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1
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Chen J, Li A, Dai J, Fu Q, Yu Z, Xu S, Zhang W, Li P. Optimal submicron roughness for balancing degradation behavior, immune modulation, and microbial adhesion on zinc-based barrier membranes. BIOMATERIALS ADVANCES 2025; 169:214146. [PMID: 39799898 DOI: 10.1016/j.bioadv.2024.214146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 11/29/2024] [Accepted: 12/06/2024] [Indexed: 01/15/2025]
Abstract
Metallic zinc (Zn) has been demonstrated to be a promising alternative to barrier membrane materials for guided bone regeneration. Surface roughness significantly affects the properties of degradable Zn-based metals, especially within the Janus micro-environments of tissue regeneration. However, the effects of optimal surface roughness on Zn remain unknown. In this study, pure Zn surfaces were fabricated with three roughness scales: nano (Sa < 0.1 μm), submicron (Sa: 0.5-1.0 μm), and micron (Sa > 1.0 μm). Submicron-scale pure Zn exhibited a moderate degradation rate in simulated body fluids, and no deep corrosion pits appeared on the surface. By contrast, the degradation rate of nano-surface pure Zn decreased significantly, while localized corrosion tended to appear on micron surfaces. In addition, the degradation rate of Zn with different roughness was overall accelerated in artificial saliva, accompanied by varying degradation morphologies. Co-culturing with submicron samples inhibited macrophage polarization to the M1 phenotype. Nano-scale surfaces promoted macrophage polarization towards the M1 phenotype and exhibited significantly reduced antibacterial rates compared to rougher surfaces. These findings demonstrate that submicron-scale pure Zn could be an optimal choice for barrier membrane surfaces.
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Affiliation(s)
- Jiahao Chen
- Center of Oral Implantology, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China
| | - An Li
- Department of Periodontology, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China
| | - Jingtao Dai
- Department of Orthodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, South Jiangnan Road No. 366, Guangzhou 510280, China
| | - Qingyun Fu
- Center of Oral Implantology, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China
| | - Zhentao Yu
- Institute of Advanced Wear & Corrosion Resistant and Functional Materials, Jinan University, Guangzhou 510632, China
| | - Shulan Xu
- Center of Oral Implantology, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China.
| | - Wentai Zhang
- Dongguan Key Laboratory of Smart Biomaterials and Regenerative Medicine, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, Guangdong 523000, China.
| | - Ping Li
- Department of Prosthodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Medical University, Guangzhou 510180, China; Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou 510180, China.
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2
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Qian Y, Chen Y, Jiang J, Pei J, Li J, Niu J, Zhu J, Yuan G. Biosafety and efficacy evaluation of a biodegradable Zn-Cu-Mn stent: A long-term study in porcine coronary artery. Bioact Mater 2025; 45:231-245. [PMID: 39654873 PMCID: PMC11626648 DOI: 10.1016/j.bioactmat.2024.11.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Revised: 11/17/2024] [Accepted: 11/17/2024] [Indexed: 12/12/2024] Open
Abstract
In this study, biodegradable Zn-Cu-Mn alloy stents were implanted into porcine coronary artery for 18 months, and the in vivo biosafety and efficacy as well as the degradation behavior were systematically studied. Results showed a rapid endothelialization of the target vessel was achieved at 1 month post-implantation. Although the lumen diameter loss and local inflammation were observed at the early stage, the stented blood vessel could gradually recover with time. The lumen diameter was already close to normal range at 12 months, indicating good bioefficacy of the stent. No adverse effect on blood indexes or local accumulation of Zn, Cu or Mn elements were found after implantation, neither the malapposition and thrombosis were observed, which exhibited good biosafety of the stents. The stent could maintain the basic structure and mechanical integrity at 6 months, and remained only approximately 26 % of the stent volume at 18 months, suggesting a desirable degradation rate. In general, the Zn-Cu-Mn alloy stent showed great advantages and prospects in clinical application.
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Affiliation(s)
- Yi Qian
- School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
- Department of Vascular & Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Yan Chen
- School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Jimiao Jiang
- School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Jia Pei
- School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Junfei Li
- Shanghai MicroPort Medical (Group) Co., Ltd, Shanghai, 201203, China
| | - Jialin Niu
- School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Jinzhou Zhu
- Department of Vascular & Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Guangyin Yuan
- School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
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3
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Dong C, Liao Z, Yin Y, Yi Y, Zhu G, Zheng T, Tan Q, Xie Y. Effects of Nanoscale precipitates on mechanical properties, corrosion resistance, and biocompatibility in Zn-Mn alloy. Sci Rep 2025; 15:5454. [PMID: 39953170 PMCID: PMC11829028 DOI: 10.1038/s41598-025-89748-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 02/07/2025] [Indexed: 02/17/2025] Open
Abstract
Controlling degradation rate is essential for the biomedical application of biodegradable Zn alloys. Alloying with soluble elements is an effective way to regulate formation of second phases, which differ in potential from the Zn matrix. The potential difference exhibits positive or negative effects on corrosion resistance. This study successfully forms MnZn13 phase with nano size by altering ECAP temperature. Subsequently, MnZn13 phase promotes grain refinement, improvement of elongation, and corrosion resistance. Higher elongation in Zn-Mn alloy with MnZn13 phase is attributed to the grain boundary sliding, deformation twins in MnZn13 phase. Meanwhile, grain boundary corrosion in Zn-Mn alloy with MnZn13 phase is incomplete. Corrosion mode of Zn-Mn alloys without MnZn13 phase is dominated by grain boundary corrosion, accompanied by pitting corrosion. The increased corrosion resistance from MnZn13 phase stems from its higher potential than Zn matrix. Zn-Mn alloys with and without MnZn13 phase show a comparable cytocompatibility and osteogenic properties. Our findings provide an effective way to regulating mechanical properties and corrosion resistance of Zn alloys via controlling precipitation.
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Affiliation(s)
- Cuilan Dong
- Nursing Department, Hunan Provincial Key Laboratory of Pediatric Orthopedics, Hunan Children's Hospital, Hunan, 410007, China
| | - Zikun Liao
- Department of Spine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China
| | - Yanyi Yin
- Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Yinzhi Yi
- Nursing Department, Hunan Provincial Key Laboratory of Pediatric Orthopedics, Hunan Children's Hospital, Hunan, 410007, China
| | - Guanghui Zhu
- Orthopedic Department, Hunan Provincial Key Laboratory of Pediatric Orthopedics, Hunan Children's Hospital, Hunan, 410007, China
| | - Tuquan Zheng
- Department of Spine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China
| | - Qian Tan
- Orthopedic Department, Hunan Provincial Key Laboratory of Pediatric Orthopedics, Hunan Children's Hospital, Hunan, 410007, China
| | - Yonghong Xie
- Orthopedic Department, Hunan Provincial Key Laboratory of Pediatric Orthopedics, Hunan Children's Hospital, Hunan, 410007, China.
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4
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Zhang T, Yu Y, Yuan W, Ren Z, Cheng Y, Wu S, Zheng Y, Xia D. Photothermally controlled ICG@ZIF-8/PLGA coating to modify the degradation behavior and biocompatibility of Zn-Li alloy for bone implants. Regen Biomater 2025; 12:rbaf001. [PMID: 40040751 PMCID: PMC11879299 DOI: 10.1093/rb/rbaf001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 12/17/2024] [Accepted: 12/27/2024] [Indexed: 03/06/2025] Open
Abstract
Biodegradable Zn alloy has recently gained attention for use in bone implants considering its biodegradability, attractive mechanical properties and bioactivity. However, excessive corrosion of Zn alloy at the early stage of implantation may cause severe cytotoxicity, resulting in insufficient osseointegration, which hinders the clinical use of Zn alloy. In this study, we designed a photothermally controlled degradative hybrid coating as a corrosion-protective barrier with the intention of preventing Zn ion burst release during the early stages of implantation and regaining the alloy's corrosion advantage later on. The coating consists of zeolite imidazole skeleton-encapsulated indocyanine green core-shell-structured nanoparticles and polylactic coglycolic acid (ICG@ZIF-8/PLGA) on pristine Zn-0.8 (wt.%) Li (ZL) alloy. The electrochemical test results indicated that coating ZL with ICG@ZIF-8/PLGA can effectively reduce its corrosion current density (icorr) from 2.48 × 10-5 A·cm-2 to 2.10 × 10-8 A·cm-2. After near-infrared (NIR) light irradiation, ICG@ZIF-8 heated PLGA coating to reach Tg, causing the coating to degrade and the icorr of the coated ZL alloy decreased to 2.50 × 10-7 A·cm-2, thus restoring corrosion advantage. Both in vitro and in vivo investigations showed that the coated ZL alloy had acceptable biocompatibility. Overall, the developed photothermally controlled coating improved the Zn alloy's resistance to corrosion and allowed for the adjustment of the Zn alloy's degradation rate through 808-nm NIR light irradiation.
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Affiliation(s)
- Ting Zhang
- Department of Dental Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, China
- National Center for Stomatology, Beijing, 100081, China
- National Clinical Research Center for Oral Diseases, Beijing, 100081, China
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, China
- Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, China
- NHC Key Laboratory of Digital Stomatology, Beijing, 100081, China
- NMPA Key Laboratory for Dental Materials, Beijing, 100081, China
- School of Materials Science and Engineering, Peking University, Beijing, 100871, China
| | - Yameng Yu
- Department of Dental Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, China
- National Center for Stomatology, Beijing, 100081, China
- National Clinical Research Center for Oral Diseases, Beijing, 100081, China
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, China
- Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, China
- NHC Key Laboratory of Digital Stomatology, Beijing, 100081, China
- NMPA Key Laboratory for Dental Materials, Beijing, 100081, China
| | - Wei Yuan
- School of Materials Science and Engineering, Peking University, Beijing, 100871, China
| | - Zeqi Ren
- School of Materials Science and Engineering, Peking University, Beijing, 100871, China
| | - Yan Cheng
- School of Materials Science and Engineering, Peking University, Beijing, 100871, China
| | - Shuilin Wu
- School of Materials Science and Engineering, Peking University, Beijing, 100871, China
| | - Yufeng Zheng
- School of Materials Science and Engineering, Peking University, Beijing, 100871, China
| | - Dandan Xia
- Department of Dental Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, China
- National Center for Stomatology, Beijing, 100081, China
- National Clinical Research Center for Oral Diseases, Beijing, 100081, China
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, China
- Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, China
- NHC Key Laboratory of Digital Stomatology, Beijing, 100081, China
- NMPA Key Laboratory for Dental Materials, Beijing, 100081, China
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5
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Su L, Liu W, Wang Y, Jiang Y, Li Z, Wang M, Liu G. Corrosion behavior, antibacterial properties and in vitro and in vivo biocompatibility of biodegradable Zn-5Cu-xMg alloy for bone-implant applications. BIOMATERIALS ADVANCES 2024; 165:214000. [PMID: 39208498 DOI: 10.1016/j.bioadv.2024.214000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 08/10/2024] [Accepted: 08/17/2024] [Indexed: 09/04/2024]
Abstract
Reasonable optimization of degradation rate, antibacterial performance and biocompatibility is crucial for the development of biodegradable zinc alloy medical implant devices with antibacterial properties. In this study, various amounts of Mg elements were incorporated into Zn5Cu alloy to modulate the degradation rate, antibacterial properties and biocompatibility. The effects of Mg contents on the microstructure, corrosion behavior, antibacterial properties and biocompatibility of Zn-5Cu-xMg alloy were extensively investigated. The results revealed that with an increase of Mg content, the amount of Mg2Zn11 phase increased and its galvanic effect with the Zn matrix was enhanced, which accelerated the corrosion process and led to higher corrosion rate and high degradation rate of the alloy. Additionally, there was an increased release of Mg2+ and Zn2+ ions from the alloy which imparted excellent resistance against Escherichia coli and Staphylococcus aureus bacteria and improved biocompatibility, subcutaneous antibacterial and immune microenvironment regulation properties. Zn-5Cu-2 Mg exhibited superior antibacterial ability, cell compatibility, proliferation effect, subcutaneous antibacterial and immune microenvironment regulation performances, which can work as a promising candidate of biodegradable antibacterial medical implants.
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Affiliation(s)
- Lin Su
- School of Materials Science and Engineering, Central South University, Changsha 410083, China
| | - Wenbin Liu
- Department of Orthopaedics, The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha 410008, China; Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Changsha, China
| | - Yanggang Wang
- School of Materials Science and Engineering, Central South University, Changsha 410083, China
| | - Yanbin Jiang
- School of Materials Science and Engineering, Central South University, Changsha 410083, China; State Key Lab for Powder Metallurgy, Central South University, Changsha 410083, China.
| | - Zhou Li
- School of Materials Science and Engineering, Central South University, Changsha 410083, China; State Key Lab for Powder Metallurgy, Central South University, Changsha 410083, China
| | - Meng Wang
- School of Materials Science and Engineering, Central South University, Changsha 410083, China
| | - Gengyan Liu
- Department of Orthopaedics, The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha 410008, China.
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6
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Li XM, Shi ZZ, Tuoliken A, Gou W, Li CH, Wang LN. Highly plastic Zn-0.3Ca alloy for guided bone regeneration membrane: Breaking the trade-off between antibacterial ability and biocompatibility. Bioact Mater 2024; 42:550-572. [PMID: 39308544 PMCID: PMC11416609 DOI: 10.1016/j.bioactmat.2024.08.049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 07/21/2024] [Accepted: 08/31/2024] [Indexed: 09/25/2024] Open
Abstract
A common problem for Zn alloys is the trade-off between antibacterial ability and biocompatibility. This paper proposes a strategy to solve this problem by increasing release ratio of Ca2+ ions, which is realized by significant refinement of CaZn13 particles through bottom circulating water-cooled casting (BCWC) and rolling. Compared with conventionally fabricated Zn-0.3Ca alloy, the BCWC-rolled alloy shows higher antibacterial abilities against E. coli and S. aureus, meanwhile much less toxicity to MC3T3-E1 cells. Additionally, plasticity, degradation uniformity, and ability to induce osteogenic differentiation in vitro of the alloy are improved. The elongation up to 49 %, which is the highest among Zn alloys with Ca, and is achieved since the sizes of CaZn13 particles and Zn grains are small and close. As a result, the long-standing problem of low formability of Zn alloys containing Ca has also been solved due to the elimination of large CaZn13 particles. The BCWC-rolled alloy is a promising candidate of making GBR membrane.
