Co-immobilization of natural marine polysaccharides and bioactive peptides on ZE21B magnesium alloy to enhance hemocompatibility and cytocompatibility.

Degradable magnesium alloy stents are considered to be ideal candidates to replace the traditional non-degradable stents for the treatment of cardiovascular diseases. However, bare magnesium alloy stents usually degrade too fast and show poor hemocompatibility and cytocompatibility, which seriously affects their clinical use. In this study, surface modification based on the MgF2 layer, polydopamine (PDA) coating, fucoidan and CAG peptides was performed on the Mg-Zn-Y-Nd (ZE21B) magnesium alloy with the purpose of improving its corrosion resistance, hemocompatibility and cytocompatibility for vascular stent application. After modification, the ZE21B alloy showed better corrosion resistance. Moreover, the lower hemolysis rate, platelet adhesion and activation, and fibrinogen adsorption and denaturation proved the improved hemocompatibility of modified ZE21B alloy in in vitro blood experiments. Furthermore, the co-immobilization of fucoidan and CAG peptides significantly promoted the adhesion, proliferation, migration and NO release of endothelial cells (ECs) on the modified ZE21B alloy, and meanwhile the modification with fucoidan and CAG peptides inhibited the adhesion and proliferation of smooth muscle cells (SMCs) and suppressed the expression of proinflammatory factors in the macrophages (MAs). The surface modification obviously enhanced the corrosion resistance, hemocompatibility and cytocompatibility of ZE21B alloy, and provided an effective strategy for the development of degradable vascular stents.

Nucleus-targeted carbon dots as peroxidase nanozyme for photoacoustic imaging and phototherapy of tumor.

High-purity carbon dots (CDs) with a highly π-conjugated sp2-hybridized graphite structure were prepared by the pulse electrolysis method using the graphite plate as raw material. Photoacoustic signal together with photothermal effect was found in the CDs-dispersed suspensions under near-infrared (NIR) irradiation. For the suspension with the CDs concentration of 500 µg/mL, the photothermal conversion efficiency is high up 64.3% and the solution's temperature can be increased to 82.2 °C under NIR irradiation. Moreover, CDs can be effectively endocytosed by human hepatoma (HepG2) cells with a few hours, act as peroxidase nanozyme to decompose H2O2 and facilitate the production of reactive oxygen species. Under NIR irradiation, CDs exhibit an outstanding apoptosis-inducing effect on HepG2 cells by the photothermal effect. In addition, in vivo experiments show that CDs can be used in photoacoustic imaging (PAI) and guiding the tumor treatment. As a result, the nucleus-targeted CDs with an unique combination of PAI and photothermal effect have potential in cancer diagnosis and treatment.

A Cu(â ¡)-eluting coating through silk fibroin film on ZE21B alloy designed for in situ endotheliazation biofunction.

In the cardiovascular field, coating containing copper used to catalyze NO (nitric oxide) production on non-degradable metal surfaces have shown unparalleled expected performance, but there are few studies on biodegradable metal surfaces. Magnesium-based biodegradable metals have been applied in cardiovascular field in large-scale because of their excellent properties. In this study, the coating of copper loaded in silk fibroin is fabricated on biodegradable ZE21B alloy. Importantly, the different content of copper is set to investigate the effects of on the degradation performance and cell behavior of magnesium alloy. Through electrochemical and immersion experiments, it is found that high content of copper will accelerate the corrosion of magnesium alloy. The reason is the spontaneous micro-batteries between copper and magnesium with the different standard electrode potentials, that is, the galvanic corrosion accelerates the corrosion of magnesium alloy. Moreover, the coating formed through silk fibroin by the right amount copper not only have a protective effect on the ZE21B alloy substrate, but also promotes the adhesion and proliferation of endothelial cells in blood vessel micro-environment. The production of NO catalyzed by copper ions makes this trend more significant, and inhibits the excessive proliferation of smooth muscle cells. These findings can provide guidance for the amount of copper in the coating on the surface of biodegradable magnesium alloy used for cardiovascular stent purpose.

Fucoidan/collagen composite coating on magnesium alloy for better corrosion resistance and pro-endothelialization potential.

