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Most acute ischemic stroke patients with large vessel occlusion require stent implantation for complete recanalization. Yet, due to ischemia-reperfusion injury, over half of these patients still experience poor prognoses. Thus, neuroprotective treatment is imperative to alleviate the ischemic brain injury, and a proof-of-concept study was conducted on “biodegradable neuroprotective stent”. This concept is premised on the hypothesis that locally released Mg2+/H2 from Mg metal within the bloodstream could offer synergistic neuroprotection against reperfusion injury in distant cerebral ischemic tissues. Initially, the study evaluated pure Mg's neuroactive potential using oxygen-glucose deprivation/reoxygenation (OGD/R) injured neuron cells. Subsequently, a pure Mg wire was implanted into the common carotid artery of the transient middle cerebral artery occlusion (MCAO) rat model to simulate human brain ischemia/reperfusion injury. In vitro analyses revealed that pure Mg extract aided mouse hippocampal neuronal cell (HT-22) in defending against OGD/R injury. Additionally, the protective effects of the Mg wire on behavioral abnormalities, neural injury, blood-brain barrier disruption, and cerebral blood flow reduction in MCAO rats were verified. Conclusively, Mg-based biodegradable neuroprotective implants could serve as an effective local Mg2+/H2 delivery system for treating distant cerebral ischemic diseases.

Soft tissue seal around the transmucosal region of dental implants is crucial for shielding oral bacterial invasion and guaranteeing the long-term functioning of implants. Compared with the robust periodontal tissue barrier around a natural tooth, the peri-implant mucosa presents a lower bonding efficiency to the transmucosal region of dental implants, due to physiological structural differences. As such, the weaker soft tissue seal around the transmucosal region can be easily broken by oral pathogens, which may stimulate serious inflammatory responses and lead to the development of peri-implant mucositis. Without timely treatment, the curable peri-implant mucositis would evolve into irreversible peri-implantitis, finally causing the failure of implantation. Herein, this review has summarized current surface modification strategies for the transmucosal region of dental implants with improved soft tissue bonding capacities (e.g., improving surface wettability, fabricating micro/nano topographies, altering the surface chemical composition and constructing bioactive coatings). Furthermore, the surfaces with advanced soft tissue bonding abilities can be incorporated with antibacterial properties to prevent infections, and/or with immunomodulatory designs to facilitate the establishment of soft tissue seal. Finally, we proposed future research orientations for developing multifunctional surfaces, thus establishing a firm soft tissue seal at the transmucosal region and achieving the long-term predictability of dental implants.

Only a few studies have examined how pore geometry affects the mechanical characteristics, biological behavior, and degradation of additively manufactured biodegradable porous magnesium. In this work, the effects of pore geometry on mechanical qualities, degradation, and biological behavior were investigated using three typical porous architectures with the same porosity. The porous structures were found to satisfy bone tissue engineering requirements because they had sufficient degradation resistance and tunable compressive characteristics. All three types of magnesium alloy scaffolds exhibited good biocompatibility. Additionally, the magnesium alloy porous structures influenced the magnesium scaffold material degradation rate and the surrounding environment, impacting the osteogenic differentiation of bone mesenchymal stem cells and bone tissue regeneration. This work offers conceptual support for optimizing pore geometry to alter the mechanical and degradable characteristics of additively manufactured porous magnesium to meet therapeutic demands.

Magnesium alloys, noted for their substantial mechanical strength and exceptional biocompatibility, are increasingly being considered for use in biodegradable implants. However, their rapid degradation and significant hydrogen release have limited their applications in orthopaedics. In this study, a novel Mg-RE-Sr alloy was created by friction stir processing to modify its microstructure and enhance its degradation performance. Through microstructural characterization, the friction stir processing effectively refined the grains, accelerated the re-dissolution of precipitates, and ensured a uniform distribution of these phases. The processed alloy demonstrated improved comprehensive properties, with an in vitro corrosion rate of approximately 0.4 mm/y and increases in ultimate tensile strength and elongation by 37 % and 166 %, respectively. Notably, in vivo experiments involving a rat subcutaneous implantation model revealed a slower degradation rate of 0.09 mm/y and a uniform degradation process, basically achieving the requirements for ideal performance in orthopaedic applications. The superior degradation characteristics were attributed to the synergistic effect of attenuated galvanic corrosion and the formation of a dense Y(OH)3/Y2O3 film induced by an exceptional microstructure with a highly solid-soluted matrix and uniformly refined precipitates. Meanwhile, the alloys exhibited excellent biocompatibility and did not cause undesirable inflammation or produce toxic degradation products. These improvements in biocompatibility and degradation characteristics indicate great promise for the use of this friction stir processed alloy in osteosynthesis systems in the clinical setting.

Zinc (Zn)-based biodegradable metals (BMs) fabricated through conventional manufacturing methods exhibit adequate mechanical strength, moderate degradation behavior, acceptable biocompatibility, and bioactive functions. Consequently, they are recognized as a new generation of bioactive metals and show promise in several applications. However, conventional manufacturing processes face formidable limitations for the fabrication of customized implants, such as porous scaffolds for tissue engineering, which are future direction towards precise medicine. As a metal additive manufacturing technology, laser powder bed fusion (L-PBF) has the advantages of design freedom and formation precision by using fine powder particles to reliably fabricate metallic implants with customized structures according to patient-specific needs. The combination of Zn-based BMs and L-PBF has become a prominent research focus in the fields of biomaterials as well as biofabrication. Substantial progresses have been made in this interdisciplinary field recently. This work reviewed the current research status of Zn-based BMs manufactured by L-PBF, covering critical issues including powder particles, structure design, processing optimization, chemical compositions, surface modification, microstructure, mechanical properties, degradation behaviors, biocompatibility, and bioactive functions, and meanwhile clarified the influence mechanism of powder particle composition, structure design, and surface modification on the biodegradable performance of L-PBF Zn-based BM implants. Eventually, it was closed with the future perspectives of L-PBF of Zn-based BMs, putting forward based on state-of-the-art development and practical clinical needs.

The poor wear and corrosion resistance of Mg alloys are hampering wider application. Micro-arc oxidation can improve the wear and corrosion resistance, but the resulting coatings have relatively low hardness, high friction coefficient, and surface porosity, rendering them susceptible to failure in the field. Herein, ZrO2 nanocrystalline and extrinsic graphite-doped MAO coatings are prepared on the ZK61 Mg alloy using a control electrolyte containing potassium fluorozirconate and nano-graphite. The ZrO2 nanocrystals formed in situ are uniformly distributed in the amorphous coating, while the extrinsic graphite is mainly located in the amorphous structure. The size and number of pores decrease after introducing ZrO2 and graphite into the MAO coating. Compared with doping with a single element, co-doping increases the content of ZrO2 and graphite in the MAO coating. Furthermore, ZrO2 densifies the porous Mg(OH)2 corrosion product and blocks the penetration of the corrosive medium to improve the corrosion resistance. The optimized sample shows corrosion potential and corrosion current density of −1.012 V and 1.425 × 10−7 A·cm−2, which are significantly better than the singly doped MAO coating. Graphite doping decreases the friction coefficient, while ZrO2 doping decreases the wear rate. The ZrO2 and graphite co-doped C10Zr10 coating demonstrates self-lubricating properties, resulting in a significantly reduced wear rate from 2.832 × 10−4 mm3·N−1·m−1 to 1.04 × 10−5 mm3·N−1·m−1. The results reveal that co-doping improves the properties of MAO coatings on Mg alloys.

