Biomaterials science and surface engineering strategies for dental peri-implantitis management.

Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.

Coatless modification of 3D-printed Ti6Al4V implants through tailored Cu ion implantation combined with UV photofunctionalization to enhance cell attachment, osteogenesis and angiogenesis.

The three-dimensional-printed Ti6Al4V implant (3DTi) has been widely accepted for the reconstruction of massive bone defects in orthopedics owing to several advantages, such as its tailored shape design, avoiding bone graft and superior bone-implant interlock. However, the osteoinduction activity of 3DTi is inadequate when applied clinically even though it exhibits osteoconduction. This study developes a comprehensive coatless strategy for the surface improvement of 3DTi through copper (Cu) ion implantation and ultraviolet (UV) photofunctionalization to enhance osteoinductivity. The newly constructed functional 3DTi (UV/Ti-Cu) achieved stable and controllable Cu doping, sustained Cu2+ releasing, and increased surface hydrophilicity. By performing cellular experiments, we determined that the safe dose range of Cu ion implantation was less than 5×1016 ions/cm2. The implanted Cu2+ enhanced the ALP activity and the apatite formation ability of bone marrow stromal cells (BMSCs) while slightly decreasing proliferation ability. When combined with UV photofunctionalization, cell adhesion and proliferation were significantly promoted and bone mineralization was further increased. Meanwhile, UV/Ti-Cu was conducive to the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro, theoretically facilitating vascular coupling osteogenesis. In conclusion, UV/Ti-Cu is a novel attempt to apply two coatless techniques for the surface modification of 3DTi. In addition, it is considered a potential bone substrate for repairing bone defects.

Composited silk fibroins ensured adhesion stability and magnetic controllability of Fe3O4-nanoparticle coating on implant for biofilm treatment.

Magnetic propulsion of nano-/micro-robots is an effective way to treat implant-associated infections by physically destroying biofilm structures to enhance antibiotic killing. However, it is hard to precisely control the propulsion in vivo. Magnetic-nanoparticle coating that can be magnetically pulled off does not need precise control, but the requirement of adhesion stability on an implant surface restricts its magnetic responsiveness. Moreover, whether the coating has been fully pulled-off or not is hard to ensure in real-time in vivo. Herein, composited silk fibroins (SFMA) are optimized to stabilize Fe3O4 nanoparticles on a titanium surface in a dry environment; while in an aqueous environment, the binding force of SFMA on titanium is significantly reduced due to hydrophilic interaction, making the coating magnetically controllable by an externally-used magnet but still stable in the absence of a magnet. The maximum working distance of the magnet can be calculated using magnetomechanical simulation in which the yielding magnetic traction force is strong enough to pull Fe3O4 nanoparticles off the surface. The pulling-off removes the biofilms that formed on the coating and enhances antibiotic killing both in vitro and in a rat sub-cutaneous implant model by up to 100 fold. This work contributes to the practical knowledge of magnetic propulsion for biofilm treatment.

Multiscale architecture design of 3D printed biodegradable Zn-based porous scaffolds for immunomodulatory osteogenesis.

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.

Effects of MgO nanoparticle addition on the mechanical properties, degradation properties, antibacterial properties and in vitro and in vivo biological properties of 3D-printed Zn scaffolds.

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.

Dual elemental doping activated signaling pathway of angiogenesis and defective heterojunction engineering for effective therapy of MRSA-infected wounds.

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.

Ca-doping interfacial engineering and glycolysis enable rapid charge separation for efficient phototherapy of MRSA-infected wounds.