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Affiliation(s)
- Xiang-Min Li
- Beijing Advanced Innovation Center for Materials Genome Engineering, State Key Laboratory for Advance Metals and Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China
| | - Zhang-Zhi Shi
- Beijing Advanced Innovation Center for Materials Genome Engineering, State Key Laboratory for Advance Metals and Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China
- Institute of Materials Intelligent Technology, Liaoning Academy of Materials, Shenyang, 110004, China
| | - Ayisulu Tuoliken
- Beijing Advanced Innovation Center for Materials Genome Engineering, State Key Laboratory for Advance Metals and Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China
| | - Wei Gou
- Beijing Advanced Innovation Center for Materials Genome Engineering, State Key Laboratory for Advance Metals and Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China
| | - Chang-Heng Li
- Beijing Advanced Innovation Center for Materials Genome Engineering, State Key Laboratory for Advance Metals and Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China
| | - Lu-Ning Wang
- Beijing Advanced Innovation Center for Materials Genome Engineering, State Key Laboratory for Advance Metals and Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China
- Institute of Materials Intelligent Technology, Liaoning Academy of Materials, Shenyang, 110004, China
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7
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Liu J, Linsley CS, Su Y, Abd-Elaziem W, Pan S, Sokoluk M, Griebel A, Chen G, Zeng Y, Murali N, Bialo S, Jiang A, Wu BM, Zhu D, Li X. Nanoparticle-Enabled Zn-0.1Mg Alloy with Long-Term Stability, Refined Degradation, and Favorable Biocompatibility for Biodegradable Implant Devices. ACS APPLIED MATERIALS & INTERFACES 2024; 16:50125-50138. [PMID: 39284011 DOI: 10.1021/acsami.4c04714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/28/2024]
Abstract
Zinc-based alloys, specifically Zn-Mg, have garnered considerable attention as promising materials for biodegradable implants due to their favorable mechanical strength, appropriate corrosion rate, and biocompatibility. Nevertheless, the alloy's lack of mechanical stability and integrity, resulting from ductility loss induced by age hardening at room temperature, hampers its practical bioapplication. In this study, ceramic nanoparticles have been successfully incorporated into the Zn-Mg alloy system, leading to a significant improvement in long-term stability as well as mechanical strength and ductility. In addition, this study represents the first investigation of Zn-based nanocomposites both in vitro and in vivo to comprehend the influence of nanoparticles on the degradation behavior and biocompatibility of the Zn system. The findings indicate that the incorporation of WC nanoparticles effectively refines and stabilizes the degradation behavior of Zn-Mg without negatively impacting the cytocompatibility of the alloy. The subcutaneous implantation and femoral implantation further prove the benefits of nanoparticle incorporation and found no negative effects. Collectively, Zn-Mg-WC nanocomposites yield great potential for implant usage.
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Affiliation(s)
- Jingke Liu
- Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, California 90024, United States
- ZanoMed Inc, Los Angeles, California 90731, United States
| | - Chase S Linsley
- Department of Bioengineering, University of California, Los Angeles, California 90024, United States
| | - Yingchao Su
- Department of Biomedical Engineering, the State University of New York at Stony Brook, Stony Brook, New York 11794, United States
| | - Walaa Abd-Elaziem
- Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, California 90024, United States
- Department of Mechanical Design and Production Engineering, Faculty of Engineering, Zagazig University, Zagazig 44519, Egypt
| | - Shuaihang Pan
- Department of Mechanical and Aerospace Engineering, University of Utah, Salt Lake City, Utah 84112, United States
| | - Maximilian Sokoluk
- Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, California 90024, United States
- ZanoMed Inc, Los Angeles, California 90731, United States
| | - Adam Griebel
- Fort Wayne Metals, Fort Wayne, Indiana 46809, United States
| | - Guancheng Chen
- Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, California 90024, United States
| | - Yuxin Zeng
- Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, California 90024, United States
| | - Narayanan Murali
- Department of Material Science and Engineering, University of California, Los Angeles, California 90024, United States
| | - Sarah Bialo
- Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, California 90024, United States
| | - Andrew Jiang
- Department of Bioengineering, University of California, Los Angeles, California 90024, United States
| | - Benjamin M Wu
- Department of Bioengineering, University of California, Los Angeles, California 90024, United States
- Division of Advanced Prosthodontics, University of California, Los Angeles, California 90024, United States
- Department of Orthopedic Surgery, University of California, Los Angeles, California 90024, United States
| | - Donghui Zhu
- Department of Biomedical Engineering, the State University of New York at Stony Brook, Stony Brook, New York 11794, United States
| | - Xiaochun Li
- Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, California 90024, United States
- Department of Material Science and Engineering, University of California, Los Angeles, California 90024, United States
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8
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Rao J, Gao H, Sun J, Yu R, Zhao D, Ding Y. A Critical Review of Biodegradable Zinc Alloys toward Clinical Applications. ACS Biomater Sci Eng 2024; 10:5454-5473. [PMID: 39082869 DOI: 10.1021/acsbiomaterials.4c00210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/03/2024]
Abstract
Biodegradable zinc (Zn) alloys stand out as promising contenders for biomedical applications due to their favorable mechanical properties and appropriate degradation rates, offering the potential to mitigate the risks and expenses associated with secondary surgeries. While current research predominantly centers on the in vitro examination of Zn alloys, notable disparities often emerge between in vivo and in vitro findings. Consequently, conducting in vivo investigations on Zn alloys holds paramount significance in advancing their clinical application. Different element compositions and processing methods decide the mechanical properties and biological performance of Zn alloys, thus affecting their suitability for specific medical applications. This paper presents a comprehensive overview of recent strides in the development of biodegradable Zn alloys, with a focus on key aspects such as mechanical properties, toxicity, animal experiments, biological properties, and molecular mechanisms. By summarizing these advancements, the paper aims to broaden the scope of research directions and enhance the understanding of the clinical applications of biodegradable Zn alloys.
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Affiliation(s)
- Jiahui Rao
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China
| | - Hairui Gao
- School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Jiwei Sun
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China
| | - Ran Yu
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China
| | - Danlei Zhao
- Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China
| | - Yumei Ding
- Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China
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9
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Meng F, Du Y. Research Progress on Laser Powder Bed Fusion Additive Manufacturing of Zinc Alloys. MATERIALS (BASEL, SWITZERLAND) 2024; 17:4309. [PMID: 39274701 PMCID: PMC11395926 DOI: 10.3390/ma17174309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 08/25/2024] [Accepted: 08/27/2024] [Indexed: 09/16/2024]
Abstract
Zinc, along with magnesium and iron, is considered one of the most promising biodegradable metals. Compared with magnesium and iron, pure Zn exhibits poor mechanical properties, despite its mild biological corrosion behavior and beneficial biocompatibility. Laser powder bed fusion (LPBF), unlike traditional manufacturing techniques, has the capability to rapidly manufacture near-net-shape components. At present, although the combination of LPBF and Zn has made great progress, it is still in its infancy. Element loss and porosity are common processing problems for LPBF Zn, mainly due to evaporation during melting under a high-energy beam. The formation quality and properties of the final material are closely related to the alloy composition, design and processing. This work reviews the state of research and future perspective on LPBF zinc from comprehensive assessments such as powder characteristics, alloy composition, processing, formation quality, microstructure, and properties. The effects of powder characteristics, process parameters and evaporation on formation quality are introduced. The mechanical, corrosion, and biocompatibility properties of LPBF Zn and their test methodologies are introduced. The effects of microstructure on mechanical properties and corrosion properties are analyzed in detail. The practical medical application of Zn is introduced. Finally, current research status is summarized together with suggested directions for advancing knowledge about LPBF Zn.
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Affiliation(s)
- Fuxiang Meng
- School of Mechanical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China
| | - Yulei Du
- School of Mechanical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China
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10
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Zhao H, Liu D, Sun S, Yu J, Bian X, Cheng X, Yang Q, Yu Y, Xu Z. PIAS3 acts as a zinc sensor under zinc deficiency and plays an important role in myocardial ischemia/reperfusion injury. Free Radic Biol Med 2024; 221:188-202. [PMID: 38750767 DOI: 10.1016/j.freeradbiomed.2024.05.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 05/10/2024] [Accepted: 05/12/2024] [Indexed: 05/30/2024]
Abstract
Alterations in zinc transporter expression in response to zinc loss protect cardiac cells from ischemia/reperfusion (I/R) injury. However, the underlying molecular mechanisms how cardiac cells sense zinc loss remains unclear. Here, we found that zinc deficiency induced ubiquitination and degradation of the protein inhibitor of activated STAT3 (PIAS3), which can alleviate myocardial I/R injury by activating STAT3 to promote the expression of ZIP family zinc transporter genes. The RING finger domain within PIAS3 is vital for PIAS3 degradation, as PIAS3-dRing (missing the RING domain) and PIAS3-Mut (zinc-binding site mutation) were resistant to degradation in the setting of zinc deficiency. Meanwhile, the RING finger domain within PIAS3 is critical for the inhibition of STAT3 activation. Moreover, PIAS3 knockdown increased cardiac Zn2+ levels and reduced myocardial infarction in mouse hearts subjected to I/R, whereas wild-type PIAS3 overexpression, but not PIAS3-Mut, reduced cardiac Zn2+ levels, and exacerbated myocardial infarction. These findings elucidate a unique mechanism of zinc sensing, showing that fast degradation of the zinc-binding regulatory protein PIAS3 during zinc deficiency can correct zinc dyshomeostasis and alleviate reperfusion injury.
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Affiliation(s)
- Huanhuan Zhao
- Department of Physiology & Pathophysiology, Tianjin Medical University, Tianjin, 300070, China.
| | - Dan Liu
- Department of Physiology & Pathophysiology, Tianjin Medical University, Tianjin, 300070, China
| | - Sha Sun
- National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
| | - Jing Yu
- Department of Physiology & Pathophysiology, Tianjin Medical University, Tianjin, 300070, China
| | - Xiyun Bian
- Tianjin Key Laboratory of Epigenetics for Organ Development of Preterm Infants, Tianjin Fifth Central Hospital, Tianjin, 300450, China
| | - Xinxin Cheng
- Department of Physiology & Pathophysiology, Tianjin Medical University, Tianjin, 300070, China.
| | - Qing Yang
- Department of Cardiology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
| | - Yonghao Yu
- Department of Anesthesiology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
| | - Zhelong Xu
- Department of Physiology & Pathophysiology, Tianjin Medical University, Tianjin, 300070, China; Department of Cardiology, General Hospital, Tianjin Medical University, Tianjin 300052, China; Department of Anesthesiology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
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11
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Li Z, Shao Y, Yang Y, Zan J. Zeolitic imidazolate framework-8: a versatile nanoplatform for tissue regeneration. Front Bioeng Biotechnol 2024; 12:1386534. [PMID: 38655386 PMCID: PMC11035894 DOI: 10.3389/fbioe.2024.1386534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 03/11/2024] [Indexed: 04/26/2024] Open
Abstract
Extensive research on zeolitic imidazolate framework (ZIF-8) and its derivatives has highlighted their unique properties in nanomedicine. ZIF-8 exhibits advantages such as pH-responsive dissolution, easy surface functionalization, and efficient drug loading, making it an ideal nanosystem for intelligent drug delivery and phototherapy. These characteristics have sparked significant interest in its potential applications in tissue regeneration, particularly in bone, skin, and nerve regeneration. This review provides a comprehensive assessment of ZIF-8's feasibility in tissue engineering, encompassing material synthesis, performance testing, and the development of multifunctional nanosystems. Furthermore, the latest advancements in the field, as well as potential limitations and future prospects, are discussed. Overall, this review emphasizes the latest developments in ZIF-8 in tissue engineering and highlights the potential of its multifunctional nanoplatforms for effective complex tissue repair.
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Affiliation(s)
- Zhixin Li
- Department of Rehabilitation, Ganzhou People’s Hospital, Ganzhou, China
| | - Yinjin Shao
- Department of Rehabilitation, Ganzhou People’s Hospital, Ganzhou, China
| | - Youwen Yang
- Institute of Additive Manufacturing, Jiangxi University of Science and Technology, Nanchang, China
| | - Jun Zan
- Institute of Additive Manufacturing, Jiangxi University of Science and Technology, Nanchang, China
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12
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Luo D, Liu Y, Li J, Liu X, Zhang R, Liu X, Zhang N, Zhang W, Liu J, Zhang L, Wang T. Systematic Analysis of the Relationship Between Elevated Zinc and Epilepsy. J Mol Neurosci 2024; 74:39. [PMID: 38581598 DOI: 10.1007/s12031-024-02213-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 03/21/2024] [Indexed: 04/08/2024]
Abstract
Previous studies have indicated a potential relationship between zinc and epilepsy. The aim of this study is to investigate the causal relationship between zinc, zinc-dependent carbonic anhydrase, and gray matter volume in brain regions enriched with zinc and epilepsy, as well as explore the possible mechanisms by which zinc contributes to epilepsy. First, this study assessed the risk causality between zinc, carbonic anhydrase, and gray matter volume alterations in zinc-enriched brain regions and various subtypes of epilepsy based on Two-sample Mendelian randomization analysis. And then, this study conducted GO/KEGG analysis based on colocalization analysis, MAGMA analysis, lasso regression, random forest model, and XGBoost model. The results of Mendelian randomization analyses showed a causal relationship between zinc, carbonic anhydrase-4, and generalized epilepsy (p = 0.044 , p = 0.010). Additionally, carbonic anhydrase-1 and gray matter volume of the caudate nucleus were found to be associated with epilepsy and focal epilepsy (p = 0.014, p = 0.003 and p = 0.022, p = 0.009). A colocalization relationship was found between epilepsy and focal epilepsy (PP.H4.abf = 97.7e - 2). Meanwhile, the MAGMA analysis indicated that SNPs associated with epilepsy and focal epilepsy were functionally localized to zinc-finger-protein-related genes (p < 1.0e - 5). The genes associated with focal epilepsy were found to have a molecular function of zinc ion binding (FDR = 2.3e - 6). After the onset of epilepsy, the function of the gene whose expression changed in the rats with focal epilepsy was enriched in the biological process of vascular response (FDR = 4.0e - 5). These results revealed mechanism of the increased risk of epilepsy caused by elevated zinc may be related to the increase of zinc ion-dependent carbonic anhydrase or the increase of the volume of zinc-rich caudate gray matter.
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Affiliation(s)
- Dadong Luo
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Yaqing Liu
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Junqiang Li
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Xuhui Liu
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Ruirui Zhang
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Xuejuan Liu
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Ningning Zhang
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Wenzhao Zhang
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Jiayi Liu
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Lan Zhang
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China
| | - Tiancheng Wang
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, China.
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13
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Roesner M, Zankovic S, Kovacs A, Benner M, Barkhoff R, Seidenstuecker M. Mechanical Properties and Corrosion Rate of ZnAg3 as a Novel Bioabsorbable Material for Osteosynthesis. J Funct Biomater 2024; 15:28. [PMID: 38391881 PMCID: PMC10890006 DOI: 10.3390/jfb15020028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 01/12/2024] [Accepted: 01/20/2024] [Indexed: 02/24/2024] Open
Abstract
Osteosynthesis in fracture treatment typically uses hardware that remains in the patient's body, which brings a permanent risk of negative side effects such as foreign body reactions or chronic inflammation. Bioabsorbable materials, however, can degrade and slowly be replaced by autologous bone tissue. A suitable material is requested to offer great biocompatibility alongside excellent mechanical properties and a reasonable corrosion rate. Zinc-silver alloys provide these characteristics, which makes them a promising candidate for research. This study investigated the aptitude as a bioabsorbable implant of a novel zinc-silver alloy containing 3.3 wt% silver (ZnAg3). Here, the tensile strength as well as the corrosion rate in PBS solution (phosphate buffered solution) of ZnAg3 were assessed. Furthermore, shear tests, including fatigue and quasi-static testing, were conducted with ZnAg3 and magnesium pins (MAGNEZIX®, Syntellix AG, Hannover, Germany), which are already in clinical use. The detected corrosion rate of 0.10 mm/year for ZnAg3 was within the proposed range for bioabsorbable implants. With a tensile strength of 237.5 ± 2.12 MPa and a shear strength of 144.8 ± 13.2 N, ZnAg3 satisfied the mechanical requirements for bioabsorbable implants. The fatigue testing did not show any significant difference between ZnAg3 and magnesium pins, whereas both materials withstood the cyclic loading. Thus, the results support the assumption that ZnAg3 is qualified for further investigation.
