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With the continuous progress and development in biomedicine, metallic biomedical materials have attracted significant attention from researchers. Due to the low compatibility of traditional metal implant materials with the human body, it is urgent to develop new biomaterials with excellent mechanical properties and appropriate biocompatibility to solve the adverse reactions caused by long-term implantation. High entropy alloys (HEAs) are nearly equimolar alloys of five or more elements, with huge compositional design space and excellent mechanical properties. In contrast, biological high-entropy alloys (Bio-HEAs) are expected to be a new bio-alloy for biomedicine due to their excellent biocompatibility and tunable mechanical properties. This review summarizes the composition system of Bio-HEAs in recent years, introduces their biocompatibility and mechanical properties of human bone adaptation, and finally puts forward the following suggestions for the development direction of Bio-HEAs: to improve the theory and simulation studies of Bio-HEAs composition design, to quantify the influence of composition, process, post-treatment on the performance of Bio-HEAs, to focus on the loss of Bio-HEAs under actual service conditions, and it is hoped that the clinical application of the new medical alloy Bio-HEAs can be realized as soon as possible.

Magnesium (Mg) and Mg alloys are considered as potential candidates for biomedical applications because of their high specific strength, low density, and elastic modulus, degradability, good biocompatibility and biomechanical compatibility. However, the rapid corrosion rate of Mg alloys results in premature loss of mechanical integrity, limiting their clinical application in load-bearing parts. Besides, the low strength of Mg alloys restricts their further application. Thus, it is essential to understand the characteristics and influencing factors of mechanical and corrosion behavior, as well as the methods to improve the mechanical performances and corrosion resistance of Mg alloys. This paper reviews the recent progress in elucidating the corrosion mechanism, optimizing the composition, and microstructure, enhancing the mechanical performances, and controlling the degradation rate of Mg alloys. In particular, the research progress of surface modification technology of Mg alloys is emphasized. Finally, the development direction of biomedical Mg alloys in the future is prospected.

Regenerative medicine is a discipline that studies how to use biological and engineering principles and operation methods to repair and regenerate damaged tissues and organs. Until now, regenerative medicine has focused mainly on the in-depth study of the pathological mechanism of diseases, the further development and application of new drugs, and tissue engineering technology strategies. The emergence of aptamers has supplemented the development methods and types of new drugs and enriched the application elements of tissue engineering technology, injecting new vitality into regenerative medicine. The role and application status of aptamers screened in recent years in various tissue regeneration and repair are reviewed, and the prospects and challenges of aptamer technology are discussed, providing a basis for the design and application of aptamers in long-term transformation.

The endogenous electrical potential generated by native bone and periosteum plays a key role in maintaining bone mass and quality. Inspired by the electrical properties of bone, different negative surface potentials are built on microspheres to restore electric microenvironment for powerful bone regeneration, which was prepared by the combination of strontium-doped barium titanate (Sr-BTO) nanoparticles and poly (lactic-co-glycolic acid) (PLGA) with high electrostatic voltage field (HEV). The surface potential was modulated through regulating the phase composition of nanoparticles in microspheres by the doping amount of strontium ion (Sr2+). As a result, the 0.1Sr-BTO/PLGA group shows the lowest surface potential and its relative permittivity is closer to natural bone. As expected, the 0.1Sr-BTO/PLGA microspheres performed cytocompatibility, osteogenic activity in vitro and enhance bone regeneration in vivo. Furthermore, the potential mechanism of Sr-BTO/PLGA microspheres to promote osteogenic differentiation was further explored. The lower surface potential generated on Sr-BTO/PLGA microspheres regulates cell membrane potential and leads to an increase in the intracellular calcium ion (Ca2+) concentration, which could activate the Calcineurin (CaN)/Nuclear factor of activated T-cells (NFAT) signaling pathway to promote osteogenic differentiation. This study established an effective method to modulate the surface potential, which provides a prospective exploration for electrical stimulation therapy. The 0.1Sr-BTO/PLGA microsphere with lower surface potential and bone-matched dielectric constant is expected to have great potential in the field of bone regeneration.

Medical metal implants are required to have excellent mechanical properties and high biocompatibility to handle the complex human environment, which is a challenge that has always existed for traditional medical metal materials. Compared to traditional medical alloys, high entropy alloys (HEAs) have a higher design freedom to allow them to carry more medical abilities to suit the human service environment, such as low elastic modulus, high biocompatible elements, potential shape memory capability. In recent years, many studies have pointed out that bio-HEAs, as an emerging medical alloy, has reached or even surpassed traditional medical alloys in various medical properties. In this review, we summarized the recent reports on novel bio-HEAs for medical implants and divide them into two groups according the properties, namely mechanical properties and biocompatibility. These new bio-HEAs are considered hallmarks of a historic shift representative of a new medical revolution.

