2
Fig. 2
Structure of the 3D bioprinted SA/Gel/C scaffold. A A schematic diagram of the structure of the bionic skin scaffold. B The appearance of the scaffold: (i) the top view and (ii) the side view of the printed scaffold, and (iii) the freeze-dried scaffold includes the dermis layer. Scanning electron microscopy images of the scaffold without fibroblasts. From left to right, the upper layer (C1, C2), lower layer (D1, D2), and side view (E1, E2). SEM images of fibroblasts on scaffolds. On day 1 after culture, fibroblasts on the upper layer (F) and sectional view (G and H)
Fig. 3
Fig. 3
Live/Dead staining at 0, 3, and 6 days after fibroblasts encapsulation in the printed scaffold. A Images of the printed fibroblasts-laden SA/Gel/C hydrogel after days 0, 3, and 6 culturing. Living cells are stained green and dead cells red. Scale bar 500 μm. B Cell viability of fibroblasts in the printed SA/Gel/C hydrogel at days 0, 3, and 6. C MTT assay of fibroblasts on scaffolds at days 0, 3, and 6
Fig. 4
Fig. 4
The gross morphology of the wound healing process for 4 weeks. Full-thickness skin defects were divided into two groups: the scaffold group and the control group, respectively
Fig. 5
Fig. 5
Representative images of H&E staining (A) and Masson’s trichrome staining (B) of the wound tissue of porcine for 2, 3, and 4 weeks postoperatively
Fig. 6
Fig. 6
Representative immunofluorescence images of cell nuclei (blue), angio-biomarkers CD31 (green) (A), CD206 (green) (B), PCNA (green) (C), and Cytokeratin AE1/AE3 (green) (D) in the control group and the scaffold group, respectively. Scale bars, 50 μm
Fig. 7
Fig. 7
Schematic diagram of the Organ Printing United System (OPUS) and printing process. The foremost part of the system has a computer-aided design system and a three-axis controller, including temperature, air pressure, mechanical control, and a cartridge unit loaded with bioink
See this image and copyright information in PMC

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