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Wang L, Jiang S, Zhou J, Gholipourmalekabadi M, Cao Y, Lin K, Zhuang Y, Yuan C. From hard tissues to beyond: Progress and challenges of strontium-containing biomaterials in regenerative medicine applications. Bioact Mater 2025; 49:85-120. [PMID: 40124596 PMCID: PMC11928986 DOI: 10.1016/j.bioactmat.2025.02.039] [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: 10/20/2024] [Revised: 02/24/2025] [Accepted: 02/25/2025] [Indexed: 03/25/2025] Open
Abstract
Tissue engineering and regenerative medicine have emerged as crucial disciplines focused on the development of new tissues and organs to overcome the limitations of traditional treatments for tissue damage caused by accidents, diseases, or aging. Strontium ion (Sr2+) has garnered significant attention for its multifaceted role in promoting regeneration medicine and therapy, especially in bone tissue regeneration. Recently, numerous studies further confirm that Sr2+ also plays a critical in soft tissue regeneration. This review firstly summarizes the influence of Sr2+ on critical biological processes such as osteogenesis, angiogenesis, immune modulation, matrix synthesis, mineralization, and antioxidative defence mechanisms. Then details the classification, properties, advantages, and limitations of Sr-containing biomaterials (SrBMs). Additionally, this review extends to the current applications of SrBMs in regenerative medicine for diverse tissues, including bone, cartilage, skeletal muscle, dental pulp, cardiac tissue, skin, hair follicles, etc. Moreover, the review addresses the challenges associated with current SrBMs and provides insights for their future designing and applications in regenerative medicine.
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Affiliation(s)
- Liyun Wang
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200011, China
| | - Shengjie Jiang
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200011, China
| | - Jialiang Zhou
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200011, China
| | - Mazaher Gholipourmalekabadi
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, 1449614535, Iran
- Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, 1449614535, Iran
| | - Yuan Cao
- Colorado College, 819 N Tejon Street Box 56, Colorado Springs, 80903, Colorado, USA
| | - Kaili Lin
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200011, China
| | - Yu Zhuang
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200011, China
| | - Changyong Yuan
- School of Stomatology, Xuzhou Medical University, Affiliated Stomatological Hospital of Xuzhou Medical University, Xuzhou, 221004, China
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Li XL, Zhao YQ, Miao L, An YX, Wu F, Han JY, Han JY, Tay FR, Mu Z, Jiao Y, Wang J. Strategies for promoting neurovascularization in bone regeneration. Mil Med Res 2025; 12:9. [PMID: 40025573 PMCID: PMC11874146 DOI: 10.1186/s40779-025-00596-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Accepted: 01/26/2025] [Indexed: 03/04/2025] Open
Abstract
Bone tissue relies on the intricate interplay between blood vessels and nerve fibers, both are essential for many physiological and pathological processes of the skeletal system. Blood vessels provide the necessary oxygen and nutrients to nerve and bone tissues, and remove metabolic waste. Concomitantly, nerve fibers precede blood vessels during growth, promote vascularization, and influence bone cells by secreting neurotransmitters to stimulate osteogenesis. Despite the critical roles of both components, current biomaterials generally focus on enhancing intraosseous blood vessel repair, while often neglecting the contribution of nerves. Understanding the distribution and main functions of blood vessels and nerve fibers in bone is crucial for developing effective biomaterials for bone tissue engineering. This review first explores the anatomy of intraosseous blood vessels and nerve fibers, highlighting their vital roles in bone embryonic development, metabolism, and repair. It covers innovative bone regeneration strategies directed at accelerating the intrabony neurovascular system over the past 10 years. The issues covered included material properties (stiffness, surface topography, pore structures, conductivity, and piezoelectricity) and acellular biological factors [neurotrophins, peptides, ribonucleic acids (RNAs), inorganic ions, and exosomes]. Major challenges encountered by neurovascularized materials during their clinical translation have also been highlighted. Furthermore, the review discusses future research directions and potential developments aimed at producing bone repair materials that more accurately mimic the natural healing processes of bone tissue. This review will serve as a valuable reference for researchers and clinicians in developing novel neurovascularized biomaterials and accelerating their translation into clinical practice. By bridging the gap between experimental research and practical application, these advancements have the potential to transform the treatment of bone defects and significantly improve the quality of life for patients with bone-related conditions.
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Affiliation(s)
- Xin-Ling Li
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Oral Implants, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China
| | - Yu-Qing Zhao
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Oral Implants, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China
| | - Li Miao
- Department of Stomatology, The Seventh Medical Center of PLA General Hospital, Beijing, 100700, China
| | - Yan-Xin An
- Department of General Surgery, The First Affiliated Hospital of Xi'an Medical University, Xi'an, 710077, China
| | - Fan Wu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Oral Implants, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China
| | - Jin-Yu Han
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Oral Implants, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China
| | - Jing-Yuan Han
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Oral Implants, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China
| | - Franklin R Tay
- Graduate School of Augusta University, Augusta, GA, 30912, USA
| | - Zhao Mu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.
| | - Yang Jiao
- Department of Stomatology, The Seventh Medical Center of PLA General Hospital, Beijing, 100700, China.
| | - Jing Wang
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Oral Implants, School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China.
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Hsu Y, He Y, Zhao X, Wang F, Yang F, Zheng Y, Zhou Y, Xia D, Liu Y. Photothermal Coating on Zinc Alloy for Controlled Biodegradation and Improved Osseointegration. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2409051. [PMID: 39807526 PMCID: PMC11884568 DOI: 10.1002/advs.202409051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 11/12/2024] [Indexed: 01/16/2025]
Abstract
Zinc (Zn) and its alloys are promising biomaterials for orthopedic applications due to their degradability and mechanical properties. Zn2+ plays a crucial role in bone formation, but excessive early release may cause cytotoxicity and inhibit osseointegration. To solve this, we developed a near-infrared (NIR) light-controlled polycaprolactone/copper-sulfur (PCL/CuS) coating that slows degradation and enhances osseointegration of Zn alloys. The zinc-lithium (Zn-Li) substrate is encapsulated with PCL, reducing Zn2+ release and maintaing biocompatibility. Controlled Zn2+ release and mild photothermal therapy via CuS nanoparticles promoted osteogenesis. In vitro studies demonstrated enhanced cell proliferation and osteogenic differentiation. In vivo Micro-Computed Tomography (Micro-CT), Scanning Electron Microscopy-Energy Dispersive Spectroscopy (SEM-EDS), and immunohistochemical analyses confirmed improved osseointegration. Mechanistic studies using RNA sequencing and Western blotting revealed that the coating promotes osteogenesis by activating the Wnt/β-catenin and inhibiting NF-κB pathways. This NIR light-controlled PCL/CuS coating successfully regulates Zn alloy degradation, enhances osseointegration via controlled Zn2+ release and mild photothermal therapy effct, presenting a promising avenue for orthopedic biomaterials.
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Affiliation(s)
- Yuchien Hsu
- Department of ProsthodonticsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
- 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 & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental MaterialsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
| | - Yunjiao He
- Department of ProsthodonticsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
- 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 & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental MaterialsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
| | - Xiao Zhao
- Department of ProsthodonticsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
- 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 & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental MaterialsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
| | - Feilong Wang
- Department of ProsthodonticsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
- 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 & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental MaterialsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
| | - Fan Yang
- Department of ProsthodonticsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
- 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 & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental MaterialsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
| | - Yufeng Zheng
- School of Materials Science and EngineeringPeking UniversityNo.5 Yi‐He‐Yuan Road, HaiDian DistrictBeijing100871China
| | - Yongsheng Zhou
- Department of ProsthodonticsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
- 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 & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental MaterialsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
| | - Dandan Xia
- 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 & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental MaterialsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
- Department of Dental MaterialsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
| | - Yunsong Liu
- Department of ProsthodonticsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
- 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 & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental MaterialsPeking University School and Hospital of StomatologyNo.22, Zhongguancun South Avenue, Haidian DistrictBeijing100081China
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Bazin T, Gaudon M, Champion E, Julien I, Prestipino C, Figueroa SJA, Duttine M, Demourgues A. Copper Versatility in Hydroxyapatite: Valence States, Clusters, and Optical Absorption Properties. Inorg Chem 2024; 63:22181-22193. [PMID: 39512229 DOI: 10.1021/acs.inorgchem.4c03795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
The solid-state reaction between a stoichiometric hydroxyapatite (HA) and CuO at temperatures above 1100 °C produces pure Cux-HA phases for x ≤ 0.7 with the general formula Ca10CuIx(PO4)6(OH)2-xOx. The Cu atoms are located at the center of the hexagonal tunnels between two hydroxyl ligands, as determined by Fourier analysis based on XRD data. During heat treatment, the reduction of Cu2+ ions into Cu+ is concomitant with the stabilization of copper in HA in the hexagonal tunnel. The incorporation of monovalent copper within the apatite, as revealed by XANES spectroscopy, explains the violet color of the samples. The incorporation of Cu+ ions, by substitution of a hydrogen atom by copper(I), results in the formation of linear O-Cu-O chains where the majority of which are isolated for x ≤ 0.3. In addition, the EXAFS investigation showed, thanks to the linear geometry of these clusters that results in multiple diffusion effects, the existence of [CuO]n chains with n ≥ 2, which only appear clearly for higher copper contents x ≥ 0.5. The strong covalency of the Cu-O bond in such a dumbbell configuration would lead to strong hybridization between the 3d and 4s orbitals of copper and the 2p orbitals of oxygen, as illustrated by ESR signals. In the case of Cu-doped HA prepared by coprecipitation and annealed at a lower temperature (T ≤ 600 °C), copper substitutes calcium according to the theoretical formula Ca10-xCux(PO4)6(OH)2, mainly at the Ca(2) site. This local environment is in line with the Jahn-Teller distortion induced by the Cu2+ ion (as evidenced by UV-vis-NIR, XPS, and XANES-EXAFS spectroscopy analyses) and also allows copper-copper interactions from one site to another, as observed by ESR spectroscopy. This versatility of copper in HA gives it optical properties that change from a violet color with near-IR absorption to a blue hue. In all cases, Cu-O-Cu interactions persist whatever the valence state, and heat treatment induces a redox phenomenon, with copper exchanging between two sites close to each other.
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Affiliation(s)
- Tiphaine Bazin
- Univ. Bordeaux, CNRS, Bordeaux INP, ICMCB, UMR 5026, F-33600 Pessac, France
- Univ. Limoges, CNRS, IRCER, UMR 7315, 12 rue Atlantis, F-87000 Limoges, France
| | - Manuel Gaudon
- Univ. Bordeaux, CNRS, Bordeaux INP, ICMCB, UMR 5026, F-33600 Pessac, France
| | - Eric Champion
- Univ. Limoges, CNRS, IRCER, UMR 7315, 12 rue Atlantis, F-87000 Limoges, France
| | - Isabelle Julien
- Univ. Limoges, CNRS, IRCER, UMR 7315, 12 rue Atlantis, F-87000 Limoges, France
| | | | - Santiago J A Figueroa
- Brazilian Synchrotron Light Laboratory (LNLS), Brazilian Center for Research in Energy and Materials (CNPEM), Campinas 13083-970, Brazil
| | - Mathieu Duttine
- Univ. Bordeaux, CNRS, Bordeaux INP, ICMCB, UMR 5026, F-33600 Pessac, France
| | - Alain Demourgues
- Univ. Bordeaux, CNRS, Bordeaux INP, ICMCB, UMR 5026, F-33600 Pessac, France
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Rajendran AK, Anthraper MSJ, Hwang NS, Rangasamy J. Osteogenesis and angiogenesis promoting bioactive ceramics. MATERIALS SCIENCE AND ENGINEERING: R: REPORTS 2024; 159:100801. [DOI: 10.1016/j.mser.2024.100801] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Abdollahi F, Saghatchi M, Paryab A, Malek Khachatourian A, Stephens ED, Toprak MS, Badv M. Angiogenesis in bone tissue engineering via ceramic scaffolds: A review of concepts and recent advancements. BIOMATERIALS ADVANCES 2024; 159:213828. [PMID: 38479240 DOI: 10.1016/j.bioadv.2024.213828] [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: 11/10/2023] [Revised: 03/08/2024] [Accepted: 03/08/2024] [Indexed: 04/05/2024]
Abstract
Due to organ donor shortages, long transplant waitlists, and the complications/limitations associated with auto and allotransplantation, biomaterials and tissue-engineered models are gaining attention as feasible alternatives for replacing and reconstructing damaged organs and tissues. Among various tissue engineering applications, bone tissue engineering has become a promising strategy to replace or repair damaged bone. We aimed to provide an overview of bioactive ceramic scaffolds in bone tissue engineering, focusing on angiogenesis and the effect of different biofunctionalization strategies. Different routes to angiogenesis, including chemical induction through signaling molecules immobilized covalently or non-covalently, in situ secretion of angiogenic growth factors, and the degradation of inorganic scaffolds, are described. Physical induction mechanisms are also discussed, followed by a review of methods for fabricating bioactive ceramic scaffolds via microfabrication methods, such as photolithography and 3D printing. Finally, the strengths and weaknesses of the commonly used methodologies and future directions are discussed.
