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International Journal of Bioprinting                                       3D-printed anistropic meniscus


            a 2 – 7-fold higher risk of osteoarthritis . Meanwhile,   studies  involving  3D printing  technique,  and provides
                                              [11]
            the remaining section of the meniscus was confirmed to   the latest, detailed and comprehensive summary about
            suffer from increased compressive pressure, accelerating   3D-printed anisotropic TEM.
            the degeneration of cartilage and ultimately osteoarthritis
            of the knee joint . Therefore, attempts to maintain the   2. Heterogeneity of meniscus
                          [12]
            integrity of the meniscus after injury have reached an   2.1. Anatomy and histology of meniscus
            overwhelming consensus. Disappointingly, with adequate
            vascularity in only 10 – 25% peripheral red-red zone,   The meniscus is a pair of crescent-shaped structures placed
            severe tears in the avascular white-white zone showed   inside the knee joint capsule, protecting the condyles
            no potential for self-repair [13,14] . Allografts of meniscus   of the femur and tibial plateau from direct contact. The
            substitutes, although effective, are clinically limited   hyaline cartilage, fibrocartilage, connective tissues, and
            by scarce sources. Some products, although already   composition of the meniscus vary in proportion to zones,
                                                                                                           [29]
            clinically applied, such as CMI  and Actifit , have a high   species, and age [14,24] . Shaped at 8 – 10 weeks of pregnancy ,
                                     ®
                                               ®
            failure rate of 30% due to a deficiency in blood supply   the medial and lateral menisci are not macroscopically
            after implantation, resulting in failure of regeneration   identical. The medial meniscus is C-shaped, approximately
            and progression of articular cartilage lesions [15,16] . On   40 – 45 mm in length and 27 mm in width, covering 51 –
            this account, tissue-engineered meniscus (TEM) shows   74% of the medial joint surface [23,30,31] . The lateral meniscus,
            promising prospects as an ideal implant in meniscus   shorter but larger than the medial meniscus, is O-shaped,
            repair [17-22] .                                   32 – 35 mm in length, and covers 75 – 93% of the joint
                                                               surface [30,31] . The posterior horn of the lateral meniscus
              The meniscus is a semilunar fibrocartilaginous tissue   is attached to the intercondylar region of the tibia,
            characterized between the fiber and hyaline cartilage,   neighboring the posterior horn of the medial meniscus .
                                                                                                           [32]
            which combines the properties of ligaments to withstand   The meniscotibial ligaments, the capsule thickening
            tensile forces and the properties of hyaline cartilage to   between the apex of the fibular head, and the inferolateral
            withstand compressive and shear forces [23,24] . However,   portion of the lateral meniscus fix the meniscus to the
            in contrast to homogeneous ligaments and cartilage,   tibia [33,34] . The meniscus is composed of the ligament of
            menisci show sophisticated heterogeneity in anatomy,   Humphrey anterior to the posterior cruciate ligament
            cell phenotypes, extracellular matrix (ECM), and   and the ligament of Wrisberg posterior to it, attaching
            biomechanical properties [25,26] . This anisotropic structure   the meniscus with the femur condyle . Moreover, the
                                                                                              [35]
            enables knee joints to adapt to flexion and rotate with   transverse ligament moves between the anterior horns
            different strains at different angles, efficiently transmitting   of the bilateral menisci, connecting them as a functional
            load and protecting articular cartilage from abrasion [27,28] .   unit .
                                                                  [35]
            Accordingly, only a TEM with bionic heterogeneity can
            adequately function as a natural meniscus in the knee joint.   Blood supply to the meniscus originates from the
            To reconstruct the heterogeneity of the meniscus, scientists   peripheral perimeniscal capillary plexus, which originates
            have attempted several three-dimensional (3D) printing   from the branches of the medial inferior, lateral inferior,
            methods, which have indicated inspiring outcomes both   and middle geniculate arteries . The meniscoligamentous
                                                                                       [36]
            in vitro and in vivo. Therefore, we systemically reviewed   complex is derived from the intermediate layer of
            the heterogeneity of the meniscus to obtain insights into   mesenchymal tissue. From the embryo to the early
            the construction of TEM with more biomimetic properties   postpartum  period,  the  meniscus  is  highly  cellular  and
            (Figure 1). The databases of PubMed, Web of Science, and   vascularized, with extensive blood supply to the whole
            Embase were searched systematically to collect relevant   tissue [13,32] . Under gradual regression of vessels, only 10 –
            reports published since January 1990. Original articles   30% of the meniscus in the outer region is vascularized at
            that  involved  anisotropic  meniscus  tissue  engineered   age 10, while vessels and nerves exist in only 10 – 25% of
            reconstruction were selected for analysis, in which   the peripheral meniscus in adults [14,37] . Due to avascularity
            articles related to 3D printing were included, and other   in the  inner portion of adults, tears  are  difficult to
            strategies,  for example, electrospinning, freeze-drying   self-repair.  Several  therapeutic  approaches  have  been
            technique, etc., were excluded from the study. In addition,   developed to repair such non-healing injuries through
            after discussing the research status and progress of 3D   angiogenesis, including vascular endothelial growth factor
            printing heterogeneous TEM, references are also provided   (VEGF),  connective tissue growth factor (CTGF), and
            in this paper for future research. Different from previous   hepatocyte growth factor (HGF), which are administered
            reviews, the present review paper focuses on the meniscus   directly into the knee joint or used as in auxiliary method
            heterogeneity and TEM strategies, especially from the   for bioengineering . Meanwhile, a decrease in cells and
                                                                              [38]

            Volume 9 Issue 3 (2023)                        360                          https://doi.org/10.18063/ijb.693
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