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International Journal of Bioprinting                                     Bioprinting in diabetic foot disease




            in dysfunctional fibroblasts to alleviate inflammation-  developed by combining nicotinamide with human
            induced damage, including direct supplementation of   dermal fibroblasts had a promoting effect on the healing
            cytokines or administration of probiotics that can regulate   of infected wounds.
            secretion of cytokine [83-85] .                       Due to the characteristics of chronic wounds such as
               Neovascularization provides immune cells, oxygen,   insufficient blood oxygen supply and difficult healing,
            and nutrients for highly metabolic wound repair and   recent studies have proposed a variety of materials and
            transport of metabolic waste, which are critical for the   methods for improving angiogenesis and local oxygen
            healing of chronic wounds in the elderly and those with   supply [94-95] . Ma et al.  added a uniform strontium silicate
                                                                               [94]
            microcirculation disorders, such as patients with severe   (SS) microcylinder to a bioink as a stable inducer of
            DFUs . In addition to chronic hypoxia and nutritional   angiogenesis in skin substitutes composed of a bioprinted
                [85]
            disorders, another serious consequence of angiogenesis   multicellular system. Inspired by symbiotic relationships,
            dysfunction is the inability to recruit sufficient endothelial   Wang  et al.   proposed  using  in situ  microfluidic-
                                                                          [95]
            progenitor cells (EPCs) to the wound surface . Hyperbaric   assisted 3D printing to incorporate unicellular microalgae
                                               [86]
            oxygen therapy can help improve angiogenesis and EPC   (Chlorella pyrenoidosa) into a scaffold to form a live
            dysfunction and promote DFU wound healing [86-87] .  photosynthetic  scaffold,  which  could  alleviate  local
                                                               hypoxia on the wound surface through the photosynthesis
            3.2. Bioprinting applications for wound chronicity  of microalgae, promote extracellular matrix synthesis,
            Although skin transplantation is still the gold standard for   and accelerate wound healing. In addition, 3D-printed
            the treatment of chronic wounds , bioprinted scaffolds   patches containing angiogenic factors could also improve
                                       [13]
            still  have  unique  advantages  compared  to  other  skin   ischemia and hypoxia on the wound surface and promote
            engineering materials in the treatment of chronic wound   wound healing [96-97] . Guan et al.  developed a bioprintable
                                                                                       [96]
            healing . In particular, they can promote healing by   peptide patch and promoted the angiogenic properties of
                  [88]
            addressing the angiogenic disorders and inflammation that   the patch by covalently coupling the peptide QHREDGS
            occur after the healing of chronic wounds, such as DFUs .   with GelMA and hyaluronic acid methacryloyl (HAMA)
                                                        [88]
            Here,  we  introduce  studies  that  employed  bioprinting   biological patches. Liao  et al.  covalently crosslinked
                                                                                        [97]
            using different functional materials in the treatment of   intravascular growth factor (VEGF) onto a biological patch
            chronic wounds.                                    composed of alginate polysaccharide and chondroitin
            3.2.1. Different scaffold materials and bioinks for   sulfate methacrylic acid groups through calcium ions and
            promoting chronic wound healing                    ultraviolet light, simplifying the single chemical coupling
            There are physical and biochemical factors involved in   step and extending the VEGF release time.
            skin engineering that cannot be accurately controlled
            by traditional techniques and cannot be fulfilled by a   3.2.2. Personalized printing and novel printing
            single  biomaterial . Therefore,  bioprinting  methods   strategies for complex wounds
                           [89]
            rely on programmable microscales to control material   The shape of DFU wounds is irregular, the depth varies, and
                                                                                  [98]
            and cell deposition, as well as combining a variety of   the structure is complex . Bioprinting fulfills the needs of
            complex materials, including natural ECM components,   personalized and accurate treatment by producing models
                                                                                                        [99]
            to simulate a repair environment with certain biological   in varying designs using different printing strategies .
            functions and skin structures, making these methods   Embedded bioprinting is a novel type of bioprinting
            incomparable to traditional skin engineering methods .   that  outperforms  traditional  bioprinting  strategies,  such
                                                        [89]
            Especially in inflammatory and infected wounds, some   as extrusion bioprinting, in terms of the fineness and
            scaffolds eliminate inflammation and infection, thereby    complexity of 3D-printed pendants or hollow structures [100] .
            promoting wound healing [90-93] . For example, Prasad et al.     It has great potential in solving the vascularization problem
                                                        [91]
            encapsulated curcumin in an oil gel 3D fiber network   in 3D-printed scaffold [101] . Embedded printing can better
            to  treat bacterial  biofilm-related infections,  such as   preserve the shape of hydrogels by printing in a prefilled
            Staphylococcus aureus, and promote DFU wound healing.   matrix [102] . In addition, a new printing strategy has been
            Xia  et al.   loaded  curcumin  into  gelatin  methacryloyl   developed that involves printing cell aggregates, without
                    [92]
            (GelMA)-containing adipose-derived stem  cells  to   using hydrogel as a biological ink, into 3D tissue constructs
            evaluate its therapeutic effect on DFU wounds through in   with a certain spatial structure and then assembling these
            vitro experiments. They found that the gel could reduce   constructs into integrated tissues [102-103] . Skylar-Scott
            apoptosis and reactive oxygen species production, which   et al. [103]  used this method to construct organ building
            could  promote  DFU  wound  healing .  Ullah  et al.    blocks (OBBs) derived from patient-specific pluripotent
                                                        [93]
                                           [92]
            demonstrated through in vivo experiments that a scaffold   stem cells and then assembled perfusion-capable vascular
            Volume 9 Issue 6 (2023)                        228                        https://doi.org/10.36922/ijb.0142
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