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Affiliation(s)
- Farnoosh Abdollahi
- Department of Dentistry, Kashan University of Medical Science, Kashan, Iran
| | - Mahshid Saghatchi
- School of Metallurgy & Materials Engineering, Iran University of Science and Technology, Tehran, Iran
| | - Amirhosein Paryab
- Department of Materials Science & Engineering, Sharif University of Technology, Tehran, Iran
| | | | - Emma D Stephens
- Department of Biomedical Engineering, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada
| | - Muhammet S Toprak
- Department of Applied Physics, Biomedical and X-ray Physics, KTH Royal Institute of Technology, SE 10691 Stockholm, Sweden
| | - Maryam Badv
- Department of Biomedical Engineering, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada; Libin Cardiovascular Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada
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El-Sayed SAM, ElShebiney S, Beherei HH, Kumar P, Choonara YE, Mabrouk M. Copper-doped magnesium phosphate nanopowders for critical size calvarial bone defect intervention. J Biomed Mater Res B Appl Biomater 2024; 112:e35376. [PMID: 38359173 DOI: 10.1002/jbm.b.35376] [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: 11/08/2023] [Revised: 12/11/2023] [Accepted: 01/02/2024] [Indexed: 02/17/2024]
Abstract
Calvarial defects of bone present difficult clinical situations, and their restoration using biocompatible materials requires special treatments that enable bone regeneration. Magnesium phosphate (MgP) is known as an osteoinductive biomaterial because it contains Mg2+ ions and P ions that enhance the activity of osteoplast cells and help in bone regeneration. In this study, MgP and CuO-doped MgP were fabricated and characterized for their physicomechanical properties, particle size, morphology, surface area, antibacterial test, and in vitro bioactivity evaluation using the following techniques: X-rays diffraction, Fourier-transformer infrared, TEM, and Brunauer, Emmett and Teller (BET) surface area, X-rays photoelectron spectroscopy (XPS), and Scanning electron microscopy (SEM). Furthermore, these nanopowders were implanted in adult inbred male Wistar rats and studied after two periods (28 and 56 days). The results demonstrated that the obtained semiamorphous powders are in nanoscale (≤ 50 nm). XPS analysis ensured the preparation of MgP as mono MgP and CuO were incorporated in the structure as Cu2+ . The bioactivity was supported by the observation of calcium phosphate layer on the nanopowders' surface. The in vivo study demonstrated success of MgP nanopowders especially those doped with CuO in restoration of calvarial defect bone. Therefore, fabricated biomaterials are of great potential in restoration of bone calvarial defects.
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Affiliation(s)
- Sara A M El-Sayed
- Refractories, Ceramics and Building Materials Department, National Research Centre, Cairo, Egypt
| | - Shaimaa ElShebiney
- Department of Narcotics, Ergogenic Aids and Poisons, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
| | - Hanan H Beherei
- Refractories, Ceramics and Building Materials Department, National Research Centre, Cairo, Egypt
| | - Pradeep Kumar
- Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Yahya E Choonara
- Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Mostafa Mabrouk
- Refractories, Ceramics and Building Materials Department, National Research Centre, Cairo, Egypt
- Academy of Scientific Research and Technology (ASRT), Cairo, 11516, Egypt
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Thoraval L, Thiébault E, Siboni R, Moniot A, Guillaume C, Jacobs A, Nedelec JM, Renaudin G, Descamps S, Valfort O, Gangloff S, Braux J, Marchat D, Velard F. The acute inflammatory response to copper(II)-doped biphasic calcium phosphates. Mater Today Bio 2023; 23:100814. [PMID: 37841800 PMCID: PMC10568289 DOI: 10.1016/j.mtbio.2023.100814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 09/05/2023] [Accepted: 09/22/2023] [Indexed: 10/17/2023] Open
Abstract
Infection and inflammation are two key features to consider to avoid septic or aseptic loosening of bone-implanted biomaterials. In this context, various approaches to fine-tune the biomaterial's properties have been studied in order to modulate the crosstalk between immune and skeletal cells. Cation-doping strategies for tuning of calcium phosphates properties has been evidenced as a promising way to control the biomaterial-induced inflammatory process, and thus improving their osteoimmunomodulatory properties. Copper(II) ions are recognized for their antibacterial potential, but the literature on their impact on particulate material-induced acute inflammation is scarce. We synthesized copper(II) ions-doped biphasic calcium phosphate (BCP), intended to exhibit osteoimmunomodulatory properties. We addressed in vitro, for the first time, the inflammatory response of human primary polymorphonuclear neutrophils (PMNs) to copper(II) ions-doped or undoped (BCP) powders, synthesized by an original and robust wet method, in the presence or absence of LPS as a costimulant to mimic an infectious environment. ELISA and zymography allowed us to evidence, in vitro, a specific increase in IL-8 and GRO-α secretion but not MIP-1β, TNF-α, or MMP-9, by PMNs. To assess in vivo relevance of these findings, we used a mouse air pouch model. Thanks to flow cytometry analysis, we highlighted an increased PMN recruitment with the copper(II) ions-doped samples compared to undoped samples. The immunomodulatory effect of copper(II) ions-doped BCP powders and the consequent induced moderate level of inflammation may promote bacterial clearance by PMNs in addition to the antimicrobial potential of the material. Copper(II) doping provides new insights into calcium phosphate (CaP)-based biomaterials for prosthesis coating or bone reconstruction by effectively modulating the inflammatory environment.
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Affiliation(s)
- L. Thoraval
- Université de Reims Champagne-Ardenne, EA4691 “Biomatériaux et Inflammation en site osseux” BIOS, Reims, France
| | - E. Thiébault
- Université de Reims Champagne-Ardenne, EA4691 “Biomatériaux et Inflammation en site osseux” BIOS, Reims, France
| | - R. Siboni
- Université de Reims Champagne-Ardenne, EA4691 “Biomatériaux et Inflammation en site osseux” BIOS, Reims, France
| | - A. Moniot
- Université de Reims Champagne-Ardenne, EA4691 “Biomatériaux et Inflammation en site osseux” BIOS, Reims, France
| | - C. Guillaume
- Université de Reims Champagne-Ardenne, EA4691 “Biomatériaux et Inflammation en site osseux” BIOS, Reims, France
| | - A. Jacobs
- Université Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, Clermont-Ferrand, France
| | - J.-M. Nedelec
- Université Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, Clermont-Ferrand, France
| | - G. Renaudin
- Université Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, Clermont-Ferrand, France
| | - S. Descamps
- Université Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF, Clermont-Ferrand, France
| | - O. Valfort
- Mines Saint-Etienne, Univ Lyon, CNRS, UMR 5307 LGF, Centre SPIN, F-42023, Saint-Etienne, France
| | - S.C. Gangloff
- Université de Reims Champagne-Ardenne, EA4691 “Biomatériaux et Inflammation en site osseux” BIOS, Reims, France
| | - J. Braux
- Université de Reims Champagne-Ardenne, EA4691 “Biomatériaux et Inflammation en site osseux” BIOS, Reims, France
| | - D. Marchat
- Mines Saint-Etienne, Univ Jean Monnet, Etablissement Français du Sang, INSERM, U 1059 Sainbiose, 42023, Saint-Etienne, France
| | - F. Velard
- Université de Reims Champagne-Ardenne, EA4691 “Biomatériaux et Inflammation en site osseux” BIOS, Reims, France
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Pillai A, Chakka J, Heshmathi N, Zhang Y, Alkadi F, Maniruzzaman M. Multifunctional Three-Dimensional Printed Copper Loaded Calcium Phosphate Scaffolds for Bone Regeneration. Pharmaceuticals (Basel) 2023; 16:ph16030352. [PMID: 36986452 PMCID: PMC10052742 DOI: 10.3390/ph16030352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/14/2023] [Accepted: 02/23/2023] [Indexed: 03/02/2023] Open
Abstract
Bone regeneration using inorganic nanoparticles is a robust and safe approach. In this paper, copper nanoparticles (Cu NPs) loaded with calcium phosphate scaffolds were studied for their bone regeneration potential in vitro. The pneumatic extrusion method of 3D printing was employed to prepare calcium phosphate cement (CPC) and copper loaded CPC scaffolds with varying wt% of copper nanoparticles. A new aliphatic compound Kollisolv MCT 70 was used to ensure the uniform mixing of copper nanoparticles with CPC matrix. The printed scaffolds were studied for physico-chemical characterization for surface morphology, pore size, wettability, XRD, and FTIR. The copper ion release was studied in phosphate buffer saline at pH 7.4. The in vitro cell culture studies for the scaffolds were performed using human mesenchymal stem cells (hMSCs). The cell proliferation study in CPC-Cu scaffolds showed significant cell growth compared to CPC. The CPC-Cu scaffolds showed improved alkaline phosphatase activity and angiogenic potential compared to CPC. The CPC-Cu scaffolds showed significant concentration dependent antibacterial activity in Staphylococcus aureus. Overall, the CPC scaffolds loaded with 1 wt% Cu NPs showed improved activity compared to other CPC-Cu and CPC scaffolds. The results showed that copper has improved the osteogenic, angiogenic and antibacterial properties of CPC scaffolds, facilitating better bone regeneration in vitro.
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10
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The Localized Ionic Microenvironment in Bone Modelling/Remodelling: A Potential Guide for the Design of Biomaterials for Bone Tissue Engineering. J Funct Biomater 2023; 14:jfb14020056. [PMID: 36826855 PMCID: PMC9959312 DOI: 10.3390/jfb14020056] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 01/11/2023] [Accepted: 01/14/2023] [Indexed: 01/20/2023] Open
Abstract
Bone is capable of adjusting size, shape, and quality to maintain its strength, toughness, and stiffness and to meet different needs of the body through continuous remodeling. The balance of bone homeostasis is orchestrated by interactions among different types of cells (mainly osteoblasts and osteoclasts), extracellular matrix, the surrounding biological milieus, and waste products from cell metabolisms. Inorganic ions liberated into the localized microenvironment during bone matrix degradation not only form apatite crystals as components or enter blood circulation to meet other bodily needs but also alter cellular activities as molecular modulators. The osteoinductive potential of inorganic motifs of bone has been gradually understood since the last century. Still, few have considered the naturally generated ionic microenvironment's biological roles in bone remodeling. It is believed that a better understanding of the naturally balanced ionic microenvironment during bone remodeling can facilitate future biomaterial design for bone tissue engineering in terms of the modulatory roles of the ionic environment in the regenerative process.
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11
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Kong Z, Wang X. Bioprinting Technologies and Bioinks for Vascular Model Establishment. Int J Mol Sci 2023; 24:891. [PMID: 36614332 PMCID: PMC9821327 DOI: 10.3390/ijms24010891] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/12/2022] [Accepted: 12/29/2022] [Indexed: 01/06/2023] Open
Abstract
Clinically, large diameter artery defects (diameter larger than 6 mm) can be substituted by unbiodegradable polymers, such as polytetrafluoroethylene. There are many problems in the construction of small diameter blood vessels (diameter between 1 and 3 mm) and microvessels (diameter less than 1 mm), especially in the establishment of complex vascular models with multi-scale branched networks. Throughout history, the vascularization strategies have been divided into three major groups, including self-generated capillaries from implantation, pre-constructed vascular channels, and three-dimensional (3D) printed cell-laden hydrogels. The first group is based on the spontaneous angiogenesis behaviour of cells in the host tissues, which also lays the foundation of capillary angiogenesis in tissue engineering scaffolds. The second group is to vascularize the polymeric vessels (or scaffolds) with endothelial cells. It is hoped that the pre-constructed vessels can be connected with the vascular networks of host tissues with rapid blood perfusion. With the development of bioprinting technologies, various fabrication methods have been achieved to build hierarchical vascular networks with high-precision 3D control. In this review, the latest advances in 3D bioprinting of vascularized tissues/organs are discussed, including new printing techniques and researches on bioinks for promoting angiogenesis, especially coaxial printing, freeform reversible embedded in suspended hydrogel printing, and acoustic assisted printing technologies, and freeform reversible embedded in suspended hydrogel (flash) technology.
