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Angolkar M, Paramshetti S, Gahtani RM, Al Shahrani M, Hani U, Talath S, Osmani RAM, Spandana A, Gangadharappa HV, Gundawar R. Pioneering a paradigm shift in tissue engineering and regeneration with polysaccharides and proteins-based scaffolds: A comprehensive review. Int J Biol Macromol 2024; 265:130643. [PMID: 38467225 DOI: 10.1016/j.ijbiomac.2024.130643] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 02/16/2024] [Accepted: 03/03/2024] [Indexed: 03/13/2024]
Abstract
In the realm of modern medicine, tissue engineering and regeneration stands as a beacon of hope, offering the promise of restoring form and function to damaged or diseased organs and tissues. Central to this revolutionary field are biological macromolecules-nature's own blueprints for regeneration. The growing interest in bio-derived macromolecules and their composites is driven by their environmentally friendly qualities, renewable nature, minimal carbon footprint, and widespread availability in our ecosystem. Capitalizing on these unique attributes, specific composites can be tailored and enhanced for potential utilization in the realm of tissue engineering (TE). This review predominantly concentrates on the present research trends involving TE scaffolds constructed from polysaccharides, proteins and glycosaminoglycans. It provides an overview of the prerequisites, production methods, and TE applications associated with a range of biological macromolecules. Furthermore, it tackles the challenges and opportunities arising from the adoption of these biomaterials in the field of TE. This review also presents a novel perspective on the development of functional biomaterials with broad applicability across various biomedical applications.
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Affiliation(s)
- Mohit Angolkar
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSSAHER), Mysuru 570015, Karnataka, India
| | - Sharanya Paramshetti
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSSAHER), Mysuru 570015, Karnataka, India
| | - Reem M Gahtani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia.
| | - Mesfer Al Shahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia.
| | - Umme Hani
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia.
| | - Sirajunisa Talath
- Department of Pharmaceutical Chemistry, RAK College of Pharmaceutical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates.
| | - Riyaz Ali M Osmani
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSSAHER), Mysuru 570015, Karnataka, India.
| | - Asha Spandana
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSSAHER), Mysuru 570015, Karnataka, India.
| | | | - Ravi Gundawar
- Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal 576104, Karnataka, India.
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2
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Babaliari E, Ranella A, Stratakis E. Microfluidic Systems for Neural Cell Studies. Bioengineering (Basel) 2023; 10:902. [PMID: 37627787 PMCID: PMC10451731 DOI: 10.3390/bioengineering10080902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 07/05/2023] [Accepted: 07/25/2023] [Indexed: 08/27/2023] Open
Abstract
Whereas the axons of the peripheral nervous system (PNS) spontaneously regenerate after an injury, the occurring regeneration is rarely successful because axons are usually directed by inappropriate cues. Therefore, finding successful ways to guide neurite outgrowth, in vitro, is essential for neurogenesis. Microfluidic systems reflect more appropriately the in vivo environment of cells in tissues such as the normal fluid flow within the body, consistent nutrient delivery, effective waste removal, and mechanical stimulation due to fluid shear forces. At the same time, it has been well reported that topography affects neuronal outgrowth, orientation, and differentiation. In this review, we demonstrate how topography and microfluidic flow affect neuronal behavior, either separately or in synergy, and highlight the efficacy of microfluidic systems in promoting neuronal outgrowth.
