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International Journal of Bioprinting                             3D-Printed scaffolds for diabetic bone defects




            rat model had been successfully constructed (Figure 6A   4. Discussion
            and B). The diabetic rats were randomly divided into four   Diabetes mellitus is a metabolic disease characterized
            groups: PCL, PCL@SS31, PCL@E7, and PCL@SS31@E7.    by hyperglycemia. In the pathological state of diabetes,
            The four groups of rats underwent surgical construction   uncontrolled regulation of blood glucose leads to chronic
            of  femoral  condylar  bone  defects  and  received  implants   damage and dysfunction in various tissues of the body,
            of the four PCL porous scaffolds, before being euthanized   especially the eyes, kidneys, heart, and bone.  Studies
                                                                                                     25
            12 weeks after the surgery (Figure 6A). The micro-CT   have shown that a high-glucose microenvironment causes
            results for the distal femurs of SD rats showed significantly   an increase in intracellular MRC electron transfer donors
            increased volumes of neoplastic bone tissue in the PCL@  (NADH and FADH ) and elevation of the electron flux
            SS31, PCL@E7, and PCL@SS31@E7 groups compared to   in  the mitochondrial  electron transfer  chain,  followed
                                                                               2
            the PCL group, as evidenced by the coronal CT images of   by hyperpolarization of the mitochondrial membrane
            the femoral condylar defect site (Figure 6C, first row); the   potential and a decrease in the efficiency of the MRC
            enlarged schematics of the reconstructed model of the bone   complex in transferring electrons. This in turn leads to the
            defect area, offered in transverse and longitudinal sections,   accumulation of electrons and excessive O  generation and
            are shown in the second and third rows in Figure 6C. In   generation of ROS, which further activate the injurious
                                                                                                2
            addition, the bone mineral density, number of trabeculae,   signaling pathway to cause apoptosis.  In addition, it
                                                                                               26
            and thickness of trabeculae increased, whereas the   has been reported that mitochondria themselves are
            trabecular separation decreased, with the most significant   targets of ROS, and when ROS accumulate excessively
            difference observed in the PCL@SS31@E7 group (Figure   or are not cleared sufficiently, they continue to impair
            6D–G).  According to these  experimental results, the   mitochondrial function in the surrounding cells, leading
            PCL@SS31@E7 porous scaffolds exhibited good effects in   to a vicious cycle. 27
            promoting bone regeneration in diabetic rats.
               Histological sections were further used to determine   Normal bone tissue growth and metabolic processes
            the effects of the four different PCL porous scaffolds on   require the coordinated participation of BMSCs,
            bone regeneration in diabetic rats. H&E staining of the   osteoblasts, and osteoclasts. In diabetic patients, the
            distal femur bone defect site in diabetic rats showed more   high-glucose microenvironment not only inhibits the
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            neoplastic bone tissue both at the interface between the   growth and differentiation of osteoblasts,  but also
            implanted scaffold and bone tissue, and inside the scaffold   inhibits the function of osteoclasts, resulting in impaired
            in the PCL@SS31@E7 group compared with the other   bone resorption and bone conversion, and weakened
                                                                              29,30
            three groups; the results were similar as verified by von   bone metabolism.   When fractures and bone defects
            Kossa staining  (Figure  7A). Quantitative analysis of the   occur in diabetic patients, the process of bone tissue
            volume of neoplastic bone tissue revealed that there was   regeneration and repair is further inhibited owing to
            more neoplastic bone tissue in the PCL@SS31, PCL@E7,   disruption of bone tissue microcirculation, reduction of
            and  PCL@SS31@E7  groups  than in  the  PCL  group,  and   stem cell sources, and activation of inflammatory factors.
            the difference was most significant in the PCL@SS31@E7   This  ultimately  leads  to  non-healing  or  delayed  healing
                                                                           31,32
            group (Figure 7B).                                 of the fracture.   Therefore, effective restoration of the
                                                               function of the intracellular MRC in the high-glucose
               H&E staining of cardiac, hepatic, and renal tissue in   microenvironment and improvement of the respiratory
            the four groups of diabetic rats did not reveal obvious   function of bone metabolism-related cells can significantly
            pathological  changes  such as  necrosis or  inflammation   improve osteogenic capacity in diabetic patients, thereby
            (Figure 7D). The body weights of the four groups of rats   promoting the regeneration and repair of bone tissue. To
            at  different  time  points  were  also  statistically  analyzed   address these issues, we used chemical bonding to modify
            and compared to further validate the biosafety of the four   3D-printed PCL porous scaffolds with peptides to promote
            different PCL porous scaffolds after implantation in rats.   the recruitment of BMSCs and target  the regulation
            There was no significant difference in body weight change   of mitochondrial respiration and constructed a bionic
            among the four groups of rats at the same time points, and   scaffold system with multifunctional properties for the
            the body weights of the rats in each group consistently   treatment of diabetic bone defects.
            showed a gradual decreasing trend over time, consistent   3D printing, an emerging technology in additive
            with the characteristics of diabetes mellitus (Figure 7C);   manufacturing, is widely used in medical fields.  3D
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            this difference was statistically significant. Based on these   printing processes can be classified, according to ISO/
            results, we conclude that PCL porous scaffolds modified   ASTM processes, into several variants: powder bed fusion,
            with E7 and/or SS31 peptides possess high biocompatibility   material extrusion, VAT photopolymerization, material
            in vivo.


            Volume 10 Issue 4 (2024)                       216                                doi: 10.36922/ijb.2379
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