Multiscale Interface Engineering for Orthopedic and Dental Implants: A Review
Source abstract
Abstract
Multiscale interface engineering has influenced the engineering of orthopedic and dental implants through the integration of macroscale architecture, micro-textured surfaces and nanoscale bio-cues. These characteristics help to increase mechanical stability and support early biological responses, as well as increase resistance to microbial colonization. Multiscale interface engineering also helps to explore fabrication schemes that facilitate load-sharing lattices and micro-roughened attachment zones, as well as immune-interactive nano-chemistry. In this study, the biological responses of protein adsorption, osteogenic differentiation, connective-tissue sealing, and macrophage polarization are investigated, together with functional barriers in stress transfer, fatigue resistance and biofilm control. New clinical data with regard to arthroplasty and dental implantology are reviewed to put these factors into perspective. Even though engineered surfaces are reliable in promoting early fixation and initial osseointegration, in the long term, their performance depends on the host’s biological variability, the mechanical forces of loading, coating integrity and peri-implant microbial pressure. Altogether, multiscale interface engineering is an evolving approach to enhancing the lifespan of implants and facilitating biologically sound skeletal and oral reconstruction. A structured literature search was conducted using PubMed, Web of Science, Scopus, and Google Scholar to identify studies published between 2000 and 2025. Approximately 320 articles were initially identified, of which about 140 relevant publications were selected for detailed review.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Bone Tissue Engineering Materials · Calcium Carbonate Crystallization and Inhibition · Bacterial biofilms and quorum sensing
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Chemistry, University of Sahiwal, Sahiwal 57000, Pakistan
Institute of Chemistry, Khwaja Fareed University of Engineering and Information Technology, Rahim Yar Khan 64200, Pakistan
References (100+)
Show source-provided references
1. Current developments in orthopaedic implant technology10.1186/s13018-025-06279-w ↗
2. The Impact of Implant Surface Modifications on the Osseointegration Process: An Overview
3. Three interfaces of the dental implant system and their clinical effects on hard and soft tissues10.1039/D1MH01621K ↗
4. Targeted Infection Control and Tissue Integration via pH-Sensitive Smart Coatings on Implant Surfaces
5. Advances in Implant Surface Technology: A Biological Perspective
6. Hybrid coatings on dental and orthopedic titanium implants: Current advances and challenges10.1002/bmm2.12105 ↗
7. Kacsó, A.-B., and Peter, I. (2025). A Review of Past Research and Some Future Perspectives Regarding Titanium Alloys in Biomedical Applications. J. Funct. Biomater., 16.10.3390/jfb16040144 ↗
8. Crupi, A., Lanzetti, J., Todaro, D., Pera, F., and Erovigni, F.M. (2025). Dental implant survival and risk of medication-related osteonecrosis in the jaws in patients undergoing antiresorptive therapy: A systematic review. Int. J. Mol. Sci., 26.10.3390/ijms26083618 ↗
9. Avcu, E., Avcu, Y.Y., Yavuzyegit, B., and Guney, M. (2025). Advances in Surface Engineering and Biocompatible Coatings for Biomedical Applications. Coatings, 15.10.3390/coatings15121475 ↗
10. Current state of art smart coatings for orthopedic implants: A comprehensive review
11. Xue, T., Attarilar, S., Liu, S., Liu, J., Song, X., Li, L., Zhao, B., and Tang, Y. (2020). Surface modification techniques of titanium and its alloys to functionally optimize their biomedical properties: Thematic review. Front. Bioeng. Biotechnol., 8.10.3389/fbioe.2020.603072 ↗