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Affiliation(s)
- Maria Roesner
- G.E.R.N. Tissue Replacement, Regeneration & Neogenesis, Department of Orthopedics and Trauma Surgery, Medical Center-Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany
| | - Sergej Zankovic
- G.E.R.N. Tissue Replacement, Regeneration & Neogenesis, Department of Orthopedics and Trauma Surgery, Medical Center-Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany
| | - Adalbert Kovacs
- Limedion GmbH, Coatings and Surface Analysis, Am Schäferstock 2-4, 68163 Mannheim, Germany
| | - Moritz Benner
- Limedion GmbH, Coatings and Surface Analysis, Am Schäferstock 2-4, 68163 Mannheim, Germany
- Quadralux e.K., Am Schäferstock 2-4, 68163 Mannheim, Germany
| | - Roland Barkhoff
- Quadralux e.K., Am Schäferstock 2-4, 68163 Mannheim, Germany
| | - Michael Seidenstuecker
- G.E.R.N. Tissue Replacement, Regeneration & Neogenesis, Department of Orthopedics and Trauma Surgery, Medical Center-Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany
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14
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Yang S, Wang W, Xu Y, Yuan Y, Hao S. Fe-Zn alloy, a new biodegradable material capable of reducing ROS and inhibiting oxidative stress. Regen Biomater 2024; 11:rbae002. [PMID: 38404619 PMCID: PMC10884730 DOI: 10.1093/rb/rbae002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 12/20/2023] [Accepted: 12/25/2023] [Indexed: 02/27/2024] Open
Abstract
Fe-based biodegradable materials have attracted significant attention due to their exceptional mechanical properties and favorable biocompatibility. Currently, research on Fe-based materials mainly focuses on regulating the degradation rate. However, excessive release of Fe ions during material degradation will induce the generation of reactive oxygen species (ROS), leading to oxidative stress and ferroptosis. Therefore, the control of ROS release and the improvement of biocompatibility for Fe-based materials are very important. In this study, new Fe-Zn alloys were prepared by electrodeposition with the intention of using Zn as an antioxidant to reduce oxidative damage during alloy degradation. Initially, the impact of three potential degradation ions (Fe2+, Fe3+, Zn2+) from the Fe-Zn alloy on human endothelial cell (EC) activity and migration ability was investigated. Subsequently, cell adhesion, cell activity, ROS production and DNA damage were assessed at various locations surrounding the alloy. Finally, the influence of different concentrations of Zn2+ in the medium on cell viability and ROS production was evaluated. High levels of ROS exhibited evident toxic effects on ECs and promoted DNA damage. As an antioxidant, Zn2+ effectively reduced ROS production around Fe and improved the cell viability on its surface at a concentration of 0.04 mmol/l. These findings demonstrate that Fe-Zn alloy can attenuate the ROS generated from Fe degradation thereby enhancing cytocompatibility.
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Affiliation(s)
- Shuaikang Yang
- School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024, PR China
| | - Weiqiang Wang
- School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024, PR China
| | - Yanan Xu
- School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024, PR China
| | - Yonghui Yuan
- Clinical Research Center for Malignant Tumor of Liaoning Province, Cancer Hospital of Dalian University of Technology, Shenyang 110042, PR China
| | - Shengzhi Hao
- School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024, PR China
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15
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Hernández-Escobar D, Pajares-Chamorro N, Chatzistavrou X, Hankenson KD, Hammer ND, Boehlert CJ. Tailored Coatings for Enhanced Performance of Zinc-Magnesium Alloys in Absorbable Implants. ACS Biomater Sci Eng 2024; 10:338-354. [PMID: 38109649 DOI: 10.1021/acsbiomaterials.3c01255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2023]
Abstract
Absorbable metals exhibit potential for next-generation temporary medical implants, dissolving safely in the body during tissue healing and regeneration. Their commercial incorporation could substantially diminish the need for additional surgeries and complications that are tied to permanent devices. Despite extensive research on magnesium (Mg) and iron (Fe), achieving the optimal combination of mechanical properties, biocompatibility, and controlled degradation rate for absorbable implants remains a challenge. Zinc (Zn) and Zn-based alloys emerged as an attractive alternative for absorbable implants, due to favorable combination of in vivo biocompatibility and degradation behavior. Moreover, the development of suitable coatings can enhance their biological characteristics and tailor their degradation process. In this work, four different biodegradable coatings (based on zinc phosphate (ZnP), collagen (Col), and Ag-doped bioactive glass nanoparticles (AgBGNs)) were synthesized by chemical conversion, spin-coating, or a combination of both on Zn-3Mg substrates. This study assessed the impact of the coatings on in vitro degradation behavior, cytocompatibility, and antibacterial activity. The ZnP-coated samples demonstrated controlled weight loss and a decreased corrosion rate over time, maintaining a physiological pH. Extracts from the uncoated, ZnP-coated, and Col-AgBGN-coated samples showed higher cell viability with increasing concentration. Bacterial viability was significantly impaired in all coated samples, particularly in the Col-AgBGN coating. This study showcases the potential of a strategic material-coating combination to effectively tackle multiple challenges encountered in current medical implant technologies by modifying the properties of absorbable metals to tailor patient treatments.
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Affiliation(s)
- David Hernández-Escobar
- Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan 48824, United States
| | - Natalia Pajares-Chamorro
- Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan 48824, United States
| | - Xanthippi Chatzistavrou
- Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan 48824, United States
- Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Kurt D Hankenson
- Department of Orthopedic Surgery, University of Michigan, Ann Arbor, Michigan 48104, United States
| | - Neal D Hammer
- Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824, United States
| | - Carl J Boehlert
- Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan 48824, United States
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16
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Chen S, Du T, Zhang H, Qi J, Zhang Y, Mu Y, Qiao A. Methods for improving the properties of zinc for the application of biodegradable vascular stents. BIOMATERIALS ADVANCES 2024; 156:213693. [PMID: 37992478 DOI: 10.1016/j.bioadv.2023.213693] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 11/02/2023] [Accepted: 11/03/2023] [Indexed: 11/24/2023]
Abstract
Biodegradable stents can support vessels for an extended period, maintain vascular patency, and progressively degrade once vascular remodeling is completed, thereby reducing the constraints of traditional metal stents. An ideal degradable stent must have good mechanical properties, degradation behavior, and biocompatibility. Zinc has become a new type of biodegradable metal after magnesium and iron, owing to its suitable degradation rate and good biocompatibility. However, zinc's poor strength and ductility make it unsuitable as a vascular stent material. Therefore, this paper reviewed the primary methods for improving the overall properties of zinc. By discussing the mechanical properties, degradation behavior, and biocompatibility of various improvement strategies, we found that alloying is the most common, simple, and effective method to improve mechanical properties. Deformation processing can further improve the mechanical properties by changing the microstructures of zinc alloys. Surface modification is an important means to improve the biological activity, blood compatibility and corrosion resistance of zinc alloys. Meanwhile, structural design can not only improve the mechanical properties of the vascular stents, but also endow the stents with special properties such as negative Poisson 's ratio. Manufacturing zinc alloys with excellent degradation properties, improved mechanical properties and strong biocompatibility and exploring their mechanism of interaction with the human body remain areas for future research.
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Affiliation(s)
- Shiliang Chen
- Faculty of Environment and Life, Beijing University of Technology, Beijing, China
| | - Tianming Du
- Faculty of Environment and Life, Beijing University of Technology, Beijing, China.
| | - Hanbing Zhang
- Faculty of Environment and Life, Beijing University of Technology, Beijing, China
| | - Jing Qi
- Faculty of Environment and Life, Beijing University of Technology, Beijing, China
| | - Yanping Zhang
- Faculty of Environment and Life, Beijing University of Technology, Beijing, China
| | - Yongliang Mu
- School of Metallurgy, Northeastern University, Shenyang, China
| | - Aike Qiao
- Faculty of Environment and Life, Beijing University of Technology, Beijing, China.
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17
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Sun Q, Zhang D, Tong X, Lin J, Li Y, Wen C. Mechanical properties, corrosion behavior, and cytotoxicity of biodegradable Zn/Mg multilayered composites prepared by accumulative roll bonding process. Acta Biomater 2024; 173:509-525. [PMID: 38006909 DOI: 10.1016/j.actbio.2023.11.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 11/11/2023] [Accepted: 11/16/2023] [Indexed: 11/27/2023]
Abstract
Zinc (Zn), magnesium (Mg), and their respective alloys have attracted great attention as biodegradable bone-implant materials due to their excellent biocompatibility and biodegradability. However, the poor mechanical strength of Zn alloys and the rapid degradation rate of Mg alloys limit their clinical application. The manufacture of Zn and Mg bimetals may be a promising way to improve their mechanical and degradation properties. Here we report on Zn/Mg multilayered composites prepared via an accumulative roll bonding (ARB) process. With an increase in the number of ARB cycles, the thicknesses of the Zn layer and the Mg layer were reduced, while a large number of heterogeneous interfaces were introduced into the Zn/Mg multilayered composites. The composite samples after 14 ARB cycles showed the highest yield strength of 411±3 MPa and highest ultimate tensile strength of 501±3 MPa among all the ARB processed samples, significantly higher than those of the Zn/Zn and Mg/Mg multilayered samples. The Zn and Mg layers remained continuous in the Zn/Mg composite samples after annealing at 150 °C for 10 min, resulting in a decrease in yield strength from 411±3 MPa to 349±3 MPa but an increase in elongation from 8±1% to 28±1%. The degradation rate of the Zn/Mg multilayered composite samples in Hanks' solution was ranged from 127±18 µm/y to 6±1 µm/y. The Zn/Mg multilayered composites showed over 100% cell viability with their 25% and 12.5% extracts in relation to MG-63 cells after culturing for 3 d, indicating excellent cytocompatibility. STATEMENT OF SIGNIFICANCE: This work reports a biodegradable Zn/Mg multilayered composite prepared by accumulative roll bonding (ARB) process. The yield and ultimate tensile strength of the Zn/Mg multilayered composites were improved due to grain refinement and the introduction of a large number of heterogeneous interfaces. The composite samples after 14 ARB cycles showed the highest yield strength of 411±3 MPa and highest ultimate tensile strength of 501±3 MPa among all the ARB processed samples. The degradation rate of the Zn/Mg multilayered composite meets the required degradation rate for biodegradable bone-implant materials. The results demonstrated that it is a very promising approach to improve the strength and biocompatibility of biodegradable Zn-based alloys.
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Affiliation(s)
- Quanxiang Sun
- School of Materials Science and Engineering, Xiangtan University, Xiangtan 411105, China
| | - Dechuang Zhang
- School of Materials Science and Engineering, Xiangtan University, Xiangtan 411105, China.
| | - Xian Tong
- Key Laboratory of Low Dimensional Materials & Application Technology, Xiangtan University, Ministry of Education, Hunan 411105, China
| | - Jianguo Lin
- Key Laboratory of Low Dimensional Materials & Application Technology, Xiangtan University, Ministry of Education, Hunan 411105, China.
| | - Yuncang Li
- School of Engineering, RMIT University, Melbourne, Victoria 3001, Australia
| | - Cuie Wen
- School of Engineering, RMIT University, Melbourne, Victoria 3001, Australia.
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18
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Liu A, Lu Y, Dai J, Wen P, Xia D, Zheng Y. Mechanical properties, in vitro biodegradable behavior, biocompatibility and osteogenic ability of additively manufactured Zn-0.8Li-0.1Mg alloy scaffolds. BIOMATERIALS ADVANCES 2023; 153:213571. [PMID: 37562158 DOI: 10.1016/j.bioadv.2023.213571] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 06/29/2023] [Accepted: 07/25/2023] [Indexed: 08/12/2023]
Abstract
Alloying and structural design provide flexibility to modulate performance of biodegradable porous implants manufactured by laser powder bed fusion (L-PBF). Herein, bulk Zn-0.8Li-0.1Mg was first fabricated to indicate the influence of the ternary alloy system on strengthening effect. Porous scaffolds with different porosities, including 60 % (P60), 70 % (P70) and 80 % (P80), were designed and fabricated to study the influence of porosity on mechanical properties, in vitro degradation behavior, biocompatibility and osteogenic ability. Pure Zn (Zn-P70) scaffolds with a porosity of 70 % were utilized for the comparison. The results showed Zn-0.8Li-0.1Mg bulks had an ultimate tensile strength of 460.78 ± 5.79 MPa, which was more than 3 times that of pure Zn ones and was the highest value ever reported for Zn alloys fabricated by L-PBF. The compressive strength (CS) and elastic modulus (E) of scaffolds decreased with increasing porosities. The CS of P70 scaffolds was 24.59 MPa, more than 2 times that of Zn-P70. The weight loss of scaffolds during in vitro immersion increased with increasing porosities. Compared with Zn-P70, a lower weight loss, better biocompatibility and improved osteogenic ability were observed for P70 scaffolds. P70 scaffolds also exhibited the best biocompatibility and osteogenic ability among all the used porosities. Influence mechanism of alloying elements and structural porosities on mechanical behaviors, in vitro biodegradation behavior, biocompatibility and osteogenic ability of scaffolds were discussed using finite element analysis and the characterization of degradation products. The results indicated that the proper design of alloying and porosity made Zn-0.8Li-0.1Mg scaffolds promising for biodegradable applications.
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Affiliation(s)
- Aobo Liu
- State Key Laboratory of Tribology in Advanced Equipment, Tsinghua University, Beijing 100084, China; Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
| | - Yupu Lu
- Department of Dental Materials, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, Beijing 100081, China
| | - Jiabao Dai
- State Key Laboratory of Tribology in Advanced Equipment, Tsinghua University, Beijing 100084, China; Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
| | - Peng Wen
- State Key Laboratory of Tribology in Advanced Equipment, Tsinghua University, Beijing 100084, China; Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China.
| | - Dandan Xia
- Department of Dental Materials, Peking University School and Hospital of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing Key Laboratory of Digital Stomatology, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, NMPA Key Laboratory for Dental Materials, Beijing 100081, China.
| | - Yufeng Zheng
- School of Materials Science and Engineering, Peking University, Beijing 100871, China..
