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1
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Heo CH, Yeo KB, Chae M, Bak SY, Choi HJ, Jeong S, Choi N, Kang SK, Jun SH, Ok MR, Kim SY. Spontaneous bone regeneration achieved through one-step alignment of human mesenchymal stem cell-embedded collagen. Acta Biomater 2025; 196:136-151. [PMID: 40054649 DOI: 10.1016/j.actbio.2025.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 02/21/2025] [Accepted: 03/04/2025] [Indexed: 03/15/2025]
Abstract
Optimizing cell-matrix interactions for effective bone regeneration remains a significant hurdle in tissue engineering. This study presents a novel approach by developing a human mesenchymal stem cells (hMSCs)-embedded 3D aligned collagen for enhanced bone regeneration. A one-step mechanical strain was applied to a mixture of hMSCs and collagen, producing an hMSC-embedded, aligned 3D collagen hydrogel patch that mimics the natural bone matrix. Notably, the hMSCs embedded in the aligned collagen spontaneously differentiated into osteoblasts without external inducing reagents. Immunofluorescence analysis revealed that the BMP2-smad1/5 signaling pathway, critical for osteogenic differentiation, were activated by aligned collagen. In vivo experiments using a calvarial defect model confirmed that this approach effectively promotes new bone formation, starting centrally within the defect rather than from the edges adjacent to the existing bone. Our findings suggest that this simple method of pre-straining to create aligned 3D collagen embedded with hMSCs holds promise as a novel cell therapy platform for bone regeneration. STATEMENT OF SIGNIFICANCE: This study introduces a novel method for enhancing bone regeneration by developing a 3D aligned collagen patch embedded with hMSCs. A single mechanical strain applied to the hMSC-collagen mixture produces an aligned collagen matrix that mimics natural bone tissue. Remarkably, the hMSCs spontaneously differentiate into osteoblasts in the absence of exogenous inducing reagents triggered by activation of the bone morphogenetic protein signaling pathway. In vivo studies using a calvarial defect model confirm effective bone regeneration, initiating the new bone generation from the center of the defect. This approach offers a promising and simple cell therapy platform for bone repair, with broad implications for tissue engineering and regenerative medicine.
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Affiliation(s)
- Cheol Ho Heo
- Department of Applied Chemistry, Kookmin University, Seoul 02707, Republic of Korea
| | - Ki Baek Yeo
- Institute for Clinical Dental Science, Korea University Medical Center, Seoul 02841, Republic of Korea
| | - Minjung Chae
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea; Department of Materials Science and Engineering, Seoul National University, Seoul 08826, Republic of Korea
| | - Seon Young Bak
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea
| | - Hyeon Jin Choi
- Chemical and Biological Integrative Research Center, Biomedical Research Division, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea
| | - Sohyeon Jeong
- Center for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea National University of Science and Technology, Seoul 02792, Republic of Korea; MEPSGEN Co. Ltd., Seoul 05836, Republic of Korea
| | - Nakwon Choi
- Center for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Department of Convergence Medicine, College of Medicine, Korea University, Seoul 02841, Republic of Korea; Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Republic of Korea
| | - Seung-Kyun Kang
- Department of Materials Science and Engineering, Seoul National University, Seoul 08826, Republic of Korea
| | - Sang Ho Jun
- Department of Oral and Maxillofacial Surgery, Korea University Anam Hospital, Seoul 02841, Republic of Korea.
| | - Myoung-Ryul Ok
- Biomaterials Research Center, Biomedical Research Division, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea National University of Science and Technology, Seoul 02792, Republic of Korea.
| | - So Yeon Kim
- Chemical and Biological Integrative Research Center, Biomedical Research Division, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea National University of Science and Technology, Seoul 02792, Republic of Korea; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea.
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Pecorini G, Domingos MAN, Richardson SM, Carmassi L, Vecchi DL, Parrini G, Puppi D. 3D printing of bacterial poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(lactide-co-glycolide) blend loaded with β-tricalcium phosphate for the development of scaffolds to support human mesenchymal stromal cell proliferation. Int J Biol Macromol 2025; 288:138744. [PMID: 39674454 DOI: 10.1016/j.ijbiomac.2024.138744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 11/20/2024] [Accepted: 12/11/2024] [Indexed: 12/16/2024]
Abstract
Polyhydroxyalkanoates (PHAs) are microbially produced aliphatic polyesters investigated for tissue engineering thanks to their biocompatibility, processability, and suitable mechanical properties. Taking advantage of these properties, the present study investigates the development by 3D printing of bacterial poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) scaffolds loaded with β-tricalcium phosphate (β-TCP) for bone tissue regeneration. PHBV blending with poly(lactide-co-glycolide) (PLGA) (30 wt%) was exploited to enhance material processability via an optimized computer-aided wet-spinning approach. In particular, PHBV/PLGA blends were loaded with different β-TCP percentages (up to 15 wt%) by suspending the ceramic particles into the polymeric solution. The composite materials were successfully fabricated into 3D scaffolds with a fully interconnected porous architecture, as demonstrated by scanning electron microscopy. The ceramic phase had a significant effect on PHBV crystallization as shown by differential scanning calorimetry, as well as on scaffold mechanical properties with a significant increase of compressive modulus in the case of 5 wt% β-TCP loading. In addition, in vitro cell culture experiments demonstrated that β-TCP loading led to a significant increase of the viability of human mesenchymal stem/stromal cells grown on the scaffolds. Taken together, our data suggest that microbial PHBV processability, biomechanical performance, and bioactivity can be improved through combined PLGA blending and β-TCP loading.
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Affiliation(s)
- Gianni Pecorini
- Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM-Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy
| | - Marco A N Domingos
- Department of Mechanical and Aerospace Engineering, School of Engineering, Faculty of Science and Engineering, Henry Royce Institute, The University of Manchester, Manchester M13 9PL, UK.
| | - Stephen M Richardson
- Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK
| | - Leonardo Carmassi
- Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM-Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy
| | - Diego Li Vecchi
- Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM-Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy
| | | | - Dario Puppi
- Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM-Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy.
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3
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Marcello E, Nigmatullin R, Basnett P, Maqbool M, Prieto MA, Knowles JC, Boccaccini AR, Roy I. 3D Melt-Extrusion Printing of Medium Chain Length Polyhydroxyalkanoates and Their Application as Antibiotic-Free Antibacterial Scaffolds for Bone Regeneration. ACS Biomater Sci Eng 2024; 10:5136-5153. [PMID: 39058405 PMCID: PMC11322914 DOI: 10.1021/acsbiomaterials.4c00624] [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: 04/02/2024] [Revised: 07/09/2024] [Accepted: 07/09/2024] [Indexed: 07/28/2024]
Abstract
In this work, we investigated, for the first time, the possibility of developing scaffolds for bone tissue engineering through three-dimensional (3D) melt-extrusion printing of medium chain length polyhydroxyalkanoate (mcl-PHA) (i.e., poly(3-hydroxyoctanoate-co-hydroxydecanoate-co-hydroxydodecanoate), P(3HO-co-3HD-co-3HDD)). The process parameters were successfully optimized to produce well-defined and reproducible 3D P(3HO-co-3HD-co-3HDD) scaffolds, showing high cell viability (100%) toward both undifferentiated and differentiated MC3T3-E1 cells. To introduce antibacterial features in the developed scaffolds, two strategies were investigated. For the first strategy, P(3HO-co-3HD-co-3HDD) was combined with PHAs containing thioester groups in their side chains (i.e., PHACOS), inherently antibacterial PHAs. The 3D blend scaffolds were able to induce a 70% reduction of Staphylococcus aureus 6538P cells by direct contact testing, confirming their antibacterial properties. Additionally, the scaffolds were able to support the growth of MC3T3-E1 cells, showing the potential for bone regeneration. For the second strategy, composite materials were produced by the combination of P(3HO-co-3HD-co-HDD) with a novel antibacterial hydroxyapatite doped with selenium and strontium ions (Se-Sr-HA). The composite material with 10 wt % Se-Sr-HA as a filler showed high antibacterial activity against both Gram-positive (S. aureus 6538P) and Gram-negative bacteria (Escherichia coli 8739), through a dual mechanism: by direct contact (inducing 80% reduction of both bacterial strains) and through the release of active ions (leading to a 54% bacterial cell count reduction for S. aureus 6538P and 30% for E. coli 8739 after 24 h). Moreover, the composite scaffolds showed high viability of MC3T3-E1 cells through both indirect and direct testing, showing promising results for their application in bone tissue engineering.
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Affiliation(s)
- Elena Marcello
- Faculty
of Science and Technology, College of Liberal Arts, University of Westminster, London W1W 6UW, U.K.
| | - Rinat Nigmatullin
- Faculty
of Science and Technology, College of Liberal Arts, University of Westminster, London W1W 6UW, U.K.
| | - Pooja Basnett
- Faculty
of Science and Technology, College of Liberal Arts, University of Westminster, London W1W 6UW, U.K.
| | - Muhammad Maqbool
- Institute
of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Erlangen 91058, Germany
- Lucideon
Ltd., Stoke-on-Trent ST4 7LQ, Staffordshire U.K.
- CAM
Bioceramics B.V., Zernikedreef
6, 2333 CL Leiden, The Netherlands
| | - M. Auxiliadora Prieto
- Polymer
Biotechnology Lab, Centro de Investigaciones Biológicas-Margarita
Salas, Spanish National Research Council
(CIB-CSIC), Madrid 28040, Spain
| | - Jonathan C. Knowles
- Division
of Biomaterials and Tissue Engineering, University College London Eastman Dental Institute, London NW3 2PF, U.K.
- Department
of Nanobiomedical Science and BK21 Plus NBM, Global Research Center
for Regenerative Medicine, Dankook University, Cheonan 31116, South Korea
| | - Aldo R. Boccaccini
- Institute
of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Erlangen 91058, Germany
| | - Ipsita Roy
- Department
of Materials Science and Engineering, Faculty of Engineering, University of Sheffield, Sheffield S3 7HQ, U.K.
- Insigneo
Institute for In Silico Medicine, University
of Sheffield, Sheffield S3 7HQ, U.K.
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Thomas S, Rajendran AR, Purushothaman B, Subramanian B. Advancing Bioactive Material for Mandibular Bone Regeneration: Transformation of Fibrous Mat into 3D Matrix Cotton for Enhanced Shape Retention and Rapid Hemostasis. ACS Biomater Sci Eng 2024; 10:5194-5209. [PMID: 39026391 DOI: 10.1021/acsbiomaterials.4c01148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/20/2024]
Abstract
Transformation of a fibrous mat into a three-dimensional (3D) scaffold opens up abundant innovative prospects in biomedical research, particularly for studying both soft as well as hard tissues. Electrospun nanofibers, which mimic the extracellular matrix have attracted significant attention in various studies. This research focuses on rapidly converting a fibrous mat made of polycaprolactone (PCL)/pluronic F-127 (PF-127) with different percentages of monetite calcium phosphate (MCP) into desirable 3D matrix cotton using a unique gas foaming technology. These matrix cottons possess biomimetic properties and have oriented porous structures. Using this innovative technique, various shapes of 3D matrix cotton, such as squares, hollow tubes, and other customizable forms, were successfully produced. Importantly, these 3D matrix cottons showed a consistent distribution of monetite particles with total porosity ranging from 90% to 98%. The structure of the 3D matrix cotton, its water/blood absorption capacity, the potential for causing non-hemolysis, and rapid hemostatic properties were thoroughly investigated. Additionally, periodontal cells were cultured on the 3D matrix cotton to assess their viability and morphology, revealing promising results. Furthermore, a coculture study involving NIH-3T3 and MG-63 cells on the 3D matrix cotton showed spheroidal formation within 24 h. Notably, in vitro assessments indicated that the matrix cotton containing 15% monetite (PCL-MMC15%) exhibited superior absorbent capabilities, excellent cell viability, and rapid hemostatic characteristics. Subsequently, the effectiveness of PCL-MMC15% in promoting mandibular bone regeneration was evaluated through an in vivo study on rabbits using a mandibular injury model. The results demonstrated that PCL-MMC15% facilitated the resolution of defects in the mandibular region by initiating new bone formation. Therefore, the presented 3D matrix cotton (PCL-MMC15%) shows significant promise for applications in both mandibular bone regeneration and hemostasis.
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Affiliation(s)
- Shalini Thomas
- National Centre for Nanoscience and Nanotechnology, University of Madras, Guindy Campus, Chennai, 600 025, India
| | - Ajay Rakkesh Rajendran
- Functional Nano-Materials (FuN) Laboratory, Department of Physics and Nanotechnology, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, TN 603203, India
| | - Bargavi Purushothaman
- Department of Oral Pathology, Saveetha Dental College and Hospital, Chennai, 600 077, India
| | - Balakumar Subramanian
- National Centre for Nanoscience and Nanotechnology, University of Madras, Guindy Campus, Chennai, 600 025, India
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Pecorini G, Braccini S, Simoni S, Corti A, Parrini G, Puppi D. Additive Manufacturing of Wet-Spun Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)-Based Scaffolds Loaded with Hydroxyapatite. Macromol Biosci 2024; 24:e2300538. [PMID: 38534197 DOI: 10.1002/mabi.202300538] [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: 11/21/2023] [Revised: 03/20/2024] [Indexed: 03/28/2024]
Abstract
Tissue engineering represents an advanced therapeutic approach for the treatment of bone tissue defects. Polyhydroxyalkanoates are a promising class of natural polymers in this context thanks to their biocompatibility, processing versatility, and mechanical properties. The aim of this study is the development by computer-aided wet-spinning of novel poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)-based composite scaffolds for bone engineering. In particular, PHBV scaffolds are loaded with hydroxyapatite (HA), an osteoinductive ceramic, in order to tailor their biological activity and mechanical properties. PHBV blending with poly(lactide-co-glycolide) (PLGA) is also explored to increase the processing properties of the polymeric mixture used for composite scaffold fabrication. Different HA percentages, up to 15% wt., can be loaded into the PHBV or PHBV/PLGA scaffolds without compromising their interconnected porous architecture, as well as the polymer morphological and thermal properties, as demonstrated by scanning electron microscopy, thermogravimetric analysis, and differential scanning calorimetry. In addition, HA loading results in increased scaffold compressive stiffness to levels comparable to those of trabecular bone tissue, as well as in higher in vitro MC3T3-E1 cell viability and production of mineralized extracellular matrix, in comparison to what observed for unloaded scaffolds. The observed mechanical and biological properties suggest the suitability of the developed scaffolds for bone engineering.