12. Sahrmann, P., Gilli, F., Wiedemeier, D.B., Attin, T., Schmidlin, P.R., and Karygianni, L. (2020). The microbiome of peri-implantitis: A systematic review and meta-analysis. Microorganisms, 8.10.3390/microorganisms8050661 ↗
13. Microbiological profile in periodontitis and peri-implantitis: A systematic review10.1615/JLongTermEffMedImplants.2022043121 ↗
14. Nanostructured titanium implant surface facilitating osseointegration from protein adsorption to osteogenesis: The example of TiO2 NTAs10.2147/IJN.S362720 ↗
15. Regulation of TiO2 nanotubes on titanium implants to orchestrate osteo/angio-genesis and osteo-immunomodulation for boosted osseointegration10.1016/j.matdes.2023.112268 ↗
16. Deans, C.F., Buckner, B.C., and Garvin, K.L. (2023). Wear, osteolysis, and aseptic loosening following total hip arthroplasty in young patients with highly cross-linked polyethylene: A review of studies with a follow-up of over 15 years. J. Clin. Med., 12.10.3390/jcm12206615 ↗
17. Cong, Y., Wang, Y., Yuan, T., Zhang, Z., Ge, J., Meng, Q., Li, Z., and Sun, S. (2023). Macrophages in aseptic loosening: Characteristics, functions, and mechanisms. Front. Immunol., 14.10.3389/fimmu.2023.1122057 ↗
18. Implant surface modifications and their impact on osseointegration and peri-implant diseases through epigenetic changes: A scoping review10.1111/jre.13273 ↗
19. Osseointegration-Related Exosomes for Surface Functionalization of Titanium Implants10.34133/bmr.0124 ↗
20. Surface morphology and chemical composition analysis of titanium dental implants using SEM and EDX10.6026/973206300200926 ↗
21. Antibacterial coatings for dental implants: A systematic review10.1016/j.dental.2024.12.001 ↗
22. Homa, K., Zakrzewski, W., Dobrzyński, W., Piszko, P.J., Piszko, A., Matys, J., Wiglusz, R.J., and Dobrzyński, M. (2024). Surface functionalization of titanium-based implants with a nanohydroxyapatite layer and its impact on osteoblasts: A systematic review. J. Funct. Biomater., 15.10.3390/jfb15020045 ↗
23. Multiscale interface engineering in biohybrid composites for biomedical applications10.1016/j.mtbio.2025.102382 ↗
24. Bridging the missing middle in osseointegration: Meso-scale topography between macro design and microroughness10.1186/s40729-025-00656-0 ↗
25. Beyond microroughness: Novel approaches to navigate osteoblast activity on implant surfaces10.1186/s40729-024-00554-x ↗
26. Multiscale Hierarchical Micro-and Nano-Surface Induced by High-Repetition-Rate Femtosecond Laser Promote Peri-Implant Osseointegration10.1021/acsabm.4c01759 ↗
27. Surface topography steer soft tissue response and antibacterial function at the transmucosal region of titanium implant10.2147/IJN.S461549 ↗
28. Zhang, Y., Gulati, K., Li, Z., Di, P., and Liu, Y. (2021). Dental implant nano-engineering: Advances, limitations and future directions. Nanomaterials, 11.10.3390/nano11102489 ↗
29. Nanotopographical cues for regulation of macrophages and osteoclasts: Emerging opportunities for osseointegration10.1186/s12951-022-01721-1 ↗
30. Li, J., Fan, H., Li, H., Hua, L., Du, J., He, Y., and Jin, Y. (2025). Recent advancements in the surface modification of additively manufactured metallic bone implants. Addit. Manuf. Front., 4.10.1016/j.amf.2025.200195 ↗
31. Additive manufacturing for biomedical bone implants: Shaping the future of bones10.1016/j.mser.2025.100931 ↗
32. A critical review on multifunctional surface strategies for titanium alloys in bioactive and durable implants10.1016/j.nxbio.2025.100009 ↗
33. Hrir, H., Boudouma, A., Ghanam, A., Ait Layachi, O., Zakir, O., and Khoumri, E. (2025). Historical and Emerging Trends in Titanium Implant Technologies: Surface Innovation and AI Integration. Biomed. Mater. Devices, 1–13.10.1007/s44174-025-00536-6 ↗
34. Ferraris, S., Hedberg, Y.S., Noël, J.J., and Spriano, S. (2022). Interactions between the physiological environment and titanium-based implant materials: From understanding to control. Nanoscale Engineering of Biomaterials: Properties and Applications, Springer Nature.10.1007/978-981-16-3667-7_1 ↗
