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International Journal of Bioprinting             3D-Bioprinted human lipoaspirate-derived cell-laden skin constructs



            foot wounds, have become a substantial social burden .   treatment approach  is based  on the concept that if  the
                                                        [2]
            Recently, with remarkable progress in regenerative   microenvironment is regarded as a macroscopic whole,
            medicine related to wound healing, skin tissue engineering   the overall regulatory direction is conducive to wound
            has spawned the emergence of skin replacement products   repair [16,17] . Therefore, we attempted to modify the usual
            for wound repair. However, in a 2016 global survey of   strategy of in vitro fabrication of highly biomimetic skin
            111 specialists, 100% of the participants believed that an   substitutes by 3D bioprinting technology to a strategy of
            ideal skin substitute had yet to be developed . This is due   rapid  in vitro fabrication and  in vivo maturation in the
                                               [3]
            to many factors, such as the material source, preparation   microenvironment. Once this attempt can be realized, the
            time,  storage  time,  medical  expense,  physiological   preclinical time consumed by 3D bioprinting technology
            function, structure reproduction, and biological stability   for wound repair will be substantially shortened.
            of previously developed tissue-engineered skin [4-7] .  Liposuction  is a  well-established procedure that is

               Recently, many tissue engineering studies have   widely used in plastic surgery, and the removed fat is
            fabricated three-dimensional (3D)-bioprinted, structurally   typically discarded as biohazardous waste . This “waste”
                                                                                                [18]
            complex scaffolds [8-10] . 3D-bioprinted structures containing   contains abundant extracellular matrix (ECM) and
            pigments, or sweat glands and hair follicles have been   mesenchymal stem cells (MSCs) that fully meet the cell and
            successfully  constructed  in vitro [11,12] .  The  emergence   material requirements for bioactive materials that support
            of these constructs is very encouraging, but their long   the repair of full-thickness skin defects. ECM is a natural
            in vitro culture time may not provide patient satisfaction   material derived from  the human  body  that  can  affect
            within a short period of time. By integrating  in situ   numerous cell processes, including cell spreading, growth,
            bioprinting system with image processing technology,   proliferation, migration, and differentiation, as well as
            autologous or allogeneic dermal fibroblasts and epidermal   organoid formation [19,20] . Decellularized ECM (dECM)
            keratinocytes can be delivered precisely to the skin defect   does not contain cellular or nuclear components, reducing
            area, which can accelerate wound healing  in vivo .   the risk of inflammatory and immune responses upon
                                                        [13]
            Jorgensen  et al.  produced  three-layer, bioprinted skin   implantation, but does retain the structural and functional
            model that encapsulated cells from a wider array of   properties  of  ECM,  including  specific  nanostructures,
            cell types, such as human keratinocytes, melanocytes,   biochemical complexity, and bioinduction properties .
                                                                                                           [21]
            fibroblasts, dermal microvascular endothelial cells, hair   Importantly, dECM can promote the production of
            follicle dermal papilla cells, and adipocytes . There is   functional tissues in  specific parts  of  the  body . These
                                                                                                      [22]
                                                [14]
            no doubt that the composition or function of the newly   advantages make dECM a promising material for
            emerging full-thickness skin constructs are increasingly   tissue engineering strategies for wound treatment. The
            similar to that of natural skin, but we should also note that   thermosensitivity of dECM enables physical crosslinking at
            most  in vitro fabricated 3D-bioprinting scaffold require   37°C, but dECM alone is unsuitable for 3D printing because
            a remarkable amount of time to complete material and   of the low  viscosity . Gelatin  methacryloyl (GelMA)
                                                                                [23]
            cell culture preparation. Confronted with urgent clinical   has photocrosslinking properties and can promote cell
            needs, rapid fabrication of 3D-bioprinting scaffolds is   adhesion, proliferation, and spreading . Hyaluronic
                                                                                                [24]
            essential for accelerating wound recovery and reducing   acid methacryloyl (HAMA) has a high hydrophilicity and
            scar formation . There remains a lack of products using   considerable  cytocompatibility,  supporting  cell growth,
                        [15]
            human materials and cells that can be fabricated within   migration, and differentiation . Photocrosslinked HAMA
                                                                                      [25]
            a few days, particularly in terms of material source and   can  improve the mechanical  properties  of  bioprinted
            preparation time. This study will focus on this perspective.  implants. Therefore, adipose-derived decellularized
                                                               extracellular matrix (adECM), together with GelMA and
               If tissue engineering is  considered an external  tool,
            the wound microenvironment itself may serve as an   HAMA, as the main components of a bioink, can provide
                                                               dual properties of photocrosslinking and thermosensitive
            internal tool to promote implant maturation. Therefore,   crosslinking, which can further improve the stability of the
            these external and internal tools could be combined to   scaffold after implantation.
            eliminate excessive steps in in vitro fabrication. Therefore,
            rapidly fabricated 3D-bioprinted scaffolds that seem like   Several studies have demonstrated the potential of
            “semifinished products” but possess biological activity could   adipose-derived stem cells (ADSCs) to promote wound
            be directly implanted into the wound, where their structure   healing [26-28] . ADSCs can differentiate into endothelial cells,
            and function would continue to improve depending on   fibroblasts, and keratinocytes and secrete cytokines that
            the wound microenvironment. We believe that this is   promote their proliferation and migration [29-32] . Biomaterial
            a valuable approach, although many details regarding   scaffolds fabricated by 3D bioprinting technology and
            the wound microenvironment remain unexplored. This   loaded  with ADSCs  can promote  the  healing  of  burn


            Volume 9 Issue 4 (2023)                         30                          https://doi.org/10.18063/ijb.718
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