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Affiliation(s)
- Eleftheria Babaliari
- Foundation for Research and Technology—Hellas (F.O.R.T.H.), Institute of Electronic Structure and Laser (I.E.S.L.), Vasilika Vouton, 70013 Heraklion, Greece;
| | - Anthi Ranella
- Foundation for Research and Technology—Hellas (F.O.R.T.H.), Institute of Electronic Structure and Laser (I.E.S.L.), Vasilika Vouton, 70013 Heraklion, Greece;
| | - Emmanuel Stratakis
- Foundation for Research and Technology—Hellas (F.O.R.T.H.), Institute of Electronic Structure and Laser (I.E.S.L.), Vasilika Vouton, 70013 Heraklion, Greece;
- Department of Physics, University of Crete, 70013 Heraklion, Greece
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Sheikh-Oleslami S, Tao B, D'Souza J, Butt F, Suntharalingam H, Rempel L, Amiri N. A Review of Metal Nanoparticles Embedded in Hydrogel Scaffolds for Wound Healing In Vivo. Gels 2023; 9:591. [PMID: 37504470 PMCID: PMC10379627 DOI: 10.3390/gels9070591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/10/2023] [Accepted: 07/11/2023] [Indexed: 07/29/2023] Open
Abstract
An evolving field, nanotechnology has made its mark in the fields of nanoscience, nanoparticles, nanomaterials, and nanomedicine. Specifically, metal nanoparticles have garnered attention for their diverse use and applicability to dressings for wound healing due to their antimicrobial properties. Given their convenient integration into wound dressings, there has been increasing focus dedicated to investigating the physical, mechanical, and biological characteristics of these nanoparticles as well as their incorporation into biocomposite materials, such as hydrogel scaffolds for use in lieu of antibiotics as well as to accelerate and ameliorate healing. Though rigorously tested and applied in both medical and non-medical applications, further investigations have not been carried out to bring metal nanoparticle-hydrogel composites into clinical practice. In this review, we provide an up-to-date, comprehensive review of advancements in the field, with emphasis on implications on wound healing in in vivo experiments.
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Affiliation(s)
- Sara Sheikh-Oleslami
- Faculty of Medicine, The University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada
| | - Brendan Tao
- Faculty of Medicine, The University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada
| | - Jonathan D'Souza
- Faculty of Engineering, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L7, Canada
| | - Fahad Butt
- Faculty of Science, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L7, Canada
| | - Hareshan Suntharalingam
- Faculty of Engineering, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L7, Canada
| | - Lucas Rempel
- Faculty of Medicine, The University of British Columbia, 317-2194 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada
| | - Nafise Amiri
- International Collaboration on Repair Discoveries, 818 West 10th Avenue, Vancouver, BC V5Z 1M9, Canada
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Yamada S, Yassin MA, Torelli F, Hansmann J, Green JBA, Schwarz T, Mustafa K. Unique osteogenic profile of bone marrow stem cells stimulated in perfusion bioreactor is Rho-ROCK-mediated contractility dependent. Bioeng Transl Med 2023; 8:e10509. [PMID: 37206242 PMCID: PMC10189446 DOI: 10.1002/btm2.10509] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/28/2023] [Accepted: 03/04/2023] [Indexed: 03/19/2023] Open
Abstract
The fate determination of bone marrow mesenchymal stem/stromal cells (BMSC) is tightly regulated by mechanical cues, including fluid shear stress. Knowledge of mechanobiology in 2D culture has allowed researchers in bone tissue engineering to develop 3D dynamic culture systems with the potential for clinical translation in which the fate and growth of BMSC are mechanically controlled. However, due to the complexity of 3D dynamic cell culture compared to the 2D counterpart, the mechanisms of cell regulation in the dynamic environment remain relatively undescribed. In the present study, we analyzed the cytoskeletal modulation and osteogenic profiles of BMSC under fluid stimuli in a 3D culture condition using a perfusion bioreactor. BMSC subjected to fluid shear stress (mean 1.56 mPa) showed increased actomyosin contractility, accompanied by the upregulation of mechanoreceptors, focal adhesions, and Rho GTPase-mediated signaling molecules. Osteogenic gene expression profiling revealed that fluid shear stress promoted the expression of osteogenic markers differently from chemically induced osteogenesis. Osteogenic marker mRNA expression, type 1 collagen formation, ALP activity, and mineralization were promoted in the dynamic condition, even in the absence of chemical supplementation. The inhibition of cell contractility under flow by Rhosin chloride, Y27632, MLCK inhibitor peptide-18, or Blebbistatin revealed that actomyosin contractility was required for maintaining the proliferative status and mechanically induced osteogenic differentiation in the dynamic culture. The study highlights the cytoskeletal response and unique osteogenic profile of BMSC in this type of dynamic cell culture, stepping toward the clinical translation of mechanically stimulated BMCS for bone regeneration.