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Tamurejo-Alonso P, González-Martín ML, Pacha-Olivenza MÁ. Electrodeposited Zinc Coatings for Biomedical Application: Morphology, Corrosion and Biological Behaviour. MATERIALS (BASEL, SWITZERLAND) 2023; 16:5985. [PMID: 37687682 PMCID: PMC10488799 DOI: 10.3390/ma16175985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 08/22/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023]
Abstract
The improvement of biodegradable metals is currently an active and promising research area for their capabilities in implant manufacturing. However, controlling their degradation rate once their surface is in contact with the physiological media is a challenge. Surface treatments are in the way of addressing the improvement of this control. Zinc is a biocompatible metal present in the human body as well as a metal widely used in coatings to prevent corrosion, due to its well-known metal protective action. These two outstanding characteristics make zinc coating worthy of consideration to improve the degradation behaviour of implants. Electrodeposition is one of the most practical and common technologies to create protective zinc coatings on metals. This article aims to review the effect of the different parameters involved in the electrochemical process on the topography and corrosion characteristics of the zinc coating. However, certainly, it also provides an actual and comprehensive description of the state-of-the-art of the use of electrodeposited zinc for biomedical applications, focusing on their capacity to protect against bacterial colonization and to allow cell adhesion and proliferation.
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Affiliation(s)
- Purificación Tamurejo-Alonso
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, University of Extremadura, 06006 Badajoz, Spain;
- University Institute of Extremadura Sanity Research (INUBE), 06006 Badajoz, Spain;
| | - María Luisa González-Martín
- University Institute of Extremadura Sanity Research (INUBE), 06006 Badajoz, Spain;
- Department of Applied Physics, Faculty of Science, University of Extremadura, 06006 Badajoz, Spain
- Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 06006 Badajoz, Spain
| | - Miguel Ángel Pacha-Olivenza
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, University of Extremadura, 06006 Badajoz, Spain;
- University Institute of Extremadura Sanity Research (INUBE), 06006 Badajoz, Spain;
- Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 06006 Badajoz, Spain
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20
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Sahibdad I, Khalid S, Chaudhry GR, Salim A, Begum S, Khan I. Zinc enhances the cell adhesion, migration, and self-renewal potential of human umbilical cord derived mesenchymal stem cells. World J Stem Cells 2023; 15:751-767. [PMID: 37545753 PMCID: PMC10401417 DOI: 10.4252/wjsc.v15.i7.751] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 05/15/2023] [Accepted: 06/06/2023] [Indexed: 07/25/2023] Open
Abstract
BACKGROUND Zinc (Zn) is the second most abundant trace element after Fe, present in the human body. It is frequently reported in association with cell growth and proliferation, and its deficiency is considered to be a major disease contributing factor.
AIM To determine the effect of Zn on in vitro growth and proliferation of human umbilical cord (hUC)-derived mesenchymal stem cells (MSCs).
METHODS hUC-MSCs were isolated from human umbilical cord tissue and characterized based on immunocytochemistry, immunophenotyping, and tri-lineage differentiation. The impact of Zn on cytotoxicity and proliferation was determined by MTT and Alamar blue assay. To determine the effect of Zn on population doubling time (PDT), hUC-MSCs were cultured in media with and without Zn for several passages. An in vitro scratch assay was performed to analyze the effect of Zn on the wound healing and migration capability of hUC-MSCs. A cell adhesion assay was used to test the surface adhesiveness of hUC-MSCs. Transcriptional analysis of genes involved in the cell cycle, proliferation, migration, and self-renewal of hUC-MSCs was performed by quantitative real-time polymerase chain reaction. The protein expression of Lin28, a pluripotency marker, was analyzed by immunocytochemistry.
RESULTS Zn at lower concentrations enhanced the rate of proliferation but at higher concentrations (> 100 µM), showed concentration dependent cytotoxicity in hUC-MSCs. hUC-MSCs treated with Zn exhibited a significantly greater healing and migration rate compared to untreated cells. Zn also increased the cell adhesion rate, and colony forming efficiency (CFE). In addition, Zn upregulated the expression of genes involved in the cell cycle (CDC20, CDK1, CCNA2, CDCA2), proliferation (transforming growth factor β1, GDF5, hypoxia-inducible factor 1α), migration (CXCR4, VCAM1, VEGF-A), and self-renewal (OCT4, SOX2, NANOG) of hUC-MSCs. Expression of Lin28 protein was significantly increased in cells treated with Zn.
CONCLUSION Our findings suggest that zinc enhances the proliferation rate of hUC-MSCs decreasing the PDT, and maintaining the CFE. Zn also enhances the cell adhesion, migration, and self-renewal of hUC-MSCs. These results highlight the essential role of Zn in cell growth and development.
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Affiliation(s)
- Iqra Sahibdad
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Shumaila Khalid
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - G Rasul Chaudhry
- Department of Biological Sciences, Oakland University, Rochester, MI 48309, United States
| | - Asmat Salim
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Sumreen Begum
- Stem Cell Research Laboratory (SCRL), Sindh Institute of Urology and Transplantation (SIUT), Karachi 74200, Sindh, Pakistan
| | - Irfan Khan
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
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21
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Wu M, Xun M, Chen Y. Adaptation of Vascular Smooth Muscle Cell to Degradable Metal Stent Implantation. ACS Biomater Sci Eng 2023. [PMID: 37364226 DOI: 10.1021/acsbiomaterials.3c00637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/28/2023]
Abstract
Iron-, magnesium-, or zinc-based metal vessel stents support vessel expansion at the period early after implantation and degrade away after vascular reconstruction, eliminating the side effects due to the long stay of stent implants in the body and the risks of restenosis and neoatherosclerosis. However, emerging evidence has indicated that their degradation alters the vascular microenvironment and induces adaptive responses of surrounding vessel cells, especially vascular smooth muscle cells (VSMCs). VSMCs are highly flexible cells that actively alter their phenotype in response to the stenting, similarly to what they do during all stages of atherosclerosis pathology, which significantly influences stent performance. This Review discusses how biodegradable metal stents modify vascular conditions and how VSMCs respond to various chemical, biological, and physical signals attributable to stent implantation. The focus is placed on the phenotypic adaptation of VSMCs and the clinical complications, which highlight the importance of VSMC transformation in future stent design.
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Affiliation(s)
- Meichun Wu
- Hengyang Medical School, University of South China, Hengyang, Hunan 410001, China
- School of Nursing, University of South China, Hengyang, Hunan 410001, China
| | - Min Xun
- Institute of Pharmacy and Pharmacology, School of Pharmaceutical Science, University of South China, Hengyang, Hunan 410001, China
| | - Yuping Chen
- Hengyang Medical School, University of South China, Hengyang, Hunan 410001, China
- Institute of Pharmacy and Pharmacology, School of Pharmaceutical Science, University of South China, Hengyang, Hunan 410001, China
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22
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Wang Y, Huang N, Yang Z. Revealing the Role of Zinc Ions in Atherosclerosis Therapy via an Engineered Three-Dimensional Pathological Model. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2300475. [PMID: 37092571 PMCID: PMC10288231 DOI: 10.1002/advs.202300475] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 04/09/2023] [Indexed: 05/03/2023]
Abstract
An incomplete understanding of the cellular functions and underlying mechanisms of zinc ions released from zinc-based stents in atherosclerosis (AS) therapy is one of the major obstacles to their clinical translation. The existing evaluation methodology using cell monolayers has limitations on accurate results due to the lack of vascular architectures and pathological features. Herein, the authors propose a 3D biomimetic AS model based on a multi-layer vascular structure comprising endothelial cells and smooth muscle cells with hyperlipidemic surroundings and inflammatory stimulations as AS-prone biochemical conditions to explore the biological functions of zinc ions in AS therapy. Concentration-dependent biphasic effects of zinc ions on cell growth are observed both in cell monolayers and 3D AS models. Nevertheless, the cells within 3D AS model exhibit more accurate biological assessments of the zinc ions, as evidenced by augmented pathological features and significantly higher half-maximal inhibitory concentration values against zinc ions. Based on such a developed 3D biomimetic AS model, the inhibitory effects on the deoxyribonucleic acid (DNA) synthesis, significantly influenced biological processes like cell motility, proliferation, and adhesion, and several potential bio-targets of zinc ions of cells are revealed.
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Affiliation(s)
- Ying Wang
- Dongguan Key Laboratory of Smart Biomaterials and Regenerative MedicineThe Tenth Affiliated Hospital of Southern Medical UniversityDongguan523059P. R. China
- Guangdong Provincial Key Laboratory of Cardiac Function and MicrocirculationGuangzhou510080P. R. China
| | - Nan Huang
- Dongguan Key Laboratory of Smart Biomaterials and Regenerative MedicineThe Tenth Affiliated Hospital of Southern Medical UniversityDongguan523059P. R. China
| | - Zhilu Yang
- Dongguan Key Laboratory of Smart Biomaterials and Regenerative MedicineThe Tenth Affiliated Hospital of Southern Medical UniversityDongguan523059P. R. China
- Guangdong Provincial Key Laboratory of Cardiac Function and MicrocirculationGuangzhou510080P. R. China
- Department of CardiologyThird People's Hospital of Chengdu Affiliated to Southwest Jiaotong UniversityChengdu610031P. R. China
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23
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Anas M, Diniz WJS, Menezes ACB, Reynolds LP, Caton JS, Dahlen CR, Ward AK. Maternal Mineral Nutrition Regulates Fetal Genomic Programming in Cattle: A Review. Metabolites 2023; 13:metabo13050593. [PMID: 37233634 DOI: 10.3390/metabo13050593] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 04/22/2023] [Accepted: 04/24/2023] [Indexed: 05/27/2023] Open
Abstract
Maternal mineral nutrition during the critical phases of fetal development may leave lifetime impacts on the productivity of an individual. Most research within the developmental origins of the health and disease (DOHaD) field is focused on the role of macronutrients in the genome function and programming of the developing fetus. On the other hand, there is a paucity of knowledge about the role of micronutrients and, specifically, minerals in regulating the epigenome of livestock species, especially cattle. Therefore, this review will address the effects of the maternal dietary mineral supply on the fetal developmental programming from the embryonic to the postnatal phases in cattle. To this end, we will draw a parallel between findings from our cattle model research with data from model animals, cell lines, and other livestock species. The coordinated role and function of different mineral elements in feto-maternal genomic regulation underlies the establishment of pregnancy and organogenesis and, ultimately, affects the development and functioning of metabolically important tissues, such as the fetal liver, skeletal muscle, and, importantly, the placenta. Through this review, we will delineate the key regulatory pathways involved in fetal programming based on the dietary maternal mineral supply and its crosstalk with epigenomic regulation in cattle.
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Affiliation(s)
- Muhammad Anas
- Department of Animal Sciences, Center for Nutrition and Pregnancy, North Dakota State University, Fargo, ND 36849, USA
| | | | - Ana Clara B Menezes
- Department of Animal Science, South Dakota State University, Brookings, SD 57007, USA
| | - Lawrence P Reynolds
- Department of Animal Sciences, Center for Nutrition and Pregnancy, North Dakota State University, Fargo, ND 36849, USA
| | - Joel S Caton
- Department of Animal Sciences, Center for Nutrition and Pregnancy, North Dakota State University, Fargo, ND 36849, USA
| | - Carl R Dahlen
- Department of Animal Sciences, Center for Nutrition and Pregnancy, North Dakota State University, Fargo, ND 36849, USA
| | - Alison K Ward
- Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada
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24
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Kabir H, Munir K, Wen C, Li Y. Microstructures, mechanical and corrosion properties of graphene nanoplatelet-reinforced zinc matrix composites for implant applications. Acta Biomater 2023; 157:701-719. [PMID: 36476647 DOI: 10.1016/j.actbio.2022.11.060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 11/28/2022] [Accepted: 11/29/2022] [Indexed: 12/12/2022]
Abstract
Zinc (Zn)-based alloys and composites are gaining increasing interest as promising biodegradable implant materials due to their appropriate biodegradation rates and biological functionalities. However, the inadequate mechanical strength and ductility of pure Zn have restricted its application. In this study, Zn matrix composites (ZMCs) reinforced with 0.1-0.4 wt.% graphene nanoplatelets (GNP) fabricated via powder metallurgy were investigated as potential biodegradable implant materials. The microstructures, mechanical properties, and corrosion behaviors of the GNP-reinforced ZMCs were characterized using optical microscopy, scanning electron microscopy combined with energy-dispersive X-ray spectroscopy, Raman spectroscopy, compression testing, and electrochemical and immersion testing in Hanks' balanced salt solution (HBSS). The microstructural study revealed that the GNP was uniformly dispersed in the ZMCs after ball milling and sintering at 420°C for 6 h. The microhardness, compressive yield strength, ultimate compressive strength, and compressive strain of the ZMC-0.2GNP were 69 HV, 123 MPa, 247 MPa, and 23 %, respectively, improvements of ∼ 18 %, 50%, ∼ 28%, and ∼ 15% compared to pure Zn. The corrosion rate of the ZMCs were lower than that of the pure Zn in HBSS, and the ZMC-0.2GNP composite exhibited the lowest corrosion rate of 0.09 mm/y as measured by electrochemical testing. Biocompatibility assessment indicated that the diluted extracts of pure Zn and GNP-reinforced ZMCs with concentrations of 12.5% and 6.25% exhibited no cytotoxicity after cell culturing for up to 5 days, and the diluted extracts of ZMC-0.2 GNP composite revealed more than 90% cell viability after cell culturing of 3 days, showing the satisfying cytocompatibility. STATEMENT OF SIGNIFICANCE: Biodegradable Zn is a promising candidate material for orthopedic implant applications. Nonetheless, the inadequate mechanical strength and ductility of pure Zn limited its clinical application. In this study, Zn matrix composites (ZMCs) reinforced with 0.1-0.4 wt.% graphene nanoplatelets (GNP) were developed via powder metallurgy, and the reinforcing efficacy of GNP on their mechanical properties was investigated. The addition of GNP significantly improved the compressive properties of ZMCs, with the Zn-0.2GNP composite exhibiting the best compressive properties, including 123 MPa compressive yield strength, 247 MPa ultimate compressive strength, and 22.9% compressive strain. Further, the 12.5% concentration extract of the ZMCs exhibited no cytotoxicity after cell culturing for 5 d toward SaOS2 cells.
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Affiliation(s)
- Humayun Kabir
- School of Engineering, RMIT University, Melbourne, Victoria 3001, Australia
| | - Khurram Munir
- School of Engineering, RMIT University, Melbourne, Victoria 3001, Australia
| | - Cuie Wen
- School of Engineering, RMIT University, Melbourne, Victoria 3001, Australia
| | - Yuncang Li
- School of Engineering, RMIT University, Melbourne, Victoria 3001, Australia.
