Biodegradable magnesium (Mg) alloys hold great promise for next-generation implantable devices, but the inherent trade-offs among degradation control, mechanical integrity, and local biological responses hinder their clinical translation. Guided by the "material plainification" concept, which advocates avoiding complex alloy components, this work presents a systematic investigation of binary Mg-xZn alloys (x = 0.5-4 wt.%) processed by thermoplastic deformation, revealing the regulatory effects of zinc (Zn) content on dynamic recrystallization and the subsequent influences on overall biomedical performance. Results demonstrate that a moderate Zn content significantly promotes grain refinement and grain boundary (GB) stability. In particular, Mg-1.25Zn alloy emerges as the optimal "window", exhibiting a refined grain size of 2.7 μm and a balanced combination of mechanical properties (YS 258 MPa, UTS 280 MPa, EL 20.6 %). Besides, this alloy forms a protective corrosion product layer with a low in vitro corrosion rate of 0.11 mm·y⁻¹ and shows superior anti-inflammatory activity in a murine implantation model. Composed of bioessential elements and featuring compositional simplicity with potential cost advantages, the fine-grained Mg-1.25Zn alloy demonstrates a favorable balance among mechanical performance, degradation behavior, and biological response, thereby supporting its further development for soft tissue anastomosis and related biomedical applications. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium alloys hold promise for next-generation implantable devices. However, balancing degradation rate, mechanical strength, and host response remains a key challenge for clinical translation. Guided by the concept of "material simplification", this study systematically investigates binary Mg-Zn alloys with Zn as the sole alloying element after thermo processing. By regulating Zn content, a composition-microstructure-property relationship is established, identifying Mg-1.25Zn as an optimal composition window. This alloy shows refined grains, favorable mechanical properties, a low in vitro corrosion rate, and anti-inflammatory activity in animal models, indicating that simple, low-cost binary alloys can achieve multifunctional performance optimization, thereby supporting its further development for soft tissue anastomosis, vascular occlusion, and related biomedical applications.

In order to advance the application of magnesium alloys as short-term implants, there is a growing need to further regulate the temporal evolution of their degradation rates to better align with clinical requirements. However, it is difficult for conventional bulk magnesium alloys. To address this limitation, this study developed a layered Mg-Mg2Zn-Mg4Zn-Mg6Zn-Mg4Zn-Mg2Zn-Mg laminate alloy (named as MZM in this study) based on a heterogeneous gradient structure (HGS) strategy, which created gradient heterogeneity in alloy composition, recrystallization degree, product layer, and interfacial features along the normal direction (ND), thereby establishing a synergistic interplay to achieve a progressively increasing degradation profile. The MZM was fabricated by stacking a series of Mg-Zn alloys with a symmetric gradient in Zn concentration (0, 2, 4, 6, 4, 2, 0 wt%) through two-pass hot rolling at nearly 400 °C, followed by quenching. The MZM alloy exhibited a low in vivo degradation rate of 0.054 ± 0.0062 mm/year, followed by an increasing rate (0.180 ± 0.003 mm/year), all within a biosafe range. This study offers important insights and provides a scientific basis for the development of next-generation biodegradable metallic materials.

Infectious bone defects pose a major clinical challenge due to persistent bacterial biofilms and dysregulated immune responses. To address these limitations, we developed an antibiotic-free bone cement by incorporating nano-magnesium oxide (Nano-MgO) into polymethylmethacrylate (PMMA), enabling simultaneous antibacterial action and immunomodulation. The Nano-MgO/PMMA bone cements demonstrated an optimal 10% increase in strength and sustained Mg2+ release (highest 2.6 mg/L with 25% MgO addition after 14 days of immersion in Hank's solution). A biphasic regulatory mechanism was identified. In the early phase, Nano-MgO promoted intracellular reactive oxygen species (ROS) production in macrophages, contributing to membrane-disruptive antibacterial activity and supporting M1-associated immune responses involved in biofilm clearance. In the later phase, the gradual release of Mg2+ facilitated macrophage M2 polarization, promoting inflammation resolution and tissue repair. These effects were validated through in vitro antibacterial and immunomodulatory assays, and further confirmed in vivo assessments using subcutaneous infection and rat femoral condyle defect models. Single-cell RNA sequencing of the peri-implant immune microenvironment revealed a time-dependent shift in inflammatory pathways, underscoring the material's dynamic immunoregulatory capacity. Collectively, Nano-MgO/PMMA represents a promising antibiotic-free strategy for managing infectious bone defects by integrating effective infection control with immune-guided tissue regeneration.