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Affiliation(s)
- Zhiyuan Kong
- Center of 3D Printing & Organ Manufacturing, School of Intelligent Medicine, China Medical University (CMU), No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China
| | - Xiaohong Wang
- Center of 3D Printing & Organ Manufacturing, School of Intelligent Medicine, China Medical University (CMU), No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China
- Key Laboratory for Advanced Materials Processing Technology, Ministry of Education & Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
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12
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Effect of doping cation on the adsorption properties of hydroxyapatite to uranium. J SOLID STATE CHEM 2023. [DOI: 10.1016/j.jssc.2022.123687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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13
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High-resolution 3D printing for healthcare. 3D Print Med 2023. [DOI: 10.1016/b978-0-323-89831-7.00013-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
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14
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Yoo KH, Kim Y, Kim YI, Bae MK, Yoon SY. Lithium doped biphasic calcium phosphate: Structural analysis and osteo/odontogenic potential in vitro. Front Bioeng Biotechnol 2022; 10:993126. [PMID: 36425651 PMCID: PMC9679216 DOI: 10.3389/fbioe.2022.993126] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 10/28/2022] [Indexed: 10/13/2023] Open
Abstract
Biphasic calcium phosphate (BCP) is generally considered a good synthetic bone graft material with osteoinductive potential. Lithium ions are trace elements that play a role in the bone-remodeling process. This study aimed to investigate the effects of lithium ions on the phase, crystal structure, and biological responses of lithium doped BCPs and to identify improvements in their osteogenic properties. Lithium-doped BCP powders with different doping levels (0, 5, 10, and 20 at%) were synthesized via the co-precipitation method. We found that the four types of lithium-doped BCP powders showed different phase compositions of hydroxyapatite and β-tricalcium phosphate. In addition, lithium ions favored entering the β-tricalcium phosphate structure at the Ca (4) sites and calcium vacancy sites [VCa(4)] up to 10 at%. This substitution improves the crystal stabilization by filling the vacancies with Ca2+ and Li+ in all Ca sites. However, when the concentration of Li ions was higher than 10 at%, lithium-induced crystal instability resulted in the burst release of lithium ions, and the osteogenic behavior of human dental pulp stem cells did not improve further. Although lithium ions regulate osteogenic properties, it is important to determine the optimal amount of lithium in BCPs. In this study, the most effective lithium doping level in BCP was approximately 10 at% to improve its biological properties and facilitate medical applications.
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Affiliation(s)
- Kyung-Hyeon Yoo
- School of Materials Science and Engineering, Pusan National University, Busan, South Korea
| | - Yeon Kim
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan, South Korea
| | - Yong-Il Kim
- Department of Orthodontics, Dental Research Institute, Pusan National University, Yangsan, South Korea
| | - Moon-Kyoung Bae
- Department of Oral Physiology, School of Dentistry, Pusan National University, Yangsan, South Korea
| | - Seog-Young Yoon
- School of Materials Science and Engineering, Pusan National University, Busan, South Korea
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15
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Hoseinzadeh A, Ghoddusi Johari H, Anbardar MH, Tayebi L, Vafa E, Abbasi M, Vaez A, Golchin A, Amani AM, Jangjou A. Effective treatment of intractable diseases using nanoparticles to interfere with vascular supply and angiogenic process. Eur J Med Res 2022; 27:232. [PMID: 36333816 PMCID: PMC9636835 DOI: 10.1186/s40001-022-00833-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Accepted: 09/30/2022] [Indexed: 11/06/2022] Open
Abstract
Angiogenesis is a vital biological process involving blood vessels forming from pre-existing vascular systems. This process contributes to various physiological activities, including embryonic development, hair growth, ovulation, menstruation, and the repair and regeneration of damaged tissue. On the other hand, it is essential in treating a wide range of pathological diseases, such as cardiovascular and ischemic diseases, rheumatoid arthritis, malignancies, ophthalmic and retinal diseases, and other chronic conditions. These diseases and disorders are frequently treated by regulating angiogenesis by utilizing a variety of pro-angiogenic or anti-angiogenic agents or molecules by stimulating or suppressing this complicated process, respectively. Nevertheless, many traditional angiogenic therapy techniques suffer from a lack of ability to achieve the intended therapeutic impact because of various constraints. These disadvantages include limited bioavailability, drug resistance, fast elimination, increased price, nonspecificity, and adverse effects. As a result, it is an excellent time for developing various pro- and anti-angiogenic substances that might circumvent the abovementioned restrictions, followed by their efficient use in treating disorders associated with angiogenesis. In recent years, significant progress has been made in different fields of medicine and biology, including therapeutic angiogenesis. Around the world, a multitude of research groups investigated several inorganic or organic nanoparticles (NPs) that had the potential to effectively modify the angiogenesis processes by either enhancing or suppressing the process. Many studies into the processes behind NP-mediated angiogenesis are well described. In this article, we also cover the application of NPs to encourage tissue vascularization as well as their angiogenic and anti-angiogenic effects in the treatment of several disorders, including bone regeneration, peripheral vascular disease, diabetic retinopathy, ischemic stroke, rheumatoid arthritis, post-ischemic cardiovascular injury, age-related macular degeneration, diabetic retinopathy, gene delivery-based angiogenic therapy, protein delivery-based angiogenic therapy, stem cell angiogenic therapy, and diabetic retinopathy, cancer that may benefit from the behavior of the nanostructures in the vascular system throughout the body. In addition, the accompanying difficulties and potential future applications of NPs in treating angiogenesis-related diseases and antiangiogenic therapies are discussed.
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Affiliation(s)
- Ahmad Hoseinzadeh
- Thoracic and Vascular Surgery Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Surgery, School of Medicine, Namazi Teaching Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamed Ghoddusi Johari
- Thoracic and Vascular Surgery Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Surgery, School of Medicine, Namazi Teaching Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Lobat Tayebi
- Marquette University School of Dentistry, Milwaukee, WI, 53233, USA
| | - Ehsan Vafa
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Milad Abbasi
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ahmad Vaez
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Golchin
- Solid Tumor Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
- Department of Clinical Biochemistry and Applied Cell Sciences, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Ali Mohammad Amani
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Jangjou
- Department of Emergency Medicine, School of Medicine, Namazi Teaching Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
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16
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Vezenkova A, Locs J. Sudoku of porous, injectable calcium phosphate cements - Path to osteoinductivity. Bioact Mater 2022; 17:109-124. [PMID: 35386461 PMCID: PMC8964990 DOI: 10.1016/j.bioactmat.2022.01.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 12/28/2021] [Accepted: 01/03/2022] [Indexed: 12/16/2022] Open
Abstract
With the increase of global population, people's life expectancy is growing as well. Humans tend to live more active lifestyles and, therefore, trauma generated large defects become more common. Instances of tumour resection or pathological conditions and complex orthopaedic issues occur more frequently increasing necessity for bone substitutes. Composition of calcium phosphate cements (CPCs) is comparable to the chemical structure of bone minerals. Their ability to self-set and resorb in vivo secures a variety of potential applications in bone regeneration. Despite the years-long research and several products already reaching the market, finding the right properties for calcium phosphate cement to be osteoinductive and both injectable and suitable for clinical use is still a sudoku. This article is focused on injectable, porous CPCs, reviewing the latest developments on the path toward finding osteoinductive material, which is suitable for injection.
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Affiliation(s)
- Agneta Vezenkova
- Rudolfs Cimdins Riga Biomaterials Innovations and Development Centre of RTU, Institute of Genera Chemical Engineering, Faculty of Materials Science and Applied Chemistry, Riga Technical University, Pulka Street 3, LV-1007, Riga, Latvia
| | - Janis Locs
- Rudolfs Cimdins Riga Biomaterials Innovations and Development Centre of RTU, Institute of Genera Chemical Engineering, Faculty of Materials Science and Applied Chemistry, Riga Technical University, Pulka Street 3, LV-1007, Riga, Latvia
- Baltic Biomaterials Centre of Excellence, Headquarters at Riga Technical University, Riga, Latvia
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17
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Aubry C, Drouet C, Azaïs T, Kim HJ, Oh JM, Karacan I, Chou J, Ben-Nissan B, Camy S, Cazalbou S. Bio-Activation of HA/β-TCP Porous Scaffolds by High-Pressure CO 2 Surface Remodeling: A Novel "Coating-from" Approach. MATERIALS (BASEL, SWITZERLAND) 2022; 15:7306. [PMID: 36295371 PMCID: PMC9610974 DOI: 10.3390/ma15207306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/07/2022] [Accepted: 10/13/2022] [Indexed: 06/16/2023]
Abstract
Biphasic macroporous Hydroxyapatite/β-Tricalcium Phosphate (HA/β-TCP) scaffolds (BCPs) are widely used for bone repair. However, the high-temperature HA and β-TCP phases exhibit limited bioactivity (low solubility of HA, restricted surface area, low ion release). Strategies were developed to coat such BCPs with biomimetic apatite to enhance bioactivity. However, this can be associated with poor adhesion, and metastable solutions may prove difficult to handle at the industrial scale. Alternative strategies are thus desirable to generate a highly bioactive surface on commercial BCPs. In this work, we developed an innovative "coating from" approach for BCP surface remodeling via hydrothermal treatment under supercritical CO2, used as a reversible pH modifier and with industrial scalability. Based on a set of complementary tools including FEG-SEM, solid state NMR and ion exchange tests, we demonstrate the remodeling of macroporous BCP surface with the occurrence of dissolution-reprecipitation phenomena involving biomimetic CaP phases. The newly precipitated compounds are identified as bone-like nanocrystalline apatite and octacalcium phosphate (OCP), both known for their high bioactivity character, favoring bone healing. We also explored the effects of key process parameters, and showed the possibility to dope the remodeled BCPs with antibacterial Cu2+ ions to convey additional functionality to the scaffolds, which was confirmed by in vitro tests. This new process could enhance the bioactivity of commercial BCP scaffolds via a simple and biocompatible approach.
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Affiliation(s)
- Clémentine Aubry
- Centre Inter-Universitaire de Recherche et d’Ingénierie des Matériaux, CNRS/UT3/INP, Université de Toulouse, 31030 Toulouse, France
- Laboratoire de Génie Chimique, CNRS/UT3/INP, Université de Toulouse, 31030 Toulouse, France
- ARN: Régulation Naturelle et Artificielle, INSERM U1212, CNRS, Université de Bordeaux, 33076 Bordeaux, France
| | - Christophe Drouet
- Centre Inter-Universitaire de Recherche et d’Ingénierie des Matériaux, CNRS/UT3/INP, Université de Toulouse, 31030 Toulouse, France
| | - Thierry Azaïs
- Laboratoire de Chimie de la Matière Condensée de Paris-UMR 7574, CNRS, Sorbonne Université, 75005 Paris, France
| | - Hyoung-Jun Kim
- Department Energy and Materials Engineering, Dongguk University, Seoul 04620, Korea
- Research Institute, National Cancer Center, Goyang 10408, Korea
| | - Jae-Min Oh
- Department Energy and Materials Engineering, Dongguk University, Seoul 04620, Korea
| | - Ipek Karacan
- University of Technology Sydney, Ultimo 2007, Australia
| | - Joshua Chou
- University of Technology Sydney, Ultimo 2007, Australia
| | | | - Séverine Camy
- Laboratoire de Génie Chimique, CNRS/UT3/INP, Université de Toulouse, 31030 Toulouse, France
| | - Sophie Cazalbou
- Centre Inter-Universitaire de Recherche et d’Ingénierie des Matériaux, CNRS/UT3/INP, Université de Toulouse, 31030 Toulouse, France
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18
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Homaeigohar S, Li M, Boccaccini AR. Bioactive glass-based fibrous wound dressings. BURNS & TRAUMA 2022; 10:tkac038. [PMID: 36196303 PMCID: PMC9519693 DOI: 10.1093/burnst/tkac038] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 07/16/2022] [Accepted: 07/20/2022] [Indexed: 11/13/2022]
Abstract
Since the discovery of silicate bioactive glass (BG) by Larry Hench in 1969, different classes of BGs have been researched over decades mainly for bone regeneration. More recently, validating the beneficial influence of BGs with tailored compositions on angiogenesis, immunogenicity and bacterial infection, the applicability of BGs has been extended to soft tissue repair and wound healing. Particularly, fibrous wound dressings comprising BG particle reinforced polymer nanofibers and cotton-candy-like BG fibers have been proven to be successful for wound healing applications. Such fibrous dressing materials imitate the physical structure of skin's extracellular matrix and release biologically active ions e.g. regenerative, pro-angiogenic and antibacterial ions, e.g. borate, copper, zinc, etc., that can provoke cellular activities to regenerate the lost skin tissue and to induce new vessels formation, while keeping an anti-infection environment. In the current review, we discuss different BG fibrous materials meant for wound healing applications and cover the relevant literature in the past decade. The production methods for BG-containing fibers are explained and as fibrous wound dressing materials, their wound healing and bactericidal mechanisms, depending on the ions they release, are discussed. The present gaps in this research area are highlighted and new strategies to address them are suggested.
