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International Journal of Bioprinting                            dECM bioink for 3D musculoskeletal tissue reg.




               The  muscle-tendon  interface  plays  a  crucial   effectively integrate with surrounding natural bone tissues.
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            physiological function by transmitting the force generated   3D bioprinting of artificial bones holds great promise for
            by muscles through tendons to the bone via the muscle-  bone TE. The bdECM bioink is highly biocompatible,
            tendon  junction  (MTJ)  to  guide  movement.   However,   capable  of  stimulating  osteogenesis  differentiation,  and
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            there is limited research on the use of 3D bioprinting   can mimic the intricate microenvironment of natural bone
            technology to repair the muscle-tendon interface. Kim et   tissue. However, this biomaterial faces challenges such as its
            al. utilized core collagen hydrogel, collagen bioink, muscle   insufficient mechanical strength, limited vascularization,
            and tendon-derived dECM, and hASC bioinks to fabricate   and susceptibility to degradation, which can result in
            in vitro MTJ constructs via modified core-sheath nozzles   tissue collapse. 64,130,131,175,176
            for 3D bioprinting (Figure 7C). The in vitro 3D MTJ models   Parthiban et al. developed a photo-crosslinked
            displayed good morphological structure and biochemical
            characteristics, warranting subsequent developments of   methacrylate bone ECM hydrogel-derived biomaterial
            MTJ tissue interfaces in vivo. 171                 (boneMA), which has the ability to promote endothelial
                                                               cell vasculogenesis, enhance the vascularization function
               The bone–cartilage interface is often damaged in   for bone regeneration, and improve bioprintability and
            osteochondral defects, and osteochondral tissue has poor   mechanical strength. These attributes highlight the
            regenerative capacity and is difficult to repair. 40,131,172,173    potential of boneMA as a promising bioink for 3D printing
            Yang et al. used decellularized cartilage ECM (cdECM)/  applications.  Lee et al. prepared an alginate (Alg)/MA-
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            alginate and alginate/hydroxyapatite bioinks to reproduce   dECM  composite  bioink  and optimized  its  printability
            a biphasic graft consisting of cartilage and subchondral   and capacity to support cell viability. Compared with pure
            bone.  In vitro tests have reported good fusion between   Alg bioink, the expression levels of the cells loaded with
            the cartilage and subchondral bone layers for a complete   structural osteogenic genes (ALP, BMP2, OCN, and OPN)
            structure. However, the efficacy of in vivo implantation has   printed by the composite bioink were markedly increased
            not been verified, and the anisotropic structural properties   (Figure 8A). However, its mechanical strength (90.4 ± 14.9
            are lacking.  Zhang et al. developed a double-layer   MPa) is still lower than that of natural bone tissue.  To
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            scaffold printed from TGF-β1-loaded cartilage dECM/SF   address this issue, the researchers combined bdECM with
            (silk fibroin) and BMP-2-loaded bone dECM/SF bioinks.   various reinforcement substances (e.g., gelatin [GEL],
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            The scaffold reportedly promoted the differentiation of   PCL,  PLLA,  nano-hydroxyapatite [nHAP] ) for
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            bone marrow MSCs and osteochondral regeneration in   3D printing to prepare reinforced composite scaffolds
            rabbit knee joint models (Figure 7D), addressing most   (Figure 8B–D).
            of the aforementioned issues except the low mechanical
            strength.  Since the  osteochondral interface  contains   To improve osteogenic performance, Kang et al.
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            vascularized  and  avascular  zones,  the  directional   utilized extrusion-based 3D printing to design a hybrid
            establishment of  vascularization remains a  challenge  in   scaffold rich in microchannel network, consisting of
            osteochondral defect repair. To tackle this issue, Terpstra   dECM, gelatin (Gel), quaternized chitosan (QCS), and
            et al. developed human umbilical vein endothelial   nHAP (the scaffold hereafter termed as dGQH). Exosomes
            cell (HUVEC)-loaded pro-angiogenic and meniscal    (Exos) isolated from human ADSCs were subsequently
            progenitor cell (MPC)-loaded anti-angiogenic bioinks   loaded into the scaffold. The researchers verified the
            combined  with  cartilage dECM  and other  microfibers   biocompatibility  and  osteogenic  characteristics  of  the
            (MFs), partitioned through 3D printing, to achieve spatial   scaffolds with various amounts of nHAP (0%, 20%, 30%,
            confinement of new blood vessels. This approach provides   and 40%). The dGQH  scaffold significantly increased the
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            a new perspective on anisotropic vascular repair of the   expression of  ALP,  RUNX2, and  OCN. In addition, the
            osteochondral interface. 174                       dGQH @Exo group also displayed a stronger angiogenic
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                                                               effect than other groups and had good bacteriostatic
            6.5. Bone                                          activity. The dGQH20@Exo scaffold also demonstrated
            Bone tissue is composed of different cells, such as bone   good bone regeneration and vascularization levels in rat
            progenitors, osteoblasts, osteocytes, and osteoclasts. It also   models of skull defects. These findings indicate that the
            contains a rich ECM that provides excellent tensile strength   composite scaffold has great potential to treat craniofacial
            and elasticity to support the body’s mechanical activities. In   bone defects.
            recent years, surgical procedures, such as bone resection,
            bone grafting, and fracture repair, have made bone tissue   6.6. Cartilage
            the second most transplanted tissue.  Bone tissue grafts   Cartilage is a type of tissue that lacks blood vessels,
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            must possess mechanical strength and biocompatibility to   lymphatics, and nerves. It is mainly composed of


            Volume 10 Issue 5 (2024)                        81                                doi: 10.36922/ijb.3418
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