35. Hamandi, F., and Goswami, T. (2022). Hierarchical structure and properties of the bone at nano level. Bioengineering, 9.10.3390/bioengineering9110677 ↗
36. Biomechanics and mechanobiology of the bone matrix10.1038/s41413-022-00223-y ↗
37. The cytoskeleton and connected elements in bone cell mechano-transduction10.1016/j.bone.2021.115971 ↗
38. Significance of mechanical loading in bone fracture healing, bone regeneration, and vascularization10.1177/20417314231172573 ↗
39. Bone hierarchical organization through the lens of materials science: Present opportunities and future challenges10.1016/j.bonr.2024.101783 ↗
40. Bone hierarchical structure: Heterogeneity and uniformity10.1002/adfm.202307026 ↗
41. Bone hierarchical structure: Spatial variation across length scales
42. Souto-Lopes, M., Fernandes, M.H., Monteiro, F.J., and Salgado, C.L. (2023). Bioengineering composite aerogel-based scaffolds that influence porous microstructure, mechanical properties and in vivo regeneration for bone tissue application. Materials, 16.10.3390/ma16124483 ↗
43. Valigurová, A., and Kolářová, I. (2023). Unrevealing the mystery of latent Leishmaniasis: What cells can host Leishmania?. Pathogens, 12.10.3390/pathogens12020246 ↗
44. Leishmania amazonensis impairs phagosome acidification in B-1 phagocytes as an unrecognized parasite infection and proliferation mechanism10.1038/s41598-025-16761-4 ↗
45. Hair, M., Yanase, R., Moreira-Leite, F., Wheeler, R.J., Sádlová, J., Volf, P., Vaughan, S., and Sunter, J.D. (2024). Whole cell reconstructions of Leishmania mexicana through the cell cycle. PLoS Pathog., 20.10.1371/journal.ppat.1012054 ↗
46. One-stage prosthodontically driven jaw reconstruction in patients with benign and malignant pathologies: A 7-to 11-year cohort study10.1111/clr.14322 ↗
47. Rates and Determinants of Prosthodontic Rehabilitation After Segmental Jaw Surgery10.1016/j.joms.2025.09.008 ↗
48. Immediate flapless full-arch rehabilitation of edentulous jaws on 4 or 6 implants according to the prosthetic-driven planning and guided implant surgery: A retrospective study on clinical and radiographic outcomes up to 10 years of follow-up10.1111/cid.13134 ↗
49. Distefano, F., Pasta, S., and Epasto, G. (2023). Titanium lattice structures produced via additive manufacturing for a bone scaffold: A review. J. Funct. Biomater., 14.10.3390/jfb14030125 ↗
50. Osseointegration in additive-manufactured titanium implants: A systematic review of animal studies on the need for surface treatment10.1016/j.heliyon.2023.e17105 ↗
51. Kim, J.-C., and Yeo, I.-S.L. (2021). Bone response to conventional titanium implants and new zirconia implants produced by additive manufacturing. Materials, 14.10.3390/ma14164405 ↗
52. Titanium alloys for biomedical applications: A review on additive manufacturing process and surface modification technology
53. Influence of rough micro-threaded and laser micro-textured implant-neck on peri-implant tissues: A systematic review10.1016/j.sdentj.2023.05.025 ↗
54. Peri-implant mucosal tissue attachment: Narrative review10.1016/j.dentre.2024.100141 ↗
55. Regulation of macrophage polarization through surface topography design to facilitate implant-to-bone osteointegration10.1126/sciadv.abf6654 ↗
56. Nanotopography in directing osteogenic differentiation of mesenchymal stem cells: Potency and future perspective10.2144/fsoa-2021-0097 ↗
57. Li, K., Lv, L., Shao, D., Xie, Y., Cao, Y., and Zheng, X. (2022). Engineering nanopatterned structures to orchestrate macrophage phenotype by cell shape. J. Funct. Biomater., 13.10.3390/jfb13010031 ↗
58. Assfalg, M. (2021). Protein adsorption and conformational changes. Molecules, 26.10.3390/molecules26237079 ↗
59. Protein adsorption on TiO2 nanostructures and its effects on surface topography and bactericidal performance10.1016/j.apsusc.2021.151779 ↗
