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International Journal of Bioprinting                  High-performance SrCS scaffolds via vat photopolymerization




            Keywords: Strontium-doped calcium silicate; 3D print-  and very fast degradation ratio pose challenges in ensuring
            ing; Vat photopolymerization; Mechanical property;   sufficient mechanical reinforcement and a biomimetic
            Biodegradability                                   microenvironment for effective bone regeneration.

                                                                  Barium   titanate-based  ceramics  (BTA)  has
                                                               demonstrated their good biocompatibility and mechanical
                                                                                                           [31]
            1. Introduction                                    properties in the application of bone tissue engineering ,
                                                               which can enhance mechanical properties as a second
            The  treatment  of  large  segmental  bone  defects  (>5   phase. For instance, Dubey et al. prepared hydroxyapatite
            cm) caused by car accidents, gunshots, and malignant   (HA) scaffold doping with 40 wt.% BTA to enhance the
            tumor  resection  is  complicated  and  has  many  clinical   compressive strength by 200% compared to undoped
            complications, which easily lead to repair failure [1,2] .   samples . Tavangar  et al.  fabricated HA-BT scaffolds
                                                                     [32]
            Therefore, large segmental bone repair remains a major   for orthopedic applications and found that the presence
            challenge in clinical treatment. The emerging bone tissue   of BTA acted as a second phase to highly increase the
            engineering (BTE) provides an ideal treatment strategy   bulk density and mechanical properties of composite
            for the repair of large segmental bone defects [3,4] . The   samples . Therefore, in this study, we proposed an
                                                                     [33]
            biomimetic three-dimensional (3D) scaffolds play a crucial   approach to improve the mechanical properties and tune
            role in BTE since they can provide the necessary mechanical   the degradation rate of SrCS scaffolds by doping BTA
            support and biomimetic microenvironment conducive   powders with different mass ratios. SrCS-BTA scaffolds
            to  cell  proliferation [5-9] .  So  far,  various  manufacturing   with biomimetic triply periodic minimal surface (TPMS)
            methods have been developed for the fabrication of   structures were fabricated by VPP. Finally, the mechanical
            biomimetic scaffolds, such as direct foaming, gel-casting,   and biological properties of the scaffolds before and after in
            and sacrificial template method [10-12] . But these conventional   vitro degradation were characterized.
            methods are restricted by the geometrical design and
            structural complexity of biomimetic structures. Additive   2. Material and methods
            manufacturing (known as 3D printing ) has been shown
                                          [13]
            through multiple studies to enable the creation of intricate   2.1. Materials
            scaffolds that can be customized to individual patients [14-17] .   SrCS powders (Xi’an Shuogu Technology Co., LTD.,
            These scaffolds possess the capacity to provide mechanical   China,) with a particle size of 3.9 μm (D ), a density of
                                                                                                 50
                                                                       3
            reinforcement to bone tissues and a microenvironment   2.90 g/cm , and a refractive index of 1.61, were used as raw
            that closely resembles that of natural bone [18-20] . Among   materials. BTA powders with a particle size of 2.2 μm (D ),
                                                                                                           50
                                                                                3
            the various additive manufacturing techniques available,   a density of 5.72 g/cm ,and a refractive index of 1.63 were
            vat photopolymerization (VPP) is a highly accurate   used as the dopant with different mass ratios of 0, 20, 30,
            method that is particularly well-suited for printing bone   and 40 wt.% (marked as SrCS, SrCS-20BTA, SrCS-30BTA,
            implants [21-24] . However, as for large segmental bone   and SrCS-40BTA). 1,6-Hexanediol  diacrylate (HDDA,
            repair, the reconstruction of vascularization capacity for   Chengdu Fourth City New Material Co., LTD., China) with
                                                                                3
            3D-printed large-size scaffolds remains a huge challenge.   a density of 1.0 g/cm  and a refractive index of 1.457 was
                                                               used as the photosensitive resin. Polymer 41000 (Lubrizol,
               Modulation of cellular behavior through intrinsic   Spain) and diphenyl (2,4,6-trimethyl benzoyl) phosphine
            properties of biomaterials provides an effective solution for   oxide (TPO; BASF, Germany) were used as the dispersant
            the complete revascularization of large-size scaffolds. For   and  photoinitiator,  respectively.  RAD  2500  (VOK,
            instance, the strontium-doped calcium silicate (SrCS) can   Germany) and anti-sedimentation thixotropic 8810 (Sago,
            significantly upregulate the expression of osteogenic genes   Germany) were used as leveling and anti-settling agents,
            and angiogenic factors by releasing Si  and Sr  ions [25-28] .   respectively. High-purity alkyl aluminum derivatives
                                                 2+
                                          4+
            Lin et al. fabricated SrCS scaffolds for osteoporotic bone   (Easepi 590, Guangyi Chemical Co., LTD., China) were
            repair, and the in vitro experiments revealed that Si  and   used as the copolymer inhibitor. Simulated body fluid
                                                     4+
            Sr  ions can promote cell viability and expression of alkaline   (SBF) (Phygene Life Sciences Company, Fujian, China)
             2+
            phosphatase (ALP) . Xing  et al. designed bioactive   was used to perform in vitro immersion tests to analyze the
                            [29]
            alginate hydrogels containing Si  and Sr  ions to activate   biodegradability of materials.
                                            2+
                                     4+
            cells in vivo, and revealed a synergistic effect of the ions
            on cell proliferation without loss of stemness . In short,   2.2. Fabrication of scaffolds
                                                [30]
            SrCS is deemed an ideal biomaterial for reconstructing   4.0 wt.% 41000 (based on powders), 0.5 wt.% TPO (based
            vascularization in repairing large segmental bone defects.   on photosensitive resin), 0.5 wt.% RAD, 0.5 wt.% 8810
            Nonetheless, its suboptimal mechanical characteristics   (based on suspension), and 0.1 wt.% copolymer inhibitor
            Volume 9 Issue 6 (2023)                        525                          https://doi.org/10.36922/ijb.1233
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