Fig. 1. Representative evidence and current research needs in orthopedic implants. Green: High demand—currently supported by limited evidence or some evidence exists but with substantial research potential; Yellow: Moderate demand—currently supported by a modest body of evidence; Red: Low demand—supported by extensive evidence, potentially reaching consensus; Gray: No evidence to date, or existing evidence is conflicting.

Fig. 2. Performance evaluation of functional Ta-based materials. (A) Scanning electron microscopy (SEM) micrographs illustrating hBMSCs adhered on porous Ta and Ti6Al4V scaffolds. (B, C) Morphological analysis of hBMSCs and fluorescence labeling with 4′,6-diamidino-2-phenylindole (DAPI) and phalloidin on the porous scaffolds. (D) Quantification of cell adhesion on the tested scaffolds. Higher optical density (OD) values indicate increased cell number, enhanced cell viability, and greater adhesion. (E) Cell proliferation on porous Ta and Ti6Al4V scaffolds. Higher OD values reflect greater cell growth or viability in the Ta group (*P < 0.05 versus Ti6Al4V group) (reproduced with permission from Ref. [22], Copyright (2018), American Chemical Society); (F) ALP staining after 7 days and 14 days incubation, Alizarin red staining after 21 days and 28 days incubation; (G) The amount of calcium ion concentration absorbed in the osteogenic induction medium every 4 days from the fourth day. Measurements were carried out in triplicate. Data were presented as mean ± SD. Statistical significance was assessed using the Student’s t-test (*P < 0.05); (H) Tartrate-resistant acid phosphatase (TRAP) staining after RANKL induction 5 days and 7 days (reproduced with permission from Ref. [25], Copyright (2017), Elsevier B.V.).

Fig. 3. Performance evaluation of functional Mg-based materials. (A-F) Proliferation and viability of MC3T3-E1 cells (A, B, C) and HUVECs (D, E, F) by Calcein acetoxymethyl ester (Calcein-AM/PI) double stain after one week cultivation. (G, H) Quantitative analysis demonstrated that high cell density was maintained in Mg group. Asterisks (*) indicate statistical significance compared with the Ti and pM groups, P < 0.05 (reproduced with permission from Ref. [61], Copyright (2020), Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.). (I-K) Radiography preoperative (I) and 6 (J, K) weeks postoperative of a 46-year-old woman. Radiolucency is visible both around the screw in the bone and dorsal to the screw in the soft-tissues. Clinically some swelling, reddening and pain were noticed. (L) A CT scan was performed 8 weeks postoperative confirming the osteolysis. The Hounsfield units are comparable to gas (reproduced with permission from Ref. [64], Copyright (2016), Orthopaedic Research Society. Published by Wiley Periodicals, Inc.).

Fig. 4. Performance evaluation of functional Cu-based materials. (A) Adhesion and morphology of human osteosarcoma cell line-63 (MG-63) cells on Ti and Ti-Cu alloy surfaces. Fluorescent images of MG-63 cells cultured on Ti and Ti-Cu alloys for 4 and 24 h, with actin stained using Rhodamine Phalloidin (red) and nuclei stained with DAPI (blue). (B) SEM micrographs showing MG‐63 cell morphology on Ti and Ti-Cu alloy surfaces after 1 and 3 days of culture (reproduced with permission from Ref. [68], Copyright (2019), Springer Science Business Media, LLC, part of Springer Nature). (C) Typical confocal images of Fn (F. nucleatum, the upper row) and Pg (P. gingivalis, the bottom row) cultured on each sample for 1 d. The green fluorescence indicated live bacteria, and the dead ones are in red, together with the results of quantification. All experiments were performed in triplicate. Scale bar is 75 μm (reproduced with permission from Ref. [99], Copyright (2023)).

Fig. 5. Performance evaluation of other functional metallic materials. (A) Representative images of bone defect healing at 15, 30, and 60 days post-implantation under different treatment conditions. The treatment groups included AB (autogenous bone), DBBM (deproteinized bovine bone mineral), SHAM (sham operation), and BAGNb (poly(butylene adipate-co-terephthalate) and niobium-containing bioactive glass scaffold); (B) Quantitative assessment of bone density across the defect region at various postoperative time points (reproduced with permission from Ref. [135], Copyright (2021), John Wiley & Sons Ltd.). (C) Fluorescence micrographs showing Hoechst-33258-stained nuclei of pre-osteoblasts cultured for 1 h and 24 h on Ti-6Al-4V and Ti-6Al-7Nb alloy surfaces. The results demonstrated that the initial cell attachment on the Ti-6Al-7Nb surface was higher than that observed on the Ti-6Al-4V alloy (reproduced with permission from Ref. [136], Copyright (2013), Wiley Periodicals, Inc.).