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25
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Wang Z, Wang W, Zhang X, Cao F, Zhang T, Bhakta Pokharel D, Chen D, Li J, Yang J, Xiao C, Ren Y, Qin G, Zhao D. Modulation of Osteogenesis and Angiogenesis Activities Based on Ionic Release from Zn-Mg Alloys. MATERIALS (BASEL, SWITZERLAND) 2022; 15:ma15207117. [PMID: 36295204 PMCID: PMC9608845 DOI: 10.3390/ma15207117] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 09/30/2022] [Accepted: 10/04/2022] [Indexed: 05/12/2023]
Abstract
The enhancement of osteogenesis and angiogenesis remains a great challenge for the successful regeneration of engineered tissue. Biodegradable Mg and Zn alloys have received increasing interest as potential biodegradable metallic materials, partially due to the biological functions of Mg2+ and Zn2+ with regard to osteogenesis and angiogenesis, respectively. In the present study, novel biodegradable Zn-xMg (x = 0.2, 0.5, 1.0 wt.%) alloys were designed and fabricated, and the effects of adding different amounts of Mg to the Zn matrix were investigated. The osteogenesis and angiogenesis beneficial effects of Zn2+ and Mg2+ release during the biodegradation were characterized, demonstrating coordination with the bone regeneration process in a dose-dependent manner. The results show that increased Mg content leads to a higher amount of released Mg2+ while decreasing the Zn2+ concentration in the extract. The osteogenesis of pre-osteoblasts was promoted in Zn-0.5Mg and Zn-1Mg due to the higher concentration of Mg2+. Moreover, pure Zn extract presented the highest activity in angiogenesis, owing to the highest concentration of Zn2+ release (6.415 μg/mL); the proliferation of osteoblast cells was, however, inhibited under such a high Zn2+ concentration. Although the concentration of Zn ion was decreased in Zn-0.5Mg and Zn-1Mg compared with pure Zn, the angiogenesis was not influenced when the concentration of Mg in the extract was sufficiently increased. Hence, Mg2+ and Zn2+ in Zn-Mg alloys show a dual modulation effect. The Zn-0.5Mg alloy was indicated to be a promising implant candidate due to demonstrating the appropriate activity in regulating osteogenesis and angiogenesis. The present work evaluates the effect of the Mg content in Zn-based alloys on biological activities, and the results provide guidance regarding the Zn-Mg composition in designs for orthopedic application.
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Affiliation(s)
- Ziming Wang
- Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
| | - Weidan Wang
- Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
- Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, China
| | - Xiuzhi Zhang
- Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
- Correspondence: (X.Z.); (D.Z.)
| | - Fang Cao
- Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
- Department of Biomedical Engineering, Dalian University of Technology, Dalian 116024, China
| | - Tianwei Zhang
- Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
- School of Mechanical Engineering, Dalian Jiaotong University, Dalian 116028, China
| | - Durga Bhakta Pokharel
- Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
- Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, China
| | - Di Chen
- Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
| | - Junlei Li
- Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
| | - Jiahui Yang
- Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
| | - Chi Xiao
- Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
| | - Yuping Ren
- School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China
| | - Gaowu Qin
- School of Materials Science and Engineering, Northeastern University, Shenyang 110819, China
| | - Dewei Zhao
- Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
- Correspondence: (X.Z.); (D.Z.)
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26
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Qiang HF, Lv ZY, Hou CY, Luo X, Li J, Liu K, Meng CX, Du WQ, Zhang YJ, Chen XM, Liu FZ. Development of biodegradable Zn-Mn-Li and CaP coatings on Zn-Mn-Li alloys and cytocompatibility evaluation for bone graft. Front Bioeng Biotechnol 2022; 10:1013097. [PMID: 36185442 PMCID: PMC9515419 DOI: 10.3389/fbioe.2022.1013097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
Zn-based alloys are considered as new kind of potential biodegradable implanted biomaterials recently. The difficulty of metal implanted biomaterials and bone tissue integration seriously affects the applications of metal implanted scaffolds in bone tissue-related fields. Herein, we self-designed Zn0.8Mn and Zn0.8Mn0.1Li alloys and CaP coated Zn0.8Mn and Zn0.8Mn0.1Li alloys, then evaluated the degradation property and cytocompatibility. The results demonstrated that the Zn0.8Mn0.1Li alloys had profoundly modified the degradation property and cytocompatibility, but Zn0.8Mn0.1Li alloys had particularly adverse effects on the surface morphology of osteoblasts. The results furtherly showed that the CaP-coated Zn0.8Mn and Zn0.8Mn0.1Li alloys scaffold had better biocompatibility, which would further guarantee the biosafety of this new kind of biodegradable Zn-based alloys implants for future clinical applications.
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Affiliation(s)
- Hui-Fen Qiang
- Department of Materials Science and Engineering, Liaocheng University, Liaocheng, China
| | - Zhao-Yong Lv
- Liaocheng People’s Hospital, Dongchangfu Hospital of Liaocheng Hospital, Liaocheng, China
| | - Cai-Yao Hou
- Department of Materials Science and Engineering, Liaocheng University, Liaocheng, China
| | - Xin Luo
- Liaocheng People’s Hospital, Dongchangfu Hospital of Liaocheng Hospital, Liaocheng, China
| | - Jun Li
- Liaocheng People’s Hospital, Dongchangfu Hospital of Liaocheng Hospital, Liaocheng, China
| | - Kun Liu
- Liaocheng People’s Hospital, Dongchangfu Hospital of Liaocheng Hospital, Liaocheng, China
| | - Chun-Xiu Meng
- Liaocheng People’s Hospital, Dongchangfu Hospital of Liaocheng Hospital, Liaocheng, China
| | - Wan-Qing Du
- Liaocheng People’s Hospital, Dongchangfu Hospital of Liaocheng Hospital, Liaocheng, China
| | - Yu-Jue Zhang
- Liaocheng People’s Hospital, Dongchangfu Hospital of Liaocheng Hospital, Liaocheng, China
- *Correspondence: Feng-Zhen Liu, ; Xi-Meng Chen, ; Yu-Jue Zhang,
| | - Xi-Meng Chen
- Liaocheng People’s Hospital, Dongchangfu Hospital of Liaocheng Hospital, Liaocheng, China
- *Correspondence: Feng-Zhen Liu, ; Xi-Meng Chen, ; Yu-Jue Zhang,
| | - Feng-Zhen Liu
- Department of Materials Science and Engineering, Liaocheng University, Liaocheng, China
- Liaocheng People’s Hospital, Dongchangfu Hospital of Liaocheng Hospital, Liaocheng, China
- *Correspondence: Feng-Zhen Liu, ; Xi-Meng Chen, ; Yu-Jue Zhang,
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27
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Zhang Z, Liu D, Chen Z, He X, Li X, Sun X. Fabrication, in vitro and in vivo properties of β-TCP/Zn composites. JOURNAL OF ALLOYS AND COMPOUNDS 2022; 913:165223. [DOI: 10.1016/j.jallcom.2022.165223] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/07/2025]
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28
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Fixation Performance of Bioabsorbable Zn-6Ag Pins for Osteosynthesis. MATERIALS 2022; 15:ma15093280. [PMID: 35591612 PMCID: PMC9101395 DOI: 10.3390/ma15093280] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 04/27/2022] [Accepted: 05/01/2022] [Indexed: 11/17/2022]
Abstract
Bioabsorbable implants have become the focus of the latest research for new bone implant materials. With favorable characteristics such as compatible mechanical characteristics, no long-term side effects, and even osteogenesis enhancing properties they seem to be the future of osteosynthesis. Besides these characteristics, they must perform on the same level as traditional implant materials regarding their mechanical support for bone healing. A particular focus in the research for bioabsorbable implants has been on metal alloys, as these have particularly good mechanical properties such as excellent maximum force and high stability. This study focused on the shear strength of new bioabsorbable zinc and magnesium pins in comparison to traditional implants such as K-wires and cancellous bone screws in bone-implant connections. During quasi-static and fatigue loading experiments, magnesium pins (MAGNEZIX, Syntellix AG, Hannover, Germany) and new zinc silver pins (Zn-6Ag) by Limedion (Limedion GmbH., Mannheim, Germany) were compared with conventional osteosynthetic materials. The pins made of the new bioabsorbable alloys withstood the cyclic loads to the same extent as the conventional osteosynthesis materials. In the quasi-static loading, it was shown that the novel Zn-6Ag from Limedion has the same shear strength as the magnesium pin from Syntellix, which is already in clinical use. In addition, the zinc pin showed significantly better shear strength compared to osteosynthesis with K-wires (p < 0.05).
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29
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Wang N, Qi D, Liu L, Zhu Y, Liu H, Zhu S. Fabrication of In Situ Grown Hydroxyapatite Nanoparticles Modified Porous Polyetheretherketone Matrix Composites to Promote Osteointegration and Enhance Bone Repair. Front Bioeng Biotechnol 2022; 10:831288. [PMID: 35295654 PMCID: PMC8919038 DOI: 10.3389/fbioe.2022.831288] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 01/17/2022] [Indexed: 12/16/2022] Open
Abstract
The repairment of critical-sized bone defects is a serious problem that stimulates the development of new biomaterials. In this study, nanohydroxyapatite (nHA)-doped porous polyetheretherketone (pPEEK) were successfully fabricated by the thermally induced phase separation method and hydrothermal treatment. Structural analysis was performed by X-ray diffraction. The water contact angles and scanning electron microscopy were measured to assess physical properties of surfaces. The mechanical strength of the composites is also determined. Microcomputed tomography is used to characterize the nHA content of the composites. The in vitro bioactivity of the composites with or without nHA was investigated by using murine pre-osteoblasts MC3T3-E1, and the results of cytotoxicity and cell proliferation assays revealed that the cytocompatibility of all specimens was good. Adherence assays were employed to examine the adhesion and morphology of cells on different materials. However, nHA-doped composites induced cell attachment and cell spreading more significantly. Osteogenic differentiation was investigated using alkaline phosphatase activity and alizarin red staining, and these in vitro results demonstrated that composites containing nHA particles enhanced osteoblast differentiation. Its effectiveness for promoting osteogenesis was also confirmed in an in vivo animal experiment using a tibial defective rat model. After 8 weeks of implantation, compared to the pure PEEK and pPEEK without nHA groups, the nHA-pPEEK group showed better osteogenic activity. The results indicate that the nHA-pPEEK composites are possibly a well-designed bone substitute for critical-sized bone defects by promoting bone regeneration and osteointegration successfully.
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Affiliation(s)
- Ningning Wang
- Department of Prosthetic Dentistry, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Desheng Qi
- College of Chemistry, Engineering Research Center of Special Engineering Plastics, Ministry of Education, Jilin University, Changchun, China
| | - Lu Liu
- Department of Stomatology, China-Japan Friendship Hospital, Jilin University, Changchun, China
| | - Yanlin Zhu
- Department of Oral Implantology, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Hong Liu
- Department of General Dentistry, School and Hospital of Stomatology, Jilin University, Changchun, China
| | - Song Zhu
- Department of Prosthetic Dentistry, School and Hospital of Stomatology, Jilin University, Changchun, China
- *Correspondence: Song Zhu,
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30
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Zhao H, Liu D, Yan Q, Bian X, Yu J, Wang J, Cheng X, Xu Z. Endoplasmic Reticulum Stress/Ca 2+-Calmodulin-Dependent Protein Kinase/Signal Transducer and Activator of Transcription 3 Pathway Plays a Role in the Regulation of Cellular Zinc Deficiency in Myocardial Ischemia/Reperfusion Injury. Front Physiol 2022; 12:736920. [PMID: 35069232 PMCID: PMC8766834 DOI: 10.3389/fphys.2021.736920] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 11/29/2021] [Indexed: 12/12/2022] Open
Abstract
Zinc homeostasis has been known to play a role in myocardial ischemia/reperfusion (I/R) injury, but the precise molecular mechanisms regulating the expression of ZIP transporters during reperfusion are still unclear. The aim of this study was to determine whether ER Stress/CaMKII/STAT3 pathway plays a role in the regulation of cellular zinc homeostasis. Zinc deficiency increased mRNA and protein expressions of the ER stress relevant markers Chop and Bip, and STAT3 phosphorylation in H9c2 or HL-1 cells, an effect that was abolished by ZnCl2. ER calcium concentration [(Ca2+)ER] was decreased and cytosolic calcium concentration [(Ca2+)I] was increased at the condition of normoxia or ischemia/reperfusion, indicating that zinc deficiency triggers ER stress and Ca2+ leak. Further studies showed that upregulation of STAT3 phosphorylation was reversed by Ca2+ chelator, indicating that intracellular Ca2+ is important for zinc deficiency-induced STAT3 activation. In support, zinc deficiency enhanced ryanodine receptors (RyR), a channel in the ER that mediate Ca2+ release, and Ca2+-calmodulin-dependent protein kinase (CaMKII) phosphorylation, implying that zinc deficiency provoked Ca2+ leak from ER via RyR and p-CaMKII is involved in STAT3 activation. Moreover, inhibition of STAT3 activation blocked zinc deficiency induced ZIP9 expression, and resulted in increased Zn2+ loss in cardiomyocytes, further confirming that STAT3 activation during reperfusion promotes the expression of ZIP9 zinc transporter to correct the imbalance in zinc homeostasis. In addition, suppressed STAT3 activation aggravated reperfusion injury. These data suggest that the ER Stress/CaMKII/STAT3 axis may be an endogenous protective mechanism, which increases the resistance of the heart to I/R.
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Affiliation(s)
- Huanhuan Zhao
- Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China
| | - Dan Liu
- Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China
| | - Qiumei Yan
- Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China
| | - Xiyun Bian
- Central Laboratory, Tianjin, China.,Tianjin Key Laboratory of Epigenetics for Organ Development in Preterm Infants, The Fifth Central Hospital of Tianjin, Tianjin, China
| | - Jing Yu
- Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China
| | - Jingjing Wang
- Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China
| | - Xinxin Cheng
- Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China
| | - Zhelong Xu
- Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China
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31
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Fang H, Qi X, Zhou S, Yang S, Hang C, Tian Y, Wang C. High-Efficient Vacuum Ultraviolet-Ozone Assist-Deposited Polydopamine for Poly(lactic- co-glycolic acid)-Coated Pure Zn toward Biodegradable Cardiovascular Stent Applications. ACS APPLIED MATERIALS & INTERFACES 2022; 14:3536-3550. [PMID: 34941257 DOI: 10.1021/acsami.1c21567] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Zinc is a prospective metal for biodegradable cardiovascular stent applications, but the excessively released Zn2+ during degradation remains a huge challenge in biocompatibility. Considerable efforts have been made to develop a high-efficient surface modification method, while maintaining adhesion strength, mechanical support, and vascular compatibility. Biomimetic polydopamine (PDA) can adhere to Zn tightly, subsequently achieving robust chemical bonds with poly(lactic-co-glycolic acid) (PLGA) coating. However, the deposition of PDA on Zn depends on the controlled conditions such as a sensitive pH and a long period of time. Herein, we introduce vacuum ultraviolet-ozone (VUV/O3) assist-deposition technology to accelerate the polymerization of PDA on pure Zn, which shortens the process to 40 min at a moderate pH of 8.5 and improves the deposition rate by 1-2 orders of magnitude under sufficient active oxygen species (ROS). Additionally, PLGA/PDA coating enhances the corrosion resistance, and their effective protection maintains the mechanical properties after long-term corrosion. Moreover, the controlled Zn2+ release contributes to the superior in vitro biocompatibility, which inhibits the hemolysis rate and smooth muscle cell (SMC) proliferation. The enhanced endothelial cell (EC) proliferation is promising to promote the re-endothelialization, avoiding in-stent restenosis and neointimal hyperplasia. Such modified Zn might be a viable candidate for the treatment of cardiovascular diseases.
