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International Journal of Bioprinting                                Bioprinting in wound dressing and healing



            Table 3. List of top 14 keywords for bioprinting in wound   interfacial tension. It reduces irritation to the surrounding
            dressing and healing                               skin tissue when applied as an extracellular matrix
                                                               substitute for the skin. Its swelling property can promptly
             No.      Freq      Centrality  Keywords           absorb tissue exudate, keep the wound clean, reduce wound
             1        44        0.14      3D bioprinting       infection, and thus accelerate wound repair. In addition, it
             2        42        0.23      Scaffold             shows excellent physical or structural similarity to natural
             3        41        0.21      In vitro             tissues and can mimic the natural extracellular matrix
             4        33        0.12      Wound healing        very well. The porous structure of hydrogels facilitates the
             5        28        0.14      Tissue               transport of oxygen, nutrients, and some growth factors.
             6        28        0.17      Stem cell            This provides a suitable spatial microenvironment for cell
             7        27        0.15      Hydrogel             growth during skin tissue regeneration and acts as a drug
                                                               delivery pathway . Therefore, biocompatible hydrogels
                                                                             [55]
             8        26        0.12      Drug delivery        have a wide range of applications in skin tissue engineering
             9        25        0.12      Tissue engineering   and biomedicine.
             10       23        0.08      Fabrication             The technologies currently used for bioprinting of
             11       19        0.12      Mesenchymal stem cell  skin are inkjet printing, laser-assisted printing, and
             12       18        0.05      Extracellular matrix  extrusion printing. To gain further insight into the use of
             13       16        0.04      Design               these printing techniques, we manually identified papers
             14       15        0.05      Keratinocyte         investigated in this work (excluding review, book chapter,
                                                               and meeting abstract). Extrusion printing is the most
            technology has so far yielded data from in vitro experiments.   commonly used technique in this topic. More than half
            Bioprinting-generated skin  is a  skin-like substitute  with   of all the papers used extrusion printing technology to
            natural skin tissue structure, which can be used to prepare   print wound dressings. Inkjet printing is also a commonly
            in vitro using cells, extracellular matrix components, and   used technology, accounting for about 35% of all papers.
            bioactive factors. Different types of cells have been used   However, inkjet  printing is not widely used in wound
            for bioprinting in vitro, so “stem cell” and “mesenchymal   dressings because of the restriction imposed on the
            stem cell” also appear in Table 3. Stem cells are cells that   concentration of bioink. Laser-assisted bioprinting has
            can renew and differentiate themselves. Stem cells for   only recently begun to be used to print wound dressings
            skin printing are epidermal stem cells, dermal stem cells,   because of its ability to kill cells. In our survey, only nine
            adipose stem cells, melanin stem cells, mesenchymal stem   articles used this technique.
            cells, etc. Stem cells are an important source of seed cells   Cluster analysis can help further understand the
            for skin bioprinting. They can solve problems that existing   different directions of investigation in this topic. Figure 8
            technologies cannot solve, such as the lack of blood vessels,   shows that 13 clusters were formed. On the whole, many
            sensory receptors, skin appendages, etc. Skardal  et al.    clusters have overlapping areas, indicating the similarities
                                                        [52]
            used laser deposition bioprinting techniques to unite stem   of their contents. This reflects that the topic of bioprinting
            cells with the potential to differentiate into blood vessels   in wound dressing and healing has not spawned many
            and found that they greatly facilitated wound healing after   subdivisions. Table 4 describes the clusters and their ID, size
            injury. Growth factor is also one of the high-frequency   (number of papers), silhouette, and respective keywords.
            keywords in Table 3. The most challenging aspect of skin   The following is a short explanation of each cluster:
            printing is achieving formation of multiple blood vessels,
            and early attempts to overcome this difficulty involve using   3.1. Hydrogel. This cluster contains a series of
            vascular endothelial growth factors and keratinized cells   works on bioprinted hydrogels. For example, Maver
            or scaffolds, but more research is needed in this area .   et al.  compared the effectiveness of bioprinted and
                                                                   [56]
                                                        [53]
            Therefore, incorporating growth factors in the ink of   electrostatically spun carboxymethylcellulose hydrogels
            bioprinting is an essential part of this topic. The keywords   as wound dressings. Diclofenac sodium and lidocaine
            “hydrogel,” “drug delivery,” and “extracellular matrix” are   were added to the hydrogel preparation for wound pain
            also included in Table 3. Hydrogels are highly hydrophilic   relief. They not only characterized the physicochemical,
            3D polymer networks prepared by chemical or physical   structural, and morphological properties of the hydrogels
            cross-linking of natural or synthetic polymers  that can   derived  from  the  two  preparations,  but  also  examined
                                                 [54]
                                                                                                   [57]
            swirl rapidly upon water absorption and maintain  their   their biocompatibility. Abasalizadeh   et al.  reviewed
            structural integrity. The physical properties of the dissolved   the hydrogels formed by alginate with inorganic cations
            hydrogel include  soft texture, high elasticity, and low   and their potential application as bioinks in bioprinting.

            Volume 9 Issue 2 (2023)                         57                       http://doi.org/10.18063/ijb.v9i2.653
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