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Affiliation(s)
- Shahin Homaeigohar
- School of Science and Engineering, University of Dundee, Dundee DD1 4HN, United Kingdom
| | - Meng Li
- Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, 91058 Erlangen, Germany
| | - Aldo R Boccaccini
- Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, 91058 Erlangen, Germany
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19
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Xu Y, Xu Y, Zhang W, Li M, Wendel HP, Geis-Gerstorfer J, Li P, Wan G, Xu S, Hu T. Biodegradable Zn-Cu-Fe Alloy as a Promising Material for Craniomaxillofacial Implants: An in vitro Investigation into Degradation Behavior, Cytotoxicity, and Hemocompatibility. Front Chem 2022; 10:860040. [PMID: 35734444 PMCID: PMC9208203 DOI: 10.3389/fchem.2022.860040] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 05/19/2022] [Indexed: 11/13/2022] Open
Abstract
Zinc-based nanoparticles, nanoscale metal frameworks and metals have been considered as biocompatible materials for bone tissue engineering. Among them, zinc-based metals are recognized as promising biodegradable materials thanks to their moderate degradation rate ranging between magnesium and iron. Nonetheless, materials’ biodegradability and the related biological response depend on the specific implant site. The present study evaluated the biodegradability, cytocompatibility, and hemocompatibility of a hot-extruded zinc-copper-iron (Zn-Cu-Fe) alloy as a potential biomaterial for craniomaxillofacial implants. Firstly, the effect of fetal bovine serum (FBS) on in vitro degradation behavior was evaluated. Furthermore, an extract test was used to evaluate the cytotoxicity of the alloy. Also, the hemocompatibility evaluation was carried out by a modified Chandler-Loop model. The results showed decreased degradation rates of the Zn-Cu-Fe alloy after incorporating FBS into the medium. Also, the alloy exhibited acceptable toxicity towards RAW264.7, HUVEC, and MC3T3-E1 cells. Regarding hemocompatibility, the alloy did not significantly alter erythrocyte, platelet, and leukocyte counts, while the coagulation and complement systems were activated. This study demonstrated the predictable in vitro degradation behavior, acceptable cytotoxicity, and appropriate hemocompatibility of Zn-Cu-Fe alloy; therefore, it might be a candidate biomaterial for craniomaxillofacial implants.
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Affiliation(s)
- Yan Xu
- Center of Oral Implantology, Stomatological Hospital, Southern Medical University, Guangzhou, China
| | - Yichen Xu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Oral Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Section Medical Materials Science and Technology, University Hospital Tübingen, Tübingen, Germany
| | - Wentai Zhang
- Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, China
| | - Ming Li
- Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, China
- Department of Materials Engineering, Sichuan Engineering Technical College, Deyang, China
| | - Hans-Peter Wendel
- Department of Thoracic and Cardiovascular Surgery, Clinical Research Laboratory, University Hospital Tübingen, Tübingen, Germany
| | - Jürgen Geis-Gerstorfer
- Section Medical Materials Science and Technology, University Hospital Tübingen, Tübingen, Germany
| | - Ping Li
- Center of Oral Implantology, Stomatological Hospital, Southern Medical University, Guangzhou, China
- Section Medical Materials Science and Technology, University Hospital Tübingen, Tübingen, Germany
- *Correspondence: Ping Li, ; Guojiang Wan, ; Shulan Xu,
| | - Guojiang Wan
- Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, China
- *Correspondence: Ping Li, ; Guojiang Wan, ; Shulan Xu,
| | - Shulan Xu
- Center of Oral Implantology, Stomatological Hospital, Southern Medical University, Guangzhou, China
- *Correspondence: Ping Li, ; Guojiang Wan, ; Shulan Xu,
| | - Tao Hu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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20
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dos Santos Gomes D, de Sousa Victor R, de Sousa BV, de Araújo Neves G, de Lima Santana LN, Menezes RR. Ceramic Nanofiber Materials for Wound Healing and Bone Regeneration: A Brief Review. MATERIALS 2022; 15:ma15113909. [PMID: 35683207 PMCID: PMC9182284 DOI: 10.3390/ma15113909] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 04/29/2022] [Accepted: 05/06/2022] [Indexed: 02/04/2023]
Abstract
Ceramic nanofibers have been shown to be a new horizon of research in the biomedical area, due to their differentiated morphology, nanoroughness, nanotopography, wettability, bioactivity, and chemical functionalization properties. Therefore, considering the impact caused by the use of these nanofibers, and the fact that there are still limited data available in the literature addressing the ceramic nanofiber application in regenerative medicine, this review article aims to gather the state-of-the-art research concerning these materials, for potential use as a biomaterial for wound healing and bone regeneration, and to analyze their characteristics when considering their application.
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Affiliation(s)
- Déborah dos Santos Gomes
- Graduate Program in Materials Science and Engineering, Federal University of Campina Grande, Campina Grande 58429-900, Brazil; (G.d.A.N.); (L.N.d.L.S.)
- Laboratory of Materials Technology, Department of Materials Engineering, Federal University of Campina Grande, Campina Grande 58429-900, Brazil
- Correspondence: (D.d.S.G.); (R.d.S.V.); (R.R.M.); Tel.: +55-083-2101-1183 (R.R.M.)
| | - Rayssa de Sousa Victor
- Graduate Program in Materials Science and Engineering, Federal University of Campina Grande, Campina Grande 58429-900, Brazil; (G.d.A.N.); (L.N.d.L.S.)
- Laboratory of Materials Technology, Department of Materials Engineering, Federal University of Campina Grande, Campina Grande 58429-900, Brazil
- Correspondence: (D.d.S.G.); (R.d.S.V.); (R.R.M.); Tel.: +55-083-2101-1183 (R.R.M.)
| | - Bianca Viana de Sousa
- Department of Chemical Engineering, Federal University of Campina Grande, Campina Grande 58429-900, Brazil;
| | - Gelmires de Araújo Neves
- Graduate Program in Materials Science and Engineering, Federal University of Campina Grande, Campina Grande 58429-900, Brazil; (G.d.A.N.); (L.N.d.L.S.)
| | - Lisiane Navarro de Lima Santana
- Graduate Program in Materials Science and Engineering, Federal University of Campina Grande, Campina Grande 58429-900, Brazil; (G.d.A.N.); (L.N.d.L.S.)
| | - Romualdo Rodrigues Menezes
- Laboratory of Materials Technology, Department of Materials Engineering, Federal University of Campina Grande, Campina Grande 58429-900, Brazil
- Correspondence: (D.d.S.G.); (R.d.S.V.); (R.R.M.); Tel.: +55-083-2101-1183 (R.R.M.)
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Silver, Copper, Magnesium and Zinc Contained Electroactive Mesoporous Bioactive S53P4 Glass–Ceramics Nanoparticle for Bone Regeneration: Bioactivity, Biocompatibility and Antibacterial Activity. J Inorg Organomet Polym Mater 2022. [DOI: 10.1007/s10904-022-02295-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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22
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Koyama S, Hamai R, Shiwaku Y, Kurobane T, Tsuchiya K, Takahashi T, Suzuki O. Angio-osteogenic capacity of octacalcium phosphate co-precipitated with copper gluconate in rat calvaria critical-sized defect. SCIENCE AND TECHNOLOGY OF ADVANCED MATERIALS 2022; 23:120-139. [PMID: 35185389 PMCID: PMC8856029 DOI: 10.1080/14686996.2022.2035193] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/20/2022] [Accepted: 01/24/2022] [Indexed: 06/14/2023]
Abstract
The objective of this study is to investigate the effects of octacalcium phosphate (OCP)-induced bone regeneration on angiogenesis regulated by the inclusion of copper ions in OCP in vitro and in vivo. Calcium (Ca)-deficient Cu-OCPs, containing 0.01 wt% Cu (low-Cu-OCP) and 0.12 wt% Cu (high-Cu-OCP), were synthesized with co7pper gluconate salt. The lattice parameters of Cu-OCPs tended to decrease slightly with Cu inclusion, as estimated by Rietveld analysis. Cu ions were released in OCP when the materials were incubated in the medium for human umbilical vein endothelial cells (HUVECs). The solubility of Cu-OCPs, estimated by the degree of supersaturation, was slightly higher than that of the original OCP. Cu-OCP tended to hydrolyze to an apatite structure while maintaining the crystal plate-like morphology when incubated with mesenchymal stem D1 cells in osteogenic media for 14 days. The specimens were characterized by selected area electron diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy. Low-Cu-OCP significantly enhanced the HUVEC capillary cross-linking density. D1 cell differentiation was inhibited with the inclusion of Cu, even at low concentrations. The composite of low-Cu-OCP with a gelatin sponge (low-Cu-OCP/Gel) significantly enhanced angiogenesis coupled with bone regeneration when implanted in a rat calvarial critical-sized defect for 4 weeks, compared with the corresponding amount of Cu-containing Gel (Cu/Gel) or OCP/Gel materials through angiography and tissue histomorphometry. These results support the proposition that angiogenesis stimulated by low-Cu-OCP is closely related with enhanced bone regeneration.
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Affiliation(s)
- Shinki Koyama
- Division of Craniofacial Function Engineering, Tohoku University Graduate School of Dentistry, Sendai, Japan
- Division of Oral and Maxillofacial Surgery, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Ryo Hamai
- Division of Craniofacial Function Engineering, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Yukari Shiwaku
- Division of Craniofacial Function Engineering, Tohoku University Graduate School of Dentistry, Sendai, Japan
- Liaison Center for Innovative Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Tsuyoshi Kurobane
- Division of Oral and Maxillofacial Surgery, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Kaori Tsuchiya
- Division of Craniofacial Function Engineering, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Tetsu Takahashi
- Division of Oral and Maxillofacial Surgery, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Osamu Suzuki
- Division of Craniofacial Function Engineering, Tohoku University Graduate School of Dentistry, Sendai, Japan
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Sutthavas P, Tahmasebi Birgani Z, Habibovic P, van Rijt S. Calcium Phosphate-Coated and Strontium-Incorporated Mesoporous Silica Nanoparticles Can Effectively Induce Osteogenic Stem Cell Differentiation. Adv Healthc Mater 2022; 11:e2101588. [PMID: 34751004 PMCID: PMC11468810 DOI: 10.1002/adhm.202101588] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 11/01/2021] [Indexed: 01/16/2023]
Abstract
Ceramic (nano)materials are promising materials for bone regeneration applications. The addition of bioinorganics such as strontium (Sr) and zinc (Zn) is a popular approach to further improve their biological performance. However, control over ion delivery is important to prevent off-target effects. Mesoporous silica nanoparticles (MSNs) are popular nanomaterials that can be designed to incorporate and controllably deliver multiple ions to steer specific regenerative processes. In this work, MSNs loaded with Sr (MSNSr ) and surface coated with a pH-sensitive calcium phosphate (MSNSr -CaP) or calcium phosphate zinc layer (MSNSr -CaZnP) are developed. The ability of the MSNs to promote osteogenesis in human mesenchymal stromal cells (hMSCs) under basic cell culture conditions is explored and compared to ion administration directly to the cell culture media. Here, it is shown that MSN-CaPs can effectively induce alkaline phosphatase (ALP) levels and osteogenic gene expression in the absence of other osteogenic stimulants, where an improved effect is observed for MSNs surface coated with multiple ions. Moreover, comparatively lower ion doses are needed when using MSNs as delivery vehicles compared to direct ion administration in the medium. In summary, the MSNs developed here represent promising vehicles to deliver (multiple) bioinorganics and promote hMSC osteogenesis in basic conditions.
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Affiliation(s)
- Pichaporn Sutthavas
- Department of Instructive Biomaterials EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityP.O. Box 616Maastricht6200 MDthe Netherlands
| | - Zeinab Tahmasebi Birgani
- Department of Instructive Biomaterials EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityP.O. Box 616Maastricht6200 MDthe Netherlands
| | - Pamela Habibovic
- Department of Instructive Biomaterials EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityP.O. Box 616Maastricht6200 MDthe Netherlands
| | - Sabine van Rijt
- Department of Instructive Biomaterials EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityP.O. Box 616Maastricht6200 MDthe Netherlands
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Maleki-Ghaleh H, Siadati MH, Omidi Y, Kavanlouei M, Barar J, Akbari-Fakhrabadi A, Adibkia K, Beygi-Khosrowshahi Y. Synchrotron SAXS/WAXS and TEM studies of zinc doped natural hydroxyapatite nanoparticles and their evaluation on osteogenic differentiation of human mesenchymal stem cells. MATERIALS CHEMISTRY AND PHYSICS 2022; 276:125346. [DOI: 10.1016/j.matchemphys.2021.125346] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Li T, Zhang T. The Application of Nanomaterials in Angiogenesis. Curr Stem Cell Res Ther 2021; 16:74-82. [PMID: 32066364 DOI: 10.2174/1574888x15666200211102203] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Revised: 12/16/2019] [Accepted: 01/07/2020] [Indexed: 02/08/2023]
Abstract
Induction of angiogenesis has enormous potential in the treatment of ischemic diseases and
the promotion of bulk tissue regeneration. However, the poor activity of angiogenic cells and proangiogenic
factors after transplantation is the main problem that imposes its wide applications. Recent
studies have found that the development of nanomaterials has solved this problem to some extent.
Nanomaterials can be mainly classified into inorganic nanomaterials represented by metals, metal oxides
and metal hydroxides, and organic nanomaterials including DNA tetrahedrons, graphene, graphene
oxide, and carbon nanotubes. These nanomaterials can induce the release of angiogenic factors
either directly or indirectly, thereby initiating a series of signaling pathways to induce angiogenesis.