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Affiliation(s)
- Hui Fang
- State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Harbin 150001, China
| | - Xiaoyun Qi
- State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Harbin 150001, China
| | - Shicheng Zhou
- State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Harbin 150001, China
| | - Shuhan Yang
- State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Harbin 150001, China
| | - Chunjin Hang
- State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Harbin 150001, China
| | - Yanhong Tian
- State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Harbin 150001, China
| | - Chenxi Wang
- State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Harbin 150001, China
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Jiang J, Qian Y, Huang H, Niu J, Yuan G. Biodegradable Zn-Cu-Mn alloy with suitable mechanical performance and in vitro degradation behavior as a promising candidate for vascular stents. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2022; 133:112652. [PMID: 35034818 DOI: 10.1016/j.msec.2022.112652] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/15/2021] [Accepted: 01/04/2022] [Indexed: 10/19/2022]
Abstract
Recently, zinc (Zn) alloy has been considered as a promising biodegradable material due to its excellent physiological degradable behavior and acceptable biocompatibility. However, poor mechanical performance limits its application as vascular stents. In this study, novel biodegradable Zn-2.2Cu-xMn (x = 0.4, 0.7, and 1.0 wt%) alloys with suitable mechanical performance were investigated. The effects of Mn addition on microstructure, mechanical properties, and in vitro degradation of Zn-2.2Cu-xMn alloys were systematically investigated. After adding Mn, dynamic recrystallization (DRX) during hot extrusion was promoted, resulting in slightly finer grain size, higher DRXed regions ratio, and weaker texture. And volume fraction and number density of second phase precipitates (micron, submicron, and nano-sized ε and MnZn13 phase) and the concentration of (Cu, Mn) in the matrix were increased. Therefore, Zn-2.2Cu-xMn alloys exhibited suitable mechanical performances (strength >310 MPa, elongation >30%) mainly due to the combination effects of grain refinement, solid solution strengthening, second phase precipitation hardening, and texture weakening. Moreover, the alloys maintained good stability of mechanical properties within 18 months and good elongation over 15% even at a high strain rate of 0.1 s-1. In addition, the alloys presented appropriate in vitro degradation rates in a basically uniform degradation mode and acceptable in vitro cytocompatibility. The above results indicated that the newly designed biodegradable Zn-2.2Cu-0.4Mn alloy with suitable comprehensive mechanical properties, appropriate degradation behavior, and acceptable cytocompatibility is a promising candidate for vascular stents.
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Affiliation(s)
- Jimiao Jiang
- National Engineering Research Center of Light Alloy Net Forming & State Key Laboratory of Metal Matrix Composite, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Yi Qian
- National Engineering Research Center of Light Alloy Net Forming & State Key Laboratory of Metal Matrix Composite, Shanghai Jiao Tong University, Shanghai 200240, China; Department of Vascular and Cardiology, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China
| | - Hua Huang
- National Engineering Research Center of Light Alloy Net Forming & State Key Laboratory of Metal Matrix Composite, Shanghai Jiao Tong University, Shanghai 200240, China.
| | - Jialin Niu
- National Engineering Research Center of Light Alloy Net Forming & State Key Laboratory of Metal Matrix Composite, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Guangyin Yuan
- National Engineering Research Center of Light Alloy Net Forming & State Key Laboratory of Metal Matrix Composite, Shanghai Jiao Tong University, Shanghai 200240, China.
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Yuan W, Xia D, Wu S, Zheng Y, Guan Z, Rau JV. A review on current research status of the surface modification of Zn-based biodegradable metals. Bioact Mater 2022; 7:192-216. [PMID: 34466727 PMCID: PMC8379348 DOI: 10.1016/j.bioactmat.2021.05.018] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/09/2021] [Accepted: 05/09/2021] [Indexed: 12/13/2022] Open
Abstract
Recently, zinc and its alloys have been proposed as promising candidates for biodegradable metals (BMs), owning to their preferable corrosion behavior and acceptable biocompatibility in cardiovascular, bone and gastrointestinal environments, together with Mg-based and Fe-based BMs. However, there is the desire for surface treatment for Zn-based BMs to better control their biodegradation behavior. Firstly, the implantation of some Zn-based BMs in cardiovascular environment exhibited intimal activation with mild inflammation. Secondly, for orthopedic applications, the biodegradation rates of Zn-based BMs are relatively slow, resulting in a long-term retention after fulfilling their mission. Meanwhile, excessive Zn2+ release during degradation will cause in vitro cytotoxicity and in vivo delayed osseointegration. In this review, we firstly summarized the current surface modification methods of Zn-based alloys for the industrial applications. Then we comprehensively summarized the recent progress of biomedical bulk Zn-based BMs as well as the corresponding surface modification strategies. Last but not least, the future perspectives towards the design of surface bio-functionalized coatings on Zn-based BMs for orthopedic and cardiovascular applications were also briefly proposed.
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Affiliation(s)
- Wei Yuan
- School of Materials Science and Engineering, Peking University, Beijing, 100871, China
| | - Dandan Xia
- School of Materials Science and Engineering, Peking University, Beijing, 100871, China
- National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, National Medical Products Administration Key Laboratory for Dental Materials, Research Center of Engineering and Technology for Digital Dentistry, Ministry of Health, Beijing, 100081, China
| | - Shuilin Wu
- School of Materials Science & Engineering, The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of China, Tianjin University, Tianjin, 300072, China
| | - Yufeng Zheng
- School of Materials Science and Engineering, Peking University, Beijing, 100871, China
- National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, National Medical Products Administration Key Laboratory for Dental Materials, Research Center of Engineering and Technology for Digital Dentistry, Ministry of Health, Beijing, 100081, China
| | - Zhenpeng Guan
- Orthopedics Department, Peking University Shougang Hospital, No. 9 Jinyuanzhuang Rd, Shijingshan District, Beijing, 100144, China
| | - Julietta V. Rau
- Istituto di Struttura della Materia, Consiglio Nazionale delle Ricerche (ISM-CNR), Via del Fosso del Cavaliere, 100-00133, Rome, Italy
- Sechenov First Moscow State Medical University, Institute of Pharmacy, Department of Analytical, Physical and Colloid Chemistry, Trubetskaya 8, build. 2, 119991, Moscow, Russia
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Biocompatibility and Electrical Stimulation of Skeletal and Smooth Muscle Cells Cultured on Piezoelectric Nanogenerators. Int J Mol Sci 2021; 23:ijms23010432. [PMID: 35008860 PMCID: PMC8745485 DOI: 10.3390/ijms23010432] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 12/28/2021] [Accepted: 12/28/2021] [Indexed: 11/29/2022] Open
Abstract
Nanogenerators are interesting for biomedical applications, with a great potential for electrical stimulation of excitable cells. Piezoelectric ZnO nanosheets present unique properties for tissue engineering. In this study, nanogenerator arrays based on ZnO nanosheets are fabricated on transparent coverslips to analyse the biocompatibility and the electromechanical interaction with two types of muscle cells, smooth and skeletal. Both cell types adhere, proliferate and differentiate on the ZnO nanogenerators. Interestingly, the amount of Zn ions released over time from the nanogenerators does not interfere with cell viability and does not trigger the associated inflammatory response, which is not triggered by the nanogenerators themselves either. The local electric field generated by the electromechanical nanogenerator–cell interaction stimulates smooth muscle cells by increasing cytosolic calcium ions, whereas no stimulation effect is observed on skeletal muscle cells. The random orientation of the ZnO nanogenerators, avoiding an overall action potential aligned along the muscle fibre, is hypothesised to be the cause of the cell-type dependent response. This demonstrates the need of optimizing the nanogenerator morphology, orientation and distribution according to the potential biomedical use. Thus, this study demonstrates the cell-scale stimulation triggered by biocompatible piezoelectric nanogenerators without using an external source on smooth muscle cells, although it remarks the cell type-dependent response.
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Xiao X, Liu E, Shao J, Ge S. Advances on biodegradable zinc-silver-based alloys for biomedical applications. J Appl Biomater Funct Mater 2021; 19:22808000211062407. [PMID: 34903075 DOI: 10.1177/22808000211062407] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
The biodegradable metals have great potential for the biomedical applications, which could be gradually degraded, absorbed, or excreted in the human body, avoiding the removal though secondary surgery. Zinc-based alloys are novel series of degradable metals for medical applications, and they are gaining lots of attention in the research field of absorbable metals. Zinc-silver (Zn-Ag) alloys show superior mechanical strength, good biodegradability, biocompatibility, and antibacterial properties, which render them to be potential candidates for biomedical applications. In this paper, we reviewed the development of Zn-Ag alloys in terms of mechanical properties, degradabilities, biocompatibilities, antibacterial properties, and potential applications in dentistry.
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Affiliation(s)
- Ximei Xiao
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China.,Department of Endodontics, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Enyang Liu
- School of Materials Science and Engineering, China University of Petroleum (East China), Qingdao, China
| | - Jinlong Shao
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China
| | - Shaohua Ge
- Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China
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Sun X, Yu X, Li W, Chen M, Liu D. Fabrication and characterization of biodegradable zinc matrix composites reinforced by uniformly dispersed beta-tricalcium phosphate via graphene oxide-assisted hetero-agglomeration. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 130:112431. [PMID: 34702516 DOI: 10.1016/j.msec.2021.112431] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 09/03/2021] [Accepted: 09/08/2021] [Indexed: 10/20/2022]
Abstract
The development of biodegradable Zn matrix composites has been considered a promising approach to achieving enhanced mechanical properties, controllable degradation rate, good biocompatibility, and good osseointegration as orthopedic implants. However, scant literature regarding Zn matrix composites has been reported because of the great difficulty in dispersing the nano-sized bioactive reinforcements uniformly within the Zn matrix. In the present study, a novel and effective method were employed to obtain Zn matrix composites reinforced by uniformly dispersed beta-tricalcium phosphate (β-TCP) via graphene oxide (GO)-assisted hetero-agglomeration and subsequent spark plasma sintering process. A very low-content (0.04 vol%) few-layered GO was used as a coupling reagent to connect the Zn matrix and nano-sized TCP particles. In an appropriate polarity solvent, the negatively charged GO sheets could combine with both the positively charged Zn powder and TCP particles by electrostatic attraction and charge neutralization. Due to the nature of hetero-agglomeration, the flexible GO sheet could adhere to the large Zn powder and attracted a certain amount of TCP particles to form a Zn/GO/TCP sandwich structure by charge neutralization thereby forming a uniform dispersion of TCP particles within Zn matrix. After the spark plasma sintering (SPS) process, the TCP particles incorporated with very thin ZnO layers (thickness of a few dozen nanometers) formed a homogeneous and unique 3D network-like distribution in as-sintered TCP/Zn composites. A unique "snap pea"-like structure was confirmed at the grain boundary of α-Zn grains, which consisted of the TCP particles as "pea" and thin ZnO layer as "pod". Due to the uniform dispersion of bioactive TCP particles and unique structure of the TCP incorporating grain boundary, as-sintered 3TCP/Zn matrix composites possessed yield strength (YS) of 140.8 ± 7.7 MPa, failure strain of 36.0 ± 2.8%, the moderate degradation rate of 19.1 ± 3.3 μm·y-1 and good cytocompatibility to MC3T3-E1 cells. Moreover, osteogenic differentiation activity evaluation revealed that the addition of TCP could significantly improve the expressions of the osteogenic differentiation-related gene (ALP) in MC3T3-E1 cells, thereby resulting in improved osteogenic capability. Therefore, biodegradable 3TCP/Zn matrix composites fabricated by GO-assisted hetero-agglomeration and subsequent SPS process could be a promising material as orthopedic implants.
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Affiliation(s)
- Xiaohao Sun
- School of Materials Science and Engineering, Tianjin University of Technology, Tianjin 300384, China.
| | - Xiao Yu
- School of Materials Science and Engineering, Tianjin University of Technology, Tianjin 300384, China
| | - Wei Li
- School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, China
| | - Minfang Chen
- National Demonstration Center for Experimental Function Materials Education, Tianjin University of Technology, Tianjin 300384, China
| | - Debao Liu
- Tianjin Key Laboratory for Photoelectric Materials and Devices, Tianjin 300384, China.
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37
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Ryzhkov NV, Nikolaev KG, Ivanov AS, Skorb EV. Infochemistry and the Future of Chemical Information Processing. Annu Rev Chem Biomol Eng 2021; 12:63-95. [PMID: 33909470 DOI: 10.1146/annurev-chembioeng-122120-023514] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Nowadays, information processing is based on semiconductor (e.g., silicon) devices. Unfortunately, the performance of such devices has natural limitations owing to the physics of semiconductors. Therefore, the problem of finding new strategies for storing and processing an ever-increasing amount of diverse data is very urgent. To solve this problem, scientists have found inspiration in nature, because living organisms have developed uniquely productive and efficient mechanisms for processing and storing information. We address several biological aspects of information and artificial models mimicking corresponding bioprocesses. For instance, we review the formation of synchronization patterns and the emergence of order out of chaos in model chemical systems. We also consider molecular logic and ion fluxes as information carriers. Finally, we consider recent progress in infochemistry, a new direction at the interface of chemistry, biology, and computer science, considering unconventional methods of information processing.
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Affiliation(s)
- Nikolay V Ryzhkov
- Infochemistry Scientific Center of ITMO University, 191002 Saint Petersburg, Russia; , , ,
| | - Konstantin G Nikolaev
- Infochemistry Scientific Center of ITMO University, 191002 Saint Petersburg, Russia; , , ,
| | - Artemii S Ivanov
- Infochemistry Scientific Center of ITMO University, 191002 Saint Petersburg, Russia; , , ,
| | - Ekaterina V Skorb
- Infochemistry Scientific Center of ITMO University, 191002 Saint Petersburg, Russia; , , ,
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38
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The impact of Zn-doped synthetic polymer materials on bone regeneration: a systematic review. Stem Cell Res Ther 2021; 12:123. [PMID: 33579372 PMCID: PMC7881550 DOI: 10.1186/s13287-021-02195-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 01/27/2021] [Indexed: 12/20/2022] Open
Abstract
Introduction To repair bone defects, a variety of bone substitution materials have been used, such as ceramics, metals, natural and synthetic polymers, and combinations thereof. In recent decades, a wide range of synthetic polymers have been used for bone regeneration. These polymers have the advantages of biocompatibility, biodegradability, good mechanical properties, low toxicity, and ease of processing. However, when used alone, they are unable to achieve ideal bone formation. Incorporating zinc (Zn) into synthetic polymers has been considered, as previous studies have shown that Zn2+ promotes stem cell osteogenesis and mineral deposition. The purpose of this systematic review was to provide an overview of the application and effectiveness of Zn in synthetic polymers for bone regeneration, whether used alone or in combination with other biomaterials. This study was performed according to the PRISMA guidelines. Materials and methods A search of the PubMed, Embase, and the Cochrane Library databases for articles published up to June 2020 revealed 153 relevant studies. After screening the titles, abstracts, and full texts, 13 articles were included in the review; 9 of these were in vitro, 3 were in vivo, and 1 included both in vitro and in vivo experiments. Results At low concentrations, Zn2+ promoted cell proliferation and osteogenic differentiation, while high-dose Zn2+ resulted in cytotoxicity and inhibition of osteogenic differentiation. Additionally, one study showed that Zn2+ reduced apatite formation in simulated body fluid. In all of the in vivo experiments, Zn-containing materials enhanced bone formation. Conclusions At appropriate concentrations, Zn-doped synthetic polymer materials are better able to promote bone regeneration than materials without Zn. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02195-y.
