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International Journal of Bioprinting                                     Bioprinting in diabetic foot disease




            Table 2. Natural polymers for scaffolds
             Polymer                         Advantages                       Disadvantages
             Natural polymer  Gelatin        Low-cost, good injectability, and possessing   Lack of thermal stability, quick degradation
                                             ability to promote cell adhesion and proliferation   rate, and poor mechanical properties
                           Collagen          No high temperatures required for pH   Poor mechanical properties, low viscosity, and
                                             neutralization and highly permeable  time-consuming gelation
                           Fibrin            Good cell adhesion and possessing ability to   Time-consuming gelation, poor mechanical
                                             promote wound healing            properties, and poor extrusion and shape
                                                                              fidelity
                           Alginate          Easily modified and maintains moist wound   Poor mechanical properties and shear thinning
                                             environment                      behavior
             Synthetic polymer  Poly(lactic-co-glycolic   Low-cost, widespread use, good mechanical   Higher temperatures and pressures needed
                           acid)             properties, and modifiable degradation rate
                           Polycaprolactone  Easy to process, good mechanical properties, and   High printing temperatures and pressures,
                                             low degradation rate             time-consuming, and low cell adhesion
                           Polyurethane      Low printing temperature, good mechanical   Additional crosslinking stage required
                                             properties and elasticity, and possessing ability to
                                             promote cell adhesion and proliferation
                           Polyethylene glycol  Promotes M2 macrophage polarization and   Time-consuming, additional processing step
                                             wound healing, good mechanical properties, and   required, and other supporting biomaterials
                                             easily modifiable                required

               In addition, the development of automated-assisted   have been widely used as biomaterials in bioprinting [34-37] .
            technology has increased the potential of in situ bioprinting   Some  synthetic  polymers, including polyurethane,
            technology [30-32] . In situ technology can be used to directly   polycaprolactone (PCL), poly(lactic-co-glycolic acids), and
            print at specific anatomical locations on living organisms   polyethylene glycol, have also been used to complement
            and design living cells, growth factors, and biomaterials   natural materials to endow them with stable structures and
            with precise positioning . Robots and handheld devices   controllable mechanical properties by mixing synthetic
                               [31]
            are commonly used to fabricate complex shapes and curved   and natural materials together [34-39] .  Table 2 summarizes
            surfaces in situ . With the help of robotics, bioprinting   these polymers in detail [34-41] .
                        [32]
            tasks can be facilitated with high accuracy and automation
            levels without exhausting the operator . Typical robotic-  2.3.2. Seed cells
                                          [32]
            assisted bioprinting includes Cartesian coordinate robots,   The  keratinocytes  and  fibroblasts  comprised in  the
            articulated robots, and parallel robots . Cubo  et al.    structure of the epidermis and dermis are the preferred
                                            [32]
                                                        [33]
                                                                                      [42]
            confirmed that a Cartesian printer can produce engineered   seed cells for skin bioprinting . Other types of seed cells,
                                                                                                  [43]
            skin that is very similar to human skin. This group used   such as melanocytes, have also been explored . For in vivo
            biological ink containing human plasma and primary   experiments, stem cells, especially mesenchymal stem
            human fibroblasts and keratinocytes obtained from skin   cells, adipose-derived stem cells, and induced pluripotent
            biopsies to print human bilayered skin and tested the   stem cells are favored by researchers due to their valuable
            function of this bilayered skin in an immunocompromised   differentiation ability and low immunogenicity [44-45] .
            mouse model .                                      However, there are still ethical concerns regarding  the
                       [33]
                                                               application of stem cell, as well as difficulties in controlling
            2.3. Bioinks                                       the  direction of  differentiation, which could  cause
                                                                                               [46]
            Bioinks  include  biomaterials  that  form  temporary   tumorigenesis if not properly controlled .
            scaffolds, seed cells, and microenvironmental factors that
            regulate cells . This bioprinting component determines   2.3.3. Regulation factors
                      [34]
            the printability of scaffolds and can be endowed with   Cytokines and chemokines are often added to
                                                                           [47]
            specific functions by adding factors [14,34] .     biological inks , but it is difficult to simulate complex
                                                               microenvironments and intercellular interactions with
            2.3.1. Biomaterials                                the addition of only one or several regulatory factors . In
                                                                                                         [48]
            The primary features of biomaterials are nontoxicity and   recent years, decellularized extracellular matrix (dECM)
            good biocompatibility . Gelatin, collagen, fibrin, alginate,   has become a new choice of bioink . It performs well
                                                                                             [49]
                             [34]
            and other natural compounds similar to the outer matrix   in skin bioprinting due to its retained partial ECM
            Volume 9 Issue 6 (2023)                        225                        https://doi.org/10.36922/ijb.0142
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