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International Journal of Bioprinting                                3D bioprinting for musculoskeletal system




            complication following bone defect repair, and the risk of   for producing functional grafts that more closely resemble
            infection is heightened in the presence of open wounds or   native tissue architectures and is therefore a promising
            orthopedic implants.                               approach to cartilage tissue repair. Recent 3D bioprinting

               When infectious bone defects occur, bacteria adhere to   studies for cartilage regeneration are listed in Table 2.
            aggregate and proliferate on the scaffold surface to form   Numerous studies have attempted to evaluate the effects
            biofilms that impair the function of osteoblasts, leading to   of formulations or physical properties of bioinks (such
            delayed union or nonunion. 75,76  It has been reported that   as  matrix  stiffness)  on  the  maintenance  of  chondrocyte
            doxycycline can be released from a 3D-bioprinted scaffold,   phenotype and subsequent influence on cartilage-specific
            which is capable of inhibiting bacteria to reduce the risk   ECM production. Conventional bioprinted hydrogels
            of infection, to promote the expression of BMP-2 for   usually have poor mechanical strength, so it is a challenge
            stimulating new bone formation.                    to engineer mechanically robust cartilage constructs that
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                                                               can withstand high load-bearing environments. A feasible
            3.2. Cartilage                                     strategy for improving the mechanical strength of tissue
            Cartilage is an important tissue responsible for a variety   constructs is to incorporate stiffer polymer components
            of critical functions, including cushioning stress, reducing   into the bioink to strengthen its network. 106,107  Inspired
            friction between adjacent bones, and composing organs.   by this strategy, an alginate  hydrogel reinforced with
            Cartilage consists mainly of proteoglycans, water, type II   short submicron polylactide was designed as a bioink
            collagen, and a few chondrocytes. The articular cartilage has   for the bioprinting of cartilaginous construct. Round
            a specific zonal orientation (superficial, middle, deep, and   chondrocytes with high cell viability were observed in the
            calcified zones), and its structure and composition vary in   bioprinted constructs which had an elastic modulus three
            a depth-dependent manner.  Trauma, aging, disease, and   times higher than that of the pristine alginate constructs.
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            other factors can increase the risk of damage to cartilage,   A similar approach was used in another study to develop
            especially articular cartilage, resulting in joint dysfunction.   fiber-reinforced cartilage ECM-based bioinks for cartilage
            According to the depth of the lesion, articular cartilage   regeneration. The incorporation of ECM promoted the
            defects can be divided into partial cartilage defects, full-  growth and chondrogenic differentiation of stem cells
            thickness cartilage defects, and osteochondral defects. Due   in the bioink. Furthermore, the bioprinted constructs
            to the inherent characteristics such as low cell density and   augmented with polycaprolactone (PCL) fibers displayed a
            absence of blood vessels and nerves, the self-healing ability   compression modulus comparable to that of native articular
            of articular cartilage is significantly limited.  Without   cartilage.  In addition to the mechanical performance
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            timely  and  potent  intervention,  chondral lesions often   required by motion forces, the engineering of biomimetic
            progress to secondary osteoarthritis, leading to severe pain   cartilage tissues should focus on their chondrogenic
            and even disability.  Eventually, patients with end-stage   function.  To address this issue, de Melo et al. developed
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            diseases have to undergo total joint replacement. Therefore,   a new tissue design option for cartilage regeneration.
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            the repair and regeneration of cartilage tissue has attracted   Based on spatially organized bioprinting, this strategy
            much attention. The common clinical treatment strategies   enables human mesenchymal stem cell (hMSC) spheroids
            for cartilage defects include debridement, bone marrow   to maintain the chondrogenic behavior without detriment
            stimulation, and osteochondral transplantation. 80,81    to the macro mechanical properties of engineered tissues.
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            Among them, debridement and bone marrow stimulation   Pei et al. used extrusion printing to construct a cartilage
            are classified as palliative treatments, which cannot   repair scaffold in which mesenchymal stem cells (MSCs)
            achieve the curative effect.  The application of transplant   were transfected with microRNA-410.  The up-regulation
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            technology is constrained by several shortcomings, such   of microRNA-410 enhanced the migration, proliferation,
            as the need for reoperation, insufficient donor tissue,   and chondrogenic differentiation of loaded cells.
            and increased risk of immune rejection and disease   Compared with the nontransfected group, the transfected
            transmission.  The current available treatments, which   group showed better cartilage regeneration in the rabbit
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            are not widely available, often result in the development of   cartilage defect model (Figure 2). Another important issue
            fibrotic tissue, which is unfavorable to the native articular   with the bioprinted grafts is their integration with native
            cartilage and increases the tendency to degeneration.    host tissue, which is deemed vital for successful cartilage
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            Thus, it is imperative to develop innovative techniques   regeneration.  In response to this concern, a visible-light-
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            capable of effectively enhancing the regeneration of   responsive bioink was designed for chondral repair. The
            cartilage tissue. The emergence of bioprinting technology   bioink  material consists  mainly  of a  dual-functionalized
            represents a significant advancement in the field of   tyramine and GelMA and tris (2,2′-bipyridyl) ruthenium
            cartilage regeneration. Bioprinting is a potential method   (II) chloride and sodium persulfate (Ru/SPS) that acts as



            Volume 10 Issue 1 (2024)                        82                          https://doi.org/10.36922/ijb.1037
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