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Affiliation(s)
- Gianni Pecorini
- BIOLab Research Group, Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM Pisa, Via Moruzzi 13, Pisa, 56124, Italy
| | - Simona Braccini
- BIOLab Research Group, Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM Pisa, Via Moruzzi 13, Pisa, 56124, Italy
| | - Stefano Simoni
- BIOLab Research Group, Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM Pisa, Via Moruzzi 13, Pisa, 56124, Italy
| | - Andrea Corti
- BIOLab Research Group, Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM Pisa, Via Moruzzi 13, Pisa, 56124, Italy
| | | | - Dario Puppi
- BIOLab Research Group, Department of Chemistry and Industrial Chemistry, University of Pisa, UdR INSTM Pisa, Via Moruzzi 13, Pisa, 56124, Italy
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6
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Liu J, Shi Y, Zhao Y, Liu Y, Yang X, Li K, Zhao W, Han J, Li J, Ge S. A Multifunctional Metal-Phenolic Nanocoating on Bone Implants for Enhanced Osseointegration via Early Immunomodulation. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2307269. [PMID: 38445899 PMCID: PMC11095205 DOI: 10.1002/advs.202307269] [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: 09/30/2023] [Revised: 01/21/2024] [Indexed: 03/07/2024]
Abstract
Surface modification is an important approach to improve osseointegration of the endosseous implants, however it is still desirable to develop a facile yet efficient coating strategy. Herein, a metal-phenolic network (MPN) is proposed as a multifunctional nanocoating on titanium (Ti) implants for enhanced osseointegration through early immunomodulation. With tannic acid (TA) and Sr2+ self-assembled on Ti substrates, the MPN coatings provided a bioactive interface, which can facilitate the initial adhesion and recruitment of bone marrow mesenchymal stem cells (BMSCs) and polarize macrophage toward M2 phenotype. Furthermore, the TA-Sr coatings accelerated the osteogenic differentiation of BMSCs. In vivo evaluations further confirmed the enhanced osseointegration of TA-Sr modified implants via generating a favorable osteoimmune microenvironment. In general, these results suggest that TA-Sr MPN nanocoating is a promising strategy for achieving better and faster osseointegration of bone implants, which can be easily utilized in future clinical applications.
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Affiliation(s)
- Jin Liu
- Department of Biomaterial & Periodontology & ImplantologySchool and Hospital of StomatologyCheeloo College of MedicineShandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesJinan250012China
| | - Yilin Shi
- Department of Biomaterial & Periodontology & ImplantologySchool and Hospital of StomatologyCheeloo College of MedicineShandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesJinan250012China
| | - Yajun Zhao
- Department of Biomaterial & Periodontology & ImplantologySchool and Hospital of StomatologyCheeloo College of MedicineShandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesJinan250012China
| | - Yue Liu
- Department of Biomaterial & Periodontology & ImplantologySchool and Hospital of StomatologyCheeloo College of MedicineShandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesJinan250012China
| | - Xiaoru Yang
- Department of Biomaterial & Periodontology & ImplantologySchool and Hospital of StomatologyCheeloo College of MedicineShandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesJinan250012China
| | - Kai Li
- Department of Biomaterial & Periodontology & ImplantologySchool and Hospital of StomatologyCheeloo College of MedicineShandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesJinan250012China
| | - Weiwei Zhao
- Department of Biomaterial & Periodontology & ImplantologySchool and Hospital of StomatologyCheeloo College of MedicineShandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesJinan250012China
| | - Jianmin Han
- Central Laboratory,Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of StomatologyBeijing100081China
| | - Jianhua Li
- Department of Biomaterial & Periodontology & ImplantologySchool and Hospital of StomatologyCheeloo College of MedicineShandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesJinan250012China
| | - Shaohua Ge
- Department of Biomaterial & Periodontology & ImplantologySchool and Hospital of StomatologyCheeloo College of MedicineShandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral DiseasesJinan250012China
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7
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Zhuikova YV, Zhuikov VA, Makhina TK, Efremov YM, Aksenova NA, Timashev PS, Bonartseva GA, Varlamov VP. Preparation and characterization of poly(3-hydroxybutyrate)/chitosan composite films using acetic acid as a solvent. Int J Biol Macromol 2023; 248:125970. [PMID: 37494998 DOI: 10.1016/j.ijbiomac.2023.125970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 06/27/2023] [Accepted: 07/22/2023] [Indexed: 07/28/2023]
Abstract
Poly(3-hydroxybutyrate) and chitosan are among the most widely used polymers for biomedical applications due to their biocompatibility, renewability and low toxicity. The creation of composite materials based on biopolymers belonging to different classes makes it possible to overcome the disadvantages of each of the components and to obtain a material with specific properties. Solving this problem is associated with difficulties in the selection of conditions and solvents for obtaining the composite material. In our study, acetic acid was used as a common solvent for hydrophobic poly(3-hydroxybutyrate) and chitosan. Mechanical, thermal, physicochemical and surface properties of the composites and homopolymers were investigated. The composite films had less crystallinity and hydrophobicity than poly(3-hydroxybutyrate), and the addition of chitosan caused an increase in moisture absorption, a decrease in contact angle and changes in mechanical properties of the poly(3-hydroxybutyrate). The inclusion of varying amounts of chitosan controlled the properties of the composite, which will be important in the future for its specific biomedical applications.
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Affiliation(s)
- Yulia V Zhuikova
- Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia.
| | - Vsevolod A Zhuikov
- Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia
| | - Tatiana K Makhina
- Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia
| | - Yuri M Efremov
- Institute for Regenerative Medicine, Sechenov University, Moscow, Russia
| | - Nadezhda A Aksenova
- Institute for Regenerative Medicine, Sechenov University, Moscow, Russia; N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Moscow, Russia
| | - Peter S Timashev
- Institute for Regenerative Medicine, Sechenov University, Moscow, Russia; World-Class Research Center "Digital Biodesign and Personalized Healthcare" Moscow, Russia; Chemistry Department, Lomonosov Moscow State University, Moscow, Russia
| | - Garina A Bonartseva
- Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia
| | - Valery P Varlamov
- Research Center of Biotechnology of the Russian Academy of Sciences, Moscow, Russia
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Yao X, Li P, Deng Y, Yang Y, Luo H, He B. Role of p53 in promoting BMP9‑induced osteogenic differentiation of mesenchymal stem cells through TGF‑β1. Exp Ther Med 2023; 25:248. [PMID: 37153899 PMCID: PMC10160913 DOI: 10.3892/etm.2023.11947] [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: 08/11/2022] [Accepted: 02/24/2023] [Indexed: 05/10/2023] Open
Abstract
Known as a tumour suppressor gene, p53 also plays a key role in controlling the differentiation of mesenchymal stem cells (MSCs). Bone morphogenetic protein 9 (BMP9) has been identified as a potent factor in inducing osteogenic differentiation of MSCs, but its relationship with p53 remains unclear. The present study revealed that TP53 was expressed at higher levels in MSCs from patients with osteoporosis and was associated with the top 10 core central genes found in the current osteoporosis genetic screen. p53 was expressed in C2C12, C3H10T1/2, 3T3-L1, MEFs, and MG-63 cell lines, and could be upregulated by BMP9, as measured by western blotting and reverse-transcription quantitative PCR (RT-qPCR). Furthermore, overexpression of p53 increased the mRNA and protein levels of osteogenic marker Runx2 and osteopontin, as evaluated by western blotting and RT-qPCR in BMP9-induced MSCs, whereas the p53 inhibitor pifithrin (PFT)-α attenuated these effects. The same trend was found in alkaline phosphatase activities and matrix mineralization, as measured by alkaline phosphatase staining and alizarin red S staining. Moreover, p53 overexpression reduced adipo-differentiation markers of PPARγ and lipid droplet formation, as measured by western blotting, RT-qPCR and oil red O staining, respectively, whereas PFT-α facilitated adipo-differentiation in MSCs. In addition, p53 promoted TGF-β1 expression and inhibition of TGF-β1 by LY364947 partially attenuated the effects of p53 on promoting BMP9-induced MSC osteo-differentiation and inhibiting adipo-differentiation. The inhibitory effect of PFT-α on osteogenic markers and the promoting effect on adipogenic markers can be reversed when combined with TGF-β1. TGF-β1 may enhance the promotion of osteo-differentiation of MSCs by p53 through inhibition of adipo-differentiation. Collectively, by promoting BMP9-induced MSCs bone differentiation and inhibiting adipose differentiation, p53 may be a novel therapeutic target for bone-related diseases.
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Affiliation(s)
- Xintong Yao
- College of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China
- Chongqing Key Laboratory for Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Peipei Li
- College of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China
- Chongqing Key Laboratory for Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Yixuan Deng
- College of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China
- Chongqing Key Laboratory for Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Yuanyuan Yang
- College of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China
- Chongqing Key Laboratory for Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Honghong Luo
- College of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China
- Chongqing Key Laboratory for Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, P.R. China
| | - Baicheng He
- College of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China
- Chongqing Key Laboratory for Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, P.R. China
- Correspondence to: Professor Baicheng He, College of Pharmacy, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong, Chongqing 400016, P.R. China
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9
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Ladhari S, Vu NN, Boisvert C, Saidi A, Nguyen-Tri P. Recent Development of Polyhydroxyalkanoates (PHA)-Based Materials for Antibacterial Applications: A Review. ACS APPLIED BIO MATERIALS 2023; 6:1398-1430. [PMID: 36912908 DOI: 10.1021/acsabm.3c00078] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/14/2023]
Abstract
The diseases caused by microorganisms are innumerable existing on this planet. Nevertheless, increasing antimicrobial resistance has become an urgent global challenge. Thus, in recent decades, bactericidal materials have been considered promising candidates to combat bacterial pathogens. Recently, polyhydroxyalkanoates (PHAs) have been used as green and biodegradable materials in various promising alternative applications, especially in healthcare for antiviral or antiviral purposes. However, it lacks a systematic review of the recent application of this emerging material for antibacterial applications. Therefore, the ultimate goal of this review is to provide a critical review of the state of the art recent development of PHA biopolymers in terms of cutting-edge production technologies as well as promising application fields. In addition, special attention was given to collecting scientific information on antibacterial agents that can potentially be incorporated into PHA materials for biological and durable antimicrobial protection. Furthermore, the current research gaps are declared, and future research perspectives are proposed to better understand the properties of these biopolymers as well as their possible applications.
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Affiliation(s)
- Safa Ladhari
- Department of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada.,Laboratory of Advanced Materials for Energy and Environment, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada
| | - Nhu-Nang Vu
- Department of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada.,Laboratory of Advanced Materials for Energy and Environment, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada
| | - Cédrik Boisvert
- Department of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada.,Laboratory of Advanced Materials for Energy and Environment, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada
| | - Alireza Saidi
- Laboratory of Advanced Materials for Energy and Environment, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada.,Institut de Recherche Robert-Sauvé en Santé et Sécurité du Travail (IRSST), 505 Boulevard de Maisonneuve Ouest, Montréal, Québec H3A 3C2, Canada
| | - Phuong Nguyen-Tri
- Department of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada.,Laboratory of Advanced Materials for Energy and Environment, Université du Québec à Trois-Rivières (UQTR), 3351 Boulevard des Forges, Trois-Rivières, Québec G8Z 4M3, Canada
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10
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Bonartsev A, Voinova V, Volkov A, Muraev A, Boyko E, Venediktov A, Didenko N, Dolgalev A. Scaffolds Based on Poly(3-Hydroxybutyrate) and Its Copolymers for Bone Tissue Engineering (Review). Sovrem Tekhnologii Med 2022; 14:78-90. [PMID: 37181830 PMCID: PMC10171059 DOI: 10.17691/stm2022.14.5.07] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Indexed: 05/16/2023] Open
Abstract
Biodegradable and biocompatible polymers are actively used in tissue engineering to manufacture scaffolds. Biomedical properties of polymer scaffolds depend on the physical and chemical characteristics and biodegradation kinetics of the polymer material, 3D microstructure and topography of the scaffold surface, as well as availability of minerals, medicinal agents, and growth factors loaded into the scaffold. However, in addition to the above, the intrinsic biological activity of the polymer and its biodegradation products can also become evident. This review provides studies demonstrating that scaffolds made of poly(3-hydroxybutyrate) (PHB) and its copolymers have their own biological activity, and namely, osteoinductive properties. PHB can induce differentiation of mesenchymal stem cells in the osteogenic direction in vitro and stimulates bone tissue regeneration during the simulation of critical and non-critical bone defects in vivo.