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Affiliation(s)
- Shuntaro Yamada
- Center of Translational Oral Research (TOR)‐Tissue Engineering Group, Department of Clinical Dentistry, Faculty of MedicineUniversity of BergenNorway
| | - Mohammed A. Yassin
- Center of Translational Oral Research (TOR)‐Tissue Engineering Group, Department of Clinical Dentistry, Faculty of MedicineUniversity of BergenNorway
| | - Francesco Torelli
- Center of Translational Oral Research (TOR)‐Tissue Engineering Group, Department of Clinical Dentistry, Faculty of MedicineUniversity of BergenNorway
| | - Jan Hansmann
- Translational Center Regenerative TherapiesFraunhofer Institute for Silicate Research ISCWürzburgGermany
- Chair of Tissue Engineering and Regenerative MedicineUniversity Hospital WürzburgWürzburgGermany
- Department of Electrical EngineeringUniversity of Applied Sciences Würzburg‐SchweinfurtSchweinfurtGermany
| | - Jeremy B. A. Green
- Centre for Craniofacial & Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial SciencesKing's College LondonUK
| | - Thomas Schwarz
- Translational Center Regenerative TherapiesFraunhofer Institute for Silicate Research ISCWürzburgGermany
| | - Kamal Mustafa
- Center of Translational Oral Research (TOR)‐Tissue Engineering Group, Department of Clinical Dentistry, Faculty of MedicineUniversity of BergenNorway
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Kontogianni GI, Loukelis K, Bonatti AF, Batoni E, De Maria C, Naseem R, Dalgarno K, Vozzi G, MacManus DB, Mondal S, Dunne N, Vitale-Brovarone C, Chatzinikolaidou M. Effect of Uniaxial Compression Frequency on Osteogenic Cell Responses in Dynamic 3D Cultures. Bioengineering (Basel) 2023; 10:bioengineering10050532. [PMID: 37237602 DOI: 10.3390/bioengineering10050532] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 04/24/2023] [Accepted: 04/24/2023] [Indexed: 05/28/2023] Open
Abstract
The application of mechanical stimulation on bone tissue engineering constructs aims to mimic the native dynamic nature of bone. Although many attempts have been made to evaluate the effect of applied mechanical stimuli on osteogenic differentiation, the conditions that govern this process have not yet been fully explored. In this study, pre-osteoblastic cells were seeded on PLLA/PCL/PHBV (90/5/5 wt.%) polymeric blend scaffolds. The constructs were subjected every day to cyclic uniaxial compression for 40 min at a displacement of 400 μm, using three frequency values, 0.5, 1, and 1.5 Hz, for up to 21 days, and their osteogenic response was compared to that of static cultures. Finite element simulation was performed to validate the scaffold design and the loading direction, and to assure that cells inside the scaffolds would be subjected to significant levels of strain during stimulation. None of the applied loading conditions negatively affected the cell viability. The alkaline phosphatase activity data indicated significantly higher values at all dynamic conditions compared to the static ones at day 7, with the highest response being observed at 0.5 Hz. Collagen and calcium production were significantly increased compared to static controls. These results indicate that all of the examined frequencies substantially promoted the osteogenic capacity.
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Affiliation(s)
| | - Konstantinos Loukelis
- Department of Materials Science and Technology, University of Crete, 70013 Heraklion, Greece
| | - Amedeo Franco Bonatti
- Research Center E. Piaggio and Department of Information Engineering, University of Pisa, 56126 Pisa, Italy
| | - Elisa Batoni
- Research Center E. Piaggio and Department of Information Engineering, University of Pisa, 56126 Pisa, Italy
| | - Carmelo De Maria
- Research Center E. Piaggio and Department of Information Engineering, University of Pisa, 56126 Pisa, Italy
| | - Raasti Naseem
- School of Engineering, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
| | - Kenneth Dalgarno
- School of Engineering, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
| | - Giovanni Vozzi
- Research Center E. Piaggio and Department of Information Engineering, University of Pisa, 56126 Pisa, Italy
| | - David B MacManus
- School of Mechanical & Manufacturing Engineering, Dublin City University, D09 W6F4 Dublin, Ireland
| | - Subrata Mondal
- School of Mechanical & Manufacturing Engineering, Dublin City University, D09 W6F4 Dublin, Ireland
