Liqiang Wang

Additive manufacturing (AM) has accelerated the evolution of metallic orthopedic implants from passive structural substitutes toward multifunctional therapeutic platforms. Leveraging the geometric freedom and compositional flexibility of AM, bioactive substances can be integrated into metallic implants through multiple strategies to regulate the peri-implant microenvironment and enhance tissue regeneration. This review summarizes recent advances in bioactive integration and responsive therapeutic release in additively manufactured metallic orthopedic implants. First, major biofunctionalization strategies are discussed, including surface modification, bulk alloying, and structurally integrated reservoirs. These approaches enable the incorporation of antibacterial, osteogenic, angiogenic, and immunomodulatory functions through localized delivery of antibiotics, bioactive ions, peptides, growth factors, and small-molecule therapeutics. Subsequently, recent progress in stimuli-responsive release systems is reviewed, including endogenous stimuli such as pH, enzymes, and reactive oxygen species, as well as exogenous stimuli such as light, magnetic fields, and electrical stimulation, which enable on-demand and microenvironment-adaptive therapy. The relationships among implant architecture, bioactive integration, and dynamic therapeutic regulation are further discussed to highlight the unique advantages of AM in constructing multifunctional implants. Finally, current challenges associated with multifunctional AM metallic implants are discussed, particularly the need to achieve synergistic biofunctionality, maintain structural and mechanical integrity under process constraints, ensure predictable therapeutic release, and establish reliable process–structure–property relationships. This review provides insights into the development of intelligent metallic implants that simultaneously provide mechanical support and actively regulate therapy.

1. Additive manufacturing (AM) is increasingly attractive for load-bearing implants because it enables patient-specific geometries, porous or lattice architectures, and local stiffness tailoring, b...

Titanium and its alloys have become the primary materials for orthopedic implants due to their excellent biocompatibility, mechanical properties, and corrosion resistance. However, traditional manufacturing techniques struggle to achieve complex porous structures, and their insufficient surface bioactivity limits their clinical performance. Additive manufacturing (AM) technology enables the precise fabrication of titanium implants with personalized shape, biomimetic porous structures, and gradient mechanical properties. The controllable porosity, pore size, and pore shape not only achieve mechanical compatibility with human bone tissue, but also provide an optimal microenvironment for cell adhesion, proliferation, and vascularization. During the process of designing porous structures, the auxiliary roles of finite element analysis (FEA) and machine learning (ML) play a crucial role in performance prediction and process optimization. To further enhance the bioactivity of AM titanium alloys, surface modification techniques such as mechanical, physical, chemical, and electrochemical methods have been widely employed. These modified coatings significantly improve the osseointegration efficiency, antibacterial properties, and corrosion resistance of implants without compromising the mechanical integrity of the substrate. Currently, AM titanium alloy implants have been successfully applied in joint replacements, dental prosthetics, and other fields. Through the synergistic effect of personalized design and surface functionalization, they demonstrate superior clinical application potential compared to traditional implants. This article systematically reviews the porous structure design, surface modification techniques, and application progress of AM titanium alloy implants, aiming to provide valuable insights for clinical applications.

Refractory high-entropy alloys (RHEAs) are being developed to meet mechanical, thermal and chemical requirements that exceed what current super-alloys can withstand. This review explains how composition design, processing routes and the resulting microstructures now combine to realize that potential. We first link phase selection in BCC-, FCC- and dual-phase RHEAs to atomic-size mismatch, mixing enthalpy and valence-electron concentration, and compare manufacturing paths ranging from arc melting to powder metallurgy, additive manufacturing and vapor deposition, showing how each reshapes grain structure and defect chemistry to improve high-temperature strength, corrosion resistance and irradiation tolerance. Computation-led tools—density-functional theory, calculation of phase diagrams and machine learning—shrink the enormous composition space and predict phase stability, transformation paths and oxidation behavior with increasing accuracy. At the same time, metastable TRIP/TWIP alloys, coherent superlattices and nanoscale heterostructures demonstrate that chemical complexity can overcome the traditional trade-off between strength, ductility and damage tolerance. We propose that combining multiscale simulation, in situ characterization and closed-loop data analysis will speed up the transition of RHEAs from laboratory studies to working engineering components.