Natural protein condensates respond to external stresses through stimuli-triggered multistage phase transitions. Reprogramming such transitions in synthetic systems is critical for rational design of self-adaptive materials with precisely regulated stimuli-responsiveness. Nevertheless, the sequence complexity of intrinsically disordered proteins (IDPs) and their competing assembly pathways often impede effective programing of multistage transitions in physiological conditions. Here, a class of short peptide synthons (Mw≈1500 Dalton) is synthesized by integrating intrinsically disordered and transiently ordered motifs derived from the low-complexity domain of IDPs. Remarkably, these peptide synthons exhibit thermoreversible quadruple phase transitions among monomers, self-coacervates, liquid crystals, and semi-crystallized solid gels. Mechanistic study reveals that the phase transitions are governed by two distinct assembly pathways, namely coacervation and fibrillization, which interact in both collaborative and competitive manners. Modifying the peptide sequence or molecular decorations allows for precise control over the phase transition temperatures, enabling sequential, multi-stage transitions to be activated by dose-dependent pathological cues (e.g., lactic acid) at the body temperature (37°C). These findings establish a highly versatile and programmable material platform to sequentially encode multistage phase behaviors into synthetic peptide assemblies, inspiring the development of next-generation disease biosensors, drug-delivery vehicles, and self-adaptive microrobots.

Modifying grain boundaries (GBs) and interfacial structures is a classic and critical strategy for altering the properties of metallic materials. Controlling grain boundaries can significantly improve the mechanical properties, corrosion resistance, and biocompatibility of biodegradable magnesium (Mg) alloys. However, the complex microstructural changes that occur during grain refinement have led to conflicting research findings regarding how GBs influence the corrosion resistance of Mg alloys. Guided by the concept of material plainification and drawing on established microstructural design principles for industrial Mg alloys, this study systematically analyzes the positive and negative roles of grain boundaries, while separately evaluating the effects of accompanying factors, including texture, twins, dislocations, and secondary phases. By integrating these factors, this research proposes a dialectical framework that elucidates how various microstructural factors influence the degradation of Mg alloys during grain refinement. This study not only provides a theoretical basis for resolving the controversy regarding grain refinement and corrosion in biodegradable Mg alloys but also offers a novel approach and practical guidance for designing high-performance, simplified-composition medical Mg alloys based on industrial experience.

ABSTRACT Epidermal bioelectronics is a transformative technology for continuous health monitoring and human‐computer interaction. However, the mechanical and physiological mismatch at the skin–device interface limits its long‐term application. Electrospun nanofiber membranes (ENMs), with their unique three‐dimensional hierarchical porous network and bionic structure, provide an ideal solution for constructing high‐performance epidermal interfaces. This review systematically summarizes the latest progress of electrospun nanofiber epidermal electrodes (ENEEs) in the field of electrophysiological monitoring: First, it elaborates on the material selection and structural design strategies of conductive nanofiber membranes, and then analyzes the role of nanofibers in reducing interface impedance and suppressing motion artifacts. This review details the functional evolution of ENEEs from conformal interface to multimodal closed‐loop systems, and their applications in high‐fidelity monitoring, such as electrocardiography (ECG), electromyography (EMG)/motor nerve conduction velocity (MCV), electroencephalography (EEG)/evoked potentials (EP), electrooculography (EOG), universal electrophysiological monitoring platforms, and multimodal integrated electrophysiological–physical–biochemical sensing systems, and discusses cross‐modal signal decoupling strategies. Finally, we discuss the future development directions of ENEEs and the key challenges faced in moving from the laboratory to commercialization, providing a comprehensive roadmap for the next generation of fiber‐based intelligent second skin.

