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International Journal of Bioprinting                             3D-printed scaffolds for osteochondral defects



            form a thrombus. As a result, mobilized MSCs and blood   parameters, such as temperature, extrusion pressure, print
            cells form hematomas to repair the cartilage defects . In   speed, speed of hydrogel crosslinking or gelation [48,49] .
                                                      [43]
            this case, only fibrocartilaginous scar tissue is generated,   ME can be used to fabricate scaffolds with relatively high
            which has more type I collagen and less type II collagen   porosity, which facilitates seed cell adhesion, proliferation,
            in the ECM. Additionally, its mechanical properties are far   chondrogenesis and osteogenic differentiation. Porous
            inferior to those of hyaline cartilage, and it does not form   structures similar to SB can be printed with thermopolymer-
            an effective and long-lasting bond with the surrounding   based ME technology to promote bone growth. The pore
            tissue.  Bone  marrow  stimulation  techniques,  including   size for the SB section of the multiphase osteochondral
            microfracture and deep drilling, use similar principles to   scaffold is usually 0.3–1.0 mm, with a porosity of 70%–
            penetrate the subchondral bone to the bone marrow cavity   80% [50,51] . ME printing technology based on bioceramics is
            and mobilize  cells to the  cartilage defect site  to achieve   mainly used in the CCZ and SB sections of osteochondral
            regenerative repair. However, the regenerative repair by   scaffolds .  In general, the  printed  bioceramic  scaffolds
                                                                      [52]
            these techniques ultimately only generates fibrocartilage   achieve low porosity (20%–60%) and small pore sizes
            tissue in the defect and does not completely regenerate the   (0.1–0.4 mm). Many scaffolds failed to produce pore sizes
            articular cartilage to restore its original functional state .  >0.3 mm to promote bone growth in the SB section [53,54] .
                                                        [44]
                                                               Although hydrogel ME printing is commonly used for the
                                                                               [55]
            3. 3D-printed osteochondral repair                 AC section, Gao et al.  fabricated a biphasic osteochondral
            materials                                          scaffold using this technique. The addition of β-tricalcium
                                                               phosphate (β-TCP) to the SB section of the hydrogel
            The articular osteochondral tissue units are an ordered   increases the mechanical stiffness and osteoinductive
            and integrated whole. In normal tissue, articular cartilage   properties of the hydrogel, while transforming growth
            polysaccharide chains have a pore size of approximately   factor-beta 1 (TGF-β1) is incorporated into the AC section
            6  nm between them and the collagen fibril network   to enhance cartilage formation.
            has a pore size of 60–200 nm and extends vertically to   MEW and ES technologies allow long filaments to
                   [45]
            the CCZ . Unlike hyaline cartilage layer, the internal   be deposited layer-by-layer through a nozzle . Its fiber
                                                                                                    [56]
            structure of CCZ and SB is much denser. This structural   diameters range from microns to nanometers. In addition,
            difference poses a major challenge for the bionic fabrication   ES is a solvent-based printing technique that deposits
            of CCZ-containing osteochondral scaffolds, particularly   material fibers randomly on a collector bed, whereas
            in the selection of the scaffold raw material and its design   MEW is a solvent-free method that regulates where and
            strategies.
                                                               how the fibers are deposited, thus controlling the final
            3.1. 3D printing techniques in osteochondral tissue   pattern. Polycaprolactone (PCL) is the most used material
            engineering                                        in MEW, as well as gels, chitosan, polyvinyl alcohol (PVA),
                                                                                        [57]
            Currently, the most common 3D printing techniques   hyaluronic acid, and collagen . Despite the increased
            for articular osteochondral scaffolds include electro-  availability of suitable materials in ES, the solvents used
                                                                                                           [58]
            spinning (ES), material extrusion (ME), stereolithography   are often biotoxic and require significant attention .
            (SLA), digital light processing (DLP), and melt electro-  When applying MEW and ES to the construction of
            writing (MEW). However, every technique has their own   articular cartilage scaffolds, the main challenge is the
            advantages and limitations, as well as their appropriate   limited total thickness of the structure printed in the Z-axis
                                                                      [59]
            printing materials. In terms of material selection, there is   direction . The current solution is to print the material
            no evidence to date that one material is definitely better   onto various collectors and body beds in order to increase
                                                                                                [60]
            than another. In general, hydrogels are mostly used for the   the structure height in the Z-axis direction . On the other
            printing of hyaline cartilage layer; bioceramics, hyaluronic   hand, given the limited height and strength of the micro/
            acid, tricalcium phosphate (TCP), and metallic materials   nanofibers, MEW and ES often produce soft scaffolds that
            are more suitable for the printing of SB . In addition, the   are well suited for the AC section manufacture of articular
                                           [46]
            development of new materials with better biocompatibility,   osteochondral scaffolds.
            plasticity, and modifiability is one of the most important   SLA  and  DLP  technologies  are  used  to  achieve
            issues in the future.                              3D-printed shapes by depositing material layer-by-layer.
               ME technology involves depositing material via nozzles   However, these technologies are not based on a nozzle
            on a print bed in the X-Y plane and then stacking it layer-  approach, but rather on a liquid material in a resin bath.
            by-layer in the Z-axis plane . It is suitable for a wide range   The difference between SLA and DLP technology is the
                                 [47]
            of materials, including thermopolymers, bioceramics, and   light source used; SLA uses a laser while the light source
                                                                                        [61]
            hydrogels. Each material requires fine-tuning of printing   of DLP comes from projection . The accuracy of SLA/
            Volume 9 Issue 4 (2023)                        134                         https://doi.org/10.18063/ijb.724
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