Moreover, appropriate surface modifications of nanomaterial facilitate a variety of functions, such as
enhancing its biocompatibility and biostability. In clinical applications, nanomaterials can promote the
proliferation and differentiation of endothelial cells or mesenchymal stem cells, thereby promoting the
migration of hemangioblast cells to form new blood vessels. This review outlines the role of nanomaterials
in angiogenesis and is intended to provide new insights into the clinical treatment of systemic
and ischemic diseases.
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Affiliation(s)
- Tianle Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Tao Zhang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
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Zhang Y, Li J, Mouser VHM, Roumans N, Moroni L, Habibovic P. Biomimetic Mechanically Strong One-Dimensional Hydroxyapatite/Poly(d,l-lactide) Composite Inducing Formation of Anisotropic Collagen Matrix. ACS NANO 2021; 15:17480-17498. [PMID: 34662097 PMCID: PMC8613905 DOI: 10.1021/acsnano.1c03905] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 10/13/2021] [Indexed: 05/25/2023]
Abstract
Natural bone is a complex composite, consisting predominantly of collagen and hydroxyapatite (HA), which form a highly organized, hierarchical structure from the nano- to the macroscale. Because of its biphasic, anisotropic, ultrafine structural design, bone tissue possesses excellent mechanical properties. Herein, inspired by the composition and microstructure of natural bone, a biphasic composite consisting of highly aligned strontium/copper-doped one-dimensional hydroxyapatite (Sr/Cu-doped 1D HA) and poly(d,l-lactide) (PDLA) was developed. The presence and alignment of Sr/Cu-doped 1D HA crystals resulted in mechanical reinforcement of the polymer matrix, including compressive and tensile strength and modulus, fracture toughness, swelling resistance, and long-term structural stability. The compressive strength, tensile strength, and Young's modulus of the biomimetic composite were comparable to that of cortical bone. Biologically, the biomimetic composite showed a sustained release of the incorporated Sr and Cu ions, facilitated mineral deposition from simulated body fluid, and supported attachment, proliferation, and alkaline phosphatase activity of human mesenchymal stromal cells (hMSCs). Moreover, the highly aligned Sr/Cu-doped 1D HA crystals in the 3D porous scaffolds induced the alignment of hMSCs and secretion of an anisotropic collagen fiber matrix in 3D. The biomimetic Sr/Cu-doped 1D HA/PDLA composite presented here contributes to the current efforts aiming at the design and development of load-bearing bioactive synthetic bone graft substitutes. Moreover, the biomimetic composite may serve as a 3D platform for studying cell-extracellular matrix interactions in bone tissue.
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Affiliation(s)
- Yonggang Zhang
- Department
of Instructive Biomaterials Engineering, Maastricht University, MERLN Institute for Technology-Inspired Regenerative
Medicine, Universiteitssingel
40, 6229 ER, Maastricht, The Netherlands
| | - Jiaping Li
- Department
of Instructive Biomaterials Engineering, Maastricht University, MERLN Institute for Technology-Inspired Regenerative
Medicine, Universiteitssingel
40, 6229 ER, Maastricht, The Netherlands
- Complex
Tissue Regeneration Department, Maastricht
University, MERLN Institute for Technology-Inspired Regenerative Medicine, Universiteitssingel 40, 6229 ER, Maastricht, The Netherlands
| | - Vivian Hilda Maria Mouser
- Orthopaedic
Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
| | - Nadia Roumans
- Department
of Cell Biology-Inspired Tissue Engineering, Maastricht University, MERLN Institute for Technology-Inspired Regenerative
Medicine, Universiteitssingel
40, 6229 ER, Maastricht, The Netherlands
| | - Lorenzo Moroni
- Complex
Tissue Regeneration Department, Maastricht
University, MERLN Institute for Technology-Inspired Regenerative Medicine, Universiteitssingel 40, 6229 ER, Maastricht, The Netherlands
| | - Pamela Habibovic
- Department
of Instructive Biomaterials Engineering, Maastricht University, MERLN Institute for Technology-Inspired Regenerative
Medicine, Universiteitssingel
40, 6229 ER, Maastricht, The Netherlands
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Kovrlija I, Locs J, Loca D. Octacalcium phosphate: Innovative vehicle for the local biologically active substance delivery in bone regeneration. Acta Biomater 2021; 135:27-47. [PMID: 34450339 DOI: 10.1016/j.actbio.2021.08.021] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 08/09/2021] [Accepted: 08/14/2021] [Indexed: 12/29/2022]
Abstract
Disadvantages of conventional drug delivery systems (DDS), such as systemic circulation, interaction with physiochemical factors, reduced bioavailability, and insufficient drug concentration at bone defect site, have underlined the importance of developing efficacious local drug delivery systems. Octacalcium phosphate (OCP) is presumed to be the precursor of biologically formed apatite, owing to its similarity to hydroxyapatite (HAp) and readiness to convert to it. Specific crystal structure of OCP is constructed of compiled apatite layers and water layers, which make possible the incorporation of various ions in its structure, making it feasible to alter the overall effect OCP has in the system. Next to that intrinsic property, characteristics as high solubility, biodegradability and osteoconductivity have made it indispensable to tailor OCP as a carrier material. In this review, we present the main characteristics and progress done on utilizing OCP as an innovative vehicle and provide suggestions for possible research pathways and advantages for local drug delivery in bone tissue engineering. STATEMENT OF SIGNIFICANCE: Octacalcium phosphate (OCP), being a precursor to biologically formed apatite, has many assets when compared to other calcium phosphates. Owing to its highly pertinent structure, it is being used as a vehicle for biologically active substances or ions for bone regeneration. However, orchestrating drug delivery systems with OCP, in order to achieve the best possible outcome, is still a pioneering concept, and the all-encompassing data is still scarce. Although several articles have been published on this matter, to this date there is no systematic overview pointing out the benefits that OCP can bring in the field of drug delivery. Here we offer a comprehensive overview, starting from the OCP synthesis to its structure, morphology, and the biological significance OCP has.
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Copper coating formed by micro-arc oxidation on pure Mg improved antibacterial activity, osteogenesis, and angiogenesis in vivo and in vitro. Biomed Microdevices 2021; 23:39. [PMID: 34302543 DOI: 10.1007/s10544-021-00573-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/25/2021] [Indexed: 01/14/2023]
Abstract
Micro-arc oxidation (MAO) was used to improve the resistance of pure magnesium (Mg). Copper (Cu), a good antibacterial, angiogenic, and osteogenic element, was added by reaction in a Cu-containing electrolyte to improve the osteogenic and pro-angiogenic activities of Mg. The surface microstructures of the resulting MAO were evaluated by a scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDS) mapping. The release of Cu ions was detected by ICP-OES. The antibacterial activity of films with different concentrations of Cu ions was assessed against Staphylococcus aureus (S. aureus). The osteogenesis of films was confirmed by cell morphology and proliferation, ALP activity, alizarin red staining, and osteogenic-related gene expression in the MC3T3-E1 cell line. The angiogenesis of the films was tested in human umbilical vein endothelial cells (HUVECs) by cell migration, tube formation, and VEGF quantification in vitro, and by a chicken embryo chorioallantoic membrane (CAM) assay in vivo. The results showed that the microporous structure was shaped by MAO, and the Cu group was denser and more uniform. The Cu coating showed effective antibacterial activity against S. aureus while also enhancing osteogenesis and angiogenesis in vitro. According to the CAM assay, the Cu group showed not only biocompatibility but also a significant angiogenic response, which was consistent with in vitro studies. The findings indicate that a Cu coating on Mg-MAO enhances osteogenesis and angiogenesis.
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Wang Y, Zhang W, Yao Q. Copper-based biomaterials for bone and cartilage tissue engineering. J Orthop Translat 2021; 29:60-71. [PMID: 34094859 PMCID: PMC8164005 DOI: 10.1016/j.jot.2021.03.003] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 02/25/2021] [Accepted: 03/01/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUD Tissue engineering using cells, scaffolds, and bioactive molecules can promote the repair and regeneration of injured tissues. Copper is an essential element for the human body that is involved in many physiological activities and in recent years, copper has been used increasingly in tissue engineering. METHODS The current advances of copper-based biomaterial for bone and cartilage tissue engineering were searched on PubMed and Web of Science. RESULTS Various forms of copper-based biomaterials, including pure copper, copper ions, copper nanoparticles, copper oxides, and copper alloy are introduced. The incorporation of copper into base materials provides unique properties, resulting in tuneable porosity, mechanical strength, degradation, and crosslinking of scaffolds. Copper also shows promising biological performance in cell migration, cell adhesion, osteogenesis, chondrogenesis, angiogenesis, and antibacterial activities. In vivo applications of copper for bone and cartilage tissue engineering are discussed. CONCLUSION This review focuses on copper's physiochemical and biological effects, and its applications in bone and cartilage tissue engineering. The potential limitations and future perspectives are also discussed. TRANSLATIONAL POTENTIAL OF THIS ARTICLE This review introduces the recent advances in copper-based biomaterial for bone and cartilage tissue engineering. This revie could guide researchers to apply copper in biomaterials, improving the generation of bone and cartilages, decrease the possibility of infection and shorten the recovery time so as to decrease medical costs.
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Affiliation(s)
- Yufeng Wang
- Department of Orthopaedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
- School of Medicine, Southeast University, Nanjing, 210009, China
| | - Wei Zhang
- School of Medicine, Southeast University, Nanjing, 210009, China
- China Orthopedic Regenerative Medicine Group (CORMed), China
| | - Qingqiang Yao
- Department of Orthopaedic Surgery, Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China
- China Orthopedic Regenerative Medicine Group (CORMed), China
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Foam Replica Method in the Manufacturing of Bioactive Glass Scaffolds: Out-of-Date Technology or Still Underexploited Potential? MATERIALS 2021; 14:ma14112795. [PMID: 34073945 PMCID: PMC8197364 DOI: 10.3390/ma14112795] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/18/2021] [Accepted: 05/21/2021] [Indexed: 01/19/2023]
Abstract
Since 2006, the foam replica method has been commonly recognized as a valuable technology for the production of highly porous bioactive glass scaffolds showing three-dimensional, open-cell structures closely mimicking that of natural trabecular bone. Despite this, there are important drawbacks making the usage of foam-replicated glass scaffolds a difficult achievement in clinical practice; among these, certainly the high operator-dependency of the overall manufacturing process is one of the most crucial, limiting the scalability to industrial production and, thus, the spread of foam-replicated synthetic bone substitutes for effective use in routine management of bone defect. The present review opens a window on the versatile world of the foam replica technique, focusing the dissertation on scaffold properties analyzed in relation to various processing parameters, in order to better understand which are the real issues behind the bottleneck that still puts this technology on the Olympus of the most used techniques in laboratory practice, without moving, unfortunately, to a more concrete application. Specifically, scaffold morphology, mechanical and mass transport properties will be reviewed in detail, considering the various templates proposed till now by several research groups all over the world. In the end, a comprehensive overview of in vivo studies on bioactive glass foams will be provided, in order to put an emphasis on scaffold performances in a complex three-dimensional environment.
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Jacobs A, Renaudin G, Charbonnel N, Nedelec JM, Forestier C, Descamps S. Copper-Doped Biphasic Calcium Phosphate Powders: Dopant Release, Cytotoxicity and Antibacterial Properties. MATERIALS 2021; 14:ma14092393. [PMID: 34064435 PMCID: PMC8124198 DOI: 10.3390/ma14092393] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 04/19/2021] [Accepted: 05/02/2021] [Indexed: 11/25/2022]
Abstract
Cytotoxicity and antibacterial properties associated with the dopant release of Cu-doped Biphasic Calcium Phosphate (BCP) powders, mainly composed of hydroxyapatite mixed with β-tricalcium phosphate powders, were investigated. Twelve BCP ceramics were synthesized at three different sintering temperatures (600 °C, 900 °C and 1200 °C) and four copper doping rates (x = 0.0, 0.05, 0.10 and 0.20, corresponding to the stoichiometric amount of copper in Ca10Cux(PO4)6(OH)2-2xO2x). Cytotoxicity assessments of Cu-doped BCP powders, using MTT assay with human-Mesenchymal Stem Cells (h-MSCs), indicated no cytotoxicity and the release of less than 12 ppm of copper into the biological medium. The antibacterial activity of the powders was determined against both Gram-positive (methicillin-sensitive (MS) and methicillin resistant (MR) Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. The Cu-doped biomaterials exhibited a strong antibacterial activity against MSSA, MRSA and E. coli, releasing approximatively 2.5 ppm after 24 h, whereas 10 ppm were required to induce an antibacterial effect against P. aeruginosa. This study also demonstrated that the culture medium used during experiments can directly impact the antibacterial effect observed; only 4 ppm of Cu2+ were effective for killing all the bacteria in a 1:500 diluted TS medium, whereas 20 ppm were necessary to achieve the same result in a rich, non-diluted standard marrow cell culture medium.
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Affiliation(s)
- Aurélie Jacobs
- Université Clermont Auvergne, Clermont Auvergne INP, CNRS, ICCF, F-63000 Clermont-Ferrand, France; (A.J.); (J.-M.N.)
| | - Guillaume Renaudin
- Université Clermont Auvergne, Clermont Auvergne INP, CNRS, ICCF, F-63000 Clermont-Ferrand, France; (A.J.); (J.-M.N.)