In the frontier of clinical translation of biodegradable magnesium (Mg), most researchers have found cavities between bone tissue and Mg-based implants. Nevertheless, the biochemical origin driving the formation of these cavities remains unknown. Here we propose that the cavities are formed as a consequence of bone resorption induced by macrophage-mediated uptake of insoluble particles produced by magnesium degradation. To verify this possibility, we collected insoluble degradation particles (DPs) of high-purity magnesium (HP-Mg) and investigated their influences on the osteoclast formation, polarization, and osteoclast bone resorption in vitro and in vivo. It was demonstrated that DPs could induce bone resorption. The DPs promoted the activation of both nuclear factor-kappa-light-chain enhancer of activated B cells (NF-kappa B) and mitogen-activated protein kinase (MAPK) signaling pathways and upregulated the expression of osteoclast-specific genes and proteins. These results confirm that the presence of DPs could induce bone resorption both in vitro and in vivo, providing a possible mechanism for forming cavities around Mg-based implants.

Due to its excellent biocompatibility and biodegradability, Mg has received widespread attention in biomaterials as implants and even bio-batteries. However, the poor corrosion resistance makes it difficult to meet the growing demand for implant materials. This study developed a biodegradable nano-heterogeneous Mg(48 wt%)Zn(52 wt%)-based metal (NHMZ) comprising nanocrystalline matrix phase Mg51Zn20 and nanoscale MgZn2 precipitates. The unique microstructure of NHMZ enhances its corrosion resistance. The spherical aberration-corrected transmission electron microscope (AC-TEM) and precession electron diffraction (PED) characterized the microstructures. The corrosion rate of NHMZ is about 0.21 mm y−1 after soaking for 4 weeks, approximately 58 % of high pure Mg. In addition, the anode discharge of NHMZ is more stable than Mg, indicating it has great potential in biological batteries. This work hopes to broaden the development direction of biodegradable metallic materials and break through the performance limitation of current biodegradable Mg alloys.

Magnesium and its alloys have been initially applied to biliary tract surgery. Currently, few reports on the degradation behavior of magnesium in the bile environment were investigated. Thus, in-depth research on the degradation behavior of Mg and its alloys in bile is beneficial to the further application of Mg in biliary tract surgery. In this study, the degradation behavior of HP-Mg (HPM) and Mg-2 wt.%Zn (MZ2) alloys in human bile and Hanks balanced salt solution (HBSS) was systematically investigated. The MZ2 alloy biliary stent was implanted into the porcine common bile duct to study the degradation behavior of MZ2 alloy in vivo, and to verify the biosafety of MZ2 alloys degradation in the bile duct. It was found that the degradation product layer formed by MZ2 alloys in bile consisted of three layers, including organic matter (fatty acid, etc.), calcium and magnesium phosphate, and Mg(OH)2/MgO, respectively from the outside to the inside. The multi-layered degradation product layer slowed down the corrosion of the Mg matrix. During the 21 days of stent implantation, the degradation rate of the MZ2 stent was about 0.83 mm/y, there was no blockage and stenosis of the tube diameter, and the bile drainage function was normal.