Methicillin-resistant Staphylococcus aureus (MRSA) is the primary pathogenic agent responsible for epidermal wound infection and suppuration, seriously threatening the life and health of human beings. To address this fundamental challenge, we propose a heterojunction nanocomposite (Ca-CN/MnS) comprised of Ca-doped g-C3N4 and MnS for the therapy of MRSA-accompanied wounds. The Ca doping leads to a reduction in both the bandgap and the singlet state S1-triplet state T2 energy gap (ΔEST). The Ca doping also facilitates the two-photon excitation, thus remarkably promoting the separation and transfer of 808 nm near-infrared (NIR) light-triggered electron-hole pairs together with the built-in electric field. Thereby, the production of reactive oxygen species and heat are substantially augmented nearby the nanocomposite under 808 nm NIR light irradiation. Consequently, an impressive photocatalytic MRSA bactericidal efficiency of 99.98 ± 0.02 % is achieved following exposure to NIR light for 20 min. The introduction of biologically functional elements (Ca and Mn) can up-regulate proteins such as pyruvate kinase (PKM), L-lactate dehydrogenase (LDHA), and calcium/calmodulin-dependent protein kinase (CAMKII), trigger the glycolysis and calcium signaling pathway, promote cell proliferation, cellular metabolism, and angiogenesis, thereby expediting the wound-healing process. This heterojunction nanocomposite, with its precise charge-transfer pathway, represents a highly effective bactericidal and bioactive system for treating multidrug-resistant bacterial infections and accelerating tissue repair. STATEMENT OF SIGNIFICANCE: Due to the bacterial resistance, developing an antibiotic-free and highly effective bactericidal strategy to treat bacteria-infected wounds is critical. We have designed a heterojunction consisting of calcium doped g-C3N4 and MnS (Ca-CN/MnS) that can rapidly kill methicillin-resistant Staphylococcus aureus (MRSA) without damaging normal tissue through a synergistic effect of two-photon stimulated photothermal and photodynamic therapy. In addition, the release of trace amounts of biofunctional elements Mn and Ca triggers glycolysis and calcium signaling pathways that promote cellular metabolism and cell proliferation, contributing to tissue repair and wound healing.

Combination of disulfiram and Copper-Cysteamine nanoparticles induces mitochondria damage and promotes apoptosis in endometrial cancer.

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[bond, double bond]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.

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

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

Electron Aggregation and Oxygen Fixation Reinforced Microwave Dynamic and Thermal Therapy for Effective Treatment of MRSA-Induced Osteomyelitis.

Antibiotics are frequently used to clinically treat osteomyelitis caused by bacterial infections. However, extended antibiotic use may result in drug resistance, which can be life threatening. Here, a heterojunction comprising Fe2 O3 /Fe3 S4 magnetic composite is constructed to achieve short-term and efficient treat osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). The Fe2 O3 /Fe3 S4 composite exhibits powerful microwave (MW) absorption properties, thereby effectively converting incident electromagnetic energy into thermal energy. Density functional theory calculations demonstrate that Fe2 O3 /Fe3 S4 possesses significant charge accumulation and oxygen-fixing capacity at the heterogeneous interface, which provides more active sites and oxygen sources for trapping electromagnetic hotspots. The finite element analysis indicates that Fe2 O3 /Fe3 S4 displays a larger electromagnetism field enhancement parameter than Fe2 O3 owing to a significant increase in electromagnetic hotspots. These hotspots contribute to charge differential accumulation and depletion motions at the interface, thereby augmenting the release of free electrons that subsequently combine with the oxygen adsorbed by Fe2 O3 /Fe3 S4 to generate reactive oxygen species (ROS) and heat. This research, which achieves extraordinary bacterial eradication through the synergistic effect of microwave thermal therapy (MWTT) and microwave dynamic therapy (MDT), presents a novel strategy for treating deep-tissue bacterial infections.

Near-infrared light responsive gold nanoparticles coating endows polyetheretherketone with enhanced osseointegration and antibacterial properties.

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.

Structural and temporal dynamics analysis of zinc-based biomaterials: History, research hotspots and emerging trends.

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.

Fabrication of a Nanoscale Magnesium/Copper Metal-Organic Framework on Zn-Based Guided Bone Generation Membranes for Enhancing Osteogenesis, Angiogenesis, and Bacteriostasis Properties.