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Affiliation(s)
- A.P. Bonartsev
- Associate Professor, Department of Bioengineering, Faculty of Biology; Lomonosov Moscow State University, 1–12 Leninskiye Gory, Moscow, 119234, Russia
| | - V.V. Voinova
- Senior Researcher, Department of Biochemistry, Faculty of Biology; Lomonosov Moscow State University, 1–12 Leninskiye Gory, Moscow, 119234, Russia
| | - A.V. Volkov
- Senior Researcher; N.N. Priorov National Medical Research Center of Traumatology and Orthopedics, 10 Priorova St., Moscow, 127299, Russia; Associate Professor, Department of Pathological Anatomy, Medical Institute; Peoples’ Friendship University of Russia, 6 Miklukho-Maklaya St., Moscow, 117198, Russia
| | - A.A. Muraev
- Professor, Department of Maxillofacial Surgery and Surgical Dentistry; Peoples’ Friendship University of Russia, 6 Miklukho-Maklaya St., Moscow, 117198, Russia
| | - E.M. Boyko
- Teacher, Essentuki Branch; Stavropol State Medical University, 310 Mira St., Stavropol, 355017, Russia
| | - A.A. Venediktov
- Director; Cardioplant LLC, 1B Tsentralnaya St., Bldg. 2, Penza, 440004, Russia
| | - N.N. Didenko
- Assistant, Department of Pathological Physiology; Stavropol State Medical University, 310 Mira St., Stavropol, 355017, Russia
| | - A.A. Dolgalev
- Associate Professor, Professor, Department of General and Pediatric Dentistry; Stavropol State Medical University, 310 Mira St., Stavropol, 355017, Russia; Head of the Center for Innovation and Technology Transfer of the Research and Innovation Association; Stavropol State Medical University, 310 Mira St., Stavropol, 355017, Russia
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11
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Shen HX, Liu JZ, Yan XQ, Yang HN, Hu SQ, Yan XL, Xu T, El Haj AJ, Yang Y, Lü LX. Hydrostatic pressure stimulates the osteogenesis and angiogenesis of MSCs/HUVECs co-culture on porous PLGA scaffolds. Colloids Surf B Biointerfaces 2022; 213:112419. [PMID: 35227994 DOI: 10.1016/j.colsurfb.2022.112419] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 02/11/2022] [Accepted: 02/16/2022] [Indexed: 01/04/2023]
Abstract
In native bone tissue regeneration, blood vessels, providing oxygen and nutrition for tissues, can promote the regeneration of bone and accelerate the repair of a defected area. In this study, Poly(D, L-lactic-co-glycolic acid) (PLGA) inverse opal scaffolds with high pore interconnectivity were fabricated and further modified with vascular endothelial growth factor (VEGF). The rat bone marrow derived mesenchymal stem cells (rMSCs) and human umbilical vein endothelial cells (HUVECs) were co-cultured onto the scaffolds to enhance vascularization for bone tissue regeneration. Cell attachment, viability, proliferation, and morphology were detected by cell counting kit-8 (CCK-8) assay, live and dead staining and scanning electron microscopy (SEM). Hydrostatic pressure with 0-279 KPa and 1 Hz one hour per day for 7 days was applied to tissue engineered bone constructs to investigate whether the loading stimulation can promote osteogenesis and angiogenesis mutually evaluated in parallel by multiple in vitro assays and in an in vivo chicken chorioallantoic membrane (CAM) model. The results indicated that the immobilization of VEGF can improve biocompatibility of PLGA scaffolds and promote cell attachment and proliferation. The cell-scaffold constructs showed higher CD31 expression because of the angiogenic differentiation of rMSCs in hydrostatic loading culture condition in vitro. The in vivo CAM model experiment demonstrated that hydrostatic loading stimulated angiogenic differentiation of rMSCs can accelerate tubulogenesis. Furthermore, the new capillaries formed in cell-scaffold constructs were conducive to calcium deposition in vivo.
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Affiliation(s)
- Hong-Xian Shen
- The Laboratory of Emergency Medicine, School of the Secondary Clinical Medicine, Xuzhou Medical University, Xuzhou 221002, China
| | - Jing-Zhi Liu
- The Laboratory of Emergency Medicine, School of the Secondary Clinical Medicine, Xuzhou Medical University, Xuzhou 221002, China
| | - Xiao-Qing Yan
- The Laboratory of Emergency Medicine, School of the Secondary Clinical Medicine, Xuzhou Medical University, Xuzhou 221002, China
| | - Hong-Ning Yang
- The Laboratory of Emergency Medicine, School of the Secondary Clinical Medicine, Xuzhou Medical University, Xuzhou 221002, China
| | - Shu-Qun Hu
- The Laboratory of Emergency Medicine, School of the Secondary Clinical Medicine, Xuzhou Medical University, Xuzhou 221002, China
| | - Xian-Liang Yan
- The Laboratory of Emergency Medicine, School of the Secondary Clinical Medicine, Xuzhou Medical University, Xuzhou 221002, China; Emergency Medicine Department of the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China
| | - Tie Xu
- The Laboratory of Emergency Medicine, School of the Secondary Clinical Medicine, Xuzhou Medical University, Xuzhou 221002, China; Emergency Medicine Department of the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China
| | - Alicia J El Haj
- Institute of Translational Medicine, University of Birmingham, Birmingham B15 2TH, UK
| | - Ying Yang
- School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent ST4 7QB, UK.
| | - Lan-Xin Lü
- The Laboratory of Emergency Medicine, School of the Secondary Clinical Medicine, Xuzhou Medical University, Xuzhou 221002, China; Emergency Medicine Department of the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
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12
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Safina I, Embree MC. Biomaterials for recruiting and activating endogenous stem cells in situ tissue regeneration. Acta Biomater 2022; 143:26-38. [PMID: 35292413 PMCID: PMC9035107 DOI: 10.1016/j.actbio.2022.03.014] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 02/28/2022] [Accepted: 03/07/2022] [Indexed: 12/20/2022]
Abstract
Over the past two decades in situ tissue engineering has emerged as a new approach where biomaterials are used to harness the body's own stem/progenitor cells to regenerate diseased or injured tissue. Immunomodulatory biomaterials are designed to promote a regenerative environment, recruit resident stem cells to diseased or injured tissue sites, and direct them towards tissue regeneration. This review explores advances gathered from in vitro and in vivo studies on in situ tissue regenerative therapies. Here we also examine the different ways this approach has been incorporated into biomaterial sciences in order to create customized biomaterial products for therapeutic applications in a broad spectrum of tissues and diseases. STATEMENT OF SIGNIFICANCE: Biomaterials can be designed to recruit stem cells and coordinate their behavior and function towards the restoration or replacement of damaged or diseased tissues in a process known as in situ tissue regeneration. Advanced biomaterial constructs with precise structure, composition, mechanical, and physical properties can be transplanted to tissue site and exploit local stem cells and their micro-environment to promote tissue regeneration. In the absence of cells, we explore the critical immunomodulatory, chemical and physical properties to consider in material design and choice. The application of biomaterials for in situ tissue regeneration has the potential to address a broad range of injuries and diseases.
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13
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He Y, Tian Y, Zhang W, Wang X, Yang X, Li B, Ge L, Bai D, Li D. Fabrication of oxidized sodium alginate-collagen heterogeneous bilayer barrier membrane with osteogenesis-promoting ability. Int J Biol Macromol 2022; 202:55-67. [PMID: 34998883 DOI: 10.1016/j.ijbiomac.2021.12.155] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 12/20/2021] [Accepted: 12/24/2021] [Indexed: 02/07/2023]
Abstract
Guided bone regeneration technique is an effective approach to repair bone defects, in which a barrier membrane is essential. However, the collagen barrier membranes commonly used lose stability quickly, leading to connective tissue invasion and failure of osteogenesis. Herein, we presented an oxidized sodium alginate (OSA)-collagen heterogeneous bilayer barrier membrane with well-controlled pore size and osteogenesis-promoting ability. The OSA crosslinking significantly improved the structural stability, compressive strength, swelling behavior, and slowed down the biodegradation rate of collagen membranes. Meanwhile, the collagen-based membranes exhibited superior cytocompatibility, osteogenesis-promotion, and barrier function against fibroblasts. Especially, the osteogenic differentiation was most promoted on the membrane with a large pore size (240-310 μm), while the barrier function was most improved on the membrane with a small pore size (30-60 μm). Then the above two membranes were combined together to obtain a heterogeneous bilayer membrane. This bilayer barrier membrane showed excellent osteogenesis-promoting ability in rats.
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Affiliation(s)
- Yiruo He
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China
| | - Ye Tian
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China
| | - Wenjie Zhang
- Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, PR China
| | - Xinghai Wang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China
| | - Xue Yang
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, PR China
| | - Bin Li
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China
| | - Liming Ge
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, PR China
| | - Ding Bai
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China.
| | - Defu Li
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
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14
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Aglan HA, Fouad-Elhady EA, Hassan RE, Sabry GM, Ahmed HH. Nanoplatforms for Promoting Osteogenesis in Ovariectomy-Induced
Osteoporosis in the Experimental Model. CURRENT NANOMEDICINE 2022; 12:44-62. [DOI: 10.2174/2468187312666220217104650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 12/19/2021] [Accepted: 01/12/2022] [Indexed: 01/05/2025]
Abstract
Background:
Osteoporosis is a debilitating bone ailment characterized by the obvious loss of bone mass and bone microarchitecture impairment.
Objective:
This study aimed to illuminate the in vivo usefulness of nanotechnology as a treatment for osteoporosis via analyzing the effectiveness of nano-hydroxyapatite (nHa), nano-hydroxy- apatite/chitosan (nHa/C), and nano-hydroxyapatite/silver (nHa/S) in mitigation of osteoporosis in ovariectomized rats.
Method:
The characterization of the nHa, nHa/C, and nHa/S was carried out using TEM, SEM, FTIR, and Zeta potential measurements. This in vivo study included 48 adult female rats that were randomized into six groups (8 rats/group): (1) Sham-operated control, (2) osteoporotic, (3) nHa, (4) nHa/C, (5) nHa/S, and (6) Fosamax®. Serum osterix level was quantified using ELISA. Femur bone morphogenetic protein 2 and SMAD1 mRNA levels were evaluated by qPCR. The femur bones were scanned by DEXA for measurement of bone mineral density and bone mineral content. In ad-dition, a histopathological examination of femur bones was performed.
Results:
The present approach denoted that the treatment with nHa, nHa/C, or nHa/S yields a signif-icant rise in serum level of osterix and mRNA levels of bone morphogenetic protein 2 and SMAD1 as well as significant enhancements of bone tissue minerals.
Conclusion:
The findings affirmed the potency of nHa, nHa/C, and nHa/S as auspicious nanoplat-forms for repairing bone defects in the osteoporotic rat model. The positive effect of the inspected nanoformulations arose from bone formation indicators in serum and tissue, and additionally, the reinforcement of bone density and content, which were verified by the histopathological description of bone tissue sections.
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Affiliation(s)
- Hadeer A. Aglan
- Hormones Department, Medicine and Clinical Studies Research Institute, National Research Centre, Giza, Egypt
- Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt
| | | | - Rasha E. Hassan
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Gilane M. Sabry
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Hanaa H. Ahmed
- Hormones Department, Medicine and Clinical Studies Research Institute, National Research Centre, Giza, Egypt
- Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Giza, Egypt
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15
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Fabrication and Characterization of Alveolus-Like Scaffolds with Control of the Pore Architecture and Gas Permeability. Stem Cells Int 2022; 2022:3437073. [PMID: 35096071 PMCID: PMC8794699 DOI: 10.1155/2022/3437073] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 12/30/2021] [Indexed: 12/31/2022] Open
Abstract
The micrometer scale sac-like alveoli are the most important and essential unit for gas exchange in the lung. Thus, design and fabrication of scaffolds for alveoli regeneration by tissue engineering approach should meet a few topography and functional requests such as large surface area, flexibility, and high gas permeability to their native counterpart. Testing the gas permeability of scaffolds through a fast and simple technique is also highly demanded to assist new scaffold development. This study fabricated alveolus-like scaffolds with regular pore shape, high pore connectivity, and high porosity produced by inverse opal technique alongside randomly distrusted porous scaffolds by salt leaching technique from two different materials (polyurethane and poly(L-lactic acid)). The scaffold surface was modified by immobilization of VEGF. A facile and new technique based on the bubble meter principle enabling to measure the gas permeability of porous scaffolds conveniently has been developed specifically. The cellular response of the scaffolds was assessed by culturing with bone marrow mesenchymal stem cells and coculturing with lung epithelial NL20 and endothelial HUVECs. Our results showed that the newly designed gas permeability device provided rapid, nondestructive, reproducible, and accurate assessment of gas permeability of different scaffolds. The porous polyurethane scaffolds made by inverse opal method had much better gas permeability than other scaffolds used in this study. The cellular work indicated that with VEGF surface modification, polyurethane inverse opal scaffolds induced alveolus-like tissues and have promising application in lung tissue engineering.
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16
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Guo W, Yang K, Qin X, Luo R, Wang H, Huang R. Polyhydroxyalkanoates in tissue repair and regeneration. ENGINEERED REGENERATION 2022. [DOI: 10.1016/j.engreg.2022.01.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
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17
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Li H, Zheng L, Wang M. Biofunctionalized Nanofibrous Bilayer Scaffolds for Enhancing Cell Adhesion, Proliferation and Osteogenesis. ACS APPLIED BIO MATERIALS 2021; 4:5276-5294. [PMID: 35007009 DOI: 10.1021/acsabm.1c00414] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
A simple and efficient method for fabricating functionalized multilayered nanofibrous scaffolds has been developed by combining electrospinning and thermally induced phase separation (TIPS) techniques. In this investigation, functionalized bilayer scaffolds were constructed using this method for bone tissue engineering, which consisted of a nanofibrous poly(lactic acid-co-glycolic acid) (PLGA) membrane as the base and a nanofibrous chitosan (CS) or gelatin (Gel) mesh as the surface layer, with the PLGA nanofibers having a biomimetic polydopamine (PDA) coating. It was shown that the PDA coating strongly bonded TIPS-formed CS or Gel networks onto PDA-coated electrospun PLGA membranes. The nanofibrous PLGA membrane provided adequate mechanical support for the whole structure, and the nanofibrous CS or Gel networks enhanced cell growth and maturation. The bioinspired surface modification of PLGA scaffolds through PDA coating could not only provide strong adhesion between the two scaffold layers but also improve biological properties of scaffolds. It was demonstrated that functionalized bilayer scaffolds could promote cell adhesion, spreading and proliferation of mouse preosteoblastic MC3T3-E1 cells and rat bone-marrow-derived stromal cells (rBMSCs). Furthermore, immunofluorescence staining and calcium deposition studies revealed that functionalized bilayer scaffolds could enhance osteogenic differentiation of MC3T3-E1 cells and rBMSCs in comparison with simple electrospun PLGA scaffolds. The functionalized bilayer scaffolds are promising structures for bone tissue engineering.