The commonly used closing clips do not fully meet clinical requirements. For instance, non-degradable titanium and plastic clips remain in the body permanently, resulting in tissue lesions due to prolonged stimulation of the surrounding tissues, and degradable polymer clips typically possess weak mechanical properties and may produce irritating degradation products. In this work, we report a promising, multifunctional, and degradable high-purity magnesium (HP-Mg) closing clip to conquer the limitations of existing clinical closing clips. The HP-Mg closing clips possess enhanced clamping capabilities, effectively avoiding hemorrhage, tissue fluid leakage, clip loosening and slipping, as well as complete degradability within approximately 360 days in vivo, mitigating the risk of permanent foreign body retention. The Mg2+ released from HP-Mg clips significantly promotes collagen synthesis in vascular smooth muscle, accelerating wound healing. Moreover, Mg2+ and H2 released from the HP-Mg clips significantly induce the apoptosis of tumor cells. In vivo mouse, rat, and minipig models validate that the degradation products of HP-Mg clips are absorbed and metabolized by tissues, and do not cause Mg2+ or H2 accumulation in major organs, pH value deviation of local tissues, severe local and systemic inflammation reactions, or artifacts in an imaging test. The self-developed biodegradable Mg closing clip received NMPA approval for marketing as a Class III medical device in 2023. The biodegradable HP-Mg closing clips offer a promising alternative to current clinical closing clips for the tubular tissues that do not require permanent closure force in laparoscopic surgery. STATEMENT OF SIGNIFICANCE: 1. We designed a biodegradable high-purity magnesium (HP-Mg) closing clip for laparoscopic surgery. It shows effective closure, complete biodegradability in vivo, no adverse reactions, and multiple biofunctions. 2. HP-Mg clips overcome limitations of current clips: non-degradable clips may cause tissue lesions, while degradable polymer clips possess weak mechanical properties and may release irritants. 3. The released Mg2+ promotes collagen synthesis, accelerating wound healing. The released Mg2+ and H2 also induce tumor cell apoptosis. 4. HP-Mg clip was issued as an innovative medical device (Innovation No.: 201,800,018) by China's NMPA in 2018 and approved for marketing (License No.: 20,233,021,931) as a Class III medical device in 2023. It is China's first bio-Mg implant and the world's first biodegradable Mg closing clip.

Metallic cardiovascular stents are crucial for preventing atherosclerosis-induced infarction by offering mechanical support. However, the effects of metal ions released from these stents on atherosclerosis remain ambiguous. This study evaluates the potential impact posed by the degradation products of magnesium-based stents, with a focus on ferroptosis, a key mechanism driving atherosclerosis. Remarkably, our results demonstrate that Mg effectively inhibits ferroptosis in human umbilical vein endothelial cells and in murine, rat and rabbit models. Our studies reveal that magnesium ions impede the dephosphorylation of ERK proteins, thereby enhancing the expression of SLC7A11 and GCL proteins via activation of the MAPK pathway mechanistically. Additionally, magnesium ions downregulate ACSL4 protein expression, leading to decreased levels of acyl-CoA and ether-phospholipids. Eventually, multiple animal experiments indicate that biodegradable Mg stents can inhibit ferroptosis and decelerate the progression of arteriosclerosis, highlighting the therapeutic potential of Mg stents in treating arteriosclerosis.

Magnesium(Mg)alloys are promising candidates for biodegradable implants and medical devices due to their bio-compatibility,mechanical properties,and ability to degrade in vivo,thereby eliminating the need for secondary removal surgeries[1,2].

Biodegradable magnesium (Mg) materials offer significant advantages in trauma care due to their degradable nature and superior mechanical properties. This study reports the first successful use of degradable Mg clips in damage control surgery for pelvic fractures, addressing challenges associated with severe hemorrhage and high mortality rates (30–70%). A 57-year-old male patient with pelvic fractures and traumatic shock underwent open reduction and internal fixation with Mg clips. At a six-month follow-up, imaging confirmed fracture healing, clip degradation, and no signs of rebleeding or infection, highlighting their effectiveness in precise hemorrhage control. Unlike traditional titanium clips, Mg clips degrade over time, eliminating the need for removal and reducing infection risks. This innovative approach combines Mg clips with conventional gauze packing, offering a more effective and safer alternative for managing pelvic trauma. Future large-scale clinical trials are necessary to validate these findings and establish Mg clips as a global standard for pelvic fracture treatment. Their portability and functionality hold promise for advancing emergency trauma care.