Recently, zinc (Zn) and its alloys have demonstrated great potential as guided bone regeneration (GBR) membranes to treat the problems of insufficient alveolar bone volume and long-term osseointegration instability during dental implantology. However, bone regeneration is a complex process consisting of osteogenesis, angiogenesis, and antibacterial function. For now, the in vivo osteogenic performance and antibacterial activity of pure Zn are inadequate, and thus fabricating a platform to endow Zn membranes with multifunctions may be essential to address these issues. In this study, various bimetallic magnesium/copper metal-organic framework (Mg/Cu-MOF) coatings were fabricated and immobilized on pure Zn. The results indicated that the degradation rate and water stability of Mg/Cu-MOF coatings could be regulated by controlling the feeding ratio of Cu2+. As the coating and Zn substrate degraded, an alkaline microenvironment enriched with Zn2+, Mg2+, and Cu2+ was generated. It significantly improved calcium phosphate deposition, differentiation of osteoblasts, and vascularization of endothelial cells in the extracts. Among them, Mg/Cu1 showed the best comprehensive performance. The superior antibacterial activity of Mg/Cu1 was demonstrated in vitro and in vivo, which indicated significantly enhanced bacteriostatic activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli as compared to that of the bare sample. Bimetallic Mg/Cu-MOF coating could properly coordinate the multifunction on a Zn membrane and could be a promising platform for promoting its bone regeneration, which could pave the way for Zn-based materials to be used as barrier membranes in oral clinical trials.

Erratum: Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects.

[This corrects the article DOI: 10.1016/j.bioactmat.2023.11.001.].

Natural Extracts for Antibacterial Applications.

Bacteria-induced epidemics and infectious diseases are seriously threatening the health of people around the world. In addition, antibiotic therapy has been inducing increasingly more serious bacterial resistance, which makes it urgent to develop new treatment strategies to combat bacteria, including multidrug-resistant bacteria. Natural extracts displaying antibacterial activity and good biocompatibility have attracted much attention due to greater concerns about the safety of synthetic chemicals and emerging drug resistance. These antibacterial components can be isolated and utilized as antimicrobials, as well as transformed, combined, or wrapped with other substances by using modern assistive technologies to fight bacteria synergistically. This review summarizes recent advances in natural extracts from three kinds of sources-plants, animals, and microorganisms-for antibacterial applications. This work discusses the corresponding antibacterial mechanisms and the future development of natural extracts in antibacterial fields.

Instant Protection Spray for Anti-Infection and Accelerated Healing of Empyrosis.

Distinct from common injuries, deep burns often require a chronic recovery cycle for healing and long-term antibiotic treatment to prevent infection. The rise of drug-resistant bacteria has caused antibiotics to no longer be perfect, and continuous drug use can easily lead to repeated infection and even death. Inspired by wild animals that chew plants to prevent wound infection, probiotic extracts with a structure similar to the tailspike of phage are obtained from Lactobacillus casei and combined with different flavones to design a series of nonantibiotic bactericides. These novel antibacterial agents are combined with a rapid gelation spray with a novel cross-angle layout to form an instant protection spray (IPS) and provide a physical and anti-infectious barrier for burns within 30 s. This IPS is able to sterilize 100.00% and 96.14% of multidrug-resistant Staphylococcus aureus (MRSA) in vitro and in vivo, respectively. In addition, it is found to effectively reduce inflammation in MRSA-infected burns in rats and to promote tissue healing.

Zeolite imidazolate framework-8 in bone regeneration: A systematic review.