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Affiliation(s)
- Huihua Li
- Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong
| | - Liwu Zheng
- Faculty of Dentistry, The University of Hong Kong, 34 Hospital Road, Sai Ying Pun, Hong Kong
| | - Min Wang
- Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong
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18
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Juhl OJ, Latifi SM, Donahue HJ. Effect of carbonated hydroxyapatite submicron particles size on osteoblastic differentiation. J Biomed Mater Res B Appl Biomater 2021; 109:1369-1379. [PMID: 33506619 DOI: 10.1002/jbm.b.34797] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 11/23/2020] [Accepted: 01/09/2021] [Indexed: 01/08/2023]
Abstract
Synthetic biomimetic carbonated hydroxyapatite (CHA) has shown significant promise in bone tissue engineering for its mechanical and chemical biocompatibility and osteogenic potential. Variations in the size of hydroxyapatite particles have also been shown to contribute to the hydroxyapatite's osteogenic success. However, synthesizing biomimetic CHA with optimal osteogenic properties using a simple synthesis methodology to make highly reproducible, biomimetic, and osteogenic CHA has not been evaluated fully. The objective of this study was to synthesize submicron CHA particles using a nanoemulsion method. We hypothesized that by varying the synthesis technique we could control particle size while still creating highly biomimetic CHA typically produced during nanoemulsion synthesis. Furthermore, we hypothesized that 500 nm CHA particles would induce greater osteoblastic differentiation compared to larger or smaller CHA particles. X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and dynamic light scattering were used to characterize the chemical composition, shape, and size of CHA synthesized through variations in pH, temperature and stirring speed during synthesis. Manipulation of pH showed the ability to selectively tailor CHA particle size from 200-900 nm in a reproducible manner while maintaining the chemical composition. In addition, 500 nm particles elicited the most rapid increase in osteoblastic differentiation and did not decrease cell viability compared to 200 and 900 nm particles.
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Affiliation(s)
- Otto J Juhl
- Department of Biomedical Engineering and Institute for Engineering and Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Seyed Mohsen Latifi
- Department of Biomedical Engineering and Institute for Engineering and Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Henry J Donahue
- Department of Biomedical Engineering and Institute for Engineering and Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
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19
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He M, Gao X, Fan Y, Xie L, Yang M, Tian W. Tannic acid/Mg 2+-based versatile coating to manipulate the osteoimmunomodulation of implants. J Mater Chem B 2021; 9:1096-1106. [PMID: 33427278 DOI: 10.1039/d0tb01577f] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Instead of directly stimulating osteogenesis, endowing an implant surface with a favourable osteoimmunomodulatory (OIM) function has emerged as a new effective strategy to enhance osteointegration. Though metal-phenolic coatings have demonstrated to possess an immunomodulatory function, their potential application in manipulating an osteoimmune response has not been well explored. Herein, in order to develop a simple, rapid and universal coating method to impart excellent OIM to hard tissue implants, tannic acid (TA) and Mg2+ were selected to form a coating on Ti plate based on metal-phenolic chemistry. Besides its virtues of simplicity, ultrafastness, low-cost, and versatility, another merit for the coating method is that it can easily combine the unique functions of metal ions and phenolic ligands. The chelated Mg2+ can not only activate macrophage polarization towards the anti-inflammatory phenotype but also directly stimulate the osteogenic differentiation of bone marrow-derived stem cells (BMSCs). TA motifs rendered the coating with an excellent reactive oxygen species (ROS) scavenging capacity. TA and Mg2+ showed synergistic effects on regulating macrophage biological behaviour, suppressing its polarization towards the M1 phenotype, and promoting its polarization towards the M2 phenotype. In vivo histological analysis also demonstrated that the TA/Mg2+ coating could effectively inhibit the host response. Finally, the formed osteoimmune environment obviously enhanced the osteogenic differentiation of BMSCs. The above results demonstrated that the designed TA/Mg2+ coating not only possessed the function of directly stimulating osteogenesis but also the function of manipulating OIM to a desired one. Hence, it has great potential to be applied on advanced hard tissue implants to enhance osteointegration.
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Affiliation(s)
- Min He
- Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
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20
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Dubey SK, Alexander A, Sivaram M, Agrawal M, Singhvi G, Sharma S, Dayaramani R. Uncovering the Diversification of Tissue Engineering on the Emergent Areas of Stem Cells, Nanotechnology and Biomaterials. Curr Stem Cell Res Ther 2020; 15:187-201. [PMID: 31957615 DOI: 10.2174/1574888x15666200103124821] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2019] [Revised: 11/11/2019] [Accepted: 11/12/2019] [Indexed: 12/23/2022]
Abstract
Damaged or disabled tissue is life-threatening due to the lack of proper treatment. Many conventional transplantation methods like autograft, iso-graft and allograft are in existence for ages, but they are not sufficient to treat all types of tissue or organ damages. Stem cells, with their unique capabilities like self-renewal and differentiate into various cell types, can be a potential strategy for tissue regeneration. However, the challenges like reproducibility, uncontrolled propagation and differentiation, isolation of specific kinds of cell and tumorigenic nature made these stem cells away from clinical application. Today, various types of stem cells like embryonic, fetal or gestational tissue, mesenchymal and induced-pluripotent stem cells are under investigation for their clinical application. Tissue engineering helps in configuring the stem cells to develop into a desired viable tissue, to use them clinically as a substitute for the conventional method. The use of stem cell-derived Extracellular Vesicles (EVs) is being studied to replace the stem cells, which decreases the immunological complications associated with the direct administration of stem cells. Tissue engineering also investigates various biomaterials to use clinically, either to replace the bones or as a scaffold to support the growth of stemcells/ tissue. Depending upon the need, there are various biomaterials like bio-ceramics, natural and synthetic biodegradable polymers to support replacement or regeneration of tissue. Like the other fields of science, tissue engineering is also incorporating the nanotechnology to develop nano-scaffolds to provide and support the growth of stem cells with an environment mimicking the Extracellular matrix (ECM) of the desired tissue. Tissue engineering is also used in the modulation of the immune system by using patient-specific Mesenchymal Stem Cells (MSCs) and by modifying the physical features of scaffolds that may provoke the immune system. This review describes the use of various stem cells, biomaterials and the impact of nanotechnology in regenerative medicine.
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Affiliation(s)
- Sunil K Dubey
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani (BITS-PILANI), Pilani Campus, Rajasthan 333031, India
| | - Amit Alexander
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER GUWAHATI), Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India, NH 37, NITS Mirza, Kamrup-781125, Guwahati (Assam), India
| | - Munnangi Sivaram
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani (BITS-PILANI), Pilani Campus, Rajasthan 333031, India
| | - Mukta Agrawal
- Rungta College of Pharmaceutical Sciences and Research, Kohka- Kurud Road, Bhilai, Chhattisgarh 490024, India
| | - Gautam Singhvi
- Department of Pharmacy, Birla Institute of Technology and Science, Pilani (BITS-PILANI), Pilani Campus, Rajasthan 333031, India
| | - Swapnil Sharma
- Department of Pharmacy, Banastahli Vidyapith, Tonk, Rajasthan 304022, India
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Wang Q, Feng Y, He M, Zhao W, Qiu L, Zhao C. A Hierarchical Janus Nanofibrous Membrane Combining Direct Osteogenesis and Osteoimmunomodulatory Functions for Advanced Bone Regeneration. ADVANCED FUNCTIONAL MATERIALS 2020. [DOI: 10.1002/adfm.202008906] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Qian Wang
- College of Polymer Science and Engineering State Key Laboratory of Polymer Materials Engineering Sichuan University Chengdu 610065 P. R. China
| | - Yunbo Feng
- College of Polymer Science and Engineering State Key Laboratory of Polymer Materials Engineering Sichuan University Chengdu 610065 P. R. China
| | - Min He
- State Key Laboratory of Oral Disease West China Hospital of Stomatology Sichuan University Chengdu Sichuan 610041 P. R. China
| | - Weifeng Zhao
- College of Polymer Science and Engineering State Key Laboratory of Polymer Materials Engineering Sichuan University Chengdu 610065 P. R. China
| | - Li Qiu
- Department of Ultrasound West China School of Medicine/West China Hospital Sichuan University Chengdu 610041 P. R. China
| | - Changsheng Zhao
- College of Polymer Science and Engineering State Key Laboratory of Polymer Materials Engineering Sichuan University Chengdu 610065 P. R. China
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22
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Wang L, Lu R, Hou J, Nan X, Xia Y, Guo Y, Meng K, Xu C, Wang X, Zhao B. Application of injectable silk fibroin/graphene oxide hydrogel combined with bone marrow mesenchymal stem cells in bone tissue engineering. Colloids Surf A Physicochem Eng Asp 2020. [DOI: 10.1016/j.colsurfa.2020.125318] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Cun X, Hosta-Rigau L. Topography: A Biophysical Approach to Direct the Fate of Mesenchymal Stem Cells in Tissue Engineering Applications. NANOMATERIALS (BASEL, SWITZERLAND) 2020; 10:E2070. [PMID: 33092104 PMCID: PMC7590059 DOI: 10.3390/nano10102070] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 10/16/2020] [Accepted: 10/16/2020] [Indexed: 12/17/2022]
Abstract
Tissue engineering is a promising strategy to treat tissue and organ loss or damage caused by injury or disease. During the past two decades, mesenchymal stem cells (MSCs) have attracted a tremendous amount of interest in tissue engineering due to their multipotency and self-renewal ability. MSCs are also the most multipotent stem cells in the human adult body. However, the application of MSCs in tissue engineering is relatively limited because it is difficult to guide their differentiation toward a specific cell lineage by using traditional biochemical factors. Besides biochemical factors, the differentiation of MSCs also influenced by biophysical cues. To this end, much effort has been devoted to directing the cell lineage decisions of MSCs through adjusting the biophysical properties of biomaterials. The surface topography of the biomaterial-based scaffold can modulate the proliferation and differentiation of MSCs. Presently, the development of micro- and nano-fabrication techniques has made it possible to control the surface topography of the scaffold precisely. In this review, we highlight and discuss how the main topographical features (i.e., roughness, patterns, and porosity) are an efficient approach to control the fate of MSCs and the application of topography in tissue engineering.
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Affiliation(s)
| | - Leticia Hosta-Rigau
- DTU Health Tech, Centre for Nanomedicine and Theranostics, Technical University of Denmark, Nils Koppels Allé, Building 423, 2800 Kgs. Lyngby, Denmark;
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Soheilmoghaddam M, Padmanabhan H, Cooper-White JJ. Biomimetic cues from poly(lactic-co-glycolic acid)/hydroxyapatite nano-fibrous scaffolds drive osteogenic commitment in human mesenchymal stem cells in the absence of osteogenic factor supplements. Biomater Sci 2020; 8:5677-5689. [PMID: 32915185 DOI: 10.1039/d0bm00946f] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Mimicking the complex hierarchical architecture of the 'osteon', the functional unit of cortical bone, from the bottom-up offers the possibility of generating mature bone tissue in tissue engineered bone substitutes. In this work, a modular 'bottom-up' approach has been developed to assemble bone niche-mimicking nanocomposite scaffolds composed of aligned electrospun nanofibers of poly(lactic-co-glycolic acid) (PLGA) encapsulating aligned rod-shape nano-sized hydroxyapatite (nHA). By encoding axial orientation of the nHA within these aligned nanocomposite fibers, significant improvements in mechanical properties, surface roughness, hydrophilicity and in vitro simulated body fluid (SBF) mineral deposition were achieved. Moreover, these hierarchical scaffolds induced robust formation of bone hydroxyapatite and osteoblastic maturation of human bone marrow-derived mesenchymal stem cells (hBMSCs) in growth media that was absent of any soluble osteogenic differentiation factors. The results of this investigation confirm that these tailored, aligned nanocomposite fibers, in the absence of media-bone inductive factors, offer the requisite biophysical and biochemical cues to hBMSCs to promote and support their differentiation into mature osteoblast cells and form early bone-like tissue in vitro.
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Affiliation(s)
- Mohammad Soheilmoghaddam
- Tissue Engineering and Microfluidics Laboratory (TE&M), Australian Institute for Bioengineering and Nanotechnology (AIBN), University Of Queensland, St Lucia, QLD, Australia.