Due to matching biomechanical properties and significant biological activity, Mg-based implants present great potential in orthopedic applications. In recent years, the biocompatibility and therapeutic effect of magnesium-based implants have been widely investigated in trauma repair. In contrast, the R&D work of Mg-based implants in spinal fusion is still limited. This review firstly introduced the general background for Mg-based implants. Secondly, the mechanical properties and degradation behaviors of Mg and its traditional and novel alloys were reviewed. Then, different surface modification techniques of Mg-based implants were described. Thirdly, this review comprehensively summarized the biological pathways of Mg degradation to promote bone formation in neuro-musculoskeletal circuit, angiogenesis with H-type vessel formation, osteogenesis with osteoblasts activation and chondrocyte ossification as an integrated system. Fourthly, this review followed the translation process of Mg-based implants via updating the preclinical studies in fracture fixation, sports trauma repair and reconstruction, and bone distraction for large bone defect. Furthermore, the pilot clinical studies were involved to demonstrate the reliable clinical safety and satisfactory bioactive effects of Mg-based implants in bone formation. Finally, this review introduced the background of spine fusion surgeryand the challenges of biological matching cage development. At last, this review prospected the translation potential of a hybrid Mg-PEEK spine fusion cage design.

In the present research, the NaF assisted plasma electrolytic oxidation (PEO) is designed to fabricate the high-content ZnO nanoparticles doped coating on AZ31B alloy. The microstructure, phase constituents and corrosion behavior of the PEO coatings are investigated systematically. The results reveal that the introduction of NaF promotes the formation of MgF2 nanophases in the passivation layer on Mg alloy, decreasing the breakdown voltage and discharge voltage. As a result, the continuous arcing caused by high discharge voltage is alleviated. With the increasing of NaF content, the Zn content in the PEO coating is enhanced and the pore size in the coating is decreased correspondingly. Due to the high-content ZnO doping, the PEO coating protected AZ31B alloy demonstrates the better corrosion resistance. Compared with the bare AZ31B alloy, the high-content ZnO doped PEO coated sample shows an increased corrosion potential from -1.465 V to -1.008 V, a decreased corrosion current density from 3.043×10-5 A·cm-2 to 3.960×10-8 A·cm-2 and an increased charge transfer resistance from 1.213×102 ohm·cm2 to 2.598×105 ohm·cm2. Besides, the high-content ZnO doped PEO coated sample also has the excellent corrosion resistance in salt solution, exhibiting no obvious corrosion after more than 2000 h neutral salt spraying and 28 days’ immersion testing. The improved corrosion resistance can be ascribed to the relative uniform distribution of ZnO in PEO coating which can transform to Zn(OH)2 and form a continuous protective layer along the corrosion interface.

Healing of fractures or bone defects is significantly hindered by overactivated osteoclasts and inhibited osteogenesis in patients with abnormal bone metabolism. Current clinical approaches using titanium alloys or stainless steel provide mechanical support but have no biological effects on bone regeneration. Therefore, designing and fabricating degradable metal materials with sufficient mechanical strength and bidirectional regulation of both osteoblasts and osteoclasts is a substantial challenge. Here, this study first reported an adaptive biodegradable Zn-0.8 Mg alloy with bidirectional regulation of bone homeostasis, which promotes osteogenic differentiation by activating the Pi3k/Akt pathway and inhibits osteoclast differentiation by inhibiting the GRB2/ERK pathway. The anti-osteolytic ability of the Zn-0.8 Mg alloy was verified in a mouse calvarial osteolysis model and its suitability for internal fracture fixation with high-strength screws was confirmed in the rabbit femoral condyle fracture model. Furthermore, in an aged postmenopausal rat femoral condyle defect model, 3D printed Zn-0.8 Mg scaffolds promoted excellent bone regeneration through adaptive structures with good mechanical properties and bidirectionally regulated bone metabolism, enabling personalized bone defect repair. These findings demonstrate the substantial potential of the Zn-0.8 Mg alloy for treating fractures or bone defects in patients with aberrant bone metabolism.

Multi-drug resistant bacterial infections pose a significant threat to human health. Thus, the development of effective bactericidal strategies is a pressing concern. In this study, a ternary heterostructure (Zn–CN/P-GO/BiS) comprised of Zn-doped graphite phase carbon nitride (g-C3N4), phosphorous-doped graphene oxide (GO) and bismuth sulphide (Bi2S3) is constructed for efficiently treating methicillin-resistant Staphylococcus aureus (MRSA)-infected wound. Zn doping-induced defect sites in g-C3N4 results in a reduced band gap (ΔE) and a smaller energy gap (ΔEST) between the singlet state S1 and triplet state T1, which favours two-photon excitation and accelerates electron transfer. Furthermore, the formation of an internal electric field at the ternary heterogeneous interface optimizes the charge transfer pathway, inhibits the recombination of electron-hole pairs, improves the photodynamic effect of g-C3N4, and enhances its catalytic performance. Therefore, the Zn–CN/P-GO/BiS significantly augments the production of reactive oxygen species and heat under 808 nm NIR (0.67 W cm−2) irradiation, leading to the elimination of 99.60% ± 0.07% MRSA within 20 min. Additionally, the release of essential trace elements (Zn and P) promotes wound healing by activating hypoxia-inducible factor-1 (HIF-1) and peroxisome proliferator-activated receptors (PPAR) signaling pathways. This work provides unique insight into the rapid antibacterial applications of trace element doping and two-photon excitation.

Bone tissue engineering is the main method for repairing large segment bone defects. In this study, a layer of bioactive MgO nanoparticles was wrapped on the surface of spherical Zn powders, which allowed the MgO nanoparticles to be incorporated into 3D-printed Zn matrix and improved the biodegradation and biocompatibility of the Zn matrix. The results showed that porous pure Zn scaffolds and Zn/MgO scaffolds with skeletal-gyroid (G) model structure were successfully prepared by selective laser melting (SLM). The average porosity of two porous scaffolds was 59.3 and 60.0%, respectively. The pores were uniformly distributed with an average pore size of 558.6–569.3 μm. MgO nanoparticles regulated the corrosion rate of scaffolds, resulting in a more uniform corrosion degradation behavior of the Zn/MgO scaffolds in simulated body fluid solution. The degradation ratio of Zn/MgO composite scaffolds in vivo was increased compared to pure Zn scaffolds, reaching 15.6% at 12 weeks. The yield strength (10.8 ± 2.4 MPa) of the Zn/MgO composite scaffold was comparable to that of cancellous bone, and the antimicrobial rate were higher than 99%. The Zn/MgO composite scaffolds could better guide bone tissue regeneration in rat cranial bone repair experiments (completely filling the scaffolds at 12 weeks). Therefore, porous Zn/MgO scaffolds with G-model structure prepared with SLM are a promising biodegradable bone tissue engineering scaffold.