Zeolite imidazolate framework-8 (ZIF-8) is a biomaterial that has been increasingly studied in recent years. It has several applications such as bone regeneration, promotion of angiogenesis, drug loading, and antibacterial activity, and exerts multiple effects to deal with various problems in the process of bone regeneration. This systematic review aims to provide an overview of the applications and effectiveness of ZIF-8 in bone regeneration. A search of papers published in the PubMed, Web of Science, Embase, and Cochrane Library databases revealed 532 relevant studies. Title, abstract, and full-text screening resulted in 39 papers being included in the review, including 39 in vitro and 22 animal studies. Appropriate concentrations of nano ZIF-8 can promote cell proliferation and osteogenic differentiation by releasing Zn2+ and entering the cell, whereas high doses of ZIF-8 are cytotoxic and inhibit osteogenic differentiation. In addition, five studies confirmed that ZIF-8 exhibits good vasogenic activity. In all in vivo experiments, nano ZIF-8 promoted bone formation. These results indicate that, at appropriate concentrations, materials containing ZIF-8 promote bone regeneration more than materials without ZIF-8, and with characteristics such as promoting angiogenesis, drug loading, and antibacterial activity, it is expected to show promising applications in the field of bone regeneration. STATEMENT OF SIGNIFICANCE: This manuscript reviewed the use of ZIF-8 in bone regeneration, clarified the biocompatibility and effectiveness in promoting bone regeneration of ZIF-8 materials, and discussed the possible mechanisms and factors affecting its promotion of bone regeneration. Overall, this study provides a better understanding of the latest advances in the field of bone regeneration of ZIF-8, serves as a design guide, and contributes to the design of future experimental studies.

A Smart Bacteria-Capture-Killing Vector for Effectively Treating Osteomyelitis Through Synergy Under Microwave Therapy.

Osteomyelitis caused by deep tissue infections is difficult to cure through phototherapy due to the poor penetration depth of the light. Herein, Cu/C/Fe3O4-COOH nanorod composites (Cu/C/Fe3O4-COOH) with nanoscale tip convex structures are successfully fabricated as a microwave-responsive smart bacteria-capture-killing vector. Cu/C/Fe3O4-COOH exhibited excellent magnetic targeting and bacteria-capturing ability due to its magnetism and high selectivity affinity to the amino groups on the surface of Staphylococcus aureus (S. aureus). Under microwave irradiation, Cu/C/Fe3O4-COOH efficiently treated S. aureus-infected osteomyelitis through the synergistic effects of microwave thermal therapy, microwave dynamic therapy, and copper ion therapy. It is calculated the electric field intensity in various regions of Cu/C/Fe3O4-COOH under microwave irradiation, demonstrating that it obtained the highest electric field intensity on the surface of copper nanoparticles of Cu/C/Fe3O4-COOH due to its high-curvature tips and metallic properties. This led to copper nanoparticles attracted more charged particles compared with other areas in Cu/C/Fe3O4-COOH. These charges are easier to escape from the high curvature surface of Cu/C/Fe3O4-COOH, and captured by adsorbed oxygen, resulting in the generation of reactive oxygen species. The Cu/C/Fe3O4-COOH designed in this study is expected to provide insight into the treatment of deep tissue infections under the irradiation of microwave.

A Dose-Dependent Spatiotemporal Response of Angiogenesis Elicited by Zn Biodegradation during the Initial Stage of Bone Regeneration.

Zinc (Zn) plays a crucial role in bone metabolism and imbues biodegradable Zn-based materials with the ability to promote bone regeneration in bone trauma. However, the impact of Zn biodegradation on bone repair, particularly its influence on angiogenesis, remains unexplored. This study reveals that Zn biodegradation induces a consistent dose-dependent spatiotemporal response in angiogenesis,both in vivo and in vitro. In a critical bone defect model, an increase in Zn release intensity from day 3 to 10 post-surgery is observed. By day 10, the CD31-positive area around the Zn implant significantly surpasses that of the Ti implant, indicating enhanced angiogenesis. Furthermore,angiogenesis exhibits a distance-dependent pattern closely mirroring the distribution of Zn signals from the implant. In vitro experiments demonstrate that Zn extraction fosters the proliferation and migration of human umbilical vein endothelial cells and upregulates the key genes associated with tube formation, such as HIF-1α and VEGF-A, peaking at a concentration of 22.5 µM. Additionally, Zn concentrations within the range of 11.25-45 µM promote the polarization of M0-type macrophages toward the M2-type, while inhibiting polarization toward the M1-type. These findings provide essential insights into the biological effects of Zn on bone repair, shedding light on its potential applications.