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International Journal of Bioprinting                Biomaterials for vascularized and innervated tissue regeneration


























            Figure 2. (A) The mechanism of peripheral nerves regulates the migration of mesenchymal stem cells and osteogenesis . Reprinted from Wang XD, Li
                                                                                        [29]
            SY, Zhang SJ, et al., Theranostics, 2020, 10(11): 4839–4850. From ref.  [29]  licensed under Creative Commons Attribution 4.0 International License. (B) The
            potential roles of neurotrophic factors in bone regeneration and remodeling . Reprinted from Su YW, Zhou XF, Foster BK, et al., Journal of Cellular
                                                             [10]
            Physiology, 2018, 233(3): 2133–2145. Copyright © 2017 John Wiley and Sons.
            with tropomyosin receptor kinase B (TrkB) receptors .   In human body, blood vessel networks are distributed
                                                        [37]
            BDNF also participates in the process of bone remodeling   throughout tissues/organs for supplying nutrients and
            by inducing osteoclast formation . Third,  recent studies   removing  metabolic  wastes.  Nervous  system  extending
                                      [38]
            found that peripheral glial cell also contribute to bone   highly branched  neural fiber networks  into  targeted
            metabolism  and  development .  For  example, paracrine   tissues/organs to establish communication by transmitting
                                    [39]
            factors (platelet-derived growth factor-AA [PDGF-AA]   electrical signals. . Developmental cues direct the
                                                                             [44]
            and oncostatin M [OSM]) secreted by Schwann cells can   formation of neural and vascular networks in an ordered
            regulate the cell behaviors of BSMCs and then participate   manner with overlapping patterns to match the architectural
            in the process of bone regeneration . Moreover, Cai et al.   and functional demands of tissues. Moreover, due to the
                                        [40]
            found that Schwann cells co-cultured with osteoblast could   anatomical similarity, blood vessels and nerves have a
            promote the proliferation, differentiation, and calcium   close interaction with each other . For instance, blood
                                                                                          [45]
            nodules deposition activity of osteoblast . Taken together,   vessels need to provide sufficient nutrients for supporting
                                           [39]
            neural system actively participates in bone development and   the development of nerves, while nerves also regulate
            remodeling through various pathways.               vasodilation and vasoconstriction via transmitting signals .
                                                                                                           [46]
               Skeletal muscle tissue is the heaviest tissue in the human   Moreover, previous studies also found that blood vessels and
                                                                                                           [47]
            body, accounting for about 45% of the body’s mass .   nerve fibers are able to share same signals and receptors .
                                                        [41]
            Muscle tissues are densely innervated with the peripheral   For example, NGF, one of the most important neurotrophic
            nerves by forming neuromuscular junctions (NMJs),   factors for neuron maturation, has a positive effect on the
            which are vital for the metabolism, maturation, and   proliferation and migration activity of endothelial cells
                                                                                                  [48,49]
            contraction of skeletal muscle . It is well known that the   through binding to its surface TrkA receptors  . Similarly,
                                    [42]
            dynamic movement of body is realized through contractile   VEGF could also promote the survival of neuron and axonal
                                                                       [50]
            force  generated  by  skeletal  muscle tissues .  Specifically,   outgrowth . Overall, considering the significant roles
                                              [2]
            somatic motor neurons trigger the release of acetylcholine   of blood vessels and nerve fibers in tissue regeneration,
            (Ach) from the axon terminal through generating action   developing novel neurovascularized biomaterials based on
            potentials. Subsequently, the released Ach can bind   3D printing technology is highly demanded.
            to acetylcholine receptor (AchR) on the surface of the   3. Skin tissues
            myofiber at NMJs, and eventually initiate the contraction of
            skeletal muscle . However, volumetric muscle loss (VML)   3.1. 3D printing for skin tissue engineering
                        [43]
            is always accompanied by significant motoneuron axotomy   At present, auto-transplantation still remains the best
            damage, resulting in permanent functional impairment .   strategy in clinical setting for treating severe and critical-size
                                                        [2]
            Hence, reconstructing NJMs is of great significance to   skin defects, in which skin tissue is harvested from one part of
            restore its physiological functions after VML.     the body and subsequently grafted to injury site in the same


            Volume 9 Issue 3 (2023)                        219                         https://doi.org/10.18063/ijb.706
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