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



            DLP conventional printing is up to 50 μm, which is    Despite their advantages of better mechanical
            between  MEW/ES  and  ME .  The  basic  materials  used   properties, higher plasticity, controlled degradation rate,
                                  [62]
            in these techniques are compatible with many of the   and availability of a wide range of sources, synthetic
            above-mentioned materials, but usually require extensive   scaffold materials are poorly biocompatible and less
            modification . SLA and DLP printing technologies are   hydrophilic and their degradation products may be toxic .
                                                                                                           [67]
                      [63]
            not as widely used in scaffold preparation as ME, probably   Bioceramics  such as  bioglass,  hydroxyapatite (HA),  and
            due to the high upfront investment and maintenance   TCP have been common scaffold materials in bone tissue
            costs of these systems. To date, SLA- and DLP-printed   engineering because of their high mechanical strength, but
            scaffolds have no porosity advantage (50%–65%) over   they also have the disadvantage of brittleness.
            other technologies . These techniques can be used to   A combination of two or more materials is used to design
                           [50]
            construct multilayered articular osteochondral scaffolds.   the ideal osteochondral scaffold in order to overcome the
            For example, Zhu  et al.  prepared a multilayered   disadvantages of a single material. Composite scaffolds
                                  [64]
            osteochondral scaffold by combining poly(ethylene glycol)   incorporate the advantages of each constituent material:
            (PEG) material with natural bovine cartilage ECM using   controlled degradation rate, good cytocompatibility and
            the DLP technique.                                 hydrophilicity, and suitable biomechanical  strength.

               Of various 3D printing solutions, ME is the most   Natural biomaterials, including ECM, are enriched
            commonly used due to its wide availability, material   with favorable molecules for cells (e.g., GAGs, collagen,
            versatility and low cost. Second, MEW and ES are mainly   and GAGs-like polysaccharides), and therefore, these
            used in the cartilage phase and their achievable scaffold   materials can be incorporated into composite scaffolds to
            thickness is limited. This so-called “limitation” makes it   enhance their affinity for the host tissue . Inspired by the
                                                                                              [68]
            suitable for the fabrication of thin and dense boundary   collagen fiber structure and ECM composition gradients
            structures, but its technical potential needs to be further   in osteochondral tissue, Qiao et al.  prepared a layered
                                                                                            [69]
            developed. The delicate connection of CCZ to the adjacent   scaffold composed of MSCs-laden GelMA hydrogel with
            structures provides excellent mechanical properties of the   zone-specific growth factor delivery and melt electro-
            entire articular osteochondral unit. In order to achieve its   written triblock polymer of poly (e-caprolactone) and poly
            maximum bionic potential, the imitation of this connection   (ethylene glycol) (PCEC) networks with depth-dependent
            should also be a key direction to be considered. Therefore,   fiber organization. It was found that the introduction of
            3D printing technology with higher precision should be a   PCEC fibers into GelMA hydrogels significantly improved
            major priority in the future.                      the mechanical strength. Considering the osteochondral
                                                               anatomy and physiology and the properties and functions
            3.2. Composition                                   of various scaffold materials, the cartilage layer prefers
            The materials used in osteochondral tissue engineering   hydrogels derived from natural or synthetic polymers
            scaffolds are mainly categorized into the following groups,   (because their hydration properties and viscoelasticity
            such as natural biomaterials, synthetic materials and   are similar to natural ECM), reinforcing materials favor
            bioceramics. Due to their composition and structure,   the subchondral bone layer, such as bioceramics and hard
            various types of osteochondral scaffolds have different   polymers, and the combination of cartilage  and bone
            biological and mechanical properties.              layer materials with a specific ratio is suitable for the
               Natural biological scaffold materials have the advantages   intermediate layer (osteochondral interface).
            of excellent biocompatibility, high degradability, and
            favorable cell attachment and proliferation for subsequent   3.3. Seed cells for the osteochondral tissue
            recruitment and infiltration. However, they also have   engineering
            disadvantages, including excessive degradation rates, poor   The seed cells are an important basis for osteochondral
            mechanical properties, and limited sources . Collagen   tissue  engineering  to  achieve  clinical  translation.
                                                [65]
            is the major constituent of osteochondral ECM and its   Currently, the most researched seed cells are various types
            role is to maintain the structural integrity of ECM .  of stem cells, including MSCs, cartilage stem/progenitor
                                                        [66]
            Studies have shown that chondrocytes in 3D collagen gels   cells, embryonic stem cells, skeletal stem cells, and induced
            maintain their normal phenotype and that collagen also   pluripotent stem cells.
            plays a crucial part in tissue repair and wound healing. The   Bone marrow-derived MSCs (BMSCs), which have
            chemical structure of chitosan is similar to that of GAGs in   a  strong proliferative  capacity,  can  easily differentiate
            the cartilage ECM and its biomimetic structure is highly   into chondrocytes and maintain their phenotype in vitro.
            conducive to the morphogenesis, differentiation, and   In  addition,  large  numbers  of  cells  can  be  obtained
            proliferation of chondrocytes.                     from many different bone marrow sites, making them


            Volume 9 Issue 4 (2023)                        135                         https://doi.org/10.18063/ijb.724
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