Ultra-low-wear polyethylene (ULWPE) is a promising material for artificial joint implants, owing to its good biocompatibility and wear resistance. However, its molecular weight is almost an order of magnitude lower than that of Ultrahigh molecular weight polyethylene (UHMWPE). The mechanism between wear resistance and the structure of ULWPE is still unknown. This study analyzed their attributes from microstructure to macroscopic performance and revealed the wear resistance mechanisms of ULWPE by conducting an in-depth investigation of four types of polyethylene, including ULWPE, UHMWPE, and high-density polyethylene. Impact tests showed that ULWPE, with a molecular weight of 282 kg/mol, exhibited an impact energy of 110 kJ/m2, surpassing the 97 kJ/m2 recorded for UHMWPE (molecular weight over 5000 kg/mol). Furthermore, tribology tests indicated that the wear rate of the most anti-wear ULWPE was 4.479 ± 0.040 mm³/Mc, which was significantly lower than the 5.601 ± 0.456 mm³/Mc for UHMWPE. The excellent mechanical properties and wear resistance of ULWPE were derived from its unique structure. Dynamic rheological assessments and thermal classification techniques confirmed that ULWPE had long-branched chains. The long-branched chains markedly increased the proportion of the high entanglement and the tie molecules in the amorphous regions, endowing it with superior toughness. At the same time, the high crystallinity of ULWPE gives it sufficient hardness and strength. The combination of high crystallinity and high entanglement endowed ULWPE with a good balance between strength and toughness, leading to its exceptional mechanical properties and wear resistance. This study provided robust data for ULWPE's clinical use and theoretical insights for designing durable, implantable polymers.

Endometrial cancer (EC) stands as one of the most prevalent gynecological malignancies affecting women, with its incidence and disease-related mortality steadily on the rise. Disulfiram (DSF), an FDA-approved medication primarily used for treating alcohol addiction, has exhibited promising anti-tumor properties. Studies have revealed DSF's capacity for enhanced anti-tumor activity, particularly when combined with copper. The novel Copper-Cysteamine (CuCy) compound, Cu3Cl(SR)2 (RCH2CH2NH2), showcases photodynamic effects and demonstrates significant anti-tumor potential under various conditions, including exposure to ultraviolet light, X-ray, microwave, and ultrasound. This study delves into exploring the synergistic anti-tumor effects and underlying mechanisms by utilizing copper-cysteamine in conjunction with DSF against endometrial cancer. The investigation involved comprehensive analyses encompassing in vitro experiments utilizing Ishikawa cells, in vivo studies, and transcriptomic analyses. Remarkably, the combined administration of both compounds at a low dose of 0.5 μM exhibited pronounced efficacy in impeding tumor growth, inhibiting blood vessel formation, and stimulating cell apoptosis. Notably, experiments involving transplanted tumors in nude mice vividly demonstrated the significant in vivo anti-tumor effects of this combination treatment. Detailed examination through transmission electron microscopy unveiled compelling evidence of mitochondrial damage, cellular swelling, and rupture, indicative of apoptotic changes in morphology due to the combined treatment. Moreover, transcriptomic analysis unveiled substantial downregulation of mitochondrial-related genes at the molecular level, coupled with a significant hindrance in the DNA repair pathway. These findings strongly suggest that the combined application of CuCy and DSF induces mitochondrial impairment in Ishikawa cells, thereby fostering apoptosis and ultimately yielding potent anti-tumor effects.

Objectives: To examine the 16-year developmental history, research hotspots, and emerging trends of zinc-based biodegradable metallic materials from the perspective of structural and temporal dynamics. Methods: The literature on zinc-based biodegradable metallic materials in WoSCC was searched. Historical characteristics, the evolution of active topics and development trends in the field of zinc-based biodegradable metallic materials were analyzed using the bibliometric tools CiteSpace and HistCite. Results: Over the past 16 years, the field of zinc-based biodegradable metal materials has remained in a hotspot stage, with extensive scientific collaboration. In addition, there are 45 subject categories and 51 keywords in different research periods, and 80 papers experience citation bursts. Keyword clustering anchored 3 emerging research subfields, namely, #1 plastic deformation #4 additive manufacturing #5 surface modification. The keyword alluvial map shows that the longest-lasting research concepts in the field are mechanical property, microstructure, corrosion behavior, etc., and emerging keywords are additive manufacturing, surface modification, dynamic recrystallization, etc. The most recent research on reference clustering has six subfields. Namely, #0 microstructure, #2 sem, #3 additive manufacturing, #4 laser powder bed fusion, #5 implant, and #7 Zn–1Mg. Conclusion: The results of the bibliometric study provide the current status and trends of research on zinc-based biodegradable metallic materials, which can help researchers identify hot spots and explore new research directions in the field.

Abstract The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance bone regeneration, but the limitations on the shape-adaptive capacity, the complexity of clinical operation, and the unsatisfied osteogenic bioactivity have greatly restricted their clinical application. In this work, we construct a mechanically robust, tailorable and water-responsive shape-memory silk fibroin/magnesium (SF/MgO) composite scaffold, which is able to quickly match irregular defects by simple trimming, thus leading to good interface integration. We demonstrate that the SF/MgO scaffold exhibits excellent mechanical stability and structure retention during the degradative process with the potential for supporting ability in defective areas. This scaffold further promotes the proliferation, adhesion and migration of osteoblasts and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. With suitable MgO content, the scaffold exhibits good histocompatibility, low foreign-body reactions (FBRs), significant ectopic mineralisation and angiogenesis. Skull defect experiments on male rats demonstrate that the cell-free SF/MgO scaffold markedly enhances bone regeneration of cranial defects. Taken together, the mechanically robust, personalised and bioactive scaffold with water-responsive shape-memory may be a promising biomaterial for clinical-size and irregular bone defect regeneration.

Abstract Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.

Laser powder bed fusion (L-PBF) of Mg alloys has provided tremendous opportunities for customized production of aeronautical and medical parts. Layer thickness (LT) is of great significance to the L-PBF process but has not been studied for Mg alloys. In this study, WE43 Mg alloy bulk cubes, porous scaffolds, and thin walls with layer thicknesses of 10, 20, 30, and 40 µm were fabricated. The required laser energy input increased with increasing layer thickness and was different for the bulk cubes and porous scaffolds. Porosity tended to occur at the connection joints in porous scaffolds for LT40 and could be eliminated by reducing the laser energy input. For thin wall parts, a large overhang angle or a small wall thickness resulted in porosity when a large layer thicknesses was used, and the porosity disappeared by reducing the layer thickness or laser energy input. A deeper keyhole penetration was found in all occasions with porosity, explaining the influence of layer thickness, geometrical structure, and laser energy input on the porosity. All the samples achieved a high fusion quality with a relative density of over 99.5% using the optimized laser energy input. The increased layer thickness resulted to more precipitation phases, finer grain sizes and decreased grain texture. With the similar high fusion quality, the tensile strength and elongation of bulk samples were significantly improved from 257 MPa and 1.41% with the 10 µm layer to 287 MPa and 15.12% with the 40 µm layer, in accordance with the microstructural change. The effect of layer thickness on the compressive properties of porous scaffolds was limited. However, the corrosion rate of bulk samples accelerated with increasing the layer thickness, mainly attributed to the increased number of precipitation phases.

In the present work, seven Mg-Zn-Ag alloys with the nominal composition of Mg96-xZnxAg4 (x = 17, 20, 23, 26, 29, 32, 35 in at.%) were prepared by induction melting and single-roller melt-spinning. The X-ray diffraction (XRD) analyses indicate the metallic glasses with three composition of Mg73Zn23Ag4, Mg70Zn26Ag4, and Mg67Zn29Ag4 were obtained successfully. The differential scanning calorimetry (DSC) measurement was used to obtain the characteristic temperature of Mg-Zn-Ag metallic glasses for the glass-forming ability analysis. The maximum glass transition temperature (Trg) was found to be 0.525 with a composition close to Mg67Zn29Ag4, which results in the best glass-forming ability. Moreover, the immersion test in simulated body fluid (SBF) demonstrate the relative homogeneous corrosion behavior of the Mg-Zn-Ag metallic glasses. The corrosion rate of Mg-Zn-Ag metallic glasses in SBF solution decreases with the increase of Zn content. The sample Mg67Zn29Ag4 has the lowest corrosion rate of 0.19 mm/yr, which could meet the clinical application requirement well. The in vitro cell experiments show that the Madin-Darby canine kidney (MDCK) cells cultured in sample Mg67Zn29Ag4 and its extraction medium have higher activity. However, the Mg-Zn-Ag metallic glasses exhibit obvious inhibitory effect on human rhabdomyosarcoma (RD) tumor cells. The present investigations on the glass-forming ability, corrosion behavior, cytocompatibility and tumor inhibition function of the Mg-Zn-Ag based metallic glass could reveal their biomedical application possibility.