| | - Nicholas Dunne
- School of Mechanical & Manufacturing Engineering, Dublin City University, D09 W6F4 Dublin, Ireland
| | | | - Maria Chatzinikolaidou
- Department of Materials Science and Technology, University of Crete, 70013 Heraklion, Greece
- Foundation for Research and Technology Hellas (FORTH)-IESL, 70013 Heraklion, Greece
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6
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The Effect of Tortuosity on Permeability of Porous Scaffold. Biomedicines 2023; 11:biomedicines11020427. [PMID: 36830961 PMCID: PMC9953537 DOI: 10.3390/biomedicines11020427] [Citation(s) in RCA: 55] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Revised: 01/25/2023] [Accepted: 01/26/2023] [Indexed: 02/05/2023] Open
Abstract
In designing porous scaffolds, permeability is essential to consider as a function of cell migration and bone tissue regeneration. Good permeability has been achieved by mimicking the complexity of natural cancellous bone. In this study, a porous scaffold was developed according to the morphological indices of cancellous bone (porosity, specific surface area, thickness, and tortuosity). The computational fluid dynamics method analyzes the fluid flow through the scaffold. The permeability values of natural cancellous bone and three types of scaffolds (cubic, octahedron pillar, and Schoen's gyroid) were compared. The results showed that the permeability of the Negative Schwarz Primitive (NSP) scaffold model was similar to that of natural cancellous bone, which was in the range of 2.0 × 10-11 m2 to 4.0 × 10-10 m2. In addition, it was observed that the tortuosity parameter significantly affected the scaffold's permeability and shear stress values. The tortuosity value of the NSP scaffold was in the range of 1.5-2.8. Therefore, tortuosity can be manipulated by changing the curvature of the surface scaffold radius to obtain a superior bone tissue engineering construction supporting cell migration and tissue regeneration. This parameter should be considered when making new scaffolds, such as our NSP. Such efforts will produce a scaffold architecturally and functionally close to the natural cancellous bone, as demonstrated in this study.
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Fattahi E, Taheri S, Schilling AF, Becker T, Pörtner R. Generation and evaluation of input values for computational analysis of transport processes within tissue cultures. Eng Life Sci 2022; 22:681-698. [PMID: 36348656 PMCID: PMC9635004 DOI: 10.1002/elsc.202100128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 01/27/2022] [Accepted: 02/11/2022] [Indexed: 11/15/2022] Open
Abstract
Techniques for tissue culture have seen significant advances during the last decades and novel 3D cell culture systems have become available. To control their high complexity, experimental techniques and their Digital Twins (modelling and computational tools) are combined to link different variables to process conditions and critical process parameters. This allows a rapid evaluation of the expected product quality. However, the use of mathematical simulation and Digital Twins is critically dependent on the precise description of the problem and correct input parameters. Errors here can lead to dramatically wrong conclusions. The intention of this review is to provide an overview of the state-of-the-art and remaining challenges with respect to generating input values for computational analysis of mass and momentum transport processes within tissue cultures. It gives an overview on relevant aspects of transport processes in tissue cultures as well as modelling and computational tools to tackle these problems. Further focus is on techniques used for the determination of cell-specific parameters and characterization of culture systems, including sensors for on-line determination of relevant parameters. In conclusion, tissue culture techniques are well-established, and modelling tools are technically mature. New sensor technologies are on the way, especially for organ chips. The greatest remaining challenge seems to be the proper addressing and handling of input parameters required for mathematical models. Following Good Modelling Practice approaches when setting up and validating computational models is, therefore, essential to get to better estimations of the interesting complex processes inside organotypic tissue cultures in the future.