The pore strategy is one of the important factors affecting the biomedical porous scaffold at the same porosity. In this work, porous scaffolds were designed based on the triply periodic minimal surface (TPMS) structure under the same porosity and different pore strategies (pore size and size continuous gradient distribution) and were successfully prepared using a novel Ni46.5Ti44.5Nb9 alloy and selective laser melting (SLM) technology. After that, the effects of the pore strategies on the microstructure, mechanical properties, and permeability of porous scaffolds were systematically investigated. The results showed that the Ni46.5Ti44.5Nb9 scaffolds have a low elastic modulus (0.80–1.05 GPa) and a high ductility (15.3–19.1%) compared with previous works. The pore size has little effect on their mechanical properties, but increasing the pore size significantly improves the permeability due to the decrease in specific surfaces. The continuous gradient distribution of the pore size changes the material distribution of the scaffold, and the smaller porosity structure has a better load-bearing capacity and contributes primarily to the high compression strength. The local high porosity structure bears more fluid flow, which can improve the permeability of the overall scaffold. This work can provide theoretical guidance for the design of porous scaffolds.

Mesenchymal stem cells (MSCs) have considerable value in regenerative medicine because of their unique properties such as pluripotency, self-renewal ability, and low immunogenicity. Isolation and purification are prerequisites for various biomedical applications of MSCs, and traditional sorting methods are often expensive, complicated, and difficult to apply on a large scale. In addition to purification, the requirement for expansion of cells also limits the further application of MSCs. The purpose of this study was to develop a unique magnetic sorting microsphere to obtain relatively pure and high-yield MSCs in an economical and effective way, that can also be used for the expansion of MSCs. Poly (ethylene glycol) (PEG)-based anti-adhesive treatment of the prepared oleic acid grafted Fe3O4-poly (lactic-co-glycolic acid) magnetic microspheres was performed, and then E7 peptide was covalently grafted onto the treated microspheres. Upon a series of characterization, the magnetic microspheres were of uniform size, and cells were unable to adhere to the PEG-treated surface. E7 grafting significantly improved cell adhesion and proliferation. The results obtained from separate culture of various cell types as well as static or dynamic co-culture showed that selective adhesion of MSCs was observed on the magnetic sorting microspheres. Furthermore, the cells expanded on the microspheres maintained their phenotype and typical differentiation potentials. The magnetic properties of the microspheres enabled sampling, distribution, and transfer of cells without the usage of trypsin digestion. And it facilitated the separation of cells and microspheres for harvesting of MSCs after digestion. These findings have promising prospects for MSC research and clinical applications.

Avascular necrosis of femoral head (ANFH) is a disease that is characterized by structural changes and collapse of the femoral head. The exact causes of ANFH are not yet clear, but small advances in etiopathogenesis, diagnosis and treatment are achieved. In this study, ß-tricalcium phosphate/poly lactic-co-glycolic acid composite scaffolds incorporated with bisperoxovanadium [bpV (pic)] (bPTCP) was fabricated through cryogenic 3D printing and were utilized to treat rat models with early ANFH, which were constructed by alcohol gavage for 6 months. The physical properties of bPTCP scaffolds and in vitro bpV (pic) release from the scaffolds were assessed. It was found that the sustained release of bpV (pic) promoted osteogenic differentiation and inhibited adipose differentiation of bone marrow-derived mesenchymal stem cells. Micro-computed tomography scanning and histological analysis confirmed that the progression of ANFH in rats was notably alleviated in bPTCP scaffolds. Moreover, it was noted that the bPTCP scaffolds inhibited phosphatase and tensin homolog and activated the mechanistic target of rapamycin signaling. The autophagy induced by bPTCP scaffolds could partially prevent apoptosis, promote osteogenesis and angiogenesis, and hence eventually prevent the progression of ANFH, suggesting that the bPTCP scaffold are promising candidate to treat ANFH.