60. Understanding the Influence of Serum Proteins Adsorption on the Mechano-Bactericidal Efficacy and Immunomodulation of Nanostructured Titanium10.1002/admi.202301021 ↗
61. Nanoscale surface topography reduces focal adhesions and cell stiffness by enhancing integrin endocytosis10.1021/acs.nanolett.1c01934 ↗
62. Tuning foreign body response with tailor-engineered nanoscale surface modifications: Fundamentals to clinical applications10.1039/D3TB01040F ↗
63. Nano-Roughness-Mediated Macrophage Polarization for Desired Host Immune Response10.1002/smsc.202300080 ↗
64. Biomaterial-mediated macrophage polarization remodeling and sequential regulation: A potential strategy in bone infections treatment10.1038/s41413-025-00471-8 ↗
65. Alfayez, E., Veschini, L., Dettin, M., Zamuner, A., Gaetani, M., Carreca, A.P., Najman, S., Ghanaati, S., Coward, T., and Di Silvio, L. (2022). DAR 16-II Primes Endothelial Cells for Angiogenesis Improving Bone Ingrowth in 3D-Printed BCP Scaffolds and Regeneration of Critically Sized Bone Defects. Biomolecules, 12.10.3390/biom12111619 ↗
66. Insights into the angiogenic effects of nanomaterials: Mechanisms involved and potential applications10.1186/s12951-019-0570-3 ↗
67. Carotenuto, F., Politi, S., Ul Haq, A., De Matteis, F., Tamburri, E., Terranova, M.L., Teodori, L., Pasquo, A., and Di Nardo, P. (2022). From soft to hard biomimetic materials: Tuning micro/nano-architecture of scaffolds for tissue regeneration. Micromachines, 13.10.3390/mi13050780 ↗
68. Gehrke, S.A., da Costa, E.M., Júnior, J.A., Eilers Treichel, T.L., Del Fabbro, M., and Scarano, A. (2025). Comparison Between Micro-and Micro-Nano Surface Texturization in the Initial Osseointegration Process: An Experimental In Vitro and In Vivo Preclinical Study. Bioengineering, 12.10.3390/bioengineering12020175 ↗
69. Inchingolo, A.M., Malcangi, G., Ferrante, L., Del Vecchio, G., Viapiano, F., Inchingolo, A.D., Mancini, A., Annicchiarico, C., Inchingolo, F., and Dipalma, G. (2023). Surface coatings of dental implants: A review. J. Funct. Biomater., 14.10.3390/jfb14050287 ↗
70. López-Valverde, N., Flores-Fraile, J., Ramírez, J.M., Macedo de Sousa, B., Herrero-Hernández, S., and López-Valverde, A. (2020). Bioactive surfaces vs. conventional surfaces in titanium dental implants: A comparative systematic review. J. Clin. Med., 9.10.3390/jcm9072047 ↗
71. Abdulghafor, M.A., Mahmood, M.K., Tassery, H., Tardivo, D., Falguiere, A., and Lan, R. (2023). Biomimetic coatings in implant dentistry: A quick update. J. Funct. Biomater., 15.10.3390/jfb15010015 ↗
72. W. Nicholson, J. (2020). Titanium alloys for dental implants: A review. Prosthesis, 2.10.3390/prosthesis2020011 ↗
73. Advances and significances of titaniumin dental implant applications10.1016/j.rechem.2024.101394 ↗
74. Łosiewicz, B., Osak, P., Nowińska, D., and Maszybrocka, J. (2025). Developments in dental implant surface modification. Coatings, 15.10.3390/coatings15010109 ↗
75. Review on the Fabrication of Surface Functional Structures for Enhancing Bioactivity of Titanium and Titanium Alloy Implants10.1186/s10033-024-01064-y ↗
76. Revolutionising orthopaedic implants—A comprehensive review on metal 3D printing with materials, design strategies, manufacturing technologies, and post-process machining advancements10.1007/s00170-024-14218-y ↗
77. Exploring the frontiers of metal additive manufacturing in orthopaedic implant development10.1016/j.mex.2024.103056 ↗
78. Zhang, Y., Fan, Z., Xing, Y., Jia, S., Mo, Z., and Gong, H. (2022). Effect of microtopography on osseointegration of implantable biomaterials and its modification strategies. Front. Bioeng. Biotechnol., 10.10.3389/fbioe.2022.981062 ↗
79. Implant-bone-interface: Reviewing the impact of titanium surface modifications on osteogenic processes in vitro and in vivo10.1002/btm2.10239 ↗
80. Advances in implant surface modifications to improve osseointegration10.1039/D1MA00675D ↗
