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International Journal of Bioprinting                               Biomimetic scaffolds for mandibular repair




            1. Introduction                                    cancellous bones.  Toosi et al. explored the use of scaffolds
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                                                               based on TPMS geometries to emulate the hierarchical
            Mandibular defects refer to missing or damaged portions   structure of human bones, proposing a patient-specific 3D
            of the mandible, or lower jawbone, resulting from various   printing solution.  These studies indicate a trend toward
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            causes such as trauma, surgical removal of tumors, congenital   personalized and refined research in TPMS, demonstrating
            abnormalities, infections, and osteoradionecrosis.  These   significant potential. However, the design of scaffolds
                                                    1,2
            defects can significantly impact a person’s ability to chew,   should not only promote osteogenesis but also support
            speak, and maintain normal facial aesthetics, leading to   angiogenesis to ensure the blood supply to the newly
            both functional and psychological issues.  Autologous   formed bone tissue. Further research is required on how to
                                               3,4
            bone grafting and allogeneic bone transplantation are   enhance the osteogenic efficiency of TPMS scaffolds and
            the primary clinical treatment methods for bone defects;   promote angiogenesis through design optimization and
            however, they have inherent limitations related to cost   functionalization strategies.
            and integration with the host bone.  A major focus in
                                          5,6
            recent research on bone defect repair and regeneration is   One promising strategy for improving osteogenic
            the application of triply periodic minimal surface (TPMS)   efficiency and angiogenesis is using composites rich in
            scaffolds in bone tissue engineering, which holds great   growth factors. In our previous studies, we loaded injectable
            promise. TPMS can be divided into Gyroid (G), Diamond   platelet-rich fibrin (I-PRF) and stromal cell-derived factor-1
            (D), and Schwarz Primitive (P) surfaces.  The G surface,   (SDF-1) into the TPMS scaffold and demonstrated that the
                                             7
            with its relatively large specific surface area and porosity,   SIT scaffold showed good biocompatibility and promoted
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            can significantly induce osteoblast differentiation.    cell migration, proliferation, and osteogenesis.  Case studies
                                                         8,9
            Previously, we demonstrated that TPMS-G surface    have shown that using bone grafts with advanced platelet-
                                                               rich fibrin (A-PRF), I-PRF, and leukocyte- and platelet-rich
            scaffolds with 70% porosity exhibited the best compressive   fibrin  (L-PRF)  can  enhance  the  quality  of  the  bone  graft
            strength and superior cell proliferation and adhesion in a   material in both maxilla and mandible. 26–28  Many studies
            mandibular defect model. 10
                                                               supported the role of the SDF-1/CXCR4 axis in angiogenesis
               Biphasic calcium phosphate (BCP) consists of    through the ERK/MAPK pathway activation. 29–31  However,
            hydroxyapatite and tricalcium phosphate (TCP). 11,12  Studies   there is limited knowledge on the underlying mechanisms of
            have demonstrated that 85% β-TCP and 15% hydroxyapatite   TPMS scaffold loaded with I-PRF and SDF-1 (SIT scaffold)
            exhibit excellent properties, such as biocompatibility,   in osteogenesis as well as angiogenesis and interaction
            mechanical strength, and osteoconductivity, and have been   between cells and scaffold materials.
            widely used in bone scaffolds. 13–16  Additive manufacturing   In the present study, we aim to verify the impact of
            methods are commonly employed for fabricating calcium   SIT scaffolds on bone marrow mesenchymal stem cells
                                     17
            phosphate-based bioceramics.  Our scaffolds feature   (BMSCs) in bone defect and examine whether SDF-1 and
            complex structures with delicate details, containing   I-PRF in SIT scaffolds can influence bone repair through the
            pores on the side walls with a maximum diameter of 0.87   MAPK pathway. Using reference-guided RNA sequencing,
            mm.  Compared to other printing strategies, such as   which is widely utilized to comprehensively delineate gene
                10
            stereolithography (SLA), digital light processing (DLP)   expression  levels  in  response  to  treatment,  we  analyzed
            offers higher resolution and accuracy, making it more   the potential of SIT scaffold in mandible reconstruction.
            suitable  for constructing  intricate  geometries. 18–20  By   Additionally, we evaluated the expression and localization
            harnessing the low viscosity of BCP ceramic particles and   of significantly different protein c-Jun in a New Zealand
            the high-resolution capabilities of DLP, the scaffolds achieve   white rabbit model of mandibular defect. The results of this
            optimal mechanical performance. 17,21  This study employed   research will enhance our understanding of the molecular
            85% β-tricalcium phosphate and 15% hydroxyapatite to   processes involved in the SIT composite scaffold and
            fabricate TPMS bone scaffolds through DLP.         contribute to the advancement of bone tissue engineering.
               Recent  studies  by  Dong  and  Zhao  (2021)  have
            highlighted the potential of TPMS scaffolds in promoting   2. Materials and methods
            bone regeneration, emphasizing that through optimized   2.1. Design and preparation of SIT scaffolds
            design and manufacturing processes, these scaffolds   Matlab R2020a was used to design G-surface scaffolds with
            can provide improved solutions for bone defect repair.    a porosity of 70%. The scaffolds were intended to have a
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            Shi et al. developed a novel gradient porous scaffold by   cylindrical shape, measuring 8 mm in diameter and 4 mm
            integrating TPMS with the sigmoid function method   in height, with a wall thickness of 0.25 mm. Cylindrical
            to facilitate the repair of mandibular bone defects by   scaffolds were constructed with an 8 mm base diameter,
            mimicking the natural gradient between cortical and   4 mm thickness, and 200 µm wall thickness. Our bone

            Volume 10 Issue 5 (2024)                       527                                doi: 10.36922/ijb.4147
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