Laser powder bed fusion (L-PBF) has been employed to additively manufacture WE43 magnesium (Mg) alloy biodegradable implants, but WE43 L-PBF samples exhibit excessively rapid corrosion. In this work, dense WE43 L-PBF samples were built with the relativity density reaching 99.9%. High temperature oxidation was performed on the L-PBF samples in circulating air via various heating temperatures and holding durations. The oxidation and diffusion at the elevated temperature generated a gradient structure composed of an oxide layer at the surface, a transition layer in the middle and the matrix. The oxide layer consisted of rare earth (RE) oxides, and became dense and thick with increasing the holding duration. The matrix was composed of α-Mg, RE oxides and Mg24RE5 precipitates. The precipitates almost disappeared in the transition layer. Enhanced passivation effect was observed in the samples treated by a suitable high temperature oxidation. The original L-PBF samples lost 40% weight after 3-day immersion in Hank's solution, and broke into fragments after 7-day immersion. The casted and solution treated samples lost roughly half of the weight after 28-day immersion. The high temperature oxidation samples, which were heated at 525 °C for 8 h, kept the structural integrity, and lost only 6.88% weight after 28-day immersion. The substantially improved corrosion resistance was contributed to the gradient structure at the surface. On one hand, the outmost dense layer of RE oxides isolated the corrosive medium; on the other hand, the transition layer considerably inhibited the corrosion owing to the lack of precipitates. Overall, high temperature oxidation provides an efficient, economic and safe approach to inhibit the corrosion of WE43 L-PBF samples, and has promising prospects for future clinical applications.

Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment. A three-dimensional (3D)-printed porous Ti6Al4V scaffold (3DTi) is an ideal material for reconstructing critical bone defects with numerous advantages over traditional implants, including a lower elasticity modulus, stronger bone-implant interlock, and larger drug-loading space. Simvastatin is a multitarget drug with anti-tumor and osteogenic potential; however, its efficiency is unsatisfactory when delivered systematically. Here, simvastatin was loaded into a 3DTi using a thermosensitive poly (lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel as a carrier to exert anti-osteosarcoma and osteogenic effects. Newly constructed simvastatin/hydrogel-loaded 3DTi (Sim-3DTi) was comprehensively appraised, and its newfound anti-osteosarcoma mechanism was explained. Specifically, in a bone defect model of rabbit condyles, Sim-3DTi exhibited enhanced osteogenesis, bone in-growth, and osseointegration compared with 3DTi alone, with greater bone morphogenetic protein 2 expression. In our nude mice model, simvastatin loading reduced tumor volume by 59%–77 % without organic damage, implying good anti-osteosarcoma activity and biosafety. Furthermore, Sim-3DTi induced ferroptosis by upregulating transferrin and nicotinamide adenine dinucleotide phosphate oxidase 2 levels in osteosarcoma both in vivo and in vitro. Sim-3DTi is a promising osteogenic bone substitute for osteosarcoma-related bone defects, with a ferroptosis-mediated anti-osteosarcoma effect.

Infections with multidrug-resistant (MDR) Gram-negative bacteria, such as MDR Escherichia coli (E. coli), remain a challenge due to the lack of safe antibiotics and high fatality rates under anti-infection therapies. This work presents a form of biomimetic intelligent catalysis inspired by the selective biocatalytic property of macrophages (MΦs), consisting of an intelligent controlling center (a living MΦ) and a Fenton reaction catalyst (Fe3O4@poly(lactic-co-glycolic acid) (PLGA) nanoparticles) for killing MDR E. coli without harming normal cells. The MΦ–Fe3O4@PLGA particles (i.e., the intelligent catalysis particles) exhibit selective biocatalysis activity toward MDR E. coli by producing H2O2 and lipid droplets (LDs). This process activates the lipid metabolism and glycan biosynthesis and metabolism pathways based on the result of RNA sequencing data analysis. The H2O2 further reacts with Fe3O4@PLGA to form highly toxic hydroxyl radicals (·OH), while the LDs contain antimicrobial peptides and can target MDR E. coli. The highly toxic ·OH and antimicrobial peptides are shown to combat with MDR E. coli, such that the antibacterial efficiency of the MΦ–Fe3O4@PLGA particles against MDR E. coli is 99.29% ± 0.31% in vitro. More importantly, after several passages, the intelligent catalysis function of the MΦ–Fe3O4@PLGA particles is well maintained. Hence, the concept of biomimetic intelligent catalysts displays potential for treating diseases other than infections.

Reconstruction of subarticular bone defects is an intractable challenge in orthopedics. The simultaneous repair of cancellous defects, fractures, and cartilage damage is an ideal surgical outcome. 3D printed porous anatomical WE43 (magnesium with 4 wt% yttrium and 3 wt% rare earths) scaffolds have many advantages for repairing such bone defects, including good biocompatibility, appropriate mechanical strength, customizable shape and structure, and biodegradability. In a previous investigation, we successfully enhanced the corrosion resistance of WE43 samples via high temperature oxidation (HTO). In the present study, we explored the feasibility and effectiveness of HTO-treated 3D printed porous anatomical WE43 scaffolds for repairing the cancellous bone defects accompanied by split fractures via in vitro and in vivo experiments. After HTO treatment, a dense oxidation layer mainly composed of Y2O3 and Nd2O3 formed on the surface of scaffolds. In addition, the majority of the grains were equiaxed, with an average grain size of 7.4 μm. Cell and rabbit experiments confirmed the non-cytotoxicity and biocompatibility of the HTO-treated WE43 scaffolds. After the implantation of scaffolds inside bone defects, their porous structures could be maintained for more than 12 weeks without penetration and for more than 6 weeks with penetration. During the postoperative follow-up period for up to 48 weeks, radiographic examinations and histological analysis revealed that abundant bone gradually regenerated along with scaffold degradation, and stable osseointegration formed between new bone and scaffold residues. MRI images further demonstrated no evidence of any obvious damage to the cartilage, ligaments, or menisci, confirming the absence of traumatic osteoarthritis. Moreover, finite element analysis and biomechanical tests further verified that the scaffolds was conducive to a uniform mechanical distribution. In conclusion, applying the HTO-treated 3D printed porous anatomical WE43 scaffolds exhibited favorable repairing effects for subarticular cancellous bone defects, possessing great potential for clinical application.