81. Velasco-Ortega, E., Pato-Mourelo, J., López-López, B., Monsalve-Guil, L., Moreno-Muñoz, J., López-López, J., Núñez-Márquez, E., Matos Garrido, N., Rondón-Romero, J.L., and Jiménez-Guerra, Á. (2025). Long-Term Clinical Study on Sandblasted–Acid-Etched Surface Dental Implants: 12-Year Follow-Up. Materials, 18.10.3390/ma18010183 ↗
82. Akbas, O., Gaikwad, A., Reck, L., Ehlert, N., Jahn, A.M., Hermsdorf, J., Winkel, A., Stiesch, M., and Greuling, A. (2025). Effects of sandblasting and acid etching on the surface properties of additively manufactured and machined titanium and their consequences for osteoblast adhesion under different storage conditions. Front. Bioeng. Biotechnol., 13.10.3389/fbioe.2025.1640122 ↗
83. Long, S., Zhu, J., Jing, Y., He, S., Cheng, L., and Shi, Z. (2023). A comprehensive review of surface modification techniques for enhancing the biocompatibility of 3D-printed titanium implants. Coatings, 13.10.3390/coatings13111917 ↗
84. Enhanced osseointegration through direct energy deposition porous coating for cementless orthopedic implant fixation10.1038/s41598-021-01739-9 ↗
85. 3D bioactive coatings with a new type of porous ridge/cavity structure10.1016/j.mtla.2021.101018 ↗
86. Fabrication of microporous coatings on titanium implants with improved mechanical, antibacterial, and cell-interactive properties10.1021/acsami.0c07234 ↗
87. Alontseva, D., Azamatov, B., Safarova, Y., Voinarovych, S., and Nazenova, G. (2023). A brief review of current trends in the additive manufacturing of orthopedic implants with thermal plasma-sprayed coatings to improve the implant surface biocompatibility. Coatings, 13.10.3390/coatings13071175 ↗
88. Recent advancement in biocompatible materials, hybrid bioactive coating, surface modification and post-processing techniques for the fabrication of biomedical implant: Critical review and future prospects10.1177/09544062241307455 ↗
89. Functionalization of a clustered TiO2 nanotubular surface with platelet derived growth factor-BB covalent modification enhances osteogenic differentiation of bone marrow mesenchymal stem cells10.1016/j.biomaterials.2019.119650 ↗
90. Antibacterial nanopatterned coatings for dental implants10.1039/D2TB01352E ↗
91. Structure Protects Function: A Multilevel Engineered Surface Modification Renders the Surface of Titanium Dental Implants Resistant to Bacterial Colonization10.1021/acsami.4c21111 ↗
92. dos Santos Calderon, P., Chairmandurai, A., Xia, X., Rocha, F.G., Camargo, S.E.A., Lakshmyya, K., Ren, F., and Esquivel-Upshaw, J.F. (2024). Impact of Silicon Carbide Coating and Nanotube Diameter on the Antibacterial Properties of Nanostructured Titanium Surfaces. Materials, 17.10.3390/ma17153843 ↗
93. Zhang, H., Wu, Z., Wang, Z., Yan, X., Duan, X., and Sun, H. (2025). Advanced surface modification techniques for titanium implants: A review of osteogenic and antibacterial strategies. Front. Bioeng. Biotechnol., 13.10.3389/fbioe.2025.1549439 ↗
94. Nanomaterial-based antimicrobial coating for biomedical implants: New age solution for biofilm-associated infections10.1021/acsomega.2c06211 ↗
95. Nanomaterial-enabled anti-biofilm strategies: New opportunities for treatment of bacterial infections10.1039/D4NR04774E ↗
96. Presenting dual-functional peptides on implant surface to direct in vitro osteogenesis and in vivo osteointegration10.1016/j.mtbio.2024.101108 ↗
97. A narrative review of recent developments in osseointegration and anti-corrosion of titanium dental implants with nano surface10.1016/j.bonr.2025.101846 ↗
98. Wang, Y., Meng, Y., Wang, Y., Yuan, S., Li, Y., Feng, Y., and Wang, Z. (2023). Application of Multiscale Hierarchical Porous Structure Design in Bone Tissue Engineering Scaffolds: A Review. Chem. Mater. Sci., preprint.10.20944/preprints202310.1082.v1 ↗
99. Hierarchically structured biomaterials for tissue regeneration10.20517/microstructures.2023.61 ↗
100. Comparative Study on Creep, Hardness, and Density Properties of Materials for Transtibial Prosthetic Socket Fabrication10.25130/tjes.32.2.37 ↗