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Affiliation(s)
- Ehsan Fattahi
- Chair of Brewing and Beverage TechnologyTUM School of Life SciencesTechnische Universität MünchenFreisingGermany
| | - Shahed Taheri
- Department of Trauma SurgeryOrthopaedics and Plastic SurgeryUniversity Medical Center GöttingenGöttingenGermany
| | - Arndt F. Schilling
- Department of Trauma SurgeryOrthopaedics and Plastic SurgeryUniversity Medical Center GöttingenGöttingenGermany
| | - Thomas Becker
- Chair of Brewing and Beverage TechnologyTUM School of Life SciencesTechnische Universität MünchenFreisingGermany
| | - Ralf Pörtner
- Institute of Bioprocess and Biosystems EngineeringHamburg University of TechnologyHamburgGermany
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Fluid Flow Analysis of Integrated Porous Bone Scaffold and Cancellous Bone at Different Skeletal Sites: In Silico Study. Transp Porous Media 2022. [DOI: 10.1007/s11242-022-01849-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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9
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Rayat Pisheh H, Ansari M, Eslami H. How is mechanobiology involved in bone regenerative medicine? Tissue Cell 2022; 76:101821. [DOI: 10.1016/j.tice.2022.101821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/27/2022] [Accepted: 05/10/2022] [Indexed: 10/18/2022]
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Wang Y, Huang H, Jia G, Zeng H, Yuan G. Fatigue and dynamic biodegradation behavior of additively manufactured Mg scaffolds. Acta Biomater 2021; 135:705-722. [PMID: 34469790 DOI: 10.1016/j.actbio.2021.08.040] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 08/22/2021] [Accepted: 08/25/2021] [Indexed: 12/16/2022]
Abstract
Additive manufacturing (AM) has enabled the fabrication of biodegradable porous metals to satisfy the desired characteristics for orthopedic applications. The geometrical design on AM biodegradable metallic scaffolds has been found to offer a favorable opportunity to regulate their mechanical and degradation performance in previous studies, however mostly confined to static responses. In this study, we presented the effect of the geometrical design on the dynamic responses of AM Mg scaffolds for the first time. Three different types of porous structures, based on various unit cells (i.e., biomimetic, diamond, and sheet-based gyroid), were established and then subjected to selective laser melting (SLM) process using group-developed Mg-Nd-Zn-Zr alloy (JDBM) powders. The topology after dynamic electropolishing, dynamic compressive properties, and dynamic biodegradation behavior of the AM Mg scaffolds were comprehensively evaluated. It was found that dynamic electropolishing effectively removed the excessive adhered powders on the surfaces and resulted in similar geometrical deviations amongst the AM Mg scaffolds, independent of their porous structures. The geometrical design significantly affected the compressive fatigue properties of the AM Mg scaffolds, of which the sheeted-based gyroid structure demonstrated a superior fatigue endurance limit of 0.85 at 106 cycles. Furthermore, in vitro dynamic immersion behaviors of the AM Mg scaffolds revealed a decent dependence on local architectures, where the sheeted-based gyroid scaffold experienced the lowest structural loss with a relatively uniform degradation mode. The obtained results indicate that the geometrical design could provide a promising strategy to develop desirable bone substitutes for the treatment of critical-size load-bearing defects. STATEMENT OF SIGNIFICANCE: Additive manufacturing (AM) has provided unprecedented opportunities to fabricate geometrically complex biodegradable scaffolds where the topological design becomes a key determinant on comprehensive performance. In this paper, we fabricate 3 AM biodegradable Mg scaffolds (i.e., biomimetic, diamond, and sheet-based gyroid) and report the effect of the geometrical design on the dynamic responses of AM Mg scaffolds for the first time. The results revealed that the sheeted-based gyroid scaffold exhibited the best combination of superior compressive fatigue properties and relatively uniform dynamic biodegradation mode, suggesting that the regulation of the porous structures could be an effective approach for the optimization of AM Mg scaffolds as to satisfy clinical requirements in orthopedic applications.
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Affiliation(s)
- Yinchuan Wang
- National Engineering Research Center of Light Alloy Net Forming & State Key Laboratory of Metal Matrix Composite, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Hua Huang
- National Engineering Research Center of Light Alloy Net Forming & State Key Laboratory of Metal Matrix Composite, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Gaozhi Jia
- National Engineering Research Center of Light Alloy Net Forming & State Key Laboratory of Metal Matrix Composite, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China; National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Hui Zeng
- National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, China.
| | - Guangyin Yuan
- National Engineering Research Center of Light Alloy Net Forming & State Key Laboratory of Metal Matrix Composite, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
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Pattanashetti NA, Torvi AI, Shettar AK, Gai PB, Kariduraganavar MY. Polysaccharides as Novel Materials for Tissue Engineering Applications. POLYSACCHARIDES 2021. [DOI: 10.1002/9781119711414.ch14] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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Abstract
Various approaches have been evaluated for developing three-dimensional (3D) scaffolds for modeling or engineering of the bone tissue. However, most of such attempts have come up short in mimicking the natural bone tissue extracellular matrix (ECM) microenvironment, especially its natural bioactive content. Here we describe the methodology for the preparation of a natural ECM-based multichannel construct as a biomimetic 3D bone tissue model. We elucidate the construction of the composite scaffold incorporating decellularized small intestinal submucosa ECM, synthetic hydroxyapatite and poly(ε-caprolactone), and the mechanical stimulation of the cell-seeded construct under bioreactor culture.