- Correspondence:
| | - Nicolas Charbonnel
- Université Clermont Auvergne, CNRS, Laboratoire Microorganismes: Genome et Environnement, F-63000 Clermont-Ferrand, France; (N.C.); (C.F.)
| | - Jean-Marie Nedelec
- Université Clermont Auvergne, Clermont Auvergne INP, CNRS, ICCF, F-63000 Clermont-Ferrand, France; (A.J.); (J.-M.N.)
| | - Christiane Forestier
- Université Clermont Auvergne, CNRS, Laboratoire Microorganismes: Genome et Environnement, F-63000 Clermont-Ferrand, France; (N.C.); (C.F.)
| | - Stéphane Descamps
- Université Clermont Auvergne, Clermont Auvergne INP, CNRS, CHU Clermont, ICCF, F-63000 Clermont-Ferrand, France;
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Jastrzębski K, Białecki J, Jastrzębska A, Kaczmarek A, Para M, Niedzielski P, Bociaga D. Induced Biological Response in Contact with Ag-and Cu-Doped Carbon Coatings for Potential Orthopedic Applications. MATERIALS 2021; 14:ma14081861. [PMID: 33918582 PMCID: PMC8070217 DOI: 10.3390/ma14081861] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 04/05/2021] [Accepted: 04/06/2021] [Indexed: 12/12/2022]
Abstract
Silver and copper as additives of various biomaterials have been reported as the potential solutions for biomedicine applications, mostly because of inducing bactericidal effects. The application of those admixtures in diamond-like carbon (DLC) coatings may be desirable for orthopedic implants. In the present manuscript, the biological effect of coatings with up to about 7 at.% and 14 at.% of, respectively, Cu and Ag is compared. The morphology, chemical structure, and composition of films deposited on AISI 316LVM and Ti6Al7Nb is characterized. The live/dead analysis conducted with Escherichia coli shows a higher bactericidal potential of silver than copper. Although the Cu-doped coatings can positively affect the proliferation of Saos-2 and EA.hy926 cell lines, the results of XTT test are on the verge of 70% of viability. Biological effect of silver on EA.hy926 cell lines is negative but that admixture ensures high proliferation of osteoblasts in contact with coatings deposited on titanium alloy (over 20% better than for substrate material). In that case, the viability is reaching about 85% for Ag-doped coatings on AISI 316LVM and 75% on Ti6Al7Nb. The results indicate that for the sake of bactericidal coatings that may promote osteointegration, the candidates are DLC with silver content no higher than 10 at.%.
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Affiliation(s)
- Krzysztof Jastrzębski
- Institute of Materials Science and Engineering, Lodz University of Technology, 1/15 Stefanowskiego St., 90-924 Lodz, Poland; (A.J.); (P.N.); (D.B.)
- Correspondence:
| | - Jerzy Białecki
- Ortopaedic Clinic of Centre of Postgraduate Medical Education in Otwock, Konarskiego 13, 05-400 Otwock, Poland; (J.B.); (M.P.)
| | - Aleksandra Jastrzębska
- Institute of Materials Science and Engineering, Lodz University of Technology, 1/15 Stefanowskiego St., 90-924 Lodz, Poland; (A.J.); (P.N.); (D.B.)
| | - Anna Kaczmarek
- Lukasiewicz Research Network-Textile Research Institute, Brzezinska 5/15, 92-103 Lodz, Poland;
| | - Marcin Para
- Ortopaedic Clinic of Centre of Postgraduate Medical Education in Otwock, Konarskiego 13, 05-400 Otwock, Poland; (J.B.); (M.P.)
| | - Piotr Niedzielski
- Institute of Materials Science and Engineering, Lodz University of Technology, 1/15 Stefanowskiego St., 90-924 Lodz, Poland; (A.J.); (P.N.); (D.B.)
| | - Dorota Bociaga
- Institute of Materials Science and Engineering, Lodz University of Technology, 1/15 Stefanowskiego St., 90-924 Lodz, Poland; (A.J.); (P.N.); (D.B.)
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Zhou L, Chen F, Hou Z, Chen Y, Luo X. Injectable self-healing CuS nanoparticle complex hydrogels with antibacterial, anti-cancer, and wound healing properties. CHEMICAL ENGINEERING JOURNAL 2021; 409:128224. [DOI: 10.1016/j.cej.2020.128224] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Influence of Cu 2+ on Osteoclast Formation and Activity In Vitro. Int J Mol Sci 2021; 22:ijms22052451. [PMID: 33671069 PMCID: PMC7957576 DOI: 10.3390/ijms22052451] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 02/24/2021] [Accepted: 02/25/2021] [Indexed: 01/28/2023] Open
Abstract
Background: Copper-containing biomaterials are increasingly applied for bone regeneration due to their pro-angiogenetic, pro-osteogenetic and antimicrobial properties. Therefore, the effect of Cu2+ on osteoclasts, which play a major role in bone remodeling was studied in detail. Methods: Human primary osteoclasts, differentiated from human monocytes were differentiated or cultivated in the presence of Cu2+. Osteoclast formation and activity were analyzed by measurement of osteoclast-specific enzyme activities, gene expression analysis and resorption assays. Furthermore, the glutathione levels of the cells were checked to evaluate oxidative stress induced by Cu2+. Results: Up to 8 µM Cu2+ did not induce cytotoxic effects. Activity of tartrate-resistant acid phosphatase (TRAP) was significantly increased, while other osteoclast specific enzyme activities were not affected. However, gene expression of TRAP was not upregulated. Resorptive activity of osteoclasts towards dentin was not changed in the presence of 8 µM Cu2+ but decreased in the presence of extracellular bone matrix. When Cu2+ was added to mature osteoclasts TRAP activity was not increased and resorption decreased only moderately. The glutathione level of both differentiating and mature osteoclasts was significantly decreased in the presence of Cu2+. Conclusions: Differentiating and mature osteoclasts react differently to Cu2+. High TRAP activities are not necessarily related to high resorption.
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Raveau S, Jordana F. Tissue Engineering and Three-Dimensional Printing in Periodontal Regeneration: A Literature Review. J Clin Med 2020; 9:jcm9124008. [PMID: 33322447 PMCID: PMC7763147 DOI: 10.3390/jcm9124008] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/06/2020] [Accepted: 12/08/2020] [Indexed: 02/06/2023] Open
Abstract
The three-dimensional printing of scaffolds is an interesting alternative to the traditional techniques of periodontal regeneration. This technique uses computer assisted design and manufacturing after CT scan. After 3D modelling, individualized scaffolds are printed by extrusion, selective laser sintering, stereolithography, or powder bed inkjet printing. These scaffolds can be made of one or several materials such as natural polymers, synthetic polymers, or bioceramics. They can be monophasic or multiphasic and tend to recreate the architectural structure of the periodontal tissue. In order to enhance the bioactivity and have a higher regeneration, the scaffolds can be embedded with stem cells and/or growth factors. This new technique could enhance a complete periodontal regeneration. This review summarizes the application of 3D printed scaffolds in periodontal regeneration. The process, the materials and designs, the key advantages and prospects of 3D bioprinting are highlighted, providing new ideas for tissue regeneration.
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Affiliation(s)
- Simon Raveau
- Dental Faculty, University of Nantes, 44000 Nantes, France;
- Dentistry Department, University Health Centre, 44000 Nantes, France
| | - Fabienne Jordana
- Dental Faculty, University of Nantes, 44000 Nantes, France;
- Dentistry Department, University Health Centre, 44000 Nantes, France
- Correspondence: ; Tel.: +33-24041-2928
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Seo JJ, Mandakhbayar N, Kang MS, Yoon JY, Lee NH, Ahn J, Lee HH, Lee JH, Kim HW. Antibacterial, proangiogenic, and osteopromotive nanoglass paste coordinates regenerative process following bacterial infection in hard tissue. Biomaterials 2020; 268:120593. [PMID: 33348262 DOI: 10.1016/j.biomaterials.2020.120593] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 11/23/2020] [Accepted: 12/06/2020] [Indexed: 12/12/2022]
Abstract
Bacterial infection raises serious concerns in tissue repair settings involved with implantable biomaterials, devastating the regenerative process and even life-threatening. When hard tissues are infected with bacteria (called 'osteomyelitis'), often the cases in open fracture or chronic inflammation, a complete restoration of regenerative capacity is significantly challenging even with highly-dosed antibiotics or surgical intervention. The implantable biomaterials are thus needed to be armored to fight bacteria then to relay regenerative events. To this end, here we propose a nanoglass paste made of ~200-nm-sized silicate-glass (with Ca, Cu) particles that are hardened in contact with aqueous medium and multiple-therapeutic, i.e., anti-bacterial, pro-angiogenic and osteopromotive. The nanoglass paste self-hardened via networks of precipitated nano-islands from leached ions to exhibit ultrahigh surface area (~300 m2/g), amenable to fill tunable defects with active biomolecular interactions. Also, the nanoglass paste could release multiple ions (silicate, calcium, and copper) at therapeutically relevant doses and sustainably (for days to weeks), implying possible roles in surrounding cells/tissues as a therapeutic-ions reservoir. The osteopromotive effects of nanoglass paste were evidenced by the stimulated osteogenic differentiation of MSCs. Also, the nanoglass paste promoted angiogenesis of endothelial cells in vitro and vasculature formation in vivo. Furthermore, the significant bactericidal effect of nanoglass paste, as assessed with E. coli and S. aureus, highlighted the role of copper played in elevating ROS level and destroying homeostasis, which salvaged tissue cells from co-cultivated bacteria contamination. When administered topically to rat tibia osteomyelitis defects, the nanoglass paste enhanced in vivo bone healing and fracture resistance. The developed nanoglass paste, given its self-setting property and the coordinated therapeutic actions, is considered to be a promising drug-free inorganic biomaterial platform for the regenerative therapy of bacteria-infected hard tissues.
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Affiliation(s)
- Jung Ju Seo
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea
| | - Nandin Mandakhbayar
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea
| | - Min Sil Kang
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea
| | - Ji-Young Yoon
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea
| | - Na-Hyun Lee
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea
| | - Junyong Ahn
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea
| | - Hae-Hyoung Lee
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea
| | - Jung-Hwan Lee
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea; Cell & Matter Institute, Dankook University, Cheonan, 31116, South Korea.
| | - Hae-Won Kim
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea; Cell & Matter Institute, Dankook University, Cheonan, 31116, South Korea.
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Sergi R, Bellucci D, Cannillo V. A Review of Bioactive Glass/Natural Polymer Composites: State of the Art. MATERIALS (BASEL, SWITZERLAND) 2020; 13:E5560. [PMID: 33291305 PMCID: PMC7730917 DOI: 10.3390/ma13235560] [Citation(s) in RCA: 72] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/02/2020] [Accepted: 12/04/2020] [Indexed: 02/07/2023]
Abstract
Collagen, gelatin, silk fibroin, hyaluronic acid, chitosan, alginate, and cellulose are biocompatible and non-cytotoxic, being attractive natural polymers for medical devices for both soft and hard tissues. However, such natural polymers have low bioactivity and poor mechanical properties, which limit their applications. To tackle these drawbacks, collagen, gelatin, silk fibroin, hyaluronic acid, chitosan, alginate, and cellulose can be combined with bioactive glass (BG) nanoparticles and microparticles to produce composites. The incorporation of BGs improves the mechanical properties of the final system as well as its bioactivity and regenerative potential. Indeed, several studies have demonstrated that polymer/BG composites may improve angiogenesis, neo-vascularization, cells adhesion, and proliferation. This review presents the state of the art and future perspectives of collagen, gelatin, silk fibroin, hyaluronic acid, chitosan, alginate, and cellulose matrices combined with BG particles to develop composites such as scaffolds, injectable fillers, membranes, hydrogels, and coatings. Emphasis is devoted to the biological potentialities of these hybrid systems, which look rather promising toward a wide spectrum of applications.
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Affiliation(s)
| | | | - Valeria Cannillo
- Dipartimento di Ingegneria Enzo Ferrari, Università degli Studi di Modena e Reggio Emilia, Via P. Vivarelli 10, 41125 Modena, Italy; (R.S.); (D.B.)