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25
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Volkov AV, Muraev AA, Zharkova II, Voinova VV, Akoulina EA, Zhuikov VA, Khaydapova DD, Chesnokova DV, Menshikh KA, Dudun AA, Makhina TK, Bonartseva GA, Asfarov TF, Stamboliev IA, Gazhva YV, Ryabova VM, Zlatev LH, Ivanov SY, Shaitan KV, Bonartsev AP. Poly(3-hydroxybutyrate)/hydroxyapatite/alginate scaffolds seeded with mesenchymal stem cells enhance the regeneration of critical-sized bone defect. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 114:110991. [PMID: 32994018 DOI: 10.1016/j.msec.2020.110991] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 04/08/2020] [Accepted: 04/18/2020] [Indexed: 01/13/2023]
Abstract
A critical-sized calvarial defect in rats is employed to reveal the osteoinductive properties of biomaterials. In this study, we investigate the osteogenic efficiency of hybrid scaffolds based on composites of a biodegradable and biocompatible polymer, poly(3-hydroxybutyrate) (PHB) with hydroxyapatite (HA) filled with alginate (ALG) hydrogel containing mesenchymal stem cells (MSCs) on the regeneration of the critical-sized radial defect of the parietal bone in rats. The scaffolds based on PHB and PHB/HA with desired shapes were prepared by two-stage salt leaching technique using a mold obtained by three-dimensional printing. To obtain PHB/HA/ALG/MSC scaffolds seeded with MSCs, the scaffolds were filled with ALG hydrogel containing MSCs; acellular PHB/ALG and PHB/ALG filled with empty ALG hydrogel were prepared for comparison. The produced scaffolds have high porosity and irregular interconnected pore structure. PHB/HA scaffolds supported MSC growth and induced cell osteogenic differentiation in a regular medium in vitro that was manifested by an increase in ALP activity and expression of the CD45 phenotype marker. The data of computed tomography and histological studies showed 94% and 92%, respectively, regeneration of critical-sized calvarial bone defect in vivo at 28th day after implantation of MSC-seeded PHB/HA/ALG/MSC scaffolds with 3.6 times higher formation of the main amount of bone tissue at 22-28 days in comparison with acellular PHB/HA/ALG scaffolds that was shown at the first time by fluorescent microscopy using the original technique of intraperitoneal administration of fluorescent dyes to living postoperative rats. The obtained in vivo results can be associated with the MSC-friendly microstructure and in vitro osteogenic properties of PHB/HA base-scaffolds. Thus, the obtained data demonstrate the potential of MSCs encapsulated in the bioactive biopolymer/mineral/hydrogel scaffold to improve the bone regeneration process in critical-sized bone defects.
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Affiliation(s)
- Alexey V Volkov
- The Peoples' Friendship University of Russia, Miklukho-Maklaya St. 6, 117198 Moscow, Russia; N.N. Priorov National Medical Research Center of Traumatology and Orthopedics of the Ministry of Health of the Russian Federation, Priorova Str. 10, 127299 Moscow, Russia
| | - Alexander A Muraev
- The Peoples' Friendship University of Russia, Miklukho-Maklaya St. 6, 117198 Moscow, Russia; I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya St. 8/2, 119991, Moscow, Russia
| | - Irina I Zharkova
- Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1, bld. 12, 119234 Moscow, Russia
| | - Vera V Voinova
- Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1, bld. 12, 119234 Moscow, Russia; A.N.Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky Ave. 33, bld. 2, 119071 Moscow, Russia
| | - Elizaveta A Akoulina
- Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1, bld. 12, 119234 Moscow, Russia; A.N.Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky Ave. 33, bld. 2, 119071 Moscow, Russia
| | - Vsevolod A Zhuikov
- A.N.Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky Ave. 33, bld. 2, 119071 Moscow, Russia
| | - Dolgor D Khaydapova
- Faculty of Soil Science, M.V.Lomonosov Moscow State University, Leninskie gory, 1, bld. 12, 119234 Moscow, Russia
| | - Dariana V Chesnokova
- Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1, bld. 12, 119234 Moscow, Russia
| | - Ksenia A Menshikh
- Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1, bld. 12, 119234 Moscow, Russia
| | - Andrej A Dudun
- Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1, bld. 12, 119234 Moscow, Russia; A.N.Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky Ave. 33, bld. 2, 119071 Moscow, Russia
| | - Tatiana K Makhina
- A.N.Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky Ave. 33, bld. 2, 119071 Moscow, Russia
| | - Garina A Bonartseva
- A.N.Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky Ave. 33, bld. 2, 119071 Moscow, Russia
| | - Teymur F Asfarov
- The Peoples' Friendship University of Russia, Miklukho-Maklaya St. 6, 117198 Moscow, Russia
| | - Ivan A Stamboliev
- The Peoples' Friendship University of Russia, Miklukho-Maklaya St. 6, 117198 Moscow, Russia
| | - Yulia V Gazhva
- Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, Minin and Pozharsky Sq. 10/1, 603005 Nizhny Novgorod, Russia
| | - Valentina M Ryabova
- Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation, Minin and Pozharsky Sq. 10/1, 603005 Nizhny Novgorod, Russia
| | - Lubomir H Zlatev
- The Peoples' Friendship University of Russia, Miklukho-Maklaya St. 6, 117198 Moscow, Russia
| | - Sergey Y Ivanov
- The Peoples' Friendship University of Russia, Miklukho-Maklaya St. 6, 117198 Moscow, Russia; I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya St. 8/2, 119991, Moscow, Russia
| | - Konstantin V Shaitan
- Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1, bld. 12, 119234 Moscow, Russia
| | - Anton P Bonartsev
- Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory 1, bld. 12, 119234 Moscow, Russia; A.N.Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky Ave. 33, bld. 2, 119071 Moscow, Russia.
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Lee J, Lee S, Ahmad T, Madhurakkat Perikamana SK, Lee J, Kim EM, Shin H. Human adipose-derived stem cell spheroids incorporating platelet-derived growth factor (PDGF) and bio-minerals for vascularized bone tissue engineering. Biomaterials 2020; 255:120192. [PMID: 32559565 DOI: 10.1016/j.biomaterials.2020.120192] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 04/06/2020] [Accepted: 06/09/2020] [Indexed: 12/12/2022]
Abstract
Stem cells with mineralized materials have been used for bone regeneration; however, engineering the complex vascularized structure of the natural bone remains a challenge. Here, we developed platelet-derived growth factor (PDGF) and bio-mineral coated fibers which were then assembled with human adipose-derived stem cells (hADSCs) to form spheroids as building blocks for vascularized bone regeneration. The PDGF incorporated within the spheroid increased the proliferation of hADSCs, which was characterized by Ki-67 staining and DNA contents. Furthermore, the PDGF enhanced not only osteogenic differentiation, but also endothelial differentiation of hADSCs; the cells within the spheroids showed significantly greater gene expression by 2.46 ± 0.14 fold for osteocalcin (OCN) and by 12.85 ± 3.36 fold for von Willebrand factor (vWF) than those without PDGF. Finally, at two months following transplantation of PDGF-incorporated spheroids onto in vivo mouse calvarial defect, the regenerated bone area (42.48 ± 10.84%) was significantly enhanced and the greatest number of capillaries and arterioles with indication of transplanted hADSCs were observed. Moreover, millimeter-scale in vitro tissue prepared by fused assembly of the spheroids exhibited greater mRNA expression-associated to endothelial lineage. Taken together, these findings indicate that stem cell spheroids incorporating PDGF and bio-minerals could be used as a module for successful vascularized bone regeneration.
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Affiliation(s)
- Jinkyu Lee
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea
| | - Sangmin Lee
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea
| | - Taufiq Ahmad
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea
| | - Sajeesh Kumar Madhurakkat Perikamana
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea
| | - Jinki Lee
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea
| | - Eun Mi Kim
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea
| | - Heungsoo Shin
- Department of Bioengineering, Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul, 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul, 04763, Republic of Korea; Institute of Nano Science and Technology, Hanyang University, Seoul, 04763, Republic of Korea.
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Jiang N, He J, Zhang W, Li D, Lv Y. Directed differentiation of BMSCs on structural/compositional gradient nanofibrous scaffolds for ligament-bone osteointegration. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 110:110711. [DOI: 10.1016/j.msec.2020.110711] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 01/26/2020] [Accepted: 01/30/2020] [Indexed: 12/11/2022]
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Voinova V, Bonartseva G, Bonartsev A. Effect of poly(3-hydroxyalkanoates) as natural polymers on mesenchymal stem cells. World J Stem Cells 2019; 11:764-786. [PMID: 31692924 PMCID: PMC6828591 DOI: 10.4252/wjsc.v11.i10.764] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 05/17/2019] [Accepted: 08/27/2019] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are stromal multipotent stem cells that can differentiate into multiple cell types, including fibroblasts, osteoblasts, chondrocytes, adipocytes, and myoblasts, thus allowing them to contribute to the regeneration of various tissues, especially bone tissue. MSCs are now considered one of the most promising cell types in the field of tissue engineering. Traditional petri dish-based culture of MSCs generate heterogeneity, which leads to inconsistent efficacy of MSC applications. Biodegradable and biocompatible polymers, poly(3-hydroxyalkanoates) (PHAs), are actively used for the manufacture of scaffolds that serve as carriers for MSC growth. The growth and differentiation of MSCs grown on PHA scaffolds depend on the physicochemical properties of the polymers, the 3D and surface microstructure of the scaffolds, and the biological activity of PHAs, which was discovered in a series of investigations. The mechanisms of the biological activity of PHAs in relation to MSCs remain insufficiently studied. We suggest that this effect on MSCs could be associated with the natural properties of bacteria-derived PHAs, especially the most widespread representative poly(3-hydroxybutyrate) (PHB). This biopolymer is present in the bacteria of mammalian microbiota, whereas endogenous poly(3-hydroxybutyrate) is found in mammalian tissues. The possible association of PHA effects on MSCs with various biological functions of poly(3-hydroxybutyrate) in bacteria and eukaryotes, including in humans, is discussed in this paper.
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Affiliation(s)
- Vera Voinova
- Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow 119234, Russia
| | - Garina Bonartseva
- A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, Russia
| | - Anton Bonartsev
- Faculty of Biology, M.V. Lomonosov Moscow State University, Moscow 119234, Russia
- A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, Russia.
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Wang Z, Sun K, He Y, Song P, Zhang D, Wang R. Preparation of hydroxyapatite-based porous materials for absorption of lead ions. WATER SCIENCE AND TECHNOLOGY : A JOURNAL OF THE INTERNATIONAL ASSOCIATION ON WATER POLLUTION RESEARCH 2019; 80:1266-1275. [PMID: 31850878 DOI: 10.2166/wst.2019.370] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
In this paper, soybean protein isolate (SPI) was used as template, hydroxyapatite was crystallized on protein chains of SPI by in-situ synthesis, then the obtained inorganic HA/biopolymer SPI composite (HA@SPI) was calcined at suitable temperature, which afforded a novel hydroxyapatite-based porous materials (HApM). The results indicated that the product showed a porous morphology structure and excellent absorption performance for Pb2+. HApM maximum removal of lead was attained (96.25%) at an initial pH value of 7.4, temperature of 25 °C and contact time of 30 min with an initial metal concentration of 60 mg/L. In order to identify composition, structure and functional groups involved in the uptake of Pb2+, Fourier transform infrared spectrometer (FTIR), thermogravimetric analysis (TG), X-ray diffraction (XRD) scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and Brunauer-Emmett-Teller (BET) analysis were carried out. Therefore, the hydroxyapatite-based porous materials (HApM) is a promising candidate for the treatment of liquid wastes containing toxic Pb2+ metal ion, heavy metal ion antidotes and other related fields.
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Affiliation(s)
- Zejun Wang
- Key Laboratory of Eco-functional Polymer Materials of the Ministry of Education, Institute of Polymer, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China E-mail:
| | - Kangqi Sun
- Key Laboratory of Eco-functional Polymer Materials of the Ministry of Education, Institute of Polymer, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China E-mail:
| | - Yufeng He
- Key Laboratory of Eco-functional Polymer Materials of the Ministry of Education, Institute of Polymer, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China E-mail:
| | - Pengfei Song
- Key Laboratory of Eco-functional Polymer Materials of the Ministry of Education, Institute of Polymer, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China E-mail:
| | - Dawei Zhang
- Key Laboratory of Eco-functional Polymer Materials of the Ministry of Education, Institute of Polymer, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China E-mail:
| | - Rongmin Wang
- Key Laboratory of Eco-functional Polymer Materials of the Ministry of Education, Institute of Polymer, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China E-mail:
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30
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Müller S, Nicholson L, Al Harbi N, Mancuso E, Jones E, Dickinson A, Wang XN, Dalgarno K. Osteogenic potential of heterogeneous and CD271-enriched mesenchymal stromal cells cultured on apatite-wollastonite 3D scaffolds. BMC Biomed Eng 2019; 1:16. [PMID: 32002516 PMCID: PMC6992429 DOI: 10.1186/s42490-019-0015-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Background Mesenchymal stromal cells (MSCs) are widely used in clinical trials for bone repair and regeneration. Despite previous evidence showing a prominent osteogenic potential of 2D cultured CD271 enriched MSCs, the osteogenic potential of CD271 enriched cells cultured on 3D scaffold is unknown. Apatite-wollastonite glass ceramic (A-W) is an osteoconductive biomaterial shown to be compatible with MSCs. This is the first study comparing the attachment, growth kinetics, and osteogenic potential of two MSC populations, namely heterogeneous plastic adherence MSCs (PA-MSCs) and CD271-enriched MSCs (CD271-MSCs), when cultured on A-W 3D scaffold. Results The paired MSC populations were assessed for their attachment, growth kinetics and ALP activity using confocal and scanning electron microscopy and the quantifications of DNA contents and p-nitrophenyl (pNP) production respectively. While the PA-MSCs and CD271-MSCs had similar expansion and tri-lineage differentiation capacity during standard 2D culture, they showed different proliferation kinetics when seeded on the A-W scaffolds. PA-MSCs displayed a well-spread attachment with more elongated morphology compared to CD271-MSCs, signifying a different level of interaction between the cell populations and the scaffold surface. Following scaffold seeding PA-MSCs fully integrated into the scaffold surface and showed a stronger propensity for osteogenic differentiation as indicated by higher ALP activity than CD271-MSCs. Furthermore, A-W scaffold seeded uncultured non-enriched bone marrow mononuclear cells also demonstrated a higher proliferation rate and greater ALP activity compared to their CD271-enriched counterpart. Conclusions Our findings suggest that CD271-positive enrichment of a population is not beneficial for osteogenesis when the cells are seeded on A-W scaffold. Furthermore, unselected heterogeneous MSCs or BM-MNCs are more promising for A-W scaffold based bone regeneration. This leads to a conclusion of broader clinical relevance for tissue engineering: on the basis of our observations here the osteogenic potential observed in 2D cell culture should not be considered indicative of likely performance in a 3D scaffold based system, even when one of the cell populations is effectively a subset of the other.