Staphylococcus aureus (S. aureus)-infected chronic osteomyelitis (COM) is one of the most devastating infectious diseases with a high recurrence rate, often leading to amputation and even death. It is incurable by all the current strategies involving the clinical use of radical debridement and systemic intravenous antibiotics. Here, we reported on a microwave (MW)-assisted therapy for COM by constructing a heterojunction formed by flake nanoflower-shaped molybdenum disulfide (MoS2) and tubular carbon nanotubes (CNTs). This composite could achieve a combination of MW thermal therapy (MTT) and MW dynamic therapy (MDT) to accurately and rapidly treat COM with deep tissue infection. In vitro and in vivo experiments showed that MoS2/CNTs were effective in non-invasively treating S. aureus-induced COM due to the heat and reactive oxygen species (ROS) produced under MW irradiation. The mechanism of heat and ROS generation was explained by MW network vector analysis, density of states (DOS), oxygen adsorption energy, differential charge and finite element (FEM) under MW irradiation. Since the Fermi layer was mainly contributed by the Mo-4d and C–2P orbitals, MoS2/CNTs could store a large amount of charge and easily release more electrons. In addition, charge accumulation and dissipation motion were strong on the surface of and inside MoS2/CNTs because of electromagnetic hot spots, resulting in the spilling out of a great deal of high-energy electrons. Due to the low oxygen adsorption energy of MoS2/CNTs-O2, these high-energy electrons combined further with the adsorbed oxygen to produce ROS.

Abstract Ferroptosis is an iron-dependent form of regulated cell death driven by the lethal lipid peroxides. Previous studies have demonstrated that inducing ferroptosis holds great potential in cancer therapy, especially for patients with traditional therapy failure. However, cancer cells can acquire ferroptosis evasion during progression. To date, the therapeutic potential of inducing ferroptosis in bladder cancer (BCa) remains unclear, and whether a ferroptosis escape mechanism exists in BCa needs further investigation. This study verified that low pathological stage BCa cells were highly sensitive to RSL3-induced ferroptosis, whereas high pathological stage BCa cells exhibited obviously ferroptosis resistance. RNA-seq, RNAi-mediated loss-of-function, and CRISPR/Cas9 experiments demonstrated that ALOX5 deficiency was the crucial factor of BCa resistance to ferroptosis in vitro and in vivo. Mechanistically, we found that ALOX5 deficiency was regulated by EGR1 at the transcriptional level. Clinically, ALOX5 expression was decreased in BCa tissues, and its low expression was associated with poor survival. Collectively, this study uncovers a novel mechanism for BCa ferroptosis escape and proposes that ALOX5 may be a valuable therapeutic target and prognostic biomarker in BCa treatment.

Magnesium-based biodegradable metals as cardiovascular stents have shown a lot of excellent performance, which have been used to treat coronary artery diseases. However, the excessive degradation rate, imperfect biocompatibility and delayed re-endothelialization still lead to a considerable challenge for its application. In this work, to overcome these shortcomings, a compound of catalyzing nitric oxide (NO) generation containing copper ions (Cu2+) and hyaluronic acid (HA), an important component of the extracellular matrix, were covalently immobilized on a hydrofluoric acid (HF)-pretreated ZE21B alloy via amination layer for improving its corrosion resistance and endothelialization. Specifically, the Cu2+chelated firmly with a cyclen 1,4,7,10-tetraazacyclododecane-N, N′, N″, N″′- tetraacetic acid (DOTA) could form a stability of hybrid coating, avoiding the explosion of Cu2+. The chelated Cu2+enabled the catalytic generation of NO and promoted the adhesion and proliferation of endothelial cells (ECs) in vascular micro-environment. In this case, the synergistic effect of NO-generation and endothelial glycocalyx molecules of HA lead to efficient ECs promotion and smooth muscle cells (SMCs) inhibition. Meanwhile, the blood compatibility also had achieved a marked improvement. Moreover, the standard electrochemical measurements indicated that the functionalized ZE21B alloy had better anti-corrosion ability. In a conclusion, the dual-functional coating displays a great potential in the field of biodegradable magnesium-based implantable cardiovascular stents.

Abstract Architected materials that consist of multiple subelements arranged in particular orders can demonstrate a much broader range of properties than their constituent materials. However, the rational design of these materials generally relies on experts’ prior knowledge and requires painstaking effort. Here, we present a data-efficient method for the high-dimensional multi-property optimization of 3D-printed architected materials utilizing a machine learning (ML) cycle consisting of the finite element method (FEM) and 3D neural networks. Specifically, we apply our method to orthopedic implant design. Compared to uniform designs, our experience-free method designs microscale heterogeneous architectures with a biocompatible elastic modulus and higher strength. Furthermore, inspired by the knowledge learned from the neural networks, we develop machine-human synergy, adapting the ML-designed architecture to fix a macroscale, irregularly shaped animal bone defect. Such adaptation exhibits 20% higher experimental load-bearing capacity than the uniform design. Thus, our method provides a data-efficient paradigm for the fast and intelligent design of architected materials with tailored mechanical, physical, and chemical properties.

The effects of pore size in additively manufactured biodegradable porous magnesium on the mechanical properties and biodegradation of the scaffolds as well as new bone formation have rarely been reported. In this work, we found that high temperature oxidation improves the corrosion resistance of magnesium scaffold. And the effects of pore size on the mechanical characteristics and biodegradation of scaffolds, as well as new bone formation, were investigated using magnesium scaffolds with three different pore sizes, namely, 500, 800, and 1400 μm (P500, P800, and P1400). We discovered that the mechanical characteristics of the P500 group were much better than those of the other two groups. In vitro and in vivo investigations showed that WE43 magnesium alloy scaffolds supported the survival of mesenchymal stem cells and did not cause any local toxicity. Due to their larger specific surface area, the scaffolds in the P500 group released more magnesium ions within reasonable range and improved the osteogenic differentiation of bone mesenchymal stem cells compared with the other two scaffolds. In a rabbit femoral condyle defect model, the P500 group demonstrated unique performance in promoting new bone formation, indicating its great potential for use in bone defect regeneration therapy.

Cancer is a major threat to human life worldwide. Traditional cancer treatments, such as chemotherapy and surgery, have major limitations and can cause irreversible damage to normal tissues while killing the cancer cells. Magnesium (Mg) alloys are widely reported novel potential biomedical materials with acceptable mechanical properties and good osteogenic and angiogenic properties. In this review, we summarize the Mg alloys for antitumor applications, including pure Mg and Mg alloys (Mg-Ag, Mg-Gd, Mg-Li-Zn, Mg-Ca-Sr-Zn, et al.) fabricated by casting and extruding, selective laser melting methods. Mg alloys can exhibit antitumor effect on bone tumor, breast cancer, and liver tumor, etal. What's more, after tumor tissue is eliminated, Mg alloys prevent tumor recurrence, fill tissue defects and promote tissue regeneration. The antitumor effects of Mg alloys are mainly due to their degradation products. Overall, Mg alloys show great potential in tumor treatments due to the dual function of antitumor and tissue regeneration.

Polyetheretherketone (PEEK) is considered as a promising dental implant material owing to its excellent physicochemical and mechanical properties. However, its wide range of applications is limited by its biologically inert nature. In this study, a near-infrared (NIR) light responsive bioactive coating with gold nanoparticles (AuNPs) and metronidazole adhered to the PEEK surface via dopamine polymerization. Compared to pure PEEK, the hydrophilicity of the treated PEEK surface was significantly improved. In addition, under NIR light, the surface coating exhibited photothermal conversion effect, and gold nanoparticles and the antibiotic can be released from the coating. This improved the antibacterial properties of PEEK materials. Moreover, the coating was more conducive to the early adhesion of bone mesenchymal stem cells. The results of in vitro and in vivo osteogenic activity studies showed that the developed coating promoted osseointegration of PEEK implants, and NIR light irradiation further improved the antibacterial ability and osteogenic activity of PEEK implants. Through RNA sequencing, the potential underlying mechanism of promoting bone formation of the AuNPs coating combined metronidazole was interpreted. In summary, the developed coating is a potential surface treatment strategy that endows PEEK with enhanced osseointegration and antibacterial properties.