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Rivera LR, Cochis A, Biser S, Canciani E, Ferraris S, Rimondini L, Boccaccini AR. Antibacterial, pro-angiogenic and pro-osteointegrative zein-bioactive glass/copper based coatings for implantable stainless steel aimed at bone healing. Bioact Mater 2020; 6:1479-1490. [PMID: 33251384 PMCID: PMC7674162 DOI: 10.1016/j.bioactmat.2020.11.001] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 10/30/2020] [Accepted: 11/01/2020] [Indexed: 01/08/2023] Open
Abstract
Stainless steel implants are suitable candidates for bone replacement due to their cytocompatibility and mechanical resistance, but they suffer from lack of bioactivity and are prone to bacterial infections. Accordingly, to overcome those limitations, in this study we developed by electrophoretic deposition (EPD), an innovative surface coating made of (i) zein, a natural fibroblast-friendly polymer, (ii) bioactive glass, a pro-osteogenic inorganic material and (iii) copper containing bioactive glass, an antibacterial and pro-angiogenic material. FESEM images confirmed that porous, uniform and free of cracks coatings were obtained by EPD; moreover, coatings were resistant to mechanical stress as demonstrated by the tape test, resulting in a 4B classification of adhesion to the substrate. The coatings were cytocompatible as indicated by metabolism evaluation of human fibroblasts, endothelial cells and mature or progenitor osteoblasts cultivated in direct contact with the specimens. They also maintained pro-osteogenic properties towards undifferentiated progenitor cells that expressed osteogenic genes after 15 days of direct cultivation. Copper conferred antibacterial properties as biofilm formation of the joint pathogens Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli was significantly reduced in comparison with copper-free coatings (p < 0.05). Moreover, this anti-infective activity resulted as targeted towards bacteria while the cells viability was preserved when cells and bacteria were cultivated in the same environment by a co-culture assay. Finally, copper ability to recruit blood vessels and to inhibit bacterial infection was confirmed in vivo where the growth of S. aureus biofilm was inhibited and the formation of new (<50 μm diameter spread) blood vessels was observed.
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Affiliation(s)
- Laura Ramos Rivera
- Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Erlangen, Germany
| | - Andrea Cochis
- Department of Health Sciences, Università del Piemonte UPO, Novara, Italy.,Center for Translational Research on Autoimmune and Allergic Diseases-CAAD, Novara, Italy
| | - Sarah Biser
- Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Erlangen, Germany
| | - Elena Canciani
- Department of Department of Biomedical, Surgical and Dental Sciences, Thin Section Lab, University of Milan, Milan, Italy
| | - Sara Ferraris
- Department of Applied Science and Technology, Politecnico di Torino, Turin, Italy
| | - Lia Rimondini
- Department of Health Sciences, Università del Piemonte UPO, Novara, Italy.,Center for Translational Research on Autoimmune and Allergic Diseases-CAAD, Novara, Italy
| | - Aldo R Boccaccini
- Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Erlangen, Germany
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Jacobs A, Renaudin G, Forestier C, Nedelec JM, Descamps S. Biological properties of copper-doped biomaterials for orthopedic applications: A review of antibacterial, angiogenic and osteogenic aspects. Acta Biomater 2020; 117:21-39. [PMID: 33007487 DOI: 10.1016/j.actbio.2020.09.044] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 09/17/2020] [Accepted: 09/21/2020] [Indexed: 12/13/2022]
Abstract
Copper is an essential trace element required for human life, and is involved in several physiological mechanisms. Today researchers have found and confirmed that Cu has biological properties which are particularly useful for orthopedic biomaterials applications such as implant coatings or biodegradable filler bone substitutes. Indeed, Cu exhibits antibacterial functions, provides angiogenic ability and favors osteogenesis; these represent major key points for ideal biomaterial integration and the healing process that follows. The antibacterial performances of copper-doped biomaterials present an interesting alternative to the massive use of prophylactic antibiotics and help to limit the development of antibiotic resistance. By stimulating blood vessel growth and new bone formation, copper contributes to the improved bio-integration of biomaterials. This review describes the bio-functional advantages offered by Cu and focuses on the antibacterial, angiogenic and osteogenic properties of Cu-doped biomaterials with potential for orthopedic applications.
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Dong C, Feng W, Xu W, Yu L, Xiang H, Chen Y, Zhou J. The Coppery Age: Copper (Cu)-Involved Nanotheranostics. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2020; 7:2001549. [PMID: 33173728 PMCID: PMC7610332 DOI: 10.1002/advs.202001549] [Citation(s) in RCA: 116] [Impact Index Per Article: 23.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 06/07/2020] [Indexed: 05/10/2023]
Abstract
As an essential trace element in the human body, transitional metal copper (Cu) ions are the bioactive components within the body featuring dedicated biological effects such as promoting angiogenesis and influencing lipid/glucose metabolism. The recent substantial advances of nanotechnology and nanomedicine promote the emerging of distinctive Cu-involved biomaterial nanoplatforms with intriguing theranostic performances in biomedicine, which are originated from the biological effects of Cu species and the physiochemical attributes of Cu-composed nanoparticles. Based on the very-recent significant progresses of Cu-involved nanotheranostics, this work highlights and discusses the principles, progresses, and prospects on the elaborate design and rational construction of Cu-composed functional nanoplatforms for a diverse array of biomedical applications, including photonic nanomedicine, catalytic nanotherapeutics, antibacteria, accelerated tissue regeneration, and bioimaging. The engineering of Cu-based nanocomposites for synergistic nanotherapeutics is also exemplified, followed by revealing their intrinsic biological effects and biosafety for revolutionizing their clinical translation. Finally, the underlying critical concerns, unresolved hurdles, and future prospects on their clinical uses are analyzed and an outlook is provided. By entering the "Copper Age," these Cu-involved nanotherapeutic modalities are expected to find more broad biomedical applications in preclinical and clinical phases, despite the current research and developments still being in infancy.
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Affiliation(s)
- Caihong Dong
- Department of UltrasoundZhongshan HospitalFudan UniversityShanghai200032P. R. China
| | - Wei Feng
- School of Life SciencesShanghai UniversityShanghai200444P. R. China
- State Key Laboratory of High Performance Ceramics and Superfine MicrostructureShanghai Institute of CeramicsChinese Academy of SciencesShanghai200050P. R. China
| | - Wenwen Xu
- Department of UltrasoundRuijin HospitalShanghai Jiaotong University School of MedicineShanghai200025P. R. China
| | - Luodan Yu
- School of Life SciencesShanghai UniversityShanghai200444P. R. China
- State Key Laboratory of High Performance Ceramics and Superfine MicrostructureShanghai Institute of CeramicsChinese Academy of SciencesShanghai200050P. R. China
| | - Huiijng Xiang
- State Key Laboratory of High Performance Ceramics and Superfine MicrostructureShanghai Institute of CeramicsChinese Academy of SciencesShanghai200050P. R. China
| | - Yu Chen
- School of Life SciencesShanghai UniversityShanghai200444P. R. China
- State Key Laboratory of High Performance Ceramics and Superfine MicrostructureShanghai Institute of CeramicsChinese Academy of SciencesShanghai200050P. R. China
| | - Jianqiao Zhou
- Department of UltrasoundRuijin HospitalShanghai Jiaotong University School of MedicineShanghai200025P. R. China
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41
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Li X, Li G, Zhang K, Pei Z, Zhao S, Li J. Cu-loaded Brushite bone cements with good antibacterial activity and operability. J Biomed Mater Res B Appl Biomater 2020; 109:877-889. [PMID: 33112029 DOI: 10.1002/jbm.b.34752] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 09/28/2020] [Accepted: 10/17/2020] [Indexed: 01/29/2023]
Abstract
Bone defect-related surgical procedures are traumatic processes carrying potential inflammation and infection risks in the clinic, which are associated with prolonged antibiotic therapy that promotes bacterial antibiotic-resistance. In the present study, Cu-loaded brushite bone cements were designed, and the properties of the bone cements were evaluated. The setting time of the cement was prolonged from 12 to 50 min as the copper content increased. All cements were anti-washout, and the injectable coefficient of the cements was approximately 88%. Scanning electron microscopy results revealed that the crystal grains grew larger and thicker as the copper content in the cement increased, and brushite was determined to be the dominant crystalline phase for all the cements. However, a small amount of newly formed calcium copper phosphate was observed in the cement. Simultaneously, band shifts were observed in the Fourier transform infrared spectroscopy results at a Cu content of 5%. Moreover, the addition of Cu improved the compressive strength of brushite cements, and all cements were degradable. Furthermore, the Cu-loaded brushite bone cements performed well in inhibiting the growth and proliferation of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, and the diameter of the inhibition zone increased with increasing copper content. The study revealed that the Cu-loaded brushite bone cements possessed good cellular affinity to mouse bone marrow stem cells when a lower dose of copper was added in vitro. These results support the great potential of injectable antibacterial brushite bone cement specifically for bone tissue defect-related repair and regeneration.
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Affiliation(s)
- Xiaoyu Li
- Central laboratory, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, Henan, China
| | - Guangda Li
- College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, Henan, China
| | - Kaili Zhang
- College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, Henan, China
| | - Zhengjun Pei
- College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, Henan, China
| | - Santuan Zhao
- College of Material Science and Engineering, Henan University of Science and Technology, Luoyang, Henan, China
| | - Jinghua Li
- College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, Henan, China
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Duan J, Chen Z, Liang X, Chen Y, Li H, Tian X, Zhang M, Wang X, Sun H, Kong D, Li Y, Yang J. Construction and application of therapeutic metal-polyphenol capsule for peripheral artery disease. Biomaterials 2020; 255:120199. [DOI: 10.1016/j.biomaterials.2020.120199] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 04/02/2020] [Accepted: 06/09/2020] [Indexed: 01/10/2023]
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Huang L, Xie YH, Xiang HB, Hou YL, Yu B. Physiochemical properties of copper doped calcium sulfate in vitro and angiogenesis in vivo. Biotech Histochem 2020; 96:117-124. [PMID: 32615821 DOI: 10.1080/10520295.2020.1776392] [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: 10/23/2022] Open
Abstract
Bone cements were prepared by mixing calcium sulfate and copper sulfate in various proportions. We examined physical and physicochemical properties of the copper doped calcium sulfates and the effects of the cements on angiogenesis in vivo. Rod shaped calcium sulfate crystals were visible by scanning electron microscopy in the cement that contained no copper sulfate, whereas plate-like crystals covered the surface of the cement with high copper content. After immersion of the cements in simulated body fluid (SBF) for 1 day, X-ray diffractometric analysis showed that gypsum precipitates had formed in the copper doped calcium sulfate. The compressive strength of the cements increased from 3.3 MPa for pure calcium sulfate to 6.4 MPa for samples with copper sulfate added. Calcium ion release was greatest from pure calcium sulfate, and the rate of copper ion release was higher for cements containing the most copper. We found that 6 weeks after implantation, more blood vessels had formed around the high copper cement than for the copper-free cement. Copper doped calcium sulfate appears to be useful for application to regenerative medicine including wound healing and bone tissue engineering.
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Affiliation(s)
- Lei Huang
- Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University , Guangzhou, China
| | - Yong Heng Xie
- Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University , Guangzhou, China
| | - Hai Bo Xiang
- Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University , Guangzhou, China
| | - Yi Long Hou
- Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University , Guangzhou, China
| | - Bin Yu
- Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University , Guangzhou, China
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A potential strategy for in-stent restenosis: Inhibition of migration and proliferation of vascular smooth muscle cells by Cu ion. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 115:111090. [PMID: 32600694 DOI: 10.1016/j.msec.2020.111090] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 05/07/2020] [Accepted: 05/08/2020] [Indexed: 11/23/2022]
Abstract
The in-stent restenosis (ISR) often happens after the implantation of metal stents, including both bare metal stents (BMSs) and drug-eluting stents (DESs). Drug release from DESs could reduce significantly the occurrence of ISR but also suppress the revascularization and cause thrombosis. In this study, the effect of Cu ion in a range of 0 to 500 μM on the migration and proliferation of rat aortic smooth muscle cells (RASMCs) was investigated by a series of in vitro experiments including wound-healing assay, cell viability assay and flow cytometric analysis. It has been found that the critical concentration of Cu ion should be at least 250 μM in order to significantly inhibit the migration of RASMCs and the proliferation of RASMCs were impeded by every dose of Cu ion used in this study. In addition, the protein level of caspase-3 was upregulated by 250 μM and 500 μM Cu2+ exposure, which might be the main reason for RASMCs apoptosis. Thus, it is proposed that ISR might be prevented by the constant release of Cu ion.
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45
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Hua J, You H, Li X, You R, Ma L. Cu(II) ion loading in silk fibroin scaffolds with silk I structure. Int J Biol Macromol 2020; 158:275-281. [PMID: 32380100 DOI: 10.1016/j.ijbiomac.2020.04.094] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 03/28/2020] [Accepted: 04/13/2020] [Indexed: 01/06/2023]
Abstract
Metal ions play important roles in the diverse biochemical reactions associated with many cell signalling pathways. The modification of biomaterials with metal ions may offer a promising approach to stimulate cellular activity for improving tissue regeneration. Here, copper ion loading as a potential therapeutic agent in silk fibroin (SF) scaffolds was investigated. Freezing-annealing was used to induce silk I crystallization for forming water-insoluble SF scaffolds. Cu(II) ions were entrapped into SF scaffolds with different ratios by forming silk I crystal networks when copper chloride dihydrate was less than 5.0 wt%, producing water-stable materials. Moreover, it was found that copper ion chelation further enhanced SF stability when a low amount copper chloride was loaded. Increasing copper chloride content weakened silk I crystallization and Cu(II) ion chelation, rendering SF scaffolds unstable in water. Above 5.0 wt% copper chloride dihydrate, silk I crystallization was prevented. Finally, silk I scaffold with 1.5 wt% copper chloride dihydrate showed the strongest water-stability and highest loading efficiency. The results provide valuable data for understanding the effect of metal ions in freezing-induced SF crystallization, and also offer options for preparing novel Cu(II)-functionalized SF scaffolds.