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Affiliation(s)
- Sylvia Müller
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Lyndsey Nicholson
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Naif Al Harbi
- School of Engineering, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Elena Mancuso
- School of Engineering, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Elena Jones
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
| | - Anne Dickinson
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Xiao Nong Wang
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Kenneth Dalgarno
- School of Engineering, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
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Di Filippo MF, Amadori S, Casolari S, Bigi A, Dolci LS, Panzavolta S. Cylindrical Layered Bone Scaffolds with Anisotropic Mechanical Properties as Potential Drug Delivery Systems. Molecules 2019; 24:E1931. [PMID: 31109143 PMCID: PMC6572119 DOI: 10.3390/molecules24101931] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Revised: 05/15/2019] [Accepted: 05/18/2019] [Indexed: 11/20/2022] Open
Abstract
3D cylindrical layered scaffolds with anisotropic mechanical properties were prepared according to a new and simple method, which involves gelatin foaming, deposition of foamed strips, in situ crosslinking, strip rolling and lyophilization. Different genipin concentrations were tested in order to obtain strips with different crosslinking degrees and a tunable stability in biological environment. Before lyophilization, the strips were curled in a concentric structure to generate anisotropic spiral-cylindrical scaffolds. The scaffolds displayed significantly higher values of stress at break and of the Young modulus in compression along the longitudinal than the transverse direction. Further improvement of the mechanical properties was achieved by adding strontium-substituted hydroxyapatite (Sr-HA) to the scaffold composition and by increasing genipin concentration. Moreover, composition modulated also water uptake ability and degradation behavior. The scaffolds showed a sustained strontium release, suggesting possible applications for the local treatment of abnormally high bone resorption. This study demonstrates that assembly of layers of different composition can be used as a tool to obtain scaffolds with modulated properties, which can be loaded with drugs or biologically active molecules providing properties tailored upon the needs.
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Affiliation(s)
| | - Sofia Amadori
- Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
| | - Sonia Casolari
- Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
| | - Adriana Bigi
- Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
| | - Luisa Stella Dolci
- Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy.
| | - Silvia Panzavolta
- Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
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32
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Xiao Q, Zhang N, Ye Z, Huang N. Microtopography based on inverse opal structures regulates the behavior of bone marrow‐derived mesenchymal stem cells. POLYM ADVAN TECHNOL 2019. [DOI: 10.1002/pat.4550] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Qian‐Ru Xiao
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical EngineeringSoutheast University Nanjing China
| | - Ning Zhang
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical EngineeringSoutheast University Nanjing China
| | - Zheng Ye
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical EngineeringSoutheast University Nanjing China
| | - Ning‐Ping Huang
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical EngineeringSoutheast University Nanjing China
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Zhou X, Zhang Q, Chen L, Nie W, Wang W, Wang H, Mo X, He C. Versatile Nanocarrier Based on Functionalized Mesoporous Silica Nanoparticles to Codeliver Osteogenic Gene and Drug for Enhanced Osteodifferentiation. ACS Biomater Sci Eng 2019; 5:710-723. [PMID: 33405833 DOI: 10.1021/acsbiomaterials.8b01110] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
To achieve enhanced stimulatory effects on the osteogenic differentiation of stem cells, the combination of dual factors with synergistic bioactivity has been regarded as the most effective and powerful strategy. In this study, polylysine-modified polyethylenimine (PEI-PLL) copolymers with various molecular weight PEI blocks were first synthesized and evaluated focusing on their cytotoxicity and gene transfection efficiency, and the results demonstrated that the synthesized copolymer PEI-PLL-25k (synthesized using 25 kDa PEI) exhibited lower cytotoxicity and higher in vitro transfection efficiency than commercial PEI-25k (Mw = 25 kDa). In order to effectively load and deliver plasmid DNA and osteogenic drug dexamethasone (DEX), PEI-PLL-25k copolymer and arginine-glycine-aspartate (RGD) peptide were successively anchored onto the surface of mesoporous silica nanoparticles (MSNs) to construct the dual-factor delivery system, which allows the surface adsorption of DNA and DEX loading in the mesopores of MSNs. The modification of PEI-PLL-25k copolymer and RGD on nanoparticles was successfully characterized by various techniques. The functionalized MSNs with RGD conjugation on the surface showed good cytocompatibility as evidenced by in vitro cell viability assays and cytoskeleton observation. The dual-factor delivery system could quickly release plasmid DNA (pDNA), while releasing DEX in a sustained manner. When cultured with the vector bearing bone morphogenetic protein-2 (BMP-2) pDNA, the transfected bone mesenchymal stem cells (BMSCs) were capable of expressing BMP-2 protein. With the simultaneous delivery of DEX and the BMP-2 gene, this dual-factor delivery system could significantly enhance the level of osteogenic differentiation of BMSCs, as demonstrated by in vitro results of alkaline phosphatase (ALP) activity, expression of osteo-related genes, and calcium deposition. Therefore, the versatile functionalized MSNs nanocarrier for codelivery of osteogenic gene and drug may be considered as a promising dual-delivery system to synergistically enhance the osteogenic outcomes of stem cells.
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Affiliation(s)
- Xiaojun Zhou
- Key Laboratory of Science and Technology of Eco-Textiles, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
| | - Qianqian Zhang
- Key Laboratory of Science and Technology of Eco-Textiles, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
| | - Liang Chen
- Key Laboratory of Science and Technology of Eco-Textiles, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
| | - Wei Nie
- Key Laboratory of Science and Technology of Eco-Textiles, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
| | - Weizhong Wang
- Key Laboratory of Science and Technology of Eco-Textiles, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
| | - Hongsheng Wang
- Key Laboratory of Science and Technology of Eco-Textiles, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
| | - Xiumei Mo
- Key Laboratory of Science and Technology of Eco-Textiles, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
| | - Chuanglong He
- Key Laboratory of Science and Technology of Eco-Textiles, Ministry of Education, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
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Singla R, Abidi SMS, Dar AI, Acharya A. Nanomaterials as potential and versatile platform for next generation tissue engineering applications. J Biomed Mater Res B Appl Biomater 2019; 107:2433-2449. [PMID: 30690870 DOI: 10.1002/jbm.b.34327] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 11/28/2018] [Accepted: 12/23/2018] [Indexed: 12/16/2022]
Abstract
Tissue engineering (TE) is an emerging field where alternate/artificial tissues or organ substitutes are implanted to mimic the functionality of damaged or injured tissues. Earlier efforts were made to develop natural, synthetic, or semisynthetic materials for skin equivalents to treat burns or skin wounds. Nowadays, many more tissues like bone, cardiac, cartilage, heart, liver, cornea, blood vessels, and so forth are being engineered using 3-D biomaterial constructs or scaffolds that could deliver active molecules such as peptides or growth factors. Nanomaterials (NMs) due to their unique mechanical, electrical, and optical properties possess significant opportunities in TE applications. Traditional TE scaffolds were based on hydrolytically degradable macroporous materials, whereas current approaches emphasize on controlling cell behaviors and tissue formation by nano-scale topography that closely mimics the natural extracellular matrix. This review article gives a comprehensive outlook of different organ specific NMs which are being used for diversified TE applications. Varieties of NMs are known to serve as biological alternatives to repair or replace a portion or whole of the nonfunctional or damaged tissue. NMs may promote greater amounts of specific interactions stimulated at the cellular level, ultimately leading to more efficient new tissue formation. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2433-2449, 2019.
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Affiliation(s)
- Rubbel Singla
- Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, 176061, India.,Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, 176061, India
| | - Syed M S Abidi
- Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, 176061, India.,Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, 176061, India
| | - Aqib Iqbal Dar
- Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, 176061, India
| | - Amitabha Acharya
- Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, 176061, India.,Academy of Scientific and Innovative Research (AcSIR), CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, 176061, India
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Yuan L, Li X, Ge L, Jia X, Lei J, Mu C, Li D. Emulsion Template Method for the Fabrication of Gelatin-Based Scaffold with a Controllable Pore Structure. ACS APPLIED MATERIALS & INTERFACES 2019; 11:269-277. [PMID: 30525427 DOI: 10.1021/acsami.8b17555] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
The porous microstructure of scaffolds is an essential consideration for tissue engineering, which plays an important role for cell adhesion, migration, and proliferation. It is crucial to choose optimum pore sizes of scaffolds for the treatment of various damaged tissues. Therefore, the proper porosity is the significant factor that should be considered when designing tissue scaffolds. Herein, we develop an improved emulsion template method to fabricate gelatin-based scaffolds with controllable pore structure. Gelatin droplets were first prepared by emulsification and then solidified by genipin to prepare gelatin microspheres. The microspheres were used as a template for the fabrication of porous scaffolds, which were gathered and tightened together by dialdehyde amylose. The results showed that emulsification can produce gelatin microspheres with narrow size distribution. The size of gelatin microspheres was easily controlled by adjusting the concentration of gelatin and the speed of mechanical agitation. The gelatin-based scaffolds presented macroporous and interconnected structure. It is interesting that the pore size of scaffolds was directly related to the size of gelatin microspheres, displaying the same trend of change in size. It indicated that the gelatin microspheres can be used as the proper template to fabricate gelatin-based scaffold with a desired pore structure. In addition, the gelatin-based scaffolds possessed good blood compatibility and cytocompatibility. Overall, the gelatin-based scaffolds exhibited great potential in tissue engineering.
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Affiliation(s)
- Lun Yuan
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering , Sichuan University , Chengdu 610065 , P. R. China
| | - Xinying Li
- College of Chemistry and Environment Protection Engineering , Southwest Minzu University , Chengdu 610041 , P. R. China
| | - Liming Ge
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering , Sichuan University , Chengdu 610065 , P. R. China
| | - Xiaoqi Jia
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering , Sichuan University , Chengdu 610065 , P. R. China
| | - Jinfeng Lei
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering , Sichuan University , Chengdu 610065 , P. R. China
| | - Changdao Mu
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering , Sichuan University , Chengdu 610065 , P. R. China
| | - Defu Li
- Department of Pharmaceutics and Bioengineering, School of Chemical Engineering , Sichuan University , Chengdu 610065 , P. R. China
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Sun F, Chen J, Jin S, Wang J, Man Y, Li J, Zou Q, Li Y, Zuo Y. Development of biomimetic trilayer fibrous membranes for guided bone regeneration. J Mater Chem B 2019; 7:665-675. [PMID: 32254799 DOI: 10.1039/c8tb02435a] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
in order to build fibrous bone tissue scaffolds for guided bone regeneration and to mimic the trilayer structure and the multifunctional properties of the natural periosteum, we fabricated two fibrous trilayer membranes by conjugate electrospinning technology, in which poly(ε-caprolactone) (PCL) fiber was designed as an outer layer, the mixed fibers of PCL and polyurethane (co-PUPCL) as the interlayer, and degradable polyurethane fibers with or without nano-hydroxyapatite (n-HA) as the inner layer (PUHA or PU). The microstructure and characteristics of the trilayer membranes were evaluated and different monolayer fibers were fabricated as the contrast samples. The tensile strength values of each layer increased from the inner layer to the outer layer in the designed structure, while the step-by-step electrospinning method produced good adhesion of different layers. Furthermore, the degradable properties and hydrophilicity of the layers changed with dissymmetric fibrous structures. Cell proliferation assay and cell morphology observation indicated that the PUHA inner fibrous layer exhibited better cell attachment and proliferation than PU. In addition, the osteogenicity of the PUHA fibrous layer has been attested through protein expression by the differentiation of rat mesenchymal stem cells (rMSCs) into the osteogenic lineage. Cell infiltration testing on the two sides of the trilayer membranes in vitro and in vivo showed that the inner layer had good cellular penetration deep into the scaffolds, whereas the cells were barred by the outer layer. We have developed a trilayer structured membrane with different polymer fibers to replicate the natural periosteum by improving functional outcomes, which is a promising fibrous scaffold for clinical use in the repair of destroyed bone.
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Affiliation(s)
- Fuhua Sun
- Research Center for Nano Biomaterials, Analytical & Testing Center, Sichuan University, Chengdu 610064, P. R. China.
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Nobile S, Nobile L. Recent Research Progress on Scaffolds for Bone Repair and Regeneration. IFMBE PROCEEDINGS 2019. [DOI: 10.1007/978-981-10-9023-3_29] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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Lyu LX, Zhang XF, Deegan AJ, Liang GF, Yang HN, Hu SQ, Yan XL, Huang NP, Xu T. Comparing hydroxyapatite with osteogenic medium for the osteogenic differentiation of mesenchymal stem cells on PHBV nanofibrous scaffolds. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2018; 30:150-161. [PMID: 30556784 DOI: 10.1080/09205063.2018.1558485] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Having advantageous biocompatibility and osteoconductive properties known to enhance the osteogenic differentiation of mesenchymal stem cells (MSCs), hydroxyapatite (HA) is a commonly used material for bone tissue engineering. What remains unclear, however, is whether HA holds a similar potential for stimulating the osteogenic differentiation of MSCs to that of a more frequently used osteogenic-inducing medium (OIM). To that end, we used PHBV electrospun nanofibrous scaffolds to directly compare the osteogenic capacities of HA with OIM over MSCs. Through the observation of cellular morphology, the staining of osteogenic markers, and the quantitative measuring of osteogenic-related genes, as well as microRNA analyses, we not only found that HA was as capable as OIM for differentiating MSCs down an osteogenic lineage; albeit, at a significantly slower rate, but also that numerous microRNAs are involved in the osteogenic differentiation of MSCs through multiple pathways involving the inhibition of cellular proliferation and stemness, chondrogenesis and adipogenesis, and the active promotion of osteogenesis. Taken together, we have shown for the first time that PHBV electrospun nanofibrous scaffolds combined with HA have a similar osteogenic-inducing potential as OIM and may therefore be used as a viable replacement for OIM for alternative in vivo-mimicking bone tissue engineering applications.
