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International Journal of Bioprinting                      Functional materials of 3D bioprinting for wound healing



            pro-inflammatory chemokines and persistently high levels   reports of 3D-bioprinted tissue-engineered scaffolds for
            of ROS at the wound site, hindering skin repair [155] . The   wound healing.
            addition of anti-inflammatory materials to 3D-bioprinted
            scaffolds can produce wound healing materials that   6. Discussion and future perspectives
            enhance the ability of inflammatory inhibitors, reduce   This  paper  introduces  various  bioprinting  methods,
            pro-inflammatory chemokines, eliminate ROS, and    functional materials, and their applications in wound
            promote macrophage polarization . Li et al. [147]  reported   dressing and skin tissue engineering. 3D bioprinting
                                       [42]
            the anti-inflammatory activity of PDA in a rat model.   emerges as an additive bio-manufacturing technique
            The 3D-bioprinted PDA-modified BC (DOPA-BC)        possessing the advantages of high resolution, flexible
            skin  scaffolds  could  prevent  inflammatory  infiltration   operation, repeatable fabrication, and high-throughput
            and promote collagen deposition and microvascular   output for printing the intricate 3D structures that match
            regeneration, which could effectively promote wound   the geometric shape of skin wound [117,158] , thus it has been
            repair in a rat diabetic skin repair model (Figure 6g).   widely used in wound dressings and skin tissue engineering
            Therefore, this DOPA-BC scaffold may be ideal for treating   scaffolds in recent years [19,43] . As one of the development
            diabetic wounds.                                   trends of advanced materials, multifunctional materials

               Traditional surgical resection of skin tumors   have become an attractive option for wound dressings and
            remains a challenge [156] . The ideal strategy is to enhance   skin tissue engineering scaffolds. However, the cytotoxicity
            postoperative wound healing and tissue regeneration   that may occur when the dosage of these multifunctional
            while removing residual tumor cells to prevent tumor   materials exceeds the cytotoxicity threshold is not
            recurrence [32,156,157] . Considering the individual needs, Ma   negligible. Moreover, unlike traditional bandages, current
            et al. [148]  successfully prepared 3D-bioprinted hydrogel   3D-bioprinted hydrogel dressings usually suffer from
            scaffolds based on sodium alginate (SA), calcium silicate   poor mechanical strength and stability although possess
            nanowires (CS), and oligomeric proanthocyanidins   multiple  functions,  and  do  not  function  on knees  and
            (OPC).  This  CS+SA+4%OPC     hydrogel  scaffold   joints for long periods due to poor adhesion. Also, current
            containing  photothermal  agent  OPC  could  inactivate   3D-bioprinted  dressings  required  more  research  in
            melanoma cells and prevent their growth by controlling   overcoming the challenges of scars, nonoxygen permeable
            high temperature through NIR irradiation. The  in vivo   and damaged skin cells [159] .
            therapeutic potential of this scaffold was evaluated using   The main distinctions of skin tissue engineering
            tumor-bearing diabetic mice, and the results are shown   compared to the wound dressing are the loaded cells
            in Figure 7a–f. Under NIR irradiation, the controllable   and bioactive factors. Whether it is to print the bionic
            photothermal properties of this scaffold induced high   skin structures with cell-encapsulating bioink, or to
            temperature to successfully ablate the tumor, so that the   inoculate cells on the noncellular-printed scaffolds, the
            wound healed without tumor recurrence. In addition,   requirements of skin tissue engineering scaffolds for
            H&E staining showed epithelialization and collagen   printing materials and conditions are stricter than that
            deposition  (Figure  7g).  Therefore,  the  CS+SA+4%OPC   of the printed dressings, such as biocompatibility and
            scaffold could effectively treat melanoma and promote   viscosity of the bioinks, suitable  temperature  and pH,
            skin wound healing.                                and sterile microenvironment for cell survival [114,160] .
               With the development of 3D bioprinting technology,   Although significant progress has been achieved in tissue
            flexible polymer materials have been used to build   engineering over the years, only a limited number of
            complex functional soft structures, that reach a modulus   bioinks have the tissue matching characteristics and the
            (103–109  Pa)  similar  to  that  of  human  tissues  (such  as   ability to promote tissue generation [161] . At present, it is still
            skin or muscle tissue), which is crucial for the process   a major challenge for skin tissue engineering to configure
            of wound repair . A recent study fabricated porous   multifunctional bioink with printability, biocompatibility,
                          [88]
            2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)-mediated   and  excellent  mechanical  integrity  under  individual
            oxidized cellulose nanofibrils (TCNFs)/casein-based   condition [162] . Therefore, the design of mixed bioink should
            composite hemostatic scaffolds with cytocompatibility   integrate the advantages of natural bioink and synthetic
            and  hemocompatibility  by  flexible  3D  bioprinting   bioink to prepare bioink that is conducive to cell growth
            (Figure 7h). Biocompatible TCNF, chitosan and casein   and can support cell survival in the printing process [160] . In
            with synergistic hemostasis mechanism could endow 3D   addition, cell encapsulation bioink can use various types of
            composite  scaffolds  with  the  ability  of  cell  attachment   cells, such as fibroblasts, keratinocytes, mesenchymal stem
            and hemostasis (Figure 7i), maximizing their potential   cells, and induced pluripotent stem cells, as cell sources [117] .
            in wound healing applications . Table 3 summarizes the   Stem cells, such as induced pluripotent stem cells, can
                                    [60]
            Volume 9 Issue 5 (2023)                        180                         https://doi.org/10.18063/ijb.757
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