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Additional file 1. Supplementary table 1. Characteristics of the studies of 39 patients with OSCC, and association between HIF-1α expression these variables.

Additional file 2. Figure S1. The original picture of western blots of Figs. 2A were shown in Figs. S1 (the red box indicated the representative picture in duplicate). Protein expression of HIF-1α in YD-10B and HSC-2 cells under hypoxic conditions by western blot analysis. All membranes were cut into small pieces and incubated with each antibodies. GAPDH was used as the control gene. Merge images indicate combination with bright field and chemiluminescence. The chemiluminescence images were time exposures of minimum (Low exposure) and maximum (High exposure) duration by the Fusion Solo Vilber Lourmat system. All images were unprocessed files.Figure S2. The original picture of western blots of Figs. 3C were shown in Figs. S2 (the red box indicated the representative picture in duplicate). Protein expression of HIF-1α and PCNA induced by miRNA-18a mimics in YD-10B cells by western blot analysis. All membranes were cut into small pieces and incubated with each antibodies. GAPDH was used as the control gene. Merge images indicate combination with bright field and chemiluminescence. The chemiluminescence images were time exposures of minimum (Low exposure) and maximum (High exposure) duration by the Fusion Solo Vilber Lourmat system. All images were unprocessed files. Figure S3. The original picture of western blots of Figs. 3C were shown in Figs. S3 (the red box indicated the representative picture in duplicate). Protein expression of HIF-1α and PCNA induced by miRNA-18a mimics in HSC-2 cells by western blot analysis. All membranes were cut into small pieces and incubated with each antibodies. GAPDH was used as the control gene. Merge images indicate combination with bright field and chemiluminescence. The chemiluminescence images were time exposures of minimum (Low exposure) and maximum (High exposure) duration by the Fusion Solo Vilber Lourmat system. All images were unprocessed files. Figure S4. The original picture of western blots of Figs. 3D were shown in Figs. S4 (the red box indicated the representative picture in duplicate). Protein expression of HIF-1α and PCNA induced by miRNA-18a mimics or miRNA-18a and CoCl2 in YD-10B cells by western blot analysis. All membranes were cut into small pieces and incubated with each antibodies. GAPDH was used as the control gene. Merge images indicate combination with bright field and chemiluminescence. The chemiluminescence images were time exposures of minimum (Low exposure) and maximum (High exposure) duration by the Fusion Solo Vilber Lourmat system. All images were unprocessed files. Figure S5. The original picture of western blots of Figs. 3D were shown in Figs. S5 (the red box indicated the representative picture in duplicate). Protein expression of HIF-1α and PCNA induced by miRNA-18a mimics or miRNA-18a and CoCl2 in HSC-2 cells by western blot analysis. All membranes were cut into small pieces and incubated with each antibodies. GAPDH was used as the control gene. Merge images indicate combination with bright field and chemiluminescence. The chemiluminescence images were time exposures of minimum (Low exposure) and maximum (High exposure) duration by the Fusion Solo Vilber Lourmat system. All images were unprocessed files.

With the development of computer-aided design/computer-aided manufacturing (CAD/CAM) technology, it has been possible to reconstruct the cranio-maxillofacial defect with more accurate preoperative planning, precise patient-specific implants (PSIs), and shorter operation times. The manufacturing processes include subtractive manufacturing and additive manufacturing and should be selected in consideration of the material type, available technology, post-processing, accuracy, lead time, properties, and surface quality. Materials such as titanium, polyethylene, polyetheretherketone (PEEK), hydroxyapatite (HA), poly-DL-lactic acid (PDLLA), polylactide-co-glycolide acid (PLGA), and calcium phosphate are used. Design methods for the reconstruction of cranio-maxillofacial defects include the use of a pre-operative model printed with pre-operative data, printing a cutting guide or template after virtual surgery, a model after virtual surgery printed with reconstructed data using a mirror image, and manufacturing PSIs by directly obtaining PSI data after reconstruction using a mirror image. By selecting the appropriate design method, manufacturing process, and implant material according to the case, it is possible to obtain a more accurate surgical procedure, reduced operation time, the prevention of various complications that can occur using the traditional method, and predictive results compared to the traditional method.