Design an implant similar to the human bone is one of the critical problems in bone tissue engineering. Metal porous scaffolds have good prospects in bone tissue replacement due to their matching elastic modulus, better strength, and biocompatibility. However, traditional processing methods are challenging to fabricate scaffolds with a porous structure, limiting the development of porous scaffolds. With the advancement of additive manufacturing (AM) and computer-aided technologies, the development of porous metal scaffolds also ushers in unprecedented opportunities. In recent years, many new metal materials and innovative design methods are used to fabricate porous scaffolds with excellent mechanical properties and biocompatibility. This article reviews the research progress of porous metal scaffolds, and introduces the AM technologies used in porous metal scaffolds. Then the applications of different metal materials in bone scaffolds are summarized, and the advantages and limitations of various scaffold design methods are discussed. Finally, we look forward to the development prospects of AM in porous metal scaffolds.

Magnesium (Mg) and its alloys have attached more and more attention because of their potential as a new type of biodegradable metal materials. In this work, AZ31/ZrO2 nanocomposites with good uniformity were prepared successfully by friction stir processing (FSP). The scanning electron microscope (SEM) and transmission electron microscope (TEM) were used to characterize the microstructure of the composites. The mechanical properties, electrochemical corrosion properties and biological properties were evaluated. In addition, the effect of reinforced particles (ZrO2) on the microstructure and properties of the composite was studied comparing with FSP AZ31 Mg alloy. The results show that compared with the base metal (BM), the AZ31/ZrO2 composite material achieves homogenization, densification, and grain refinement after FSP. The combination of dynamic recrystallization and ZrO2 particles leads to grain refinement of Mg alloy, and the average grain size of AZ31/ZrO2 composites is 3.2 μm. After FSP, the c-axis of grain is deflected under the compression stress of shoulder and the shear stress of pin. The ultimate tensile strength (UTS) and yield strength (YS) of BM were 283 and 137 MPa, respectively, the UTS and YS of AZ31/ZrO2 composites were 427 and 217 MPa, respectively. The grain refinement and Orowan strengthening are the major strengthening mechanisms. Moreover, the corrosion resistance in simulated body fluid of Mg alloy is improved by grain refinement and the barrier effect of ZrO2.

Functional gradient materials (FGMs), as a modern group of materials, can provide multiple functions and are able to well mimic the hierarchical and gradient structure of natural systems. Because biomedical implants usually substitute the bone tissues and bone is an organic, natural FGM material, it seems quite reasonable to use the FGM concept in these applications. These FGMs have numerous advantages, including the ability to tailor the desired mechanical and biological response by producing various gradations, such as composition, porosity, and size; mitigating some limitations, such as stress-shielding effects; improving osseointegration; and enhancing electrochemical behavior and wear resistance. Although these are beneficial aspects, there is still a notable lack of comprehensive guidelines and standards. This paper aims to comprehensively review the current scenery of FGM metallic materials in the biomedical field, specifically its dental and orthopedic applications. It also introduces various processing methods, especially additive manufacturing methods that have a substantial impact on FGM production, mentioning its prospects and how FGMs can change the direction of both industry and biomedicine. Any improvement in FGM knowledge and technology can lead to big steps toward its industrialization and most notably for much better implant designs with more biocompatibility and similarity to natural tissues that enhance the quality of life for human beings.

Titanium and its alloys have superb biocompatibility, low elastic modulus, and favorable corrosion resistance. These exceptional properties lead to its wide use as a medical implant material. Titanium itself does not have antibacterial properties, so bacteria can gather and adhere to its surface resulting in infection issues. The infection is among the main reasons for implant failure in orthopedic surgeries. Nano-modification, as one of the good options, has the potential to induce different degrees of antibacterial effect on the surface of implant materials. At the same time, the nano-modification procedure and the produced nanostructures should not adversely affect the osteogenic activity, and it should simultaneously lead to favorable antibacterial properties on the surface of the implant. This article scrutinizes and deals with the surface nano-modification of titanium implant materials from three aspects: nanostructures formation procedures, nanomaterials loading, and nano-morphology. In this regard, the research progress on the antibacterial properties of various surface nano-modification of titanium implant materials and the related procedures are introduced, and the new trends will be discussed in order to improve the related materials and methods.

With the continuous progress and development in the biomedicine field, metallic biomedical materials have attracted the considerable attention of researchers, but the related procedures need to be further developed. Since the traditional metal implant materials are not highly compatible with the human body, the modern materials with excellent mechanical properties and proper biocompatibility should be developed urgently in order to solve any adverse reactions caused by the long-term implantations. The advent of the high-entropy alloy (HEA) as an innovative and advanced idea emerged to develop the medical implant materials through the specific HEA designs. The properties of these HEA materials can be predicted and regulated. In this paper, the progression and application of titanium-based HEAs, as well as their preparation and biological evaluation methods, are comprehensively reviewed. Additionally, the prospects for the development and use of these alloys in implant applications are put forward.