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International Journal of Bioprinting                           3D bioprinting techniques & hydrogels materials




            3.2.3. Hydrogels made from various                 molecules constitute a strategy for bone tissue engineering.
            composite materials                                Herein, we will discuss enhancing  the biofunctions of
            Some researchers have attempted to use two or more   hydrogel-mediated osteochondral repair using cells and
            composite hydrogels to treat OCDs. Polymeric scaffolds are   growth factors.
            extensively utilized in bone tissue engineering due to their
            biocompatibility, ductility, and customizability. Compared   3.3.1. Mesenchymal stem cells
            with other polymers, polycaprolactone (PCL) has greater   Mesenchymal stem cells (MSCs) come from a wide
            toughness, elasticity, and mechanical strength and is the   range of sources and can differentiate into bone cells and
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            most prevalently employed synthetic polymer. 168,169  Chen   chondrocytes that play important roles in tissue repair.
            et al. fabricated a 3D bioprinting biphasic scaffold, where   Shim  et  al.  3D-printed  a  hydrogel  scaffold  containing
            the cartilage phase scaffold consisted of alginate saline gel   human turbinate-derived MSCs (hTMSCs), and the
            and PCL, and the bone phase scaffold was loaded with   scaffold demonstrated good osteochondral regeneration
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            HAP in the PCL.  This hybrid scaffold exhibits an ideal   in rabbits.  Gao et al. uniformly printed human MSCs
                          170
            biological response both in the short and long term, and   on polymerized poly(ethylene glycol) (PEG)-GelMA,
            it has the potential to be used as an interface material for   and the scaffold demonstrated remarkable osteogenic and
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            cartilage and bone.                                chondrogenic differentiation.  Zhang et al. fabricated a
                                                               composite scaffold with HAP and a hydrogel and gradient-
               Owing to the deficiency of bone-induced characteristics,   loaded BMSCs onto the scaffold in accordance with
            the  utilization of  PCL  in bone tissue engineering  is   osteochondral characteristics, demonstrating favorable
            limited.   Currently,  numerous  studies  have  endeavored   osteochondral repair effects in rabbit models. 180
                  171
            to  coat  porous  scaffolds  with  certain  natural  biological
            materials to enhance their cell adhesion.  The cartilage   Furthermore,  chronic  inflammation  within  the  joint
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            ECM is a special type of natural biological material and   reduces chondrogenesis and MSC motility, leading to
            also a fiber-reinforced composite material, and it can   cartilage matrix interpretation and thus exacerbating
                                                                                                 181,182
            increase the expression of collagen II and aggrecan in   the  progression  of  osteochondral  injury.    Therefore,
            chondrocytes, thereby increasing cell adhesion.  Li et al.   inhibiting the inflammatory microenvironment is key
                                                  173
            designed a double-layered scaffold; the cartilage layer was   for  effectively  repairing OCDs caused by  inflammatory
            composed of ECM, polycaprolactone (PCL), and hydrogel,   diseases,  such  as  OA.  Liu  et  al.  designed  a  3D-printed
            and the subchondral bone layer was composed of PCL and   multilayer hydrogel scaffold loaded with BMSCs. The PCL
            polydopamine (PDA) modified with magnesium oxide   layer combines with β-TCP for bone regeneration, whereas
            (MgO) nanoparticles. The scaffold effectively regenerated   PCL/methacrylated hyaluronic acid (MeHA) combines
            bone and cartilage simultaneously in rats. 174     with Kartogenin (KGN) for cartilage regeneration.
                                                               Diclofenac sodium (DC)-supported hydrogel coating was
               Additionally, researchers are applying natural   applied to the top of the articular facing stent to inhibit
            compounds to bone tissue engineering. Honokiol  is the   the inflammatory microenvironment  (Figure 3i). This
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            main bisphenol compound isolated from Magnolia trees   composite scaffold can effectively promote osteochondral
            and is reported to have a wide range of biological activities   repair by promoting the deposition of ECM proteins and
            and low cytotoxicity.  Zhu et al. used ECM, polyethylene   suppressing the production of interleukin-1β.
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            glycol diacrylate (PEGDA), and honokiol to develop
            hydrogel scaffolds, and the 3D-printed hydrogel scaffolds   Promoting cartilage vascularization is also a major
            exhibited excellent osteochondral regeneration ability. 176  challenge in bone tissue engineering. Although cartilage
                                                               templates are well-vascularized  in vivo, vascularization
               Owing to the varying advantages and disadvantages   begins peripherally, and the central region of cartilage
            of different materials, fabricating scaffolds by combining   remains  vascular-free.  To  address  this  issue,  Daly  et al.
            multiple materials can address the various requirements   developed a 3D-printed hydrogel scaffold loaded with
            of osteochondral repair. However, the complex fabrication   MSCs, promoting vascularization after implantation with
            process may be a major factor limiting its application. In the   the potential to repair large bone defects. 184
            future, it is imperative to identify more suitable materials
            and simplify the production process (Table 3).        In bioprinting, the contact between cells and the cell
                                                               contact-dependent signal is blocked due to the trapping
            3.3. Enhancement of the biofunctions of            effect of the hydrogel, resulting in the loss of their biological
            hydrogel-based osteochondral repair                activity.  The spheroid, a multicellular aggregate with a
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            In addition to the recruitment of cells, such as MSCs, or   microenvironment similar to native tissue, is an advanced
            bioactive factors to promote bone repair, the direct delivery   printing unit with the potential to become a bioink for
            of homologous or dissimilar MSCs and the stimulation of   bone tissue engineering. Its extensive intercellular contact

            Volume 10 Issue 6 (2024)                        77                                doi: 10.36922/ijb.4472
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