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International Journal of Bioprinting                                           Robotic in situ bioprinting


            4.2. Bone                                          former, which covers the excised total thickness wound

            Bone fracture healing and the realization of the function   with autologous skin graft, has been considered the gold
            of bones to withstand and adapt to mechanical stresses   standard treatment. However, the applicability of grafts
            are results of the synergic effect of bone cells, extracellular   is limited by the supply of available donor sites; thus, it
            matrix, and bioactive molecules. Vascularized bone graft   is difficult to repair skin damage covering a large area.
            has been recognized as the gold standard in the field of   3D bioprinting is able to deliver bio-inks to specific sites
            bone healing for four decades. Approximately a couple   for the reconstruction of damaged skin with biomimetic
            of million bone grafts are performed yearly across the   functions and activities. Recently, there has been
            globe to treat bone lesions. These traditional technologies   remarkable progress in the field of skin bioprinting, which
            for repairing defects based on autogenous or allogeneic   shows great potential in revolutionizing the paradigm of
            bone grafts have several limitations, including donor-  treatment in injury and surgery. By vividly mimicking
            site availability and morbidity, graft incorporation and   the layered architecture, consisting of epidermis and
            remodeling, low biological properties, and high cost. 3D   dermis, damaged skins have been repaired successfully
            bioprinting provides novel solutions to these enormous   through bioprinting. Lee  et  al. revealed the potential of
            clinical challenges. In particular, repairing bone damage   3D bioprinting for tissue engineering using human skin
            by direct  in situ 3D bioprinting has been viewed as   as a prototypical example. The fabricated constructs were
            a promising entrance for applying 3D bioprinting in   cultured and exposed to the air-liquid interface to promote
            clinical settings. Some reports have evaluated in situ 3D   maturation and stratification. The fabricated skin can be
            bioprinting for clinical use or injury repair, demonstrating   viewed as morphologically and biologically representative
            the employability of this technology in healing damaged   of  in vivo human skin tissue, as indicated by histology
                                                                                                           [52]
            bones.  According  to Keriquel  et al., automatic robotic   and  immunofluorescence  characterization  results .
            bioprinting can be employed by surgeons to achieve   Cubo et al. performed 3D bioprinting of human bilayered
            precise cellular implantation at a micron or millimeter   skin  using  bio-inks  containing human  plasma,  primary
            scale. Mesenchymal stromal cells with collagen and   human fibroblasts, and keratinocytes. Long-term in vivo
            nano-hydroxyapatite were successfully printed for in vivo   analysis of the structure and function of the printed skin
            bone regeneration in a calvaria defect model in mice .   using an immunodeficient mice model verified that the
                                                        [50]
            After hematoxylin-eosin-safran staining, the histologic   bioengineered skin obtained by the Cartesian printer was
                                                                                     [53]
            evaluation of  in vivo bone repair in a calvaria defect in   very similar to human skin . Albanna et al. conducted
            mice at 1 and 2 months is shown in Figure 4B. Li et al.   validation testing of a mobile skin bioprinting system that
            developed  an in situ  3D  bioprinting  technology  based   offers rapid on-site management of extensive wounds.
            on a robotic manipulator to repair long segmental bone   Through printing layered autologous dermal fibroblasts
            defects in a living swine model. By robotic-assisted means,   and epidermal keratinocytes in a hydrogel carrier,
            the operation time was significantly reduced, which may   the excisional wounds showed rapid closure, reduced
                                                                                                     [54]
            be beneficial  to patients . Lipskas  et al. combined 3D   contraction, and accelerated re-epithelialization .
                                [40]
            bioprinting and robotic-assisted minimally invasive   4.4. Other tissues or organs
            surgery techniques to improve regenerative medicine. They
            investigated the remote center of motion, which is critical   Repair and regeneration of other tissues  or organs,
            to minimally invasive surgery, followed by biomaterial   including muscle, vascular, neural structures, and liver,
            development. The repair of knee defects was used as an   through 3D bioprinting have also been successfully
            example of the application of in vivo 3D printing .  developed, thus providing potential clinical applications.
                                                  [51]
                                                               Chen et al. used a combination of 3D printing with digital
            4.3. Skin                                          near-infrared photopolymerization to perform proof-of-
            Skin, which consists of epidermis, dermis, and subcutaneous   concept in vivo noninvasive bioprinting. The bio-ink was
            tissue, is the largest organ in the human body. It serves   printed in situ into a customized ear-like construct, with
            as a protective barrier against mechanical, thermal, and   chondrification and a muscle tissue, layer-by-layer without
            physical injuries as well as hazardous substances. The skin   surgical implantation . Lee et al. constructed vascular
                                                                                [55]
            performs physiological functions, including physiological   channels and created adjacent capillary networks through
            metabolism and nerve conduction. Its self-regeneration   a natural maturation process based on 3D bioprinting.
            process is slow, in which wounds beyond 4 cm in diameter   The connection of capillary networks to the large perfused
                                                                                                           [56]
            do not repair well without intervention. Conventional   vascular channels was realized by the presented means .
            methods for repairing skin wounds include autologous   Owens et al. fabricated fully biological grafts, composed of
            skin transplantation and artificial skin substitutes. The   cells and cell-secreted material, with reliable reproducibility


            Volume 9 Issue 1 (2023)                        104                      https://doi.org/10.18063/ijb.v9i1.629
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