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International Journal of Bioprinting                                     Bioprinting in diabetic foot disease




            channels in a high-cell-density matrix through embedded   4. Bioprinting applications for unique
            printing. This study indicated that embedded bioprinting   diabetic foot disease characteristics
            can be used to create functional tissue or organ structures,
            especially vascular structures, and has broad application   In 2019, the International Working Group on the Diabetic
            prospects in the field of regenerative medicine, especially   Foot (IWGDF) proposed eight key factors of the diabetic
            in the treatment of DFU chronic wounds in patients with   foot classification score based on a literature review and
            angiogenic disorders [102-103] .                   expert opinions to provide guidance for the management
               To produce customized tissue-engineered skin for   of DFU infection and the blood circulation reconstruction,
                                                               although they believe that there is still no classification that
            chronic and irregular wound treatment, Wu  et al. [104]    can predict the outcome of a single ulcer (Figure 2) [107] . The
            developed a planar/curved bioprintable hydrogel. The   main eight factors are end-stage renal disease, peripheral
            hydrogel was composed of polyurethane and gelatin and   arterial  disease,  loss  of  protective  sensation,  infection  ,
            contained three kinds of cells: fibroblasts, keratinocytes,   depth, location (forefoot/hindfoot), size of ulcers, and
            and endothelial progenitor cells [104] . Moreover, this curved   number (single/multiple) of ulcers [107] . In addition, the
            bioprintable hydrogel with three cell types could promote   chronic wounds of patients with diabetic foot disease also
            complete repair of chronic irregular wound in a rat model   have a unique high-glucose environment that affects wound
            after 28 days, which proved the enormous application   healing [108] . To treat DFU wounds using bioprinting, new
            potential of this hydrogel that allows customization   treatment  options  tailored  to  the  characteristics  of  DFU
            according to wound shape in chronic wound healing [104] .   wounds should be developed.
            The integrated development of in situ printing technology
            and bioprinting systems mentioned above also meets the    Here, we introduce recent bioprinting applications for
            requirements of on-site on-demand production and rapid   unique diabetic foot disease characteristics in detail.
            treatment in the future [104-105] .
               Usually, DFU patients have significant differences in   4.1. Imaging and algorithm technology-assisted
            wound depth [15] . Therefore, DFU may involve repairing   bioprinting for DFU treatment
            different types of tissue interfaces [106] . The organizational   Traditional imaging methods, such as 3D magnetic
            interface is a key structure in coordinating the interaction   resonance imaging (MRI), are used to evaluate the blood
                                                                                     [10,107]
            between two different organizations, and the possible   circulation of DFU wounds  . To further enhance the
            damage to the organizational interface that may occur   ability of bioprinting to accurately evaluate DFU wounds
            in DFU patients including skin, neurovascular/muscular   and reconstruct biomimetic tissues, more auxiliary imaging
                                                                                                        [109-112]
            interfaces, and even cartilage–bone interfaces [10,106] . The   and modeling methods have been developed  .
                                                                       [109]
            self-healing ability of these organizational interfaces   Tian et al.   proposed to quantitatively describe the 3D
            is  usually  limited [106] .  Transplantation  of autologous,   structure of skin collagen tissue using fractal dimension
            allogeneic, or synthetic grafts is currently being used   analysis after analyzing skin under different pathological
                                                                                [110]
            to treat tissue interfaces with limited effectiveness [13,15] ,   conditions. Xu  et al.   subsequently used small angle
            mainly due to the inability to form multilayer structures   X-ray  scattering (SAXS) combined with  the  potential
            similar to tissue interfaces in a short period of time [106] .   fractal characteristics of collagen to design a analysis tool
            Computer-assisted bioprinting technology makes     for quantitating collagen to evaluate dermis and grafts and
            it possible for various biomaterials to be accurately   verified the analysis effect in a diabetic mouse model. In
                                                                               [111]
            arranged layer by layer in space [102-103] . The use of   addition, Pena et al.   used two infrared cameras and an
            biomaterials such as cells and cytokines for personalized   infrared projector to form a WoundVue camera for initial
            modeling and printing of patient wounds has great   DFU wound measurement and periodic detection and
            application prospects in DFU wound interface tissue   evaluated the reliability of the camera by comparing the
            repair [106] . However, the current physical and chemical   wound area, depth, and other indicators measured by the
                                                                                                           [112]
            properties of biomaterials and the accuracy of bioprinting   camera and an established Visitrak system. Parsa et al.
            methods cannot meet the requirements for repairing   proposed that optical coherence tomography (OCT) can
            complex tissue interface structures [106] . Although   be used to evaluate DFU wound characteristics and blood
            bioprinting can build nanoscale constructs, it cannot   flow through a single-center nonrandomized observational
            simultaneously maintain the activity of seed cells and   study to improve guidance for treatment option selection.
            the microenvironment  [106] . Therefore, further studies to   Algorithm-assisted bioprinting is also a new strategy
            explore suitable biomaterials and bioprinting strategies   for improving the therapeutic effect of bioprinting on
            for repairing tissue interfaces through bioprinting are   DFU wounds [113-117] . Li  et al. [114]  developed a step-by-
            warranted in the future.                           step algorithm that combined adaptive mesh generation


            Volume 9 Issue 6 (2023)                        229                        https://doi.org/10.36922/ijb.0142
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