Germ agglutinin staining, is reduced on UV-LIPSS Ti6Al7Nb. Together, these results support a design strategy in which surface nano-patterning alone, without altering bulk alloy chemistry, can both promote osseointegration and reduce bacterial colonisation on orthopaedic implants. Luo et al. extended the design freedom from the surface to the whole by combining alloys with additive manufacturing used for guided bone regeneration (GBR). Luo et al. use selective laser melting to fabricate Ti-xCu meshes (x = 0, 4, 6, 8 wt%) tailored for personalized GBR in dental implantology. Increasing Cu content promotes Ti₂Cu precipitation in the α-Ti matrix and increases copper ion release, but without sacrificing corrosion resistance in physiological media. Alloys containing more than 4 wt% Cu achieve over 90% reduction of S. aureus and E. coli, while Ti-6Cu, in particular, balances high antibacterial efficacy with favourable osteoblast proliferation, up-regulation of osteogenic genes, and an anti-inflammatory shift in macrophage-related markers. This work exemplifies how composition-microstructure design can be leveraged to integrate antibacterial and immunomodulatory functions into load-bearing metallic meshes for complex maxillofacial defects.Stress shielding at the bone-implant interface remains a central concern in orthopaedics, especially as porous, lattice-like designs become mainstream. Amadasi et al. address this issue with an integrated experimental and analytical framework that quantifies how porous metal scaffolds share load with cortical bone. Using bovine cortical bone blocks with machined cavities housing CoCrMo or Ti6Al4V scaffolds (porous or full-density), the authors combine axial compression tests, digital image correlation, finite element analysis, and a spring-based analytical model to resolve strain distributions in the bone. Porous scaffolds drive bone strain patterns closer to those of intact bone than full-density inserts, confirming their potential to mitigate stress shielding. Within this space, Ti6Al4V scaffolds provide more favourable reaction forces and strain transfer than CoCrMo, and scaffolds with 1,000 μm pores outperform 500 μm pores in restoring physiologic load transfer. These insights offer practical guidance for selecting both material and pore architecture in next-generation joint and spine implants.The Topic also highlights the opportunities and pitfalls of degradable metallic devices in the vascular system. Oliver et al. report a brief research study on braided bioresorbable flow diverters (BRFDs) fabricated from an iron-manganese-nitrogen (FeMnN) alloy, evaluated in the rabbit elastase-induced aneurysm model. In a rabbit elastase-induced aneurysm model, FeMnN BRFDs are deployed and followed for 3 months. Despite earlier benchtop data showing adequate radial strength, flow diversion and MRI compatibility, most aneurysms remain incompletely occluded at the study endpoint. Angiography, gross inspection and histology reveal that the FeMnN wires resorb and fragment too rapidly at the aneurysm neck, so that the braid loses mechanical continuity before a stable neointimal layer can fully seal the aneurysm. Importantly, where FeMnN wires persist they are well integrated into neotissue, indicating that the alloy is biologically acceptable and that the limitation is primarily a resorption-mechanics mismatch rather than a failure of tissue healing. As such, this"negative"in vivo outcome is a constructive boundary condition for future designs, emphasising that wire diameter, braid architecture and corrosion kinetics must be co-optimised to align scaffold persistence with the 6-12-month time window typically required for intracranial aneurysm occlusion.Taken together, the four contributions in Metallic Biomaterials for Medical Applications -Volume II illustrate a coherent design philosophy for metallic implants. UV-LIPSS surface engineering offers a purely physical, contamination-free route to improve bone-implant integration and reduce biofilm formation on established titanium alloys. Compositionally tailored, 3D-printed Ti-Cu meshes demonstrate how additive manufacturing can encode antibacterial and immunomodulatory behaviour into patient-specific dental devices. Mechanically informed studies of porous Ti6Al4V and CoCrMo scaffolds clarify how pore size, porosity and alloy stiffness govern load transfer and strain fields in cortical bone, with direct implications for long-term bone preservation. Finally, the FeMnN BRFD work illustrates that degradability per se is not an advantage unless the degradation profile is carefully matched to the biomechanics and healing timelines of the target vascular bed.Although the authors contributing to this Topic work in Germany, Italy, China and the United States, the clinical questions they address are truly global. For example, ageing populations and high rates of osteoporosis-related fragility fractures in Latin America are expected to increase the demand for joint replacement and fracture fixation, often in health systems with constrained resources. In such settings, robust metallic implants that resist infection, preserve bone stock and avoid costly revision surgery are particularly valuable. Similarly, dental implantology in regions such as Brazil and other parts of Latin America must contend with population-specific bone density distributions and variable access to advanced imaging and customised devices, reinforcing the importance of designs that are both biofunctional and cost-effective. Collaborations that link centres with strong biomaterials research capabilities in Europe, Asia, North America and Latin America will therefore be essential to translate the concepts showcased in this Topic into widely accessible clinical solutions.Looking ahead, several concrete directions emerge. First, there is a need for multi-objective optimisation frameworks that treat alloy composition, processing parameters,...