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He J, Fang J, Wei P, Li Y, Guo H, Mei Q, Ren F. Cancellous bone-like porous Fe@Zn scaffolds with core-shell-structured skeletons for biodegradable bone implants. Acta Biomater 2021; 121:665-681. [PMID: 33242640 DOI: 10.1016/j.actbio.2020.11.032] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 11/19/2020] [Accepted: 11/19/2020] [Indexed: 12/31/2022]
Abstract
Three-dimensional (3D) porous zinc (Zn) with a moderate degradation rate is a promising candidate for biodegradable bone scaffolds. However, fabrication of such scaffolds with adequate mechanical properties remains a challenge. Moreover, the composition, crystallography and microstructure of the in vivo degradation products formed at or near the implant-bone interface are still not precisely known. Here, we have fabricated porous Fe@Zn scaffolds with skeletons consisting of an inner core layer of Fe and an outer shell layer of Zn using template-assisted electrodeposition technique, and systematically evaluated their porous structure, mechanical properties, degradation mechanism, antibacterial ability and in vitro and in vivo biocompatibility. In situ site-specific focused ion beam micromilling and transmission electron microscopy were used to identify the in vivo degradation products at the nanometer scale. The 3D porous Fe@Zn scaffolds show similar structure and comparable mechanical properties to human cancellous bone. The degradation rates can be adjusted by varying the layer thickness of Zn and Fe. The antibacterial rates reach over 95% against S. aureus and almost 100% against E. coli. A threshold of released Zn ion concentration (~ 0.3 mM) was found to determine the in vitro biocompatibility. Intense new bone formation and ingrowth were observed despite with a slight inflammatory response. The in vivo degradation products were identified to be equiaxed nanocrystalline zinc oxide with dispersed zinc carbonate. This study not only demonstrates the feasibility of porous Fe@Zn for biodegradable bone implants, but also provides significant insight into the degradation mechanism of porous Zn in physiological environment.
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Affiliation(s)
- Jin He
- Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China; School of Power and Mechanical Engineering, Wuhan University, Wuhan, Hubei 430072, China
| | - Ju Fang
- Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Pengbo Wei
- Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Yulei Li
- Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Hui Guo
- Centre of experimental animal, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
| | - Qingsong Mei
- School of Power and Mechanical Engineering, Wuhan University, Wuhan, Hubei 430072, China
| | - Fuzeng Ren
- Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
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Kim YJ, Lee J, Im GB, Song J, Song J, Chung J, Yu T, Bhang SH. Dual Ion Releasing Nanoparticles for Modulating Osteogenic Cellular Microenvironment of Human Mesenchymal Stem Cells. MATERIALS (BASEL, SWITZERLAND) 2021; 14:412. [PMID: 33467673 PMCID: PMC7830414 DOI: 10.3390/ma14020412] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 01/12/2021] [Accepted: 01/13/2021] [Indexed: 12/11/2022]
Abstract
In this study we developed a dual therapeutic metal ion-releasing nanoparticle for advanced osteogenic differentiation of stem cells. In order to enhance the osteogenic differentiation of human mesenchymal stem cells (hMSCs) and induce angiogenesis, zinc (Zn) and iron (Fe) were synthesized together into a nanoparticle with a pH-sensitive degradation property. Zn and Fe were loaded within the nanoparticles to promote early osteogenic gene expression and to induce angiogenic paracrine factor secretion for hMSCs. In vitro studies revealed that treating an optimized concentration of our zinc-based iron oxide nanoparticles to hMSCs delivered Zn and Fe ion in a controlled release manner and supported osteogenic gene expression (RUNX2 and alkaline phosphatase) with improved vascular endothelial growth factor secretion. Simultaneous intracellular release of Zn and Fe ions through the endocytosis of the nanoparticles further modulated the mild reactive oxygen species generation level in hMSCs without cytotoxicity and thus improved the osteogenic capacity of the stem cells. Current results suggest that our dual ion releasing nanoparticles might provide a promising platform for future biomedical applications.
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Affiliation(s)
- Yu-Jin Kim
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea; (Y.-J.K.); (G.-B.I.); (J.S.)
| | - Jaeyoung Lee
- Department of Chemical Engineering, Kyung Hee University, Youngin 17104, Korea; (J.L.); (J.S.)
| | - Gwang-Bum Im
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea; (Y.-J.K.); (G.-B.I.); (J.S.)
| | - Jihun Song
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea; (Y.-J.K.); (G.-B.I.); (J.S.)
| | - Jiwoo Song
- Department of Chemical Engineering, Kyung Hee University, Youngin 17104, Korea; (J.L.); (J.S.)
- BK21 FOUR Integrated Engineering Program, Department of Chemical Engineering, Kyung Hee University, Youngin 17104, Korea
| | - Jiyong Chung
- Department of Chemical Engineering, Kyung Hee University, Youngin 17104, Korea; (J.L.); (J.S.)
- BK21 FOUR Integrated Engineering Program, Department of Chemical Engineering, Kyung Hee University, Youngin 17104, Korea
| | - Taekyung Yu
- Department of Chemical Engineering, Kyung Hee University, Youngin 17104, Korea; (J.L.); (J.S.)
- BK21 FOUR Integrated Engineering Program, Department of Chemical Engineering, Kyung Hee University, Youngin 17104, Korea
| | - Suk Ho Bhang
- School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea; (Y.-J.K.); (G.-B.I.); (J.S.)
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Development of a high-strength Zn-Mn-Mg alloy for ligament reconstruction fixation. Acta Biomater 2021; 119:485-498. [PMID: 33130305 DOI: 10.1016/j.actbio.2020.10.032] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 09/30/2020] [Accepted: 10/21/2020] [Indexed: 12/26/2022]
Abstract
Although various biodegradable materials have been investigated for ligament reconstruction fixation in the past decades, only few of them possess a combination of high mechanical properties, appropriate degradation rate, good biocompatibility, and osteogenic effect, thus limiting their clinical applications. A high-strength Zn-0.8Mn-0.4Mg alloy (i.e., Zn08Mn04Mg) with yield strength of 317 MPa was developed to address this issue. The alloy showed good biocompatibility and promising osteogenic effect in vitro. The degradation effects of Zn08Mn04Mg interference screws on the interface between soft tissue and bone were investigated in anterior cruciate ligament (ACL) reconstruction in rabbits. Compared to Ti6Al4V, the Zn alloy screws significantly accelerated the formation of new bone and further induced partial tendon mineralization, which promoted tendon-bone integration. The newly developed screws are believed to facilitate early joint function recovery and rehabilitation training and also avoid screw breakage during insertion, thereby contributing to an extensive clinical prospect.
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Li Y, Pavanram P, Zhou J, Lietaert K, Bobbert FSL, Kubo Y, Leeflang MA, Jahr H, Zadpoor AA. Additively manufactured functionally graded biodegradable porous zinc. Biomater Sci 2021; 8:2404-2419. [PMID: 31993592 DOI: 10.1039/c9bm01904a] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Topological design provides additively manufactured (AM) biodegradable porous metallic biomaterials with a unique opportunity to adjust their biodegradation behavior and mechanical properties, thereby satisfying the requirements for ideal bone substitutes. However, no information is available yet concerning the effect of topological design on the performance of AM porous zinc (Zn) that outperforms Mg and Fe in biodegradation behavior. Here, we studied one functionally graded and two uniform AM porous Zn designs with diamond unit cell. Cylindrical specimens were fabricated from pure Zn powder by using a powder bed fusion technique, followed by a comprehensive study on their static and dynamic biodegradation behaviors, mechanical properties, permeability, and biocompatibility. Topological design, indeed, affected the biodegradation behavior of the specimens, as evidenced by 150% variations in biodegradation rate between the three different designs. After in vitro dynamic immersion for 28 days, the AM porous Zn had weight losses of 7-12%, relying on the topological design. The degradation rates satisfied the desired biodegradation time of 1-2 years for bone substitution. The mechanical properties of the biodegraded specimens of all the groups maintained within the range of those of cancellous bone. As opposed to the trends observed for other biodegradable porous metals, after 28 days of in vitro biodegradation, the yield strengths of the specimens of all the groups (σy = 7-14 MPa) increased consistently, as compared to those of the as-built specimens (σy = 4-11 MPa). Moreover, AM porous Zn showed excellent biocompatibility, given that the cellular activities in none of the groups differed from the Ti controls for up to 72 h. Using topological design of AM porous Zn for controlling its mechanical properties and degradation behavior is thus clearly promising, thereby rendering flexibility to the material to meet a variety of clinical requirements.
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Affiliation(s)
- Y Li
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628 CD, The Netherlands.
| | - P Pavanram
- Department of Anatomy and Cell Biology, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - J Zhou
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628 CD, The Netherlands.
| | - K Lietaert
- 3D Systems - LayerWise NV, Grauwmeer 14, Leuven 3001, Belgium and Department of Materials Engineering, KU Leuven, Kasteelpark Arenberg 44, Leuven 3001, Belgium
| | - F S L Bobbert
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628 CD, The Netherlands.
| | - Yusuke Kubo
- Department of Anatomy and Cell Biology, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - M A Leeflang
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628 CD, The Netherlands.
| | - H Jahr
- Department of Anatomy and Cell Biology, University Hospital RWTH Aachen, Aachen 52074, Germany and Department of Orthopedic Surgery, Maastricht UMC+, Maastricht 6202 AZ, The Netherlands
| | - A A Zadpoor
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628 CD, The Netherlands.
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Li GN, Zhu SM, Nie JF, Zheng Y, Sun Z. Investigating the stress corrosion cracking of a biodegradable Zn-0.8 wt%Li alloy in simulated body fluid. Bioact Mater 2020; 6:1468-1478. [PMID: 33251383 PMCID: PMC7674163 DOI: 10.1016/j.bioactmat.2020.10.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 10/14/2020] [Accepted: 10/14/2020] [Indexed: 12/14/2022] Open
Abstract
Stress corrosion cracking (SCC) may lead to brittle, unexpected failure of medical devices. However, available researches are limited to Mg-based biodegradable metals (BM) and pure Zn. The stress corrosion behaviors of newly-developed Zn alloys remain unclear. In the present work, we conducted slow strain rate testing (SSRT) and constant-load immersion test on a promising Zn-0.8 wt%Li alloy in order to investigate its SCC susceptibility and examine its feasibility as BM with pure Zn as control group. We observed that Zn-0.8 wt%Li alloy exhibited low SCC susceptibility. This was attributed to variations in microstructure and deformation mechanism after alloying with Li. In addition, both pure Zn and Zn-0.8 wt%Li alloy did not fracture over a period of 28 days during constant-load immersion test. The magnitude of applied stress was close to physiological condition and thus, we proved the feasibility of both materials as BM.
The deformation mechanisms of pure Zn and Zn-0.8 wt%Li alloy were different. For pure Zn, surface curvatures provided sites for SCC initiation. Only shallow cracks on corrosion layer were observed for Zn-0.8 wt%Li alloy. Both materials did not fracture after constant-load immersion test.
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Affiliation(s)
- Guan-Nan Li
- Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing, 100871, China
| | - Su-Ming Zhu
- Department of Materials Science and Engineering, Monash University, Clayton, Australia
| | - Jian-Feng Nie
- Department of Materials Science and Engineering, Monash University, Clayton, Australia
| | - Yufeng Zheng
- Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing, 100871, China.,International Research Organization for Advanced Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-Ku, Kumamoto, 860-8555, Japan
| | - Zhili Sun
- State Key Laboratory for Turbulence and Complex System, College of Engineering, Peking University, Beijing, 100871, China
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Zhang W, Li P, Shen G, Mo X, Zhou C, Alexander D, Rupp F, Geis-Gerstorfer J, Zhang H, Wan G. Appropriately adapted properties of hot-extruded Zn-0.5Cu-xFe alloys aimed for biodegradable guided bone regeneration membrane application. Bioact Mater 2020; 6:975-989. [PMID: 33102940 PMCID: PMC7560602 DOI: 10.1016/j.bioactmat.2020.09.019] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 09/18/2020] [Accepted: 09/18/2020] [Indexed: 12/27/2022] Open
Abstract
Appropriately adapted comprehensive mechanical properties, degradation behavior and biocompatibility are prerequisites for the application of Zn-based biodegradable implants. In this study, hot-extruded Zn-0.5Cu-xFe (x = 0.1, 0.2 and 0.4 wt%) alloys were fabricated as candidates for biodegradable materials for guided bone regeneration (GBR) membranes. The hot-extrusion process and Cu alloying were expected mostly to enhance the mechanical properties, and the Fe alloying was added mainly for regulating the degradation. The microstructure, mechanical properties and in vitro degradation behavior were systematically investigated. The ZnCuFe alloys were composed of a Zn matrix and FeZn13 phase. With increasing Fe content, a higher FeZn13 phase precipitation with larger particles was observed. Since elongation declined significantly until fracture with increasing Fe content up to 0.4 wt%, the ZnCuFe (0.2 wt%) alloy achieved a good balance between mechanical strength and ductility, with an ultimate tensile strength of 202.3 MPa and elongation at fracture of 41.2%. Moreover, the addition of Fe successfully accelerated the degradation of ZnCuFe alloys. The ZnCuFe (0.2 wt%) alloy showed relatively uniform corrosion in the long-term degradation test. Furthermore, extracts of the ZnCuFe (0.2 wt%) alloy showed no apparent cytotoxic effects against L929 fibroblasts, Saos-2 osteoblasts or TAg periosteal cells. The ZnCuFe (0.2 wt%) alloy exhibited the potential to inhibit bacterial adhesion of Streptococcus gordonii and mixed oral bacteria. Our study provides evidence that the ZnCuFe (0.2 wt%) alloy can represent a promising material for the application as a suitable GBR membrane.