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Affiliation(s)
- Lan-Xin Lyu
- a Emergency Center of the Affiliated Hospital of Xuzhou Medical University, Institute of Emergency Rescue Medicine, Key Laboratory of New Drugs and Clinical Application , Xuzhou Medical University , Xuzhou , China.,b State Key Laboratory of Bioelectronics , School of Biology Science and Medical Engineering, Southeast University , Nanjing , China
| | - Xiao-Feng Zhang
- b State Key Laboratory of Bioelectronics , School of Biology Science and Medical Engineering, Southeast University , Nanjing , China
| | - Anthony J Deegan
- c Department of Bioengineering , University of Washington , Seattle , WA , USA
| | - Gao-Feng Liang
- d Department of Medical School, Henan University of Science and Technology , Luoyang , China
| | - Hong-Ning Yang
- a Emergency Center of the Affiliated Hospital of Xuzhou Medical University, Institute of Emergency Rescue Medicine, Key Laboratory of New Drugs and Clinical Application , Xuzhou Medical University , Xuzhou , China
| | - Shu-Qun Hu
- a Emergency Center of the Affiliated Hospital of Xuzhou Medical University, Institute of Emergency Rescue Medicine, Key Laboratory of New Drugs and Clinical Application , Xuzhou Medical University , Xuzhou , China
| | - Xian-Liang Yan
- a Emergency Center of the Affiliated Hospital of Xuzhou Medical University, Institute of Emergency Rescue Medicine, Key Laboratory of New Drugs and Clinical Application , Xuzhou Medical University , Xuzhou , China
| | - Ning-Ping Huang
- b State Key Laboratory of Bioelectronics , School of Biology Science and Medical Engineering, Southeast University , Nanjing , China
| | - Tie Xu
- a Emergency Center of the Affiliated Hospital of Xuzhou Medical University, Institute of Emergency Rescue Medicine, Key Laboratory of New Drugs and Clinical Application , Xuzhou Medical University , Xuzhou , China.,e Emergency Center , Nanjing Jiangning Hospital , Nanjing , China
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Liu S, Mou S, Zhou C, Guo L, Zhong A, Yang J, Yuan Q, Wang J, Sun J, Wang Z. Off-the-Shelf Biomimetic Graphene Oxide-Collagen Hybrid Scaffolds Wrapped with Osteoinductive Extracellular Matrix for the Repair of Cranial Defects in Rats. ACS APPLIED MATERIALS & INTERFACES 2018; 10:42948-42958. [PMID: 30421913 DOI: 10.1021/acsami.8b11071] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Hydrogels such as type I collagen (COL) have been widely studied in bone tissue repair, whereas their weak mechanical strength has limited their clinical application. By adding graphene oxide (GO) nanosheets, researchers have successfully improved the mechanical properties and biocompatibility of the hydrogels. However, for large bone defects, the osteoinductive and cell adhesion ability of the GO hybrid hydrogels need to be improved. Mesenchymal stem cell (MSC) secreted extracellular matrix (ECM), which is an intricate network, could provide a biomimetic microenvironment and functional molecules that enhance the cell proliferation and survival rate. To synergize the advantages of MSC-ECM with GO-COL hybrid implants, we developed a novel ECM scaffold construction method. First, an osteoinductive extracellular matrix (OiECM) was created by culturing osteodifferentiated bone marrow mesenchymal stem cells (BMSCs) for 21 days. Then, the GO-COL scaffold was fully wrapped with the OiECM to construct the OiECM-GO-COL composite for implantation. The morphology, physical properties, biocompatibility, and osteogenic performance of the OiECM-GO-COL implants were assessed in vitro and in vivo (5 mm rat cranial defect model). Both gene expression and cell level assessments suggested that the BMSCs cultured on OiECM-GO-COL implants had a higher proliferation rate and osteogenic ability compared to the COL or GO-COL groups. In vivo results showed that the OiECM-GO-COL implants achieved better repair effects in a rat critical cranial defect model, whereas bone formation in other groups was limited. This study provides a promising strategy, which greatly improves the osteogenic ability and biocompatibility of the GO hydrogels without the procedure of seeding and culturing MSCs on scaffolds in vitro, demonstrating its potential as an off-the-shelf method for bone tissue engineering.
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Affiliation(s)
- Shaokai Liu
- Department of Plastic Surgery, Union Hospital, Tongji Medical College , Huazhong University of Science and Technology , 1277 Jiefang Avenue , Wuhan 430022 , China
| | - Shan Mou
- Department of Plastic Surgery, Union Hospital, Tongji Medical College , Huazhong University of Science and Technology , 1277 Jiefang Avenue , Wuhan 430022 , China
| | - Chuchao Zhou
- Department of Plastic Surgery, Union Hospital, Tongji Medical College , Huazhong University of Science and Technology , 1277 Jiefang Avenue , Wuhan 430022 , China
| | - Liang Guo
- Department of Plastic Surgery, Union Hospital, Tongji Medical College , Huazhong University of Science and Technology , 1277 Jiefang Avenue , Wuhan 430022 , China
| | - Aimei Zhong
- Department of Plastic Surgery, Union Hospital, Tongji Medical College , Huazhong University of Science and Technology , 1277 Jiefang Avenue , Wuhan 430022 , China
| | - Jie Yang
- Department of Plastic Surgery, Union Hospital, Tongji Medical College , Huazhong University of Science and Technology , 1277 Jiefang Avenue , Wuhan 430022 , China
| | - Quan Yuan
- Department of Plastic Surgery, Union Hospital, Tongji Medical College , Huazhong University of Science and Technology , 1277 Jiefang Avenue , Wuhan 430022 , China
| | - Jiecong Wang
- Department of Plastic Surgery, Union Hospital, Tongji Medical College , Huazhong University of Science and Technology , 1277 Jiefang Avenue , Wuhan 430022 , China
| | - Jiaming Sun
- Department of Plastic Surgery, Union Hospital, Tongji Medical College , Huazhong University of Science and Technology , 1277 Jiefang Avenue , Wuhan 430022 , China
| | - Zhenxing Wang
- Department of Plastic Surgery, Union Hospital, Tongji Medical College , Huazhong University of Science and Technology , 1277 Jiefang Avenue , Wuhan 430022 , China
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Ataie M, Shabani I, Seyedjafari E. Surface mineralized hybrid nanofibrous scaffolds based on poly(l
-lactide) and alginate enhances osteogenic differentiation of stem cells. J Biomed Mater Res A 2018; 107:586-596. [DOI: 10.1002/jbm.a.36574] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2018] [Revised: 10/03/2018] [Accepted: 10/27/2018] [Indexed: 12/20/2022]
Affiliation(s)
- Maryam Ataie
- Department of Biomedical Engineering; Amirkabir University of Technology; Tehran Iran
| | - Iman Shabani
- Department of Biomedical Engineering; Amirkabir University of Technology; Tehran Iran
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Wang S, Hu F, Li J, Zhang S, Shen M, Huang M, Shi X. Design of electrospun nanofibrous mats for osteogenic differentiation of mesenchymal stem cells. NANOMEDICINE : NANOTECHNOLOGY, BIOLOGY, AND MEDICINE 2018; 14:2505-2520. [PMID: 28554595 DOI: 10.1016/j.nano.2016.12.024] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Revised: 12/20/2016] [Accepted: 12/30/2016] [Indexed: 01/09/2023]
Abstract
The clinical translation potential of mesenchymal stem cells (MSCs) in regenerative medicine has been greatly exploited. With the merits of high surface area to volume ratio, facile control of components, well retained topography, and the capacity to mimic the native extracellular matrix (ECM), nanofibers have received a great deal of attention as bone tissue engineering scaffolds. Electrospinning has been considered as an efficient approach for scale-up fabrication of nanofibrous materials. Electrospun nanofibers are capable of stimulating cell-matrix interaction to form a cell niche, directing cellular behavior, and promoting the MSCs adhesion and proliferation. In this review, we give a comprehensive literature survey on the mechanisms of electrospun nanofibers in supporting the MSCs differentiation. Specifically, the influences of biological and physical osteogenic inductive cues on the MSCs osteogenic differentiation are reviewed. Along with the significant advances in the field, current research challenges and future perspectives are also discussed.
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Affiliation(s)
- Shige Wang
- College of Science, University of Shanghai for Science & Technology, Shanghai, PR China; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, PR China; State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, People's Republic of China
| | - Fei Hu
- College of Science, University of Shanghai for Science & Technology, Shanghai, PR China
| | - Jingchao Li
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, PR China
| | - Shuping Zhang
- College of Science, University of Shanghai for Science & Technology, Shanghai, PR China
| | - Mingwu Shen
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, PR China
| | - Mingxian Huang
- College of Science, University of Shanghai for Science & Technology, Shanghai, PR China.
| | - Xiangyang Shi
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, PR China; CQM-Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, Funchal, Portugal.
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Ding Q, Qu Y, Shi K, He X, Chen Z, Yang Y, Wang X, Qian Z. Preparation of Bone Marrow Mesenchymal Stem Cells Combined with Hydroxyapatite/Poly(d,l-lactide) Porous Microspheres for Bone Regeneration in Calvarial Defects. ACS APPLIED BIO MATERIALS 2018; 1:1084-1093. [PMID: 34996148 DOI: 10.1021/acsabm.8b00312] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Qiuxia Ding
- Department of Gynaecology and Obstetrics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
| | - Ying Qu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of China
| | - Kun Shi
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of China
| | - Xinye He
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of China
| | - Zhengqiong Chen
- Department of Gynaecology and Obstetrics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
| | - Ying Yang
- Department of Gynaecology and Obstetrics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
| | - Xiangwei Wang
- Department of Urology, Center of Nephrology, General Hospital of Shenzhen University, Shenzhen 518055, China
| | - Zhiyong Qian
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of China
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Cai Y, Gao T, Fu S, Sun P. Development of zoledronic acid functionalized hydroxyapatite loaded polymeric nanoparticles for the treatment of osteoporosis. Exp Ther Med 2018; 16:704-710. [PMID: 30116324 PMCID: PMC6090242 DOI: 10.3892/etm.2018.6263] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Accepted: 09/29/2017] [Indexed: 01/12/2023] Open
Abstract
The present study formulated a hydroxyapatite (HA)-coated lipid nanoparticle loaded with zoledronic acid to treat patients with osteoporosis (OP). HA-coated zoledronic acid loaded lipid bilayer nanoparticles (HZL NPs) were prepared using methods of extrusion and precipitation. Nanosized particles were prepared with the aim of increasing gradual and prolonged drug release and inducing toxicity of osteoblasts. Cellular morphology was investigated by scanning electron microscopy, which revealed clear spherical shaped NPs ~200 nm in size that could treat osteopores in the bone. In addition, a typical biphasic release pattern was observed that could be attributed to the presence of drug on the outer surface as well as on the inner core of the NPs. There was sustained release behavior [38.17±2.12% (pH 7.4) and 64.2±3.75% (pH 5) at 48 h] of the drug that maintained the drug reservoir effect at the bone site. Furthermore, HZL NPs increased the cytotoxicity of HFOb 1.19 cells and increased the proportion of cells in the early (18.1±12.4%), late (28.7±3.7%) and necrotic (67.5±1.2%) phases of apoptosis. Most importantly, HZL in the lipid nanoparticle exhibited a strong affinity towards HA, further enhancing its efficacy in the treatment of OP.