Corrosion caused by the active chemical properties of magnesium (Mg) alloys seriously restricts their applications in aerospace, transportation, biomedicine, and other fields. Although micro-arc oxidation (MAO) coatings can provide some corrosion protection for Mg alloys, their microporous structure is prone to localized corrosion. Herein, nanoflower-shaped zinc phosphate is prepared and hydrophobically modified. The commercial glue is used to bond the nanoflower-shaped zinc phosphate particle arrays to the MAO-coated AZ31B alloy substrate to produce a two-layer composite coating with superhydrophobic properties. The composite coating exhibits obvious repulsive effects in salt and acidic solutions as indicated by contact angles of 160° and 156°, respectively. The composite coating has improved electrochemical properties and immersion corrosion in both the salt and acidic solutions compared to the substrate and MAO-coated sample. Moreover, the composite coating retains the long-term superhydrophobic effects under different conditions such as immersion in salt and acidic solutions, water scouring, and sunlight exposure, which well indicates commercial applications.

Selective endovascular hypothermia has been used to provide cooling-induced cerebral neuroprotection, but current catheters do not support thermally-insulated transfer of cold infusate, which results in an increased exit temperature, causes hemodilution, and limits its cooling efficiency. Herein, air-sprayed fibroin/silica-based coatings combined with chemical vapor deposited parylene-C capping film was prepared on catheter. This coating features in dual-sized-hollow-microparticle incorporated structures with low thermal conductivity. The infusate exit temperature is tunable by adjusting the coating thickness and infusion rate. No peeling or cracking was observed on the coatings under bending and rotational scenarios in the vascular models. Its efficiency was verified in a swine model, and the outlet temperature of coated catheter (75 μm thickness) was 1.8–2.0 °C lower than that of the uncoated one. This pioneering work on catheter thermal insulation coatings may facilitate the clinical translation of selective endovascular hypothermia for neuroprotection in patients with acute ischemic stroke.

In contrast to polymer bioresorbable stents (BRS) that exhibited suboptimal performance in clinical trials due to their deficient mechanical properties, metallic BRS with improved mechanical strength have made their way into the clinic and have demonstrated more promising results. In the roadmap of research and development of metallic BRS, magnesium and iron based biodegradable metal stents had been clinically used, and the zinc based biodegradable metal stents had been trailed in Mini-Pigs. In this mini-review paper, we demonstrate the current technology levels and point out the future R&D direction of metallic BRS. Magnesium based BRS should target for decreasing struct thickness meanwhile balancing with enough supporting strength. Iron based BRS should move towards high efficient absorption, conversion, metabolism, elimination of its degradation products. Zn based BRS should strive to improve mechanical stability, creep resistance and biocompatibility. Future R&D directions of metallic BRS should move towards new materials such as Molybdenum, intelligent stent integrated with degradable biosensors, and new stent with multiple biofunctions, such as NO release.

Biomedical implants and devices for tissue engineering in clinics, mainly made of polymers and stiff metallic materials, require possibly secondary surgery or life-long medicine. Biodegradable metals for biomedical implants and devices exhibit huge potential to improve the prognosis of patients. In this work, we developed a new type of biodegradable binary zinc (Zn) alloys with 16 rare earth elements (REEs) including Sc, Y, La to Nd, and Sm to Lu, respectively. The effects of REEs on the alloy microstructure, mechanical properties, corrosion behavior and in vitro and in vivo biocompatibility of Zn were systematically investigated using pure Zn as control. All Zn-RE alloys generally exhibited improved mechanical properties, and biocompatibilities compared to pure Zn, especially the tensile strength and ductility of Zn-RE alloys were dramatically enhanced. Among the Zn-RE alloys, different REEs presented enhancement effects at varied extent. Y, Ho and Lu were the three elements displaying greatest improvements in majority of alloys properties, while Eu, Gd and Dy exhibited least improvement. Furthermore, the Zn-RE alloys were comparable with other Zn alloys and also exhibited superior properties to Mg-RE alloys. The in vivo experiment using Zn–La, Zn–Ce, and Zn–Nd alloys as tibia bone implants in rabbit demonstrated the excellent tissue biocompatibility and much more obvious osseointegration than the pure Zn control group. This work presented the significant potential of the developed Zn-RE binary alloys as novel degradable metal for biomedical implants and devices.

Developing new photocatalytic materials is one of the most promising strategies to address bacterial infection during wound healing without bacterial drug resistance, but their poor photocatalytic activity ultimately limits their therapeutic efficacy. In this work, a metal–organic framework‐based S‐scheme heterostructure (Ag2S@PB) is prepared to rapidly treat open wounds caused by bacterial infection, which effectively establishes and retains spatially isolated redox centers through an S‐scheme charge‐transfer pathway. Additionally, the formation of an interface electric field and covalent FeS bridge bonding in the heterogeneous interface endows the heterojunction with a much stronger charge separation and transfer capability than bare Ag2S, which significantly enhances the photocatalytic performance and stability, consequently generating more radical oxygen species. Meanwhile, the introduction of Prussian blue greatly improves the photothermal effect of the Ag2S@PB under 808 nm near‐infrared light. Therefore, under illumination for 20 min, the Ag2S@PB shows a desirable antibacterial efficiency of 99.92% against Staphylococcus aureus and 99.86% against Escherichia coli. The in vivo wound repair experiment shows that the Ag2S@PB has good tissue repair effects and can expedite wound healing. This work will provide insights for designing highly efficient photoresponsive materials to treat bacterial wound infections.

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

The widespread use of orthopedic implants to support or replace bones is increasingly threatened by the risk of incurable bacterial infections, impenetrable microbial biofilms, and irreversible antibiotic resistance. In the past, the development of anti-infective biomaterials focused solely on direct antibacterial properties while ignoring the host's immune response. Inspired by the clearance of infection by the innate neutrophil response and participation in anti-infectious immunity of Zn ions, we report an innovative neutrophil extracellular traps (NETs) strategy, induced by biodegradable pure Zn, which achieved therapeutic efficacy toward biomaterial-related infections. Our in vitro and in vivo data showed that pure Zn was favorable for NETs formation by promoting the release of DNA fibers and granule proteins in a reactive oxygen species (ROS)-dependent manner, thereby retraining and degrading bacteria with an efficiency of up to 99.5%. Transcriptome analysis revealed that cytoskeletal rearrangement and toll-like receptor (TLR) signaling pathway were also involved in Zn-induced NETs formation. Furthermore, the in vivo results of a Staphylococcus aureus (S. aureus)-infected rat model verified that pure Zn potentiated the bactericidal capability of neutrophils around implants, and promoted osseointegration in S. aureus-infected rat femurs. This antibacterial immunity concept lays a foundation for the development of other antibacterial biomaterials and holds great promise for treating orthopedic infections.