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Affiliation(s)
- Wentai Zhang
- Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China
| | - Ping Li
- Section Medical Materials Science and Technology, University Hospital Tübingen, Osianderstrasse 2-8, Tübingen, 72076, Germany
| | - Gang Shen
- Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China
| | - Xiaoshan Mo
- Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China
| | - Chao Zhou
- Beijing Advanced Innovation Center for Materials Genome Engineering, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China
| | - Dorothea Alexander
- Department of Oral and Maxillofacial Surgery, University Hospital Tübingen, Osianderstrasse 2-8, Tübingen, 72076, Germany
| | - Frank Rupp
- Section Medical Materials Science and Technology, University Hospital Tübingen, Osianderstrasse 2-8, Tübingen, 72076, Germany
| | - Jürgen Geis-Gerstorfer
- Section Medical Materials Science and Technology, University Hospital Tübingen, Osianderstrasse 2-8, Tübingen, 72076, Germany.,Section Medical Materials Science and Technology, University Hospital Tübingen, Osianderstrasse 2-8, Tübingen, 72076, Germany
| | - Haijun Zhang
- Department of Interventional and Vascular Surgery, The Tenth People's Hospital of Shanghai, Tongji University, Shanghai, 200072, China.,National United Engineering Laboratory for Biomedical Material Modification, Branden Industrial Park, Qihe Economic & Development Zone, Dezhou, Shandong, 251100, China
| | - Guojiang Wan
- Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China
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Cho YS, Kim HK, Ghim MS, Hong MW, Kim YY, Cho YS. Evaluation of the Antibacterial Activity and Cell Response for 3D-Printed Polycaprolactone/Nanohydroxyapatite Scaffold with Zinc Oxide Coating. Polymers (Basel) 2020; 12:E2193. [PMID: 32992820 PMCID: PMC7601629 DOI: 10.3390/polym12102193] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 09/22/2020] [Accepted: 09/23/2020] [Indexed: 12/30/2022] Open
Abstract
Among 3D-printed composite scaffolds for bone tissue engineering, researchers have been attracted to the use of zinc ions to improve the scaffold's anti-bacterial activity and prevent surgical site infection. In this study, we assumed that the concentration of zinc ions released from the scaffold will be correlated with the thickness of the zinc oxide coating on 3D-printed scaffolds. We investigated the adequate thickness of zinc oxide coating by comparing different scaffolds' characteristics, antibacterial activity, and in vitro cell response. The scaffolds' compressive modulus decreased as the zinc oxide coating thickness increased (10, 100 and 200 nm). However, the compressive modulus of scaffolds in this study were superior to those of other reported scaffolds because our scaffolds had a kagome structure and were made of composite material. In regard to the antibacterial activity and in vitro cell response, the in vitro cell proliferation on scaffolds with a zinc oxide coating was higher than that of the control scaffold. Moreover, the antibacterial activity of scaffolds with 100 or 200 nm-thick zinc oxide coating on Escherichia coli was superior to that of other scaffolds. Therefore, we concluded that the scaffold with a 100 nm-thick zinc oxide coating was the most appropriate scaffold to use as a bone-regenerating scaffold, given its mechanical property, its antibacterial activity, and its in vitro cell proliferation.
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Affiliation(s)
- Yong Sang Cho
- Medical IT Convergence Research Section, Daegu-Gyeongbuk Research Center, Electronics and Telecommunications Research Institute (ETRI), 1, Techno Sunhwan-ro 10-gil, Dalseong-gun, Daegu 42994, Korea;
| | - Hee-Kyeong Kim
- Department of Mechanical Engineering, College of Engineering, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Korea; (H.-K.K.); (M.-S.G.)
| | - Min-Soo Ghim
- Department of Mechanical Engineering, College of Engineering, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Korea; (H.-K.K.); (M.-S.G.)
| | - Myoung Wha Hong
- Department of Orthopedics, Daejeon St. Mary’s Hospital, The Catholic University of Korea, 64 Daeheung-ro, Jung-gu, Daejeon 34943, Korea;
| | - Young Yul Kim
- Department of Orthopedics, Daejeon St. Mary’s Hospital, The Catholic University of Korea, 64 Daeheung-ro, Jung-gu, Daejeon 34943, Korea;
| | - Young-Sam Cho
- Department of Mechanical Engineering, College of Engineering, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Korea; (H.-K.K.); (M.-S.G.)
- Department of Mechanical Design Engineering, College of Engineering, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Korea
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Yue R, Niu J, Li Y, Ke G, Huang H, Pei J, Ding W, Yuan G. In vitro cytocompatibility, hemocompatibility and antibacterial properties of biodegradable Zn-Cu-Fe alloys for cardiovascular stents applications. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 113:111007. [DOI: 10.1016/j.msec.2020.111007] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 03/09/2020] [Accepted: 04/20/2020] [Indexed: 12/26/2022]
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He J, Li DW, He FL, Liu YY, Liu YL, Zhang CY, Ren F, Ye YJ, Deng XD, Yin DC. A study of degradation behaviour and biocompatibility of Zn-Fe alloy prepared by electrodeposition. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 117:111295. [PMID: 32919656 DOI: 10.1016/j.msec.2020.111295] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 06/17/2020] [Accepted: 07/14/2020] [Indexed: 12/20/2022]
Abstract
Zinc is a biodegradable metal, which exhibits more moderate biodegradability than magnesium and iron, so that it has great application potential in the field of biomedical materials. Alloying of zinc and iron may lead to producing a new type of implant material Zn-Fe alloy, which might be able to meet the requirements for a moderate degradation rate. However, due to the huge difference in the melting point between zinc and iron, the preparation of Zn-Fe alloy is quite challenging and hence rarely reported. In this study, we show that Zn-Fe alloys can be successfully prepared by electrodeposition technology. The microstructures, composition, degradation properties and biocompatibility of the Zn-Fe alloys were systematically studied. The results showed that the content of iron in the alloys ranged from 0 to 8 wt%, depending on the concentration of Fe ions and the current density. In the alloys, the major's phases were η, δ and Г1, and they were mainly affected by the ion concentration in the electrolyte. In the in vitro immersion tests, the Zn-Fe alloy ZF2-1 showed the highest immersion corrosion rate, while ZF3-1 showed the highest electrochemical corrosion rate. Moreover, we found that the corrosion rates of the alloys were significantly higher than that of the pure Fe. In the in vivo experiments, we confirmed that the Zn-Fe alloy possessed good biocompatibility. These results demonstrate that the electrodeposition technology is a good method to prepare Zn-Fe alloys, and the Zn-Fe alloys prepared by this method are potentially promising materials for biomedical applications.
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Affiliation(s)
- Jin He
- School of Life Sciences, Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an 710072, PR China; Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, PR China; School of Power and Mechanical Engineering, Wuhan University, Wuhan 430072, PR China
| | - Da-Wei Li
- School of Life Sciences, Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an 710072, PR China
| | - Feng-Li He
- School of Life Sciences, Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an 710072, PR China; School of Material Engineering, Xi'an Aeronautical University, Xi'an 710077, PR China
| | - Yang-Yang Liu
- School of Life Sciences, Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an 710072, PR China
| | - Ya-Li Liu
- School of Life Sciences, Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an 710072, PR China
| | - Chen-Yan Zhang
- School of Life Sciences, Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an 710072, PR China
| | - Fuzeng Ren
- Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, PR China
| | - Ya-Jing Ye
- School of Life Sciences, Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an 710072, PR China
| | - Xu-Dong Deng
- School of Life Sciences, Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an 710072, PR China
| | - Da-Chuan Yin
- School of Life Sciences, Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an 710072, PR China.
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Cockerill I, Su Y, Lee JH, Berman D, Young ML, Zheng Y, Zhu D. Micro-/Nanotopography on Bioresorbable Zinc Dictates Cytocompatibility, Bone Cell Differentiation, and Macrophage Polarization. NANO LETTERS 2020; 20:4594-4602. [PMID: 32401528 DOI: 10.1021/acs.nanolett.0c01448] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
Bioresorbable metals are quickly advancing in the field of regenerative medicine for their promises of tissue restoration without adverse consequences from their lifelong presence. Zn has recently risen to the top of bioresorbable metals with great potential as a medical implant. However, cell adhesion and colonization on the Zn substrate surface remains challenging, which could damper interfacial tissue-implant integration. Inspired by the fact that surface topography can regulate cell function and fate, we hypothesize that topography on bioresorbable Zn can dictate material biocompatibility, cell differentiation, and immunomodulation. To verify this, surface-engineered Zn plates with nano-, submicro-, and microtopographies were systematically investigated. The microscale topography exhibited increased adhesion, pronounced self-renewal, and enhanced osteogenic differentiation of bone cells as well as less macrophage inflammatory polarization, reduced platelet adhesion, and better hemocompatibility. Thus, surface topography could be a viable strategy to enhance bioresorbable Zn's biocompatibility and integration with surrounding tissues while reducing inflammation.
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Affiliation(s)
- Irsalan Cockerill
- Department of Biomedical Engineering, University of North Texas, Denton, Texas 76207, United States
- Department of Materials Science and Engineering, University of North Texas, Denton, Texas 76207, United States
| | - Yingchao Su
- Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York 11794, United States
| | - Ji Hyung Lee
- Department of Materials Science and Engineering, University of North Texas, Denton, Texas 76207, United States
| | - Diana Berman
- Department of Materials Science and Engineering, University of North Texas, Denton, Texas 76207, United States
| | - Marcus L Young
- Department of Materials Science and Engineering, University of North Texas, Denton, Texas 76207, United States
| | - Yufeng Zheng
- Department of Materials Science and Engineering, Peking University, Beijing 100871, China
| | - Donghui Zhu
- Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York 11794, United States
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Wallace RG, Kenealy MR, Brady AJ, Twomey L, Duffy E, Degryse B, Caballero-Lima D, Moyna NM, Custaud MA, Meade-Murphy G, Morrin A, Murphy RP. Development of dynamic cell and organotypic skin models, for the investigation of a novel visco-elastic burns treatment using molecular and cellular approaches. Burns 2020; 46:1585-1602. [PMID: 32475797 DOI: 10.1016/j.burns.2020.04.036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 04/27/2020] [Accepted: 04/28/2020] [Indexed: 01/26/2023]
Abstract
BACKGROUND Burn injuries are a major cause of morbidity and mortality worldwide. Despite advances in therapeutic strategies for the management of patients with severe burns, the sequelae are pathophysiologically profound, up to the systemic and metabolic levels. Management of patients with a severe burn injury is a long-term, complex process, with treatment dependent on the degree and location of the burn and total body surface area (TBSA) affected. In adverse conditions with limited resources, efficient triage, stabilisation, and rapid transfer to a specialised intensive care burn centre is necessary to provide optimal outcomes. This initial lag time and the form of primary treatment initiated, from injury to specialist care, is crucial for the burn patient. This study aims to investigate the efficacy of a novel visco-elastic burn dressing with a proprietary bio-stimulatory marine mineral complex (MXC) as a primary care treatment to initiate a healthy healing process prior to specialist care. METHODS A new versatile emergency burn dressing saturated in a >90% translucent water-based, sterile, oil-free gel and carrying a unique bio-stimulatory marine mineral complex (MXC) was developed. This dressing was tested using LabSkin as a burn model platform. LabSkin a novel cellular 3D-dermal organotypic full thickness human skin equivalent, incorporating fully-differentiated dermal and epidermal components that functionally models skin. Cell and molecular analysis was carried out by in vitro Real-Time Cellular Analysis (RTCA), thermal analysis, and focused transcriptomic array profiling for quantitative gene expression analysis, interrogating both wound healing and fibrosis/scarring molecular pathways. In vivo analysis was also performed to assess the bio-mechanical and physiological effects of this novel dressing on human skin. RESULTS This hybrid emergency burn dressing (EBD) with MXC was hypoallergenic, and improved the barrier function of skin resulting in increased hydration up to 24 h. It was demonstrated to effectively initiate cooling upon application, limiting the continuous burn effect and preventing local tissue from damage and necrosis. xCELLigence RTCA® on primary human dermal cells (keratinocyte, fibroblast and micro-vascular endothelial) demonstrated improved cellular function with respect to tensegrity, migration, proliferation and cell-cell contact (barrier formation) [1]. Quantitative gene profiling supported the physiological and cellular function finding. A beneficial quid pro quo regulation of genes involved in wound healing and fibrosis formation was observed at 24 and 48 h time points. CONCLUSION Utilisation of this EBD + MXC as a primary treatment is an effective and easily applicable treatment in cases of burn injury, proving both a cooling and hydrating environment for the wound. It regulates inflammation and promotes healing in preparation for specialised secondary burn wound management. Moreover, it promotes a healthy remodelling phenotype that may potentially mitigate scarring. Based on our findings, this EBD + MXC is ideal for use in all pre-hospital, pre-surgical and resource limited settings.
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Affiliation(s)
- Robert G Wallace
- Center for Preventive Medicine, School of Health & Human Performance, Dublin City University, Dublin 9, Ireland
| | - Mary-Rose Kenealy
- Center for Preventive Medicine, School of Health & Human Performance, Dublin City University, Dublin 9, Ireland
| | - Aidan J Brady
- Center for Preventive Medicine, School of Health & Human Performance, Dublin City University, Dublin 9, Ireland
| | - Laura Twomey
- Center for Preventive Medicine, School of Health & Human Performance, Dublin City University, Dublin 9, Ireland; Technological University Dublin, Ireland
| | - Emer Duffy
- School of Chemical Sciences, Dublin City University, Dublin 9, Ireland
| | - Bernard Degryse
- Center for Preventive Medicine, School of Health & Human Performance, Dublin City University, Dublin 9, Ireland; Integrative Cell & Molecular Physiology Group, School of Health & Human Performance, Dublin City University, Dublin 9, Ireland
| | | | - Niall M Moyna
- Center for Preventive Medicine, School of Health & Human Performance, Dublin City University, Dublin 9, Ireland
| | | | | | - Aoife Morrin
- School of Chemical Sciences, Dublin City University, Dublin 9, Ireland
| | - Ronan P Murphy
- Center for Preventive Medicine, School of Health & Human Performance, Dublin City University, Dublin 9, Ireland; Integrative Cell & Molecular Physiology Group, School of Health & Human Performance, Dublin City University, Dublin 9, Ireland.
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50
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Guillory RJ, Kolesar TM, Oliver AA, Stuart JA, Bocks ML, Drelich JW, Goldman J. Zn 2+-dependent suppression of vascular smooth muscle intimal hyperplasia from biodegradable zinc implants. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 111:110826. [PMID: 32279804 PMCID: PMC7962177 DOI: 10.1016/j.msec.2020.110826] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 03/04/2020] [Accepted: 03/07/2020] [Indexed: 11/18/2022]
Abstract
Biodegradable arterial implants based on zinc have been found to suppress neointimal hyperplasia, suggesting that biodegradable materials containing zinc may be used to construct vascular implants with a reduced rate of restenosis. However, the molecular mechanism has remained unclear. In this report, we show that zinc-containing materials can be used to prevent neointimal formation when implanted into the rat aorta. Indeed, neointimal cells were significantly more TUNEL positive and alpha-actin negative at the interface of biodegradable zinc vs. biostable platinum implants, in association with greater caspase-3 activity. Although zinc stimulated extensive neointimal smooth muscle cell (SMC) death, macrophage and proinflammatory markers CD68 and iNOS were not increased in neointimal tissue relative to biostable platinum control implants. Using arterial explants, ionic zinc was confirmed to promote SMC apoptosis by activating the caspase apoptotic signaling pathway. These observations suggest that zinc-containing materials can be used to construct vascular implants such as stents with reduced neointimal hyperplasia.
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Affiliation(s)
- Roger J Guillory
- Department of Biomedical Engineering, Michigan Technological University, USA.
| | - Timothy M Kolesar
- Department of Biomedical Engineering, Michigan Technological University, USA
| | - Alexander A Oliver
- Department of Biomedical Engineering, Michigan Technological University, USA
| | | | - Martin L Bocks
- Case Western Reserve University School of Medicine, UH Rainbow Babies & Children's Hospital, Cleveland, OH, USA
| | - Jaroslaw W Drelich
- Department of Materials Science and Engineering, Michigan Technological University, USA
| | - Jeremy Goldman
- Department of Biomedical Engineering, Michigan Technological University, USA.
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