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Affiliation(s)
- Jinsheng Hua
- Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230036, China
| | - Haining You
- State Key Laboratory for Hubei New Textile Materials and Advanced Processing Technologies, School of Textile Science and Engineering, Wuhan Textile University, Wuhan 430200, China
| | - Xiufang Li
- State Key Laboratory for Hubei New Textile Materials and Advanced Processing Technologies, School of Textile Science and Engineering, Wuhan Textile University, Wuhan 430200, China
| | - Renchuan You
- State Key Laboratory for Hubei New Textile Materials and Advanced Processing Technologies, School of Textile Science and Engineering, Wuhan Textile University, Wuhan 430200, China.
| | - Likun Ma
- Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230036, China.
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Lin Z, Cao Y, Zou J, Zhu F, Gao Y, Zheng X, Wang H, Zhang T, Wu T. Improved osteogenesis and angiogenesis of a novel copper ions doped calcium phosphate cement. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 114:111032. [PMID: 32993975 DOI: 10.1016/j.msec.2020.111032] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 04/06/2020] [Accepted: 04/28/2020] [Indexed: 11/30/2022]
Abstract
Improving the angio1genesis potential of bone-repairing materials is vital for the repair of cancerous bone defects. It can further facilitate the delivery of active substances with osteogenesis and anti-tumor functions, ultimately promoting the formation of new bone tissues. Copper ions (Cu2+) have been proved to be beneficial to angiogenesis. This study developed a new type of Cu-containing calcium phosphate cement (Cu-CPC) by incorporating with copper phosphate (CuP) nanoparticles with a photothermal anti-tumor effect. The results revealed that the main phases of all hydrated CPCs were hydroxyapatite, unreacted tricalcium phosphate and calcium carbonate. But the hydration products of CPC became thinner after the incorporation of Cu2+. With the increase of CuP concentration, the setting time of CPC was prolonged while the injectability and the compressive strength were increased. The release concentration of Cu2+in vitro was among 0.01 to 0.74 mg/mL, which showed a positive relation with CuP content. Mouse bone marrow stromal cells (mBMSCs) displayed higher adhesion activity, proliferation performance and expression of osteogenic genes and proteins on CPC with 0.01 wt% CuP (0.01Cu-CPC) and 0.05 wt% CuP (0.05Cu-CPC). When human umbilical vein endothelial cells were co-cultured with 0.01Cu-CPC and 0.05Cu-CPC extracts, the proliferation and angiogenesis-related gene and protein expression were significantly increased, and the in vitro tube formation capacity was promoted. However, higher CuP content inhibited the proliferation of mBMSCs. In conclusion, CPC with 0.01 wt% and 0.05 wt% CuP nanoparticles has the potential to promote bone formation around cancerous bone defects, which would be promising for bone regeneration and treatment of bone tumors.
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Affiliation(s)
- Zefeng Lin
- Guangdong Key Lab of Orthopedic Technology and Implant Materials, General Hospital of Southern Theater Command of PLA, Guangzhou 510010, China
| | - Yannan Cao
- Department of Stomatology, Affiliated Hospital of Jiangnan University, Wuxi 214000, China
| | - Jianming Zou
- Department of Stomatology, Affiliated Hospital of Jiangnan University, Wuxi 214000, China
| | - Fangyong Zhu
- Department of Stomatology, Affiliated Hospital of Jiangnan University, Wuxi 214000, China
| | - Yufeng Gao
- Department of Stomatology, Affiliated Hospital of Jiangnan University, Wuxi 214000, China
| | - Xiaofei Zheng
- Institute of Orthopedic Diseases and Center for Joint Surgery and Sports Medicine, the First Affiliated Hospital, Jinan University, Guangzhou 510632, China
| | - Huajun Wang
- Institute of Orthopedic Diseases and Center for Joint Surgery and Sports Medicine, the First Affiliated Hospital, Jinan University, Guangzhou 510632, China
| | - Tao Zhang
- Guangdong Key Lab of Orthopedic Technology and Implant Materials, General Hospital of Southern Theater Command of PLA, Guangzhou 510010, China.
| | - Tingting Wu
- Institute of Orthopedic Diseases and Center for Joint Surgery and Sports Medicine, the First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
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Wolf-Brandstetter C, Beutner R, Hess R, Bierbaum S, Wagner K, Scharnweber D, Gbureck U, Moseke C. Multifunctional calcium phosphate based coatings on titanium implants with integrated trace elements. Biomed Mater 2020; 15:025006. [DOI: 10.1088/1748-605x/ab5d7b] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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48
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Chetan, Vijayalakshmi U. A systematic review of the interaction and effects generated by antimicrobial metallic substituents in bone tissue engineering. Metallomics 2020; 12:1458-1479. [DOI: 10.1039/d0mt00127a] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Changes brought about by metal ions and metal nanoparticles within bacterial cells and the damage caused to the cellular membrane upon contact with negatively charged surface components.
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Affiliation(s)
- Chetan
- Department of Chemistry
- School of Advanced Sciences
- Vellore Institute of Technology
- Vellore-632 014
- India
| | - Uthirapathy Vijayalakshmi
- Department of Chemistry
- School of Advanced Sciences
- Vellore Institute of Technology
- Vellore-632 014
- India
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49
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Albulescu R, Popa AC, Enciu AM, Albulescu L, Dudau M, Popescu ID, Mihai S, Codrici E, Pop S, Lupu AR, Stan GE, Manda G, Tanase C. Comprehensive In Vitro Testing of Calcium Phosphate-Based Bioceramics with Orthopedic and Dentistry Applications. MATERIALS (BASEL, SWITZERLAND) 2019; 12:3704. [PMID: 31717621 PMCID: PMC6888321 DOI: 10.3390/ma12223704] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 10/29/2019] [Accepted: 11/05/2019] [Indexed: 02/07/2023]
Abstract
Recently, a large spectrum of biomaterials emerged, with emphasis on various pure, blended, or doped calcium phosphates (CaPs). Although basic cytocompatibility testing protocols are referred by International Organization for Standardization (ISO) 10993 (parts 1-22), rigorous in vitro testing using cutting-edge technologies should be carried out in order to fully understand the behavior of various biomaterials (whether in bulk or low-dimensional object form) and to better gauge their outcome when implanted. In this review, current molecular techniques are assessed for the in-depth characterization of angiogenic potential, osteogenic capability, and the modulation of oxidative stress and inflammation properties of CaPs and their cation- and/or anion-substituted derivatives. Using such techniques, mechanisms of action of these compounds can be deciphered, highlighting the signaling pathway activation, cross-talk, and modulation by microRNA expression, which in turn can safely pave the road toward a better filtering of the truly functional, application-ready innovative therapeutic bioceramic-based solutions.
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Affiliation(s)
- Radu Albulescu
- Victor Babes National Institute of Pathology, Biochemistry-Proteomics Department, 050096 Bucharest, Romania; (R.A.); (L.A.); (M.D.); (I.D.P.); (S.M.); (E.C.); (S.P.); (A.-R.L.); (G.M.)
- Department Pharmaceutical Biotechnology, National Institute for Chemical-Pharmaceutical R&D, 031299, Bucharest, Romania
| | - Adrian-Claudiu Popa
- National Institute of Materials Physics, 077125 Magurele, Romania (G.E.S.)
- Army Centre for Medical Research, 010195 Bucharest, Romania
| | - Ana-Maria Enciu
- Victor Babes National Institute of Pathology, Biochemistry-Proteomics Department, 050096 Bucharest, Romania; (R.A.); (L.A.); (M.D.); (I.D.P.); (S.M.); (E.C.); (S.P.); (A.-R.L.); (G.M.)
- Department of Cellular and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050047 Bucharest, Romania
| | - Lucian Albulescu
- Victor Babes National Institute of Pathology, Biochemistry-Proteomics Department, 050096 Bucharest, Romania; (R.A.); (L.A.); (M.D.); (I.D.P.); (S.M.); (E.C.); (S.P.); (A.-R.L.); (G.M.)
| | - Maria Dudau
- Victor Babes National Institute of Pathology, Biochemistry-Proteomics Department, 050096 Bucharest, Romania; (R.A.); (L.A.); (M.D.); (I.D.P.); (S.M.); (E.C.); (S.P.); (A.-R.L.); (G.M.)
- Department of Cellular and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050047 Bucharest, Romania
| | - Ionela Daniela Popescu
- Victor Babes National Institute of Pathology, Biochemistry-Proteomics Department, 050096 Bucharest, Romania; (R.A.); (L.A.); (M.D.); (I.D.P.); (S.M.); (E.C.); (S.P.); (A.-R.L.); (G.M.)
| | - Simona Mihai
- Victor Babes National Institute of Pathology, Biochemistry-Proteomics Department, 050096 Bucharest, Romania; (R.A.); (L.A.); (M.D.); (I.D.P.); (S.M.); (E.C.); (S.P.); (A.-R.L.); (G.M.)
| | - Elena Codrici
- Victor Babes National Institute of Pathology, Biochemistry-Proteomics Department, 050096 Bucharest, Romania; (R.A.); (L.A.); (M.D.); (I.D.P.); (S.M.); (E.C.); (S.P.); (A.-R.L.); (G.M.)
| | - Sevinci Pop
- Victor Babes National Institute of Pathology, Biochemistry-Proteomics Department, 050096 Bucharest, Romania; (R.A.); (L.A.); (M.D.); (I.D.P.); (S.M.); (E.C.); (S.P.); (A.-R.L.); (G.M.)
| | - Andreea-Roxana Lupu
- Victor Babes National Institute of Pathology, Biochemistry-Proteomics Department, 050096 Bucharest, Romania; (R.A.); (L.A.); (M.D.); (I.D.P.); (S.M.); (E.C.); (S.P.); (A.-R.L.); (G.M.)
- Cantacuzino National Medico-Military Institute for Research and Development, 050096 Bucharest, Romania
| | - George E. Stan
- National Institute of Materials Physics, 077125 Magurele, Romania (G.E.S.)
| | - Gina Manda
- Victor Babes National Institute of Pathology, Biochemistry-Proteomics Department, 050096 Bucharest, Romania; (R.A.); (L.A.); (M.D.); (I.D.P.); (S.M.); (E.C.); (S.P.); (A.-R.L.); (G.M.)
| | - Cristiana Tanase
- Victor Babes National Institute of Pathology, Biochemistry-Proteomics Department, 050096 Bucharest, Romania; (R.A.); (L.A.); (M.D.); (I.D.P.); (S.M.); (E.C.); (S.P.); (A.-R.L.); (G.M.)
- Cajal Institute, Titu Maiorescu University, 004051 Bucharest, Romania
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50
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Boffito M, Pontremoli C, Fiorilli S, Laurano R, Ciardelli G, Vitale-Brovarone C. Injectable Thermosensitive Formulation Based on Polyurethane Hydrogel/Mesoporous Glasses for Sustained Co-Delivery of Functional Ions and Drugs. Pharmaceutics 2019; 11:E501. [PMID: 31581422 PMCID: PMC6835912 DOI: 10.3390/pharmaceutics11100501] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 09/06/2019] [Accepted: 09/19/2019] [Indexed: 11/16/2022] Open
Abstract
Mini-invasively injectable hydrogels are widely attracting interest as smart tools for the co-delivery of therapeutic agents targeting different aspects of tissue/organ healing (e.g., neo-angiogenesis, inflammation). In this work, copper-substituted bioactive mesoporous glasses (Cu-MBGs) were prepared as nano- and micro-particles and successfully loaded with ibuprofen through an incipient wetness method (loaded ibuprofen approx. 10% w/w). Injectable hybrid formulations were then developed by dispersing ibuprofen-loaded Cu-MBGs within thermosensitive hydrogels based on a custom-made amphiphilic polyurethane. This procedure showed almost no effects on the gelation potential (gelation at 37 °C within 3-5 min). Cu2+ and ibuprofen were co-released over time in a sustained manner with a significantly lower burst release compared to MBG particles alone (burst release reduction approx. 85% and 65% for ibuprofen and Cu2+, respectively). Additionally, released Cu2+ species triggered polyurethane chemical degradation, thus enabling a possible tuning of gel residence time at the pathological site. The overall results suggest that hybrid injectable thermosensitive gels could be successfully designed for the simultaneous localized co-delivery of multiple therapeutics.
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Affiliation(s)
- Monica Boffito
- Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.
| | - Carlotta Pontremoli
- Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.
| | - Sonia Fiorilli
- Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.
| | - Rossella Laurano
- Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.
| | - Gianluca Ciardelli
- Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.
| | - Chiara Vitale-Brovarone
- Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy.
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