Additive manufacturing (AM) for biomedical metals presents revolutionary opportunities for producing personalized, complex structured biomedical components. However, the high nonlinearity and complexity of the manufacturing process pose significant challenges to the performance consistency of biomedical metals. Traditional trial-and-error approaches and experience-based optimization methods are increasingly inadequate for meeting the demands of high-reliability medical applications. In recent years, machine learning (ML) has emerged as a powerful data-driven tool, deeply integrating into every stage of AM for biomedical metals and providing a driving force for its intelligent transformation and upgrading. This review outlines three key applications of ML in biomedical metal AM: at the property prediction stage, ML enables forward prediction of performance characteristics by establishing precise mapping relationships between process parameters and macrostructure quality, microstructure, and mechanical/functional properties; at the process optimization level, ML-driven inverse optimization algorithms efficiently navigate high-dimensional parameter spaces to achieve both single-objective perfection and multi-objective balancing; at the quality monitoring and control level, ML enables real-time diagnosis of manufacturing defects and even closed-loop adaptive control by integrating multiple in situ sensor data. This review explores how ML can facilitate the biomedical metals during the AM process and outlines its future development toward fully integrated intelligent design and manufacturing processes.

Lattice structures show advantages in mechanical properties and energy absorption efficiency owing to their lightweight, high strength and adjustable geometry. This article reviews lattice structure classification, design and applications, especially those based on additive manufacturing (AM) technology. This article first introduces the basic concepts and classification of lattice structures, including the classification based on topological shapes, such as strut, surface, shell, hollow-strut, and so on, and the classification based on the deformation mechanism. Then, the design methods of lattice structure are analyzed in detail, including the design based on basic unit, mathematical algorithm and gradient structure. Next, the effects of different lattice elements, relative density, material system, load direction and fabrication methods on the mechanical performance of AM-produced lattice structures are discussed. Finally, the advantages of lattice structures in energy absorption performance are summarized, aiming at providing theoretical guidance for further optimizing and expanding the engineering application potential of lattices.

Modeling strategies play a crucial role in determining the unit shapes of triply periodic minimal surface (TPMS), significantly affecting the mechanical and permeability properties of porous scaffolds. In this study, two distinct strategies including surface thickening and surface filling were used to construct scaffold models based on four basic TPMS structures (Primitive [P], Gyroid [G], Diamond [D], and I-graph-wrapped package [IW-P]). These models were successfully prepared using TC4 alloy and selective laser melting technology. Macro/micro morphology, mechanical properties, and permeability tests of porous implants were carried out. The results indicate that the scaffolds effectively replicated the designed models, exhibiting mechanical properties that match those of human tissue. The elastic modulus ranges from 3.03 to 4.57 GPa, and the tensile strength varies between 135.78 and 250.90 MPa. The surface thickening strategy alters the material distribution within the unit, enhancing load uniformity on the scaffolds, thereby increasing the strength of the scaffolds with G, D, and IW-P units, while reducing stress fluctuations during compression. In contrast, the surface filling structure exhibits excellent permeability, with permeability rates falling within the range of 0.88 to 1.91 × 10-9 m2, aligning with the permeability performance of trabecular bone. This study offers new insights into the design of porous scaffold models tailored for various application scenarios.

Excellent mechanical properties and biocompatibility are the most sought-after attributes in biomedical materials for the regeneration of damaged tissues. However, conventional dense titanium alloys possess a modulus significantly higher than that of human tissues, leading to potential stress-shielding effects. Medical porous titanium alloys can reduce the elastic modulus of the material, promote tissue fixation and vascular regeneration, and improve the suitability for human tissue properties. With the continuous development of technology, the preparation process of porous titanium alloys has undergone a series of multifaceted transformations and improvements in the aspects of powder sintering, fiber preparation, and additive manufacturing processes, and its structural characteristics and mechanical properties are constantly evolving in a controllable direction. Alongside the enhancement of the material’s mechanical properties through porous design, optimization of the properties at the implant-tissue interface also leads to improved antimicrobial and osteogenic properties of porous titanium. Due to the complex internal structure of porous titanium alloys, surface modification is mainly carried out in fluid media, which is realized by morphological modification and the introduction of functional substances. Over time, the surface modification of porous titanium alloys for medical applications has progressed from morphological modification and introduction of chemical composition to the loading of bioactive substances. This evolution aims to enhance safety and efficiency in the use of these materials. This paper reviews the preparation and surface modification processes of porous titanium alloys for medical use and summarizes the advantages, disadvantages, and influencing factors among different processes, with a view to providing new ideas for the development of porous implants for medical use.