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



            (OA). In addition, their pathological characteristics are   However, there are also disadvantages, such as excessive
            also different. Osteochondral lesions usually require   tissue fibrosis, grafts sinking, abnormal bone formation,
            surgical treatment. If fibrocartilage is formed with different   excessive cartilage growth, and scaffold separation .
                                                                                                           [6]
            biomechanical properties  from hyaline cartilage, it  will   Compared to articular osteochondral tissue, single- or
            cause degeneration of the adjacent normal cartilage and   double-layered scaffolds lack a “boundary structure”
            subchondral bone, eventually leading to severe pain,   between cartilage and bone, that is, calcified cartilage
            joint deformity, and mobility loss . The different causes   zone (CCZ) . This usually causes an imbalance in
                                       [1]
                                                                         [7]
            of osteochondral defects contribute to the complexity of   the microenvironmental homeostasis of the articular
            their treatment. Significant progress has been made in the   cartilage and subchondral bone, as well as altered stress
            repair of articular cartilage defects in recent decades, but   transmission patterns, ultimately leading to repair failure.
            osteochondral defects deep into subchondral bone have   In order to achieve complete biomimicry, researchers
            not gained much attention.                         have designed a strategy for constructing a multilayered
               The current treatment options for osteochondral defects   osteochondral scaffold with a boundary layer structure.
            include nonsurgical and surgical treatments, such as joint   With the advent of additive manufacturing technology in
            debridement, microfracture, autologous osteochondral   recent years, 3D printing has developed rapidly, providing
            grafting or mosaic inlay, matrix-associated autologous   new tools and technical methods to solve this challenge.
            chondrocyte implantation (MACI), and autologous    As shown in Figure 1, this paper summarizes the anatomy,
            chondrocyte implantation (ACI) . Although conventional   physiology, pathology and restoration mechanisms of the
                                      [2]
            osteochondral repair strategies have their corresponding   articular osteochondral  unit, and reviews  the necessity
            advantages, their inherent disadvantages are also evident.   for a boundary layer structure in osteochondral tissue
            For example, arthroscopic debridement is not effective;   engineering scaffolds and the strategy for constructing
            microfracture repair tends to form fibrocartilage rather   the scaffolds using 3D printing.
            than normal hyaline cartilage ; autologous or allogeneic
                                    [3]
            osteochondral implantation have a limited source of graft   2. Osteochondral tissue: Anatomy and
            tissue  and high incidence in the area of the graft origin; the   physiology, pathology, and restoration
                [4]
            defective area repair does not fit the surrounding articular   mechanisms
            cartilage; and among other problems. Therefore, their
            clinical practical restorative results are not satisfactory.   2.1. Anatomy and physiology
            Cell-based treatments, such as ACI and MACI, also involve   The articular osteochondral structure can be roughly
            the possibility of fibrocartilage production in the repair   divided  into  five  layers  according  to  the  biological
            area, incomplete filling of the repair, and poor integration   differences in fiber orientation, cell morphology and
            with the surrounding tissues, and their actual results have   density, content of glycosaminoglycans (GAGs), collagen
            not been uniformly accepted. As a result, there is a lack of   and water, and their corresponding mechanical gradients.
            practical and effective treatment for osteochondral defects   As shown in Figure 2A and C, the five layers are superficial
            in clinical practice.                              layer,  intermediate layer (transitional  layer),  deep  layer
                                                               (radial layer), calcified cartilage layer, and subchondral
               The development of tissue engineering techniques   bone layer. The first three layers are generally referred to
            offers a novel approach to the treatment of osteochondral   as hyaline cartilage layer. There is a tidemark structure
            defects. Long-term restorative results can be achieved   that connects the relatively soft articular cartilage to hard
            through the use of an integrated tissue-engineered   calcified cartilage. The subchondral bone lies beneath the
            osteochondral bionic scaffold, combined with the   calcified cartilage layer, and the structure formed by the
            relevant  advantages  of  existing  treatment  methods   interlocking of these two layers is called cement line .
                                                                                                        [8]
            and  a  systematic  and  personalized  postoperative
            rehabilitation program. Tissue engineering technology   2.1.1. Hyaline cartilage layer
            aims to repair the structure and function of damaged   The superficial layer comprises 10%–20% of the total
            tissue by combining seed cells and growth factors with   thickness of hyaline cartilage layer and is characterized
            material scaffolds. The articular cartilage is relatively   by thin and densely arranged collagen fibers that run
            homogeneous  in composition  and simple  in structure   parallel  to  the  cartilage  surface.  This  layer  has  a  high
            with no complex vascular system . Due to its low   density of chondrocyte distribution with a long, thin, and
                                          [5]
            difficulty of tissue engineering, it is considered the most   flattened morphology . The chondrocytes in this area are
                                                                                [9]
            promising alternative for osteochondral defect treatment.   primarily associated with the outward tissue growth and
            Since the 1990s, research into articular osteochondral   are referred to as persistent chondrocytes. The uppermost
            tissue engineering has made significant progress.   area of the superficial layer is overlaid with a thin layer


            Volume 9 Issue 4 (2023)                        130                         https://doi.org/10.18063/ijb.724
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