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Affiliation(s)
- Yunlu Cai
- Department of Orthopedics, The Eighth People's Hospital of Shanghai, Shanghai 200235, P.R. China
| | - Tiantian Gao
- Department of Orthopedics, The Eighth People's Hospital of Shanghai, Shanghai 200235, P.R. China
| | - Shiping Fu
- Department of Orthopedics, The Eighth People's Hospital of Shanghai, Shanghai 200235, P.R. China
| | - Ping Sun
- Department of Orthopedics, The Eighth People's Hospital of Shanghai, Shanghai 200235, P.R. China
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Ahmad T, Shin HJ, Lee J, Shin YM, Perikamana SKM, Park SY, Jung HS, Shin H. Fabrication of in vitro 3D mineralized tissue by fusion of composite spheroids incorporating biomineral-coated nanofibers and human adipose-derived stem cells. Acta Biomater 2018; 74:464-477. [PMID: 29803004 DOI: 10.1016/j.actbio.2018.05.035] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Revised: 05/18/2018] [Accepted: 05/22/2018] [Indexed: 12/24/2022]
Abstract
Development of a bone-like 3D microenvironment with stem cells has always been intriguing in bone tissue engineering. In this study, we fabricated composite spheroids by combining functionalized fibers and human adipose-derived stem cells (hADSCs), which were fused to form a 3D mineralized tissue construct. We prepared fragmented poly (ι-lactic acid) (PLLA) fibers approximately 100 μm long by partial aminolysis of electrospun fibrous mesh. PLLA fibers were then biomineralized with various concentrations of NaHCO3 (0.005, 0.01, and 0.04 M) to form mineralized fragmented fibers (mFF1, mFF2, and mFF3, respectively). SEM analysis showed that the minerals in mFF2 and mFF3 completely covered the fiber surface, and surface chemistry analysis confirmed the presence of hydroxyapatite peaks. Additionally, mFFs formed composite spheroids with hADSCs, demonstrating that the cells were strongly attached to mFFs and homogeneously distributed throughout the spheroid. In vitro culture of spheroids in the media without osteogenic supplements showed significantly enhanced expression of osteogenic genes including Runx2 (20.83 ± 2.83 and 22.36 ± 2.18 fold increase), OPN (14.24 ± 1.71 and 15.076 ± 1.38 fold increase), and OCN (4.36 ± 0.41 and 5.63 ± 0.51 fold increase) in mFF2 and mFF3, respectively, compared to the no mineral fiber group. In addition, mineral contents were significantly increased at day 7. Blocking the biomineral-mediated signaling by PSB 603 significantly down regulated the expression of these genes in mFF3 at day 7. Finally, we fused composite spheroids to form a mineralized 3D tissue construct, which maintained the viability of cells and showed pervasively distributed minerals within the structure. Our composite spheroids could be used as an alternative platform for the development of in vitro bone models, in vivo cell carriers, and as building blocks for bioprinting 3D bone tissue. STATEMENT OF SIGNIFICANCE This manuscript described our recent work for the preparation of biomimeral-coated fibers that can be assembled with mesenchymal stem cells and provide bone-like environment for directed control over osteogenic differentiation. Biomineral coating onto synthetic, biodegradable single fibers was successfully carried out using multiple steps, combination of template protein coating inspired from mussel adhesion and charge-charge interactions between template proteins and mineral ions. The biomineral-coated single micro-scale fibers (1-2.5 μm in diameter) were then assembled with human adipose tissue derived stem cells (hADSCs). The assembled structure exhibited spheroidal architecture with few hundred micrometers. hADSCs within the spheroids were differentiated into osteogenic lineage in vitro and mineralized in the growth media. These spheroids were fused to form in vitro 3D mineralized tissue with larger size.
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Affiliation(s)
- Taufiq Ahmad
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
| | - Hyeok Jun Shin
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
| | - Jinkyu Lee
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
| | - Young Min Shin
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
| | - Sajeesh Kumar Madhurakat Perikamana
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
| | - So Yeon Park
- School of Advanced Materials Science & Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Hyun Suk Jung
- School of Advanced Materials Science & Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Heungsoo Shin
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
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Lü L, Deegan A, Musa F, Xu T, Yang Y. The effects of biomimetically conjugated VEGF on osteogenesis and angiogenesis of MSCs (human and rat) and HUVECs co-culture models. Colloids Surf B Biointerfaces 2018; 167:550-559. [PMID: 29730577 DOI: 10.1016/j.colsurfb.2018.04.060] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 04/09/2018] [Accepted: 04/29/2018] [Indexed: 10/17/2022]
Abstract
The purpose of this work was to investigate if the biomimetically conjugated VEGF and HUVECs co-culture could modulate the osteogenic and angiogenic differentiation of MSCs derived from rat and human bone marrow (rMSCs and hMSCs). After treated by ammonia plasma, Poly(lactic-co-glycolic acid) (PLGA) electrospun nanofibers were immobilized with VEGF through heparin to fulfil the sustained release. The proliferation capacity of rMSCs and hMSCs on neat PLGA nanofibers (NF) and VEGF immobilized NF (NF-VEGF) surfaces were assessed by CCK-8 and compared when MSCs were mono-cultured and co-cultured with HUVECs. The effect of VEGF and HUVECs co-culturing on osteogenic and angiogenic differentiation of rMSCs and hMSCs were investigated by calcium deposits and CD31 expression on NF and NF-VEGF surfaces. The results indicated that VEGF has been biomimetically immobilized onto PLGA nanofibers surface and kept sustained release successfully. The CD31 staining results showed that both VEGF and HUVECs co-culture could enhance the angiogenesis of rMSCs and hMSCs. However, the proliferation and osteogenic differentiation of MSCs when cultured with VEGF and HUVECs showed a species dependent response. Taken together, VEGF immobilization and co-culture with HUVECs promoted angiogenesis of MSCs, indicating a good strategy for vascularization in bone tissue engineering.
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Affiliation(s)
- Lanxin Lü
- Emergency Center of the Affiliated Hospital of Xuzhou Medical University, Institute of Emergency Rescue Medicine, Xuzhou Medical University, Xuzhou, 221002, China; Institute for Science and Technology in Medicine, School of Medicine, Keele University, Stoke-on-Trent, ST4 7QB, UK
| | - Anthony Deegan
- Institute for Science and Technology in Medicine, School of Medicine, Keele University, Stoke-on-Trent, ST4 7QB, UK
| | - Faiza Musa
- Institute for Science and Technology in Medicine, School of Medicine, Keele University, Stoke-on-Trent, ST4 7QB, UK
| | - Tie Xu
- Emergency Center of the Affiliated Hospital of Xuzhou Medical University, Institute of Emergency Rescue Medicine, Xuzhou Medical University, Xuzhou, 221002, China.
| | - Ying Yang
- Institute for Science and Technology in Medicine, School of Medicine, Keele University, Stoke-on-Trent, ST4 7QB, UK.
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Reinwald Y, El Haj AJ. Hydrostatic pressure in combination with topographical cues affects the fate of bone marrow-derived human mesenchymal stem cells for bone tissue regeneration. J Biomed Mater Res A 2018; 106:629-640. [PMID: 28984025 PMCID: PMC5813264 DOI: 10.1002/jbm.a.36267] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 09/13/2017] [Accepted: 09/18/2017] [Indexed: 12/16/2022]
Abstract
Topographical and mechanical cues are vital for cell fate, tissue development in vivo, and to mimic the native cell growth environment in vitro. To date, the combinatory effect of mechanical and topographical cues as not been thoroughly investigated. This study investigates the effect of PCL nanofiber alignment and hydrostatic pressure on stem cell differentiation for bone tissue regeneration. Bone marrow-derived human mesenchymal stem cells were seeded onto standard tissue culture plastic and electrospun random and aligned nanofibers. These substrates were either cultured statically or subjected to intermittent hydrostatic pressure at 270 kPa, 1 Hz for 60 min daily over 21 days in osteogenic medium. Data revealed higher cell metabolic activities for all mechanically stimulated cell culture formats compared with non-stimulated controls; and random fibers compared with aligned fibers. Fiber orientation influenced cell morphology and patterns of calcium deposition. Significant up-regulation of Collagen-I, ALP, and Runx-2 were observed for random and aligned fibers following mechanical stimulation; highest levels of osteogenic markers were expressed when hydrostatic pressure was applied to random fibers. These results indicate that fiber alignment and hydrostatic pressure direct stem cell fate and are important stimulus for tissue regeneration. © 2017 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: A: 629-640, 2018.
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Affiliation(s)
- Yvonne Reinwald
- Institute of Science and Technology in Medicine, Keele University, Medical School, Guy Hilton Research Centre, UHNMStoke‐on‐TrentUnited Kingdom
- Department of Engineering, School of Science and TechnologyNottingham Trent UniversityNottinghamUnited Kingdom
| | - Alicia J. El Haj
- Institute of Science and Technology in Medicine, Keele University, Medical School, Guy Hilton Research Centre, UHNMStoke‐on‐TrentUnited Kingdom
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Enhanced Tissue Compatibility of Polyetheretherketone Disks by Dopamine-Mediated Protein Immobilization. Macromol Res 2018. [DOI: 10.1007/s13233-018-6018-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Chen Z, Bachhuka A, Wei F, Wang X, Liu G, Vasilev K, Xiao Y. Nanotopography-based strategy for the precise manipulation of osteoimmunomodulation in bone regeneration. NANOSCALE 2017; 9:18129-18152. [PMID: 29143002 DOI: 10.1039/c7nr05913b] [Citation(s) in RCA: 87] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Immune cells play vital roles in regulating bone dynamics. Successful bone regeneration requires a favourable osteo-immune environment. The high plasticity and diversity of immune cells make it possible to manipulate the osteo-immune response of immune cells, thus modulating the osteoimmune environment and regulating bone regeneration. With the advancement in nanotechnology, nanotopographies with different controlled surface properties can be fabricated. On tuning the surface properties, the osteo-immune response can be precisely modulated. This highly tunable characteristic and immunomodulatory effects make nanotopography a promising strategy to precisely manipulate osteoimmunomdulation for bone tissue engineering applications. This review first summarises the effects of the immune response during bone healing to show the importance of regulating the immune response for the bone response. The plasticity of immune cells is then reviewed to provide rationales for manipulation of the osteoimmune response. Subsequently, we highlight the current types of nanotopographies applied in bone biomaterials and their fabrication techniques, and explain how these nanotopographies modulate the immune response and the possible underlying mechanisms. The effects of immune cells on nanotopography-mediated osteogenesis are emphasized, and we propose the concept of "nano-osteoimmunomodulation" to provide a valuable strategy for the development of nanotopographies with osteoimmunomodulatory properties that can precisely regulate bone dynamics.
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Affiliation(s)
- Zetao Chen
- Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, Guangdong, People's Republic of China
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Sankar S, Sharma CS, Rath SN, Ramakrishna S. Electrospun Fibers for Recruitment and Differentiation of Stem Cells in Regenerative Medicine. Biotechnol J 2017; 12. [PMID: 28980771 DOI: 10.1002/biot.201700263] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2017] [Revised: 09/12/2017] [Indexed: 11/11/2022]
Abstract
Electrospinning is a popular technique used to mimic the natural sub-micron features of the native tissue. The ultra-fine fibers provide a favorable extracellular matrix-like environment for regulation of cellular functions. This article summarizes and reviews the current advances in electrospun fiber application and focuses on the novel strategies applied for tissue regeneration and repair. It explores the different factors affecting the attachment and proliferation of mesenchymal stem cells (MSCs) on the electrospun substrates. The influence of different features of electrospun fibers in the differentiation of MSCs into specific lineages (bone, cartilage, tendon/ligament, and nerves) has been elaborated. In addition, the different techniques to mimic the hierarchical features of tissues and its effect on cellular functions are reviewed. Additionally, the new developments like three-dimensional (3D) electrospinning, 3D spheroid double strategy and the comparative analysis of dynamic and static culture on electrospun scaffolds are discussed. With the intricate understanding of the interaction between the cells and the electrospun fiber matrix we can aim to combine the newer strategies to overcome the existing challenges and improve the potential application of electrospun fibers in the field of tissue regeneration and repair.
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Affiliation(s)
- Sharanya Sankar
- Department of Biomedical Engineering, Indian Institute of Technology, Telangana-502285, Hyderabad, India
| | - Chandra S Sharma
- Department of Chemical Engineering, Indian Institute of Technology, Telangana-502285, Hyderabad, India
| | - Subha N Rath
- Department of Biomedical Engineering, Indian Institute of Technology, Telangana-502285, Hyderabad, India
| | - Seeram Ramakrishna
- Center for Nanofibers & Nanotechnology, National University of Singapore, 110077, Singapore
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Li J, Zhang J, Chen Y, Kawazoe N, Chen G. TEMPO-Conjugated Gold Nanoparticles for Reactive Oxygen Species Scavenging and Regulation of Stem Cell Differentiation. ACS APPLIED MATERIALS & INTERFACES 2017; 9:35683-35692. [PMID: 28944661 DOI: 10.1021/acsami.7b12486] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Abstract
Controlling the differentiation of human mesenchymal stem cells (hMSCs) shows a great potential in regenerative medicine. Because overproduced reactive oxygen species (ROS) have an obvious inhibitory effect on the differentiation and functions of hMSCs, it is highly desirable to develop an effective strategy for ROS scavenging and stem cell differentiation controlling. In this study, gold nanoparticles (Au NPs) with an average size of 40 nm were conjugated with 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) to endow them with ROS-scavenging capacity while holding the beneficial effect of Au NPs. The TEMPO-conjugated Au NPs (Au-PEG-TEMPO NPs) were used for the culture of hMSCs to investigate their effect on ROS scavenging, proliferation, and osteogenic and adipogenic differentiation of hMSCs. The Au-PEG-TEMPO NPs had a negligible influence on cell viability and proliferation of hMSCs and could effectively reduce the ROS level of hMSCs under H2O2-exposed conditions because of their excellent cellular uptake. Similar to the counterparts without surface TEMPO modification (Au-mPEG NPs), the Au-PEG-TEMPO NPs could promote the osteogenic differentiation of hMSCs, whereas they could inhibit the adipogenic differentiation of hMSCs. The results indicated that the TEMPO-conjugated Au NPs had high scavenging capacity for overproduced ROS and maintained the promotive effect of Au NPs on osteogenic differentiation of hMSCs without the inhibitory effect of free TEMPO. This study offers a promising strategy for ROS scavenging to control stem cell differentiation in stem cell transplantation and regenerative medicine.
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Affiliation(s)
- Jingchao Li
- Research Center for Functional Materials, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan
- Department of Materials Science and Engineering, Graduate School of Pure and Applied Sciences, University of Tsukuba , 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan
| | - Jing Zhang
- Research Center for Functional Materials, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan
- Department of Materials Science and Engineering, Graduate School of Pure and Applied Sciences, University of Tsukuba , 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan
| | - Ying Chen
- Research Center for Functional Materials, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan
- Department of Materials Science and Engineering, Graduate School of Pure and Applied Sciences, University of Tsukuba , 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan
| | - Naoki Kawazoe
- Research Center for Functional Materials, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan
| | - Guoping Chen
- Research Center for Functional Materials, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan
- Department of Materials Science and Engineering, Graduate School of Pure and Applied Sciences, University of Tsukuba , 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan
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