A new ternary compound, Mg11-xZnxSr in the Mg-Zn-Sr system was observed and studied using Scanning Electron Microscopy (SEM), Energy-Dispersive Spectroscope (EDS), X-Ray Diffraction (XRD) and Transmission Electron Microscopy (TEM). The XRD patterns were refined by the Rietveld refinement method and the results revealed that the crystallized Mg11-xZnxSr phase belonged to tetragonal I41/amd space group and had the Cd11Ba prototype. The Mg atoms were successfully doped into Zn11Sr crystal lattice by occupying Zn atomic sites. Moreover, the Rietveld refinement and computational results demonstrated a gradual decrease in the a-axis and c-axis lattice parameters with decreasing concentration levels of Mg coordination substitution in the lattice of Mg11-xZnxSr compound. The elastic constants and modulus of the Mg11-xZnxSr compounds calculated by first-principles calculations (FPC) indicated they were increased with the increasing of Zn content. The variation of hardness, d-band widths and the total density of states for Mg11-xZnxSr compounds with Zn content was discussed.

Polyetheretherketone (PEEK) has been an alternative material for titanium in bone defect repair, but its clinical application is limited by its poor osseointegration. In this study, a porous structural design and activated surface modification were used to enhance the osseointegration capacity of PEEK materials. Porous PEEK scaffolds were manufactured via fused deposition modeling and a polydopamine (PDA) coating chelated with magnesium ions (Mg2+) was utilized on the surface. After surface modification, the hydrophilicity of PEEK scaffolds was significantly enhanced, and bioactive Mg2+ could be released. In vitro results showed that the activated surface could promote cell proliferation and adhesion and contribute to osteoblast differentiation and mineralization; the released Mg2+ promoted angiogenesis and might contribute to the formation of osteogenic H-type vessels. Furthermore, porous PEEK scaffolds were implanted in rabbit femoral condyles for in vivo evaluation of osseointegration. The results showed that the customized three-dimensional porous structure facilitated vascular ingrowth and bone ingrowth within the PEEK scaffolds. The PDA coating enhanced the interfacial osseointegration of porous PEEK scaffolds and the released Mg2+ accelerated early bone ingrowth by promoting early angiogenesis during the coating degradation process. This study provides an efficient solution for enhancing the osseointegration of PEEK materials, which has high potential for translational clinical applications.

Zinc (Zn) is a new class of bioresorbable metal that has potential for cardiovascular stent material, orthopedic implants, wound closure devices, etc. However, pure Zn is not ideal for these applications due to its low mechanical strength and localized degradation behavior. Alloying is the most common/effective way to overcome this limitation. Still, the choice of alloying element is crucial to ensure the resulting alloy possesses sufficient mechanical strength, suitable degradation rate, and acceptable biocompatibility. Hereby, we proposed to blend selective transition metals (i.e., vanadium-V, chromium-Cr, and zirconium-Zr) to improve Zn's properties. These selected transition metals have similar properties to Zn and thus are beneficial for the metallurgy process and mechanical property. Furthermore, the biosafety of these elements is of less concern as they all have been used as regulatory approved medical implants or a component of an implant such as Ti6Al4V, CoCr, or Zr-based dental implants. Our study showed the first evidence that blending with transition metals V, Cr, or Zr can improve Zn's properties as bioresorbable medical implants. In addition, three in vivo implantation models were explored in rats: subcutaneous, aorta, and femoral implantations, to target the potential clinical applications of bioresorbable Zn implants.

Endowing implant surfaces with combined antibacterial and osteogenic properties by drug-loaded coatings has made great strides, but how to achieve the combined excellence of infection-triggered bactericidal and in vivo-proven osteogenic activities without causing bacterial resistance still remains a formidable challenge. Herein, antimicrobial peptides (AMPs) with osteogenic fragments were designed and complexed on the surface of silver nanoparticle (AgNP) through hydrogen bonding, and the collagen structure-bionic silk fibroin (SF) was applied to carry AgNPs@ AMPs to achieve infection-triggered antibacterial and osteointegration. As verified by TEM, AMPs contributed to the dispersion and size-regulation of AgNPs, with a particle size of about 20 nm, and a clear protein corona structure was observed on the particle surface. The release curve of silver ion displayed that the SF-based coating owned sensitive pH-responsive properties. In the antibacterial test against S.aureus for up to 21 days, the antibacterial rate had always remained above 99%. Meanwhile, the underlying mechanism was revealed, originating from the destruction of the bacterial cell membranes and ROS generation. The SF-based coating was conducive to the adhesion, diffusion, and proliferation of bone marrow stem cells (BMSCs) on the surface, and promoted the expression of osteogenic genes and collagen secretion. The in vivo implantation results showed that compared with the untreated Ti implants, SF-based coating enhanced osseointegration at week 4 and 8. Overall, the AgNPs@AMPs-loaded SF-based coating presented the ability to synergistically inhibit bacteria and promote osseointegration, possessing tremendous potential application prospects in bone defects and related-infection treatments.

Additive manufacturing has received attention for the fabrication of medical implants that have customized and complicated structures. Biodegradable Zn metals are revolutionary materials for orthopedic implants. In this study, pure Zn porous scaffolds with diamond structures were fabricated using customized laser powder bed fusion (L-PBF) technology. First, the mechanical properties, corrosion behavior, and biocompatibility of the pure Zn porous scaffolds were characterized in vitro. The scaffolds were then implanted into the rabbit femur critical-size bone defect model for 24 weeks. The results showed that the pure Zn porous scaffolds had compressive strength and rigidity comparable to those of cancellous bone, as well as relatively suitable degradation rates for bone regeneration. A benign host response was observed using hematoxylin and eosin (HE) staining of the heart, liver, spleen, lungs, and kidneys. Moreover, the pure Zn porous scaffold showed good biocompatibility and osteogenic promotion ability in vivo. This study showed that pure Zn porous scaffolds with customized structures fabricated using L-PBF represent a promising biodegradable solution for treating large bone defects.

Infections caused by bacteria threaten human health, so how to effectively kill bacteria is an urgent problem. We therefore synthesized a NH2-MIL-125-GO-Pt ternary composite heterojunction with graphene oxide (GO) and platinum (Pt) nanoparticles co-doped with metal-organic framework (NH2-MIL-125) for use in photocatalytic and photothermal synergistic disinfection under white light irradiation. Due to the good conductivity of GO and the Schottky junction between Pt and MOF, the doping of GO and Pt will effectively separate and transfer the photogenerated electron-hole pairs generated by NH2-MIL-125, thereby effectively improving the photocatalytic efficiency of NH2-MIL-125. Meanwhile, NH2-MIL-125-GO-Pt has good photothermal effect under white light irradiation. Therefore, the NH2-MIL-125-GO-Pt composite can be used for effective sterilization. The antibacterial efficiency of NH2-MIL-125-GO-Pt against Staphylococcus aureus and Escherichia coli were as high as 99.94% and 99.12%, respectively, within 20 min of white light irradiation. In vivo experiments showed that NH2-MIL-125-GO-Pt could effectively kill bacteria and promote wound healing. This work brings new insights into the use of NH2-MIL-125-based photocatalyst materials for rapid disinfection of environments with pathogenic microorganisms.

Zinc (Zn) is a promising bioresorbable implant material with more moderate degradation rate compared to magnesium (Mg) and iron (Fe). However, the low mechanical strength and localized degradation behavior of pure Zn limit its clinical applications. Alloying is one of the most effective ways to overcome these limitations. After screening the alloying element candidates regarding their potentials for improvement on the degradation and biocompatibility, we proposed Fe as the alloying element for Zn, and investigated the in vitro and in vivo performances of these alloys in both subcutaneous and femoral tissues. Results showed that the uniformly distributed secondary phase in Zn–Fe alloys significantly improved the mechanical property and facilitated uniform degradation, which thus enhanced their biocompatibility, especially the Zn-0.4Fe alloy. Moreover, these Zn–Fe alloys showed outstanding antibacterial property. Taken together, Zn–Fe alloys could be promising candidates as bioresorbable medical implants for various cardiovascular, wound closure, and orthopedic applications.