Magnesium alloy stents (MAS) have broad application prospects in the treatment of cardiovascular diseases. However, poor corrosion resistance and biocompatibility greatly limit the clinical application of MAS. In this work, the coating consisting of MgF2 layer, polydopamine layer, fucoidan and collagen IV was constructed on Mg-Zn-Y-Nd (ZE21B) alloy to improve its corrosion resistance and pro-endothelialization potential. The fucoidan and collagen IV in the coating could obviously enhance the hemocompatibility and pro-endothelialization potential respectively. Compared with bare ZE21B alloy, the fucoidan/collagen composite coating modified ZE21B alloy possessed lower corrosion current density and better corrosion resistance. Moreover, the modified ZE21B alloy exhibited relatively low hemolysis rate, fibrinogen adsorption and platelet adhesion in the blood experiments, suggesting the improved hemocompatibility. Furthermore, the modified ZE21B alloy favorably supported the adhesion and proliferation of vascular endothelial cells (ECs) and effectively regulated the phenotype of smooth muscle cells (SMCs), thus improving the pro-endothelialization potential of vascular stent materials. The fucoidan/collagen composite coating can significantly improve the corrosion resistance and pro-endothelialization potential of ZE21B alloy, showing great potential in the development of degradable MAS.

Long-circulating gambogic acid-loaded nanodiamond composite nanosystem with inhibition of cell migration for tumor therapy.

Herein, ultra dispersed and stably suspended nanodiamonds (NDs) were demonstrated to have a high load capacity, sustained release, and ability to serve as a biocompatible vehicle for delivery anticancer drugs. NDs with size of 50-100 nm exhibited good biocompatibility in normal human liver (L-02) cells. In particular, 50 nm ND not only promoted the noticeable proliferation of the L-02 cells but also can effectively inhibited the migration of human liver carcinoma (HepG2) cells. The gambogic acid-loaded nanodiamond (ND/GA) complex assembled by π-π stacking exhibits ultrasensitive and apparent suppression efficiency on the proliferation of HepG2 cells through high internalization and less efflux compared to free GA. More importantly, the ND/GA system can significantly increase the intracellular reactive oxygen species (ROS) levels in HepG2 cells and thus induce the cell apoptosis. The increase in intracellular ROS levels causes damage to the mitochondrial membrane potential (MMP) and activates cysteinyl aspartate specific proteinase 3 (Caspase-3) and cysteinyl aspartate specific proteinase 9 (Caspase-9), which leads to the occurrence of apoptosis. In vivo experiments also confirmed that the ND/GA complex has a much higher anti-tumor capability than free GA. Thus, the current ND/GA system is promising for cancer therapy.

Surface modification of biodegradable magnesium alloy with poly (L-lactic acid) and sulfonated hyaluronic acid nanoparticles for cardiovascular application.

Magnesium (Mg) and its alloys have attracted extensive attention of researchers in the field of cardiovascular implants due to their good mechanical properties and biosafety. Constructing a multifunctional hybrid coating seems to be an effective strategy to address the insufficient endothelialization and poor corrosion resistance of Mg alloy vascular stents. In this study, a dense layer of magnesium fluoride (MgF2) was prepared on the surface of Mg alloy aiming at better corrosion resistance; Thereafter, sulfonated hyaluronic acid (S-HA) was made into small sized nanoparticles (NP) which were deposited on the MgF2 surface by self-assembly method, followed with poly-L-lactic acid (PLLA) coating preparation by one-step pulling method. The blood and cell tests showed that the composite coating had good blood compatibility, pro-endothelial, anti-hyperplasia and anti-inflammatory functions. Compared to current clinical PLLA@ Rapamycin coating, our PLLA/NP@S-HA coating showed better functions of promoting endothelial cells growth. These results strongly furnished a promising and feasible strategy for the surface modification of Mg-based degradable cardiovascular stents.

Degradation behavior of ZE21C magnesium alloy suture anchors and their effect on ligament-bone junction repair.

Current materials comprising suture anchors used to reconstruct ligament-bone junctions still have limitation in biocompatibility, degradability or mechanical properties. Magnesium alloys are potential bone implant materials, and Mg2+ has been shown to promote ligament-bone healing. Here, we used Mg-2 wt.% Zn-0.5 wt.% Y-1 wt.% Nd-0.5 wt.% Zr (ZE21C) alloy and Ti6Al4V (TC4) alloy to prepare suture anchors to reconstruct the patellar ligament-tibia in SD rats. We studied the degradation behavior of the ZE21C suture anchor via in vitro and in vivo experiments and assessed its reparative effect on the ligament-bone junction. In vitro, the ZE21C suture anchor degraded gradually, and calcium and phosphorus products accumulated on its surface during degradation. In vivo, the ZE21C suture anchor could maintain its mechanical integrity within 12 weeks of implantation in rats. The tail of the ZE21C suture anchor in high stress concentration degraded rapidly during the early implantation stage (0-4weeks), while bone healing accelerated the degradation of the anchor head in the late implantation stage (4-12weeks). Radiological, histological, and biomechanical assays indicated that the ZE21C suture anchor promoted bone healing above the suture anchor and fibrocartilaginous interface regeneration in the ligament-bone junction, leading to better biomechanical strength than the TC4 group. Hence, this study provides a basis for further research on the clinical application of degradable magnesium alloy suture anchors.

