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



            Table 3. 3D-bioprinted skin tissue engineering scaffolds for wound healing applications
             Main components              Representative functional materials  Properties for accelerating wound healing  Ref.
             PCL/PPSu/AgNO                AgNO                          Antibacterial                   [145]
                        3                     3
             Gel/GelMA/Silver/ PDGF-BB    Silver                        Antibacterial                   [25]
             GelMA/Cur                    Cur                           Antioxidant                     [146]
             BC/PDA                       PDA                           Anti-inflammatory               [147]
             CS/SA/OPC                    OPC                           Antitumor                       [148]
             TCNFs/CS/Casein              CS/Casein                     Hemostasis                      [60]
             CS/α-tocopherol              α-tocopherol                  Antibacterial, antioxidant      [149]
             PLLA/PPy                     PPy                           Conductive                      [150]
             dECM/1-vinylimidazole ([VBIM]Cl)/  [VBIM]Cl/QCS            Antibacterial, hemostasis       [151]
             QCS/Gel
             SA/Gel/Paeoniflorin          Paeoniflorin                  Anti-inflammatory               [49]
            Abbreviations: BC, bioceramic; CS, chitosan; Cur, curcumin; dECM, decellularized extracellular matrix; Gel, gelatin; GelMA, gelatin methacryloyl;
            OPC, oligomeric proanthocyanidin; PCL, polycaprolactone; PDA, polydopamine; PDGF-BB, platelet-derived growth factor-BB; PLLA, poly-l-lactide;
            PPSu, poly(1,3-propylene succinate); PPy, polypyrrole; QCS, quaternized chitosan; SA, sodium alginate; TNCFs, 2,2,6,6-tetramethylpiperidine 1-oxyl
            (TEMPO)-mediated oxidized cellulose nanofibrils.

            differentiate into various types of skin cells, but they are   complex microenvironment effects in vivo also make the
            sensitive to the shear stress imposed on the cells during   experimental results uncertain, which is a very important
            printing and are difficult to survive [161] . Autologous cells   limitation for translation [166] . Therefore, clinical validation
            from patients are the source of gold-standard cells in skin   should be carried out in larger skin defect models or
            bioprinting. While reproducing all functions of tissues and   chronic skin wound models, so as to enable their direct
            organs, they have no rejection reaction to patients, and   application in the future [167] .
            can survive with sufficient vitality and maintain functions   It can be predicted that combining the most advanced
            during the printing process. However, the normalization   tissue engineering strategies and the achievements of
            and  standardization  of  human  clinical  trials  related  to   current and ongoing research; it is very promising to develop
            3D  bioprinting  cell-encapsulated  bioinks  before  skin   fully functional bioprinted skin. Recent in situ bioprinting
            bioprinting can be translated to clinical application is   research has shed light on the concept of biological
            another challenge, and it will take several years to develop   manufacturing of tissue directly in the living body .
                                                                                                           [46]
            a dedicated regulatory framework or dedicated regulatory   Advanced  in situ 3D bioprinting technology to combine
            guidance to make 3D bioprinting sustainable [163] .
                                                               multiple functional materials and bioactive factors to create
               Another challenging problem that prevents skin   fully functional bioprinted skin is a rapid skin construction
            regeneration is angiogenesis during skin repair [107] . The   technology with lower rejection rate. In addition, it can create
            skin structure needs highly developed vascular network to   specific organs from patients’ cells in lesser time and lower
            supply nutrients and oxygen [164] . In addition, the bioprinting   cost, thus making the research and development process
            of complete skin with multilayer complex structure is still a   simpler, faster, and better. Moreover,  in  situ bioprinting
            difficult problem in tissue engineering. The thickness and   should be integrated with other functions, such as real-
            texture of the epidermis, dermis, and subcutaneous adipose   time monitoring, higher degrees of freedom, equipment
            layer of the bioprinted skin should match the patient’s   miniaturization, and dynamic surface printing [44,46] . In short,
            natural skin, while the recovery of multiple functional   the structural complexity of the bioprinted skin structure
            skin appendages, such as sweat glands, hair follicles, and   requires further enhancements through the collective efforts
            sebaceous glands, should be consistent with the normal   of various technologies, in a bid to create a fully functional
            skin anatomical structure and function [117,165] . At present,   skin with lesser time and lower cost.
            for most wound healing materials,  the exploration of
            their mechanism and the evaluation of their therapeutic
            effects are carried out in animal models, such as mice. The   7. Conclusion
            phenomena and effects observed in animal models may   3D-bioprinted wound dressings and skin tissue engineering
            not be fully applicable to humans [166] . For example, there   scaffolds have been widely used for skin wound repair. They
            are some significant differences between mice and humans   are made of natural or synthetic polymers and can promote
            in inflammatory reaction and cell behavior, and the   wound repair and tissue regeneration. At present, the main

            Volume 9 Issue 5 (2023)                        182                         https://doi.org/10.18063/ijb.757
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