Abstract Objectives Exosomes are essential mediators of intercellular communication as they transport proteins and RNAs between cells. Owing to their tumor‐targeting capacity, immune compatibility, low toxicity, and long half‐life, mesenchymal stem cell‐derived exosomes have great potential for the development of novel antitumor strategies. In this context, the role of exosomes produced by adipose‐derived mesenchymal stem cells (ADSCs) for the treatment of bladder cancer (BC) remains unclear. Here, we investigated the use of ADSCs as a source of therapeutic exosomes, as well as their efficacy in delivering the tumor suppressor miR‐138‐5p in BC. Methods ADSCs stably expressing miR‐138‐5p were established using Lentivirus infection, and ADSC‐derived miR‐138‐5p exosomes (Exo‐miR‐138‐5p) were isolated from the cell culture medium. The effect of Exo‐miR‐138‐5p on BC cell migration, invasion, and proliferation was evaluated in vitro using wound healing, transwell invasion, and proliferation assays. The in vivo effect of Exo‐miR‐138‐5p was investigated using a subcutaneous xenograft mouse model. Results Exo‐miR‐138‐5p prevented the migration, invasion, and proliferation of BC cells in vitro. Moreover, ADSC‐derived exosomes could penetrate tumor tissues and successfully deliver miR‐138‐5p to suppress the growth of xenograft tumors in vivo. Conclusions The present results reveal that ADSC‐derived exosomes are an effective delivery vehicle for small molecule drugs in vivo, and exosome‐delivered miR‐138‐5p is a promising therapeutic agent for BC treatment.

Laser powder bed fusion (L-PBF) of magnesium (Mg) alloy porous scaffolds is expected to solve the dual challenges from customized structures and biodegradable functions required for repairing bone defects. However, one of the key technical difficulties lies in the poor L-PBF process performance of Mg, contributed by the high susceptibility to oxidation, vaporization, thermal expansion, and powder attachment etc. This work investigated the influence of L-PBF energy input and scanning strategy on the formation quality of porous scaffolds by using WE43 powder, and characterized the microstructure, mechanical properties, biocompatibility, biodegradation and osteogenic effect of the as-built WE43 porous scaffolds. With the customized energy input and scanning strategy, the relative density of struts reached over 99.5%, and the geometrical error between the designed and the fabricated porosity declined to below 10%. Massive secondary phases including intermetallic precipitates and oxides were observed. The compressive strength (4.37–23.49 MPa) and elastic modulus (154.40–873.02 MPa) were comparable to those of cancellous bone. Good biocompatibility was observed by in vitro cell viability and in vivo implantation. The biodegradation of as-built porous scaffolds promoted the osteogenic effect, but the structural integrity devastated after 12 h by the immersion tests in Hank's solution and after 4 weeks by the implantation in rabbits' femur, indicating an excessively rapid degradation rate.

Abstract The repair of critical diaphyseal defects of lower weight-bearing limbs is an intractable problem in clinical practice. From December 2017, we prospectively applied 3D printed porous Ti6Al4V scaffolds to reconstruct this kind of bone defect. All patients experienced a two-stage surgical process, including thorough debridement and scaffold implantation. With an average follow-up of 23.0 months, ten patients with 11 parts of bone defects were enrolled in this study. The case series included three females and seven males, their defect reasons included seven parts of osteomyelitis and four parts of aseptic nonunion. The bone defects located at femur (five parts) and tibia (six parts), with an average defect distance of 12.2 cm. Serial postoperative radiologic follow-ups displayed a continuous process of new bone growing and remodeling around the scaffold. One patient suffered tibial varus deformity, and he underwent a revision surgery. The other nine patients achieved scaffold stability. No scaffold breakage occurred. In conclusion, the implantation of 3D printed Ti6Al4V scaffold was feasible and effective to reconstruct critical bone defects of lower limbs without additional bone grafting. Graphical abstract

The fast development of biomaterials science and engineering has generated significant number of studies and publications as well as tremendous amount of research data. A methodology is needed to translate such research data and results to validated scientific evidence. This article for the first time proposes the concept and methodology of evidence-based biomaterials research, which is to use evidence-based research approach represented by systematic reviews to generate evidence for answering scientific questions related to biomaterials. After briefly introducing the advancement of biomaterials since 1950s, the scientific and engineering nature of biomaterials are discussed along with the roadmap of biomaterials translation from basic research to commercialized medical products, and the needs of scientific evidence. Key information of the evidence-based approach such as its origination from evidence-based medicine, levels of evidence, systematic review and meta-analysis, differences between systematic and narrative reviews is then highlighted. Applications with a step-by-step procedure of conducting evidence-based biomaterials research, three examples of biomaterials research using evidence-based approach to generate scientific evidence, and opportunities and challenges of evidence-based biomaterials research are presented. With its notable impact on the practice of medicine, the evidence-based approach is also expected to make influential contributions to the biomaterials field.

Nanorods can induce mechano-puncture of Staphylococcus aureus (S. aureus) that often impairs osseointegration of orthopedic implants, while the critical nanorod top sharpness able to puncture S. aureus and the predominant contributor between top sharpness and length to mechano-puncture activity remains elusive. Herein, we fabricated three kinds of Al2O3-wrapped nanorods patterned arrays with different lengths and top sharpness. The top-sharp nanorods have lengths of 469 and 884 nm and the shorter show a length identical to the top-flat nanorods. Driven by the equivalent adhesive force of S. aureus, the top-flat nanorods deform cell envelops, showing a bacteriostatic rate of 29% owing to proliferation-inhibited manner. The top-sharp nanorods puncture S. aureus, showing a bactericidal rate of 96% for the longer, and 98% for the shorter that simultaneously exhibits fair osseointegration in bacteria-infected rat tibias, identifying top sharpness as a predominate contributor to mechano-puncture activity. Based on finite-element simulation, such top-flat nanorod derives the maximum stress (Smax) of 5.65 MPa on cell wall, lower than its ultimate-tensile-strength (13 MPa); while such top-sharp and shorter nanorod derives Smax of 20.15 MPa to puncture cell envelop. Moreover, a critical top conical angle of 138° is identified for nanorods able to puncture S. aureus.

Bacterial infections are a serious public health issue that threatens the lives of patients because of their ability to induce other lethal complications without prompt treatment. Conventional antibiotic therapy can cause bacterial resistance and other adverse effects. It is highly desirable to develop effective and antibiotic‐independent therapeutic strategies to treat various kinds of bacterial infections. Herein, sonodynamic‐enhanced piezoelectric materials MoS2 and Cu2Oheterostructure that responds to exogenous ultrasound (US) and generates reactive oxygen for Staphylococcus aureus elimination are developed. It is shown in the results that the polariton charge induced by piezoelectric MoS2 nanosheets under US irradiation can accelerate the transfer of electric in Cu2O. Furthermore, US irradiation induces valence conversion from Cu(I) to Cu(II), which can accelerate glutathione oxidation significantly and destroy the bacterial antioxidant defense system. Hence, the as‐prepared piezoelectric‐enhanced sonosensitizer possesses a highly effective antibacterial efficacy of 99.85% against S. aureus under US irradiation for 20 min, with good biocompatibility. Herein, effective ultrasonic piezocatalytic therapy is offered through constructing heterogeneous interfaces with ultrasonic piezoelectric response.