The enhanced antibacterial effect of BNNS_Van@CS/MAO coating on Mg alloy for orthopedic applications.

The development of multifunctional Mg-based active implants with controllable degradation and antibacterial capabilities has become a hotspot in the research field of biodegradable metallic materials. To this end, a BN nanosheets (BNNS) _vancomycin (Van) @chitosan (CS) nanocomposite coating containing two antibacterial components (BNNS and Van) was prepared on Mg alloys via a micro-arc oxidation (MAO) pre-treatment combined with following electrodeposition. The related characterizations of the coating show that the composite coating has a high roughness, hydrophobicity and fair corrosion resistance. In vitro antibacterial experiments show that the BNNS_Van@CS/MAO composite coating have obvious inhibitory effect on the growth of both E. coli and S. aureus. The antibacterial effect of the BNNS_Van@CS/MAO composite coating was attributed to the synergistic effect of CS, BNNS and Van. This study provides a valuable surface modification strategy for developing multifunctional Mg-based implants with good corrosion resistance and antibacterial properties.

Design of single-phased magnesium alloys with typically high solubility rare earth elements for biomedical applications: Concept and proof.

Rare earth elements (REEs) have been long applied in magnesium alloys, among which the mischmetal-containing WE43 alloy has already got the CE mark approval for clinical application. A considerable amount of REEs (7 wt%) is needed in that multi-phased alloy to achieve a good combination of mechanical strength and corrosion resistance. However, the high complex RE addition accompanied with multiple second phases may bring the concern of biological hazards. Single-phased Mg-RE alloys with simpler compositions were proposed to improve the overall performance, i.e., "Simpler alloy, better performance". The single-phased microstructure can be successfully obtained with typical high-solubility REEs (Ho, Er or Lu) through traditional smelting, casting and extrusion in a wide compositional range. A good corrosion resistance with a macroscopically uniform corrosion mode was guaranteed by the homogeneously single-phased microstructure. The bimodal-grained structure with plenty of sub-grain microstructures allow us to minimize the RE addition to <1 wt%, without losing mechanical properties. The single-phased Mg-RE alloys show comparable mechanical properties to the clinically-proven Mg-based implants. They exhibited similar in-vitro and in-vivo performances (without local or systematic toxicity in SD-rats) compared to a high purity magnesium. In addition, metal elements in our single-phased alloys can be gradually excreted through the urinary system and digestive system, showing no consistent accumulation of RE in main organs, i.e., less burden on organs. The novel concept in this study focuses on the simplification of Mg-RE based alloys for biomedical purpose, and other biodegradable metals with single-phased microstructures are expected to be explored.

Recent advances on the mechanical behavior of zinc based biodegradable metals focusing on the strain softening phenomenon.

Zinc based biodegradable metals (BMs) show great potential to be used in various biomedical applications, owing to their superior biodegradability and biocompatibility. Some high-strength (ultimate tensile strength > 600 MPa) Zn based BMs have already been developed through alloying and plastic working, making their use in load-bearing environments becomes a reality. However, different from Mg and Fe based BMs, Zn based BMs exhibit significant "strain-softening" effect that leads to limited uniform deformation. Non-uniform deformation is detrimental to Zn based devices or implants, which will possibly lead to unexpected failure. People might be misled by the considerable fracture elongation of Zn based BMs. Thus, it is important to specify uniform elongation as a term of mechanical requirements for Zn based BMs. In this review, recent advances on the mechanical properties of Zn based BMs have been comprehensively summarized, especially focusing on the strain softening phenomenon. At first, the origin and evaluation criteria of strain softening were introduced. Secondly, the effects of alloying elements (including element type, single or multiple addition, and alloying content) and microstructural characteristics (grain size, constituent phase, phase distribution, etc.) on mechanical properties (especially for uniform elongation) of Zn based BMs were summarized. Finally, how to get a good balance between strength and uniform elongation was generally discussed based on the service environment. In addition, possible ways to minimize or eliminate the strain softening effect were also proposed, such as controlling of twins, solute clusters, and grain boundary characteristics. All these items above would be helpful to understand the mechanical instability of Zn based BMs, and to make the full usage of them in the future medical device design. STATEMENT OF SIGNIFICANCE: Biodegradable metals (BMs) is a hotspot in the field of metallic biomaterials. Fracture elongation is normally adopted to quantify the deformability of Mg and Fe based BMs owing to their negligible necking strain, yet the strain softening would occur in Zn based BMs, which is extremely detrimental to performance of their medical device. In this review paper, a better understanding the mechanical performance of Zn-based BMs with the term "uniform elongation" instead of "fracture elongation" was depicted, and possible ways to minimize or eliminate the strain softening effect were also proposed, such as twins, solute clusters, self-stable dislocation network, and grain boundary characteristics. It would be helpful to understand the mechanical instability of Zn based BMs and making full usage of it in the future medical device design.