This study evaluates a novel biodegradable magnesium (Mg) mesh for abdominal wall repair. Current synthetic meshes present clinical limitations, while Mg alloys offer favorable mechanical properties and biodegradability that remain underexplored. The Mg mesh was characterized through tensile/burst testing and finite element analysis, demonstrating sufficient strength (initial: 167.2 ± 5.9 N/cm; 1 month: 55.9 ± 1.6 N/cm) to withstand tensile breaking strength of abdominal wall (16 N/cm). Degradation studies revealed faster rates in simulated body fluid (2.62 mm/year) versus Hanks' solution (1.14 mm/year), with 60% structural integrity maintained after 8 weeks in vivo. Biocompatibility assessment using human skin fibroblasts showed >60% viability (Grade 0-1 cytotoxicity) across extract concentrations, with 60% concentration enhancing proliferation. In rat abdominal wall defect models, the Mg mesh exhibited superior performance to polypropylene meshes, demonstrating reduced foreign body reaction and upregulated collagen III/V expression. Proteomic analysis (TMT), PCR, and Western blot confirmed enhanced wound healing mechanisms. The mesh maintained tight tissue integration throughout degradation while providing mechanical support matching physiological demands. These findings collectively indicate that the biodegradable Mg mesh combines: (1) appropriate time-dependent mechanical properties, (2) controlled degradation matching tissue regeneration timelines, (3) excellent cytocompatibility with pro-proliferative effects, and (4) improved healing outcomes compared to standard polypropylene meshes. The results support its potential as a next-generation material for abdominal wall reconstruction, addressing key limitations of permanent synthetic meshes through its optimal balance of biomechanical performance and bioresorbability. Further clinical studies are warranted to validate these promising preclinical outcomes.

Biodegradable magnesium (Mg)-based metals can undergo spontaneous corrosion and full degradation in the human body, releasing magnesium ions, hydroxides, and hydrogen. Mg and its alloys have shown preliminary success as an implantable biomaterial. Current research on biodegradable Mg-based metals addresses clinical challenges, including material design and preparation, property enhancement, and exploring relevant biological functions. This review provides a comprehensive overview of the biomedical applications of Mg-based implants across eight fields: cardiovascular, orthopedics, stomatology, general surgery, neurosurgery, fat metabolism, and other potential areas, building upon previously published work. The challenges and prospects of biodegradable Mg-based implants in these application fields are discussed.

Neurosurgery is a clinical discipline that employs surgical and interventional approaches to diagnose and treat neurological disorders. Cranioplasty, a crucial neurosurgical procedure for repairing calvarial defects, relies heavily on the selection of implant material, which directly impacts functional recovery, cosmetic outcomes, and long-term patient prognosis. Various defects constrain conventional cranioplasty materials, whereas biodegradable magnesium alloys have demonstrated transformative potential in neurosurgery due to their biocompatibility, biodegradability, and osteogenic/angiogenic properties. However, rapid degradation and inadequate mechanical performance limit its further application. This study addresses these limitations through heterostructured engineering in Mg-Zn alloys. In vitro and in vivo evaluations revealed that the heterostructured Mg-1.25Zn exhibits biocompatibility, immunomodulatory properties, and a dual capacity to enhance osseous regeneration and meningeal functional restoration. These findings signify a shift in material design that transitions from mere anatomical closure to functional reconstruction, exploring synergistic calvarial-meningeal repair strategies to tailor to the needs of complex clinical scenarios. With ongoing material optimisation and future clinical validation, the heterostructured Mg-1.25Zn holds promise as a paradigmatic material for next-generation calvarial defect repair, bridging the gap between structural restoration and holistic neurological recovery.