Sustained delivery of gambogic acid from mesoporous rod-structure hydroxyapatite for efficient in vitro cancer therapy.

Inspired by the critical role of nanocarrier in biomaterials modification, we synthesized a mesoporous rod-structure hydroxyapatite (MR-HAp) nanoparticles for boosting gambogic acid (GA) bioavailability in cells and improving the tumor therapy. As expected, the GA loading ratio of MR-HAp was up to about 96.97% and GA-loaded MR-HAp (MR-HAp/GA) demonstrates a sustained release performance. Furthermore, a substantial improvement was observed in inhibiting the cell proliferation and inducing the apoptosis of HeLa cells, as the cell viability was decreased to 89.6% and the apoptosis was increased to 49.2% when the cells treated with MR-HAp/GA at a GA concentration of 1 µg/mL for 72 h. The remarkable inhibition effect of cell proliferation and the enhanced inducing apoptosis are attributed to the increasing intracellular reactive oxygen species level and reduced mitochondrial membrane potential. This result provides a promising and facile approach for highly efficient tumor treatment.

pH Stimuli-Responsive, Rapidly Self-healable Coatings Enhanced the Corrosion Resistance and Osteogenic Differentiation of Mg-1Ca Osteoimplant.

Mg-Ca alloys have emerged as a promising research direction for biomedical implants in the orthopedic field. However, their clinical use is deterred by their fast corrosion rate. In this work, a pH stimuli-responsive silk-halloysite (HNT)/phytic acid (PA) self-healing coating (Silk-HNT/PA) is constructed to slow down the corrosion rate of Mg-1Ca alloy and its cell viability and osteogenic differentiation ability are enhanced. The Silk-HNT/PA coating exhibits appealing active corrosion protection, by eliciting pH-triggerable self-healing effects, while simultaneously affording superior biocompatibility and osteogenic differentiation ability. Moreover, in vivo studies by histological analysis also demonstrate better osseointegration for the Silk-HNT/PA coated Mg-1Ca alloy. In summary, the Silk-HNT/PA coating in the present study has great potential in enhancing the biomedical utility of Mg alloys.

Tailoring ZE21B Alloy with Nature-Inspired Extracellular Matrix Secreted by Micro-Patterned Smooth Muscle Cells and Endothelial Cells to Promote Surface Biocompatibility.

Delayed surface endothelialization is a bottleneck that restricts the further application of cardiovascular stents. It has been reported that the nature-inspired extracellular matrix (ECM) secreted by the hyaluronic acid (HA) micro-patterned smooth muscle cells (SMC) and endothelial cells (EC) can significantly promote surface endothelialization. However, this ECM coating obtained by decellularized method (dECM) is difficult to obtain directly on the surface of degradable magnesium (Mg) alloy. In this study, the method of obtaining bionic dECM by micro-patterning SMC/EC was further improved, and the nature-inspired ECM was prepared onto the Mg-Zn-Y-Nd (ZE21B) alloy surface by self-assembly. The results showed that the ECM coating not only improved surface endothelialization of ZE21B alloy, but also presented better blood compatibility, anti-hyperplasia, and anti-inflammation functions. The innovation and significance of the study is to overcome the disadvantage of traditional dECM coating and further expand the application of dECM coating to the surface of degradable materials and materials with different shapes.

A biodegradable magnesium alloy vascular stent structure: Design, optimisation and evaluation.

The existing biodegradable magnesium alloy stent (BMgS) structure is prone to problems, such as insufficient support capacity and early fracture at areas of concentrated stress. Herein, a stent structural design, which reduced the cross section of the traditional sin-wave stent by nearly 30% and introduces a regular arc structure in the middle of the support ring. The influence of the dual-parameter design of bending radius (r) and ring length (L) on plastic deformation, expansion and compression resistance performances are discussed. The non-dominated sorting genetic algorithm II (NSGA-II) was used to search for the optimal solution. It was found that the introduction of parameter r effectively improved the plastic deformation and expansion performance, and the reduction of L improved stent compression resistance. Finally, an optimized stent configuration was obtained. In vitro mechanical tests, including balloon inflation, radial strength and flexibility, verified the simulation results. The radial strength for the optimised stent increases by approximately 40% compared with that for the sinusoidal stent. Microarea X-ray diffraction result shows that the circumferential residual stress for the optimised stent decreases by half compared with that for the sinusoidal stent, thus effectively reducing the stress concentration phenomenon. STATEMENT OF SIGNIFICANCE: Despite current progress in BMgS research, the optimal design of the structure is limited. We present a new type of structurally designed stent. The performance of this stent was analysed by a finite element method and experimentally verified. The structural design positively influenced stent performance.

Rapid screening alloying elements for improved corrosion resistance on the Mg(0001) surface using first principles calculations.

The poor corrosion resistance of Mg alloys is a major challenge for their applications. The corrosion of Mg alloys is mainly controlled by the anodic dissolution of Mg and the cathodic hydrogen evolution reaction (HER), which is closely related to the stability and the hydrogen adsorption of the Mg surface. In this work, the effects of alloying elements (As, Ge, Cd, Zn, Ga, Al, and Y) on the stability and the hydrogen adsorption of a Mg(0001) surface have been studied based on first principles calculations. We have developed a horizontally integrated approach to evaluate their effects on corrosion resistance using parameters such as the surface energy, vacancy formation energy, Bader charge, electron density distribution, and the adsorption free energy of H atom at different adsorbed sites. We found that the doped atoms could significantly change the surface atomic structure and electron transfer on the Mg surface. These behaviors modified the energy required to detach the nearest neighbors of doped atoms from the Mg surface, the adsorption free energy of H atoms, and the stable adsorption sites of H atoms on the Mg surface, which regulate the corrosion resistance of Mg alloys. Interestingly, we found that Y doping on the Mg surface increased the corrosion resistance and our new method had tremendous potential in the rapid screening of alloying elements that could improve the stability of Mg alloys and inhibit the hydrogen evolution reaction.

Sol-gel coating loaded with inhibitor on ZE21B Mg alloy for improving corrosion resistance and endothelialization aiming at potential cardiovascular application.

To improve the service performance of vascular stents, we designed/selected a series of organic compounds from commercial drugs, natural plants, and marine life as the potential corrosion inhibitors for ZE21B alloy. Paeonol condensation tyrosine (PCTyr) Schiff base was found to be the most efficient inhibitor among them. The biocompatible, self-healing, anti-corrosive sol-gel coating loaded with corrosion inhibitor was fabricated on the Mg substrate through a convenient dip-coating tactic. The corrosion resistance, self-healing ability, cytotoxicity, and hemocompatibility of the coated sample were evaluated. These results suggested the potentiality of Schiff base inhibitor-loaded sol-gel coating for enhanced corrosion protection and desired biocompatibility of bioabsorbable cardiovascular implants.

Microstructural Evolution and Mechanical Properties of Graphene Oxide-Reinforced Ti6Al4V Matrix Composite Fabricated Using Spark Plasma Sintering.

To achieve a further reduction in weight of titanium alloys and to satisfy the increasing demand of energy-saving for aerospace and automotive applications, a graphene oxide nanosheet-reinforced Ti6Al4V (GO/TC4) composite was successfully fabricated using spark plasma sintering (SPS). Contrary to the Widmanstätten microstructure of a monolithic TC4 sample, the microstructure of the composites displayed a typical basket-weave structure in virtue of the introduced residual tensile stress generated from the mismatch of coefficients of thermal expansion (CTE) between GO and TC4 during the phase transformation. Meanwhile, the in situ-formed TiC nanolayer and diffusion layer were identified at the GO-TC4 interface, which is expected to endow a stronger interfacial bonding. As compared with the TC4 sample, the TC4 composite with the addition of 0.27 wt.% GO exhibited a 0.2% yield strength of 921.8 MPa, an ultimate tensile strength of 1040.1 MPa, and an elongation of 5.3%, displaying a better balance of strength and ductility than that of the composite with a higher GO addition (0.54 wt.%). The synergetic strengthening mechanisms such as Orowan strengthening, enhanced dislocation density strengthening, and load transfer were confirmed. Among them, load transfer contributed greatly to the strength of the composites due to improved interfacial bonding between the GO fillers and TC4 matrix.