Over the last decade, due to the disadvantages of conventional implant materials in skull bone defects, there has been a high demand for alternative biodegradable materials. As a typical biodegradable metal, magnesium (Mg) and its alloy have been successfully researched in various fields and applied in clinical in recent years, but none of them are about osteointegration, especially in cranioplasty. This study aims to explore the effect of Mg-based alloy skull repairment (MASR) on bone healing for the first time. The results verify that the high pure magnesium (HPM) and Mg-2 wt% Zn alloys can promote skull bone repair and induce the M2-like polarization of macrophages. Meanwhile, we also confirmed the pro-osteogenic function of induced M2-like macrophages on the bone marrow stem cells. Moreover, due to the close interaction of MASR and intracranial microenvironment, we clarified its immune regulatory function and underlying mechanisms on the microglia. The Mg-2Zn alloy presented a lower degradation rate, greater mechanical strength, and less influence on bone structure, and the MASR may serve as a potential clinical approach.

Fabrication of mineralized materials through the nature-mimicking dynamic biomineralization process has attracted great interest but remains a huge challenge till now. Here, a drug-mineralized hydrogel (DMH) with spontaneous dynamic mineralization behaviors is reported, which highly mimics the dynamic mineralization process of natural tissues. The hydrogel is facilely fabricated via directly mixing sodium hyaluronate (HA) with alendronate sodium (ADA) and CaCl2 in deionized water. The resultant hydrogel possesses a white-to-semi-transparent transition and a soft-to-hard transition during incubation at 37 degrees C. Mechanism studies reveal that the spontaneous dynamic change of the hydrogel is ascribed to the HA-regulated dynamic mineralization of ADA/Ca2+ complexes, where amorphous ADA/Ca2+ complexes will gradually transform into mineral crystals with the prolongation of incubation time. Owing to the dynamic transformation process, the DMH shows excellent injectability and moldability at the initial stage. More importantly, the DMH exhibits a sustained release behavior of ADA in vitro, superior adhesiveness with bone, biodegradability, and good biocompatibility. As a result, the developed DMH demonstrates promising uses for accelerating bone repair in a rat cranial defect model. Overall, the research provides a general strategy to prepare drug-mineralized hydrogels with spontaneous dynamic mineralization behaviors, which may find potential uses in various biomedical fields. The drug-mineralized hydrogel (DMH) is prepared by simple mixing of alendronate sodium (ADA), Ca2+, and sodium hyaluronate (HA). The obtained hydrogel undergoes a spontaneous dynamic mineralization process characterized by a phase transformation from loosely amorphous to densely mineral structure and an in situ mechanical reinforcement property. The resultant DMH shows sustained release of ADA drug and promising use for accelerating bone repair.image

M2 macrophages promote adipose tissue thermogenesis which dissipates energy in the form of heat to combat obesity. However, the regulation of M2 macrophages by thermogenic adipocytes is unclear. Here, it is identified magnesium (Mg) as a thermogenic adipocyte-secreted factor to promote M2 macrophage polarization. Mg transporter Cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) induced by ADRB3-PKA-CREB signaling in thermogenic adipocytes during cold exposure mediates Mg efflux and Mg in turn binds to the DFG motif in mTOR to facilitate mTORC2 activation and M2 polarization in macrophages. In obesity, downregulation of CNNM4 expression inhibits Mg secretion from thermogenic adipocytes, which leads to decreased M2 macrophage polarization and thermogenesis. As a result, CNNM4 overexpression in adipocytes or Mg supplementation in adipose tissue ameliorates obesity by promoting thermogenesis. Importantly, an Mg wire implantation (AMI) approach is introduced to achieve adipose tissue-specific long-term Mg supplement. AMI promotes M2 macrophage polarization and thermogenesis and ameliorates obesity in mice. Taken together, a reciprocal regulation of thermogenic adipocytes and M2 macrophages important for thermogenesis is identified, and AMI is offered as a promising strategy against obesity.