Advances in coatings on magnesium alloys for cardiovascular stents - A review.

Magnesium (Mg) and its alloys, as potential biodegradable materials, have drawn wide attention in the cardiovascular stent field because of their appropriate mechanical properties and biocompatibility. Nevertheless, the occurrence of thrombosis, inflammation, and restenosis of implanted Mg alloy stents caused by their poor corrosion resistance and insufficient endothelialization restrains their anticipated clinical applications. Numerous surface treatment tactics have mainly striven to modify the Mg alloy for inhibiting its degradation rate and enduing it with biological functionality. This review focuses on highlighting and summarizing the latest research progress in functionalized coatings on Mg alloys for cardiovascular stents over the last decade, regarding preparation strategies for metal oxide, metal hydroxide, inorganic nonmetallic, polymer, and their composite coatings; and the performance of these strategies in regulating degradation behavior and biofunction. Potential research direction is also concisely discussed to help guide biological functionalized strategies and inspire further innovations. It is hoped that this review can give assistance to the surface modification of cardiovascular Mg-based stents and promote future advancements in this emerging research field.

Investigation of Mg-xLi-Zn alloys for potential application of biodegradable bone implant materials.

Implant therapy after osteosarcoma surgery is a major clinical challenge currently, especially the requirements for mechanical properties, degradability of the implants, and their inhibition of residual tumor cells. Biodegradable magnesium (Mg) alloy as medical bone implant material has full advantages and huge potential development space. Wherein, Mg-lithium (Li) based alloy, as an ultra-light alloy, has good properties for implants under certain conditions, and both Mg and Li have inhibitory effects on tumor cells. Therefore, Mg-Li alloy is expected to be applied in bone implant materials for mechanical supporting and inhibiting tumor cells simultaneously. In this contribution, the Mg-xLi-Zinc (Zn) series alloys (x = 3 wt%, 6 wt%, 9 wt%) were prepared to study the influence of different elements and contents on the structure and properties of the alloy, and the biosafety of the alloy was also evaluated. Our data showed that the yield strength, tensile strength, and elongation of as-cast Mg-xLi-Zn alloy were higher than those of as-cast Mg-Zn alloy; Mg-xLi-Zn alloy can kill osteosarcoma cells (MG-63) in a concentration-dependent manner, wherein Mg-3Li-Zn alloy (x = 3 wt%) and Mg-6Li-Zn alloy (x = 6 wt%) promoted the proliferation of osteoblasts (MC3T3) at a certain concentration of Li. In summary, our study demonstrated that the Mg-6Li-Zn alloy could be potentially applied as a material of orthopedic implant for its excellent multi-functions.

Influence of the second phase on protein adsorption on biodegradable Mg alloys' surfaces: Comparative experimental and molecular dynamics simulation studies.

The effect of the second phase on the mechanical properties and corrosion resistance of Mg alloys has been systematically studied. However, there is limited information on the effect of the second phase on protein adsorption behavior. In the present study, the effect of the second phase on protein adsorption on the surfaces of biodegradable Mg alloys was investigated using experimental methods and molecular dynamics (MD) simulations. The experimental results showed that the effect of the second phase on fibrinogen adsorption was type-dependent. Fibrinogen preferentially adsorbed on Y-, Ce-, or Nd-involved second phases, while the second phase containing Zn inhibited its adsorption. MD simulations revealed the mechanism of the second phase that influenced protein adsorption in terms of charge distribution, surface-protein interaction energy, and water molecule distribution. Our studies proposed a deep understanding of the design of Mg-based biomaterials with superior biocompatibility. STATEMENT OF SIGNIFICANCE: Mechanical properties, uniform degradation, and biocompatibility must be considered while designing biomedical Mg alloys. To improve the mechanical properties and corrosion resistance of Mg alloys, the second phase is usually required. However, the effects of the second phase on biocompatibility of Mg alloys have been rarely reported. Here, the influence of the second phase on protein adsorption was experimentally studied by designing Mg alloys with different types of second phase. The first principle calculation and MD simulation were used to reveal the mechanism by which the second phase influences protein adsorption. This work could be used to better elucidate the protein adsorption mechanisms and design principles to improve the biocompatibility of Mg alloys.