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13
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Advanced 3D Cell Culture Techniques in Micro-Bioreactors, Part II: Systems and Applications. Processes (Basel) 2020. [DOI: 10.3390/pr9010021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
In this second part of our systematic review on the research area of 3D cell culture in micro-bioreactors we give a detailed description of the published work with regard to the existing micro-bioreactor types and their applications, and highlight important results gathered with the respective systems. As an interesting detail, we found that micro-bioreactors have already been used in SARS-CoV research prior to the SARS-CoV2 pandemic. As our literature research revealed a variety of 3D cell culture configurations in the examined bioreactor systems, we defined in review part one “complexity levels” by means of the corresponding 3D cell culture techniques applied in the systems. The definition of the complexity is thereby based on the knowledge that the spatial distribution of cell-extracellular matrix interactions and the spatial distribution of homologous and heterologous cell–cell contacts play an important role in modulating cell functions. Because at least one of these parameters can be assigned to the 3D cell culture techniques discussed in the present review, we structured the studies according to the complexity levels applied in the MBR systems.
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14
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Advanced 3D Cell Culture Techniques in Micro-Bioreactors, Part I: A Systematic Analysis of the Literature Published between 2000 and 2020. Processes (Basel) 2020. [DOI: 10.3390/pr8121656] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Bioreactors have proven useful for a vast amount of applications. Besides classical large-scale bioreactors and fermenters for prokaryotic and eukaryotic organisms, micro-bioreactors, as specialized bioreactor systems, have become an invaluable tool for mammalian 3D cell cultures. In this systematic review we analyze the literature in the field of eukaryotic 3D cell culture in micro-bioreactors within the last 20 years. For this, we define complexity levels with regard to the cellular 3D microenvironment concerning cell–matrix-contact, cell–cell-contact and the number of different cell types present at the same time. Moreover, we examine the data with regard to the micro-bioreactor design including mode of cell stimulation/nutrient supply and materials used for the micro-bioreactors, the corresponding 3D cell culture techniques and the related cellular microenvironment, the cell types and in vitro models used. As a data source we used the National Library of Medicine and analyzed the studies published from 2000 to 2020.
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Pedrini F, Hausen M, Gomes R, Duek E. Enhancement of cartilage extracellular matrix synthesis in Poly(PCL-TMC)urethane scaffolds: a study of oriented dynamic flow in bioreactor. Biotechnol Lett 2020; 42:2721-2734. [PMID: 32785804 DOI: 10.1007/s10529-020-02983-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 08/08/2020] [Indexed: 01/17/2023]
Abstract
The development of new technologies to produce three-dimensional and biocompatible scaffolds associated with high-end cell culture techniques have shown to be promising for the regeneration of tissues and organs. Some biomedical devices, as meniscus prosthesis, require high flexibility and tenacity and such features are found in polyurethanes which represent a promising alternative. The Poly(PCL-TMC)urethane here presented, combines the mechanical properties of PCL with the elasticity attributed by TMC and presents great potential as a cellular carrier in cartilage repair. Scanning electron microscopy showed the presence of interconnected pores in the three-dimensional structure of the material. The scaffolds were submitted to proliferation and cell differentiation assays by culturing mesenchymal stem cells in bioreactor. The tests were performed in dynamic flow mode at the rate of 0.4 mL/min. Laser scanning confocal microscopy analysis showed that the flow rate promoted cell growth and cartilage ECM synthesis of aggrecan and type II collagen within the Poly(PCL-TMC)urethane scaffolds. This study demonstrated the applicability of the polymer as a cellular carrier in tissue engineering, as well as the ECM was incremented only when under oriented flow rate stimuli. Therefore, our results may also provide data on how oriented flow rate in dynamic bioreactors culture can influence cell activity towards cartilage ECM synthesis even when specific molecular stimuli are not present. This work addresses new perspectives for future clinical applications in cartilage tissue engineering when the molecular factors resources could be scarce for assorted reasons.
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Affiliation(s)
- Flavia Pedrini
- Department of Physiological Sciences, Faculty of Medical Sciences and Health, Pontifical Catholic University of São Paulo (PUC/SP), Joubert Wey, 290, Sorocaba, 18030-070, Brazil. .,Postgraduate Program in Biotechnology and Environmental Monitoring, Federal University of São Carlos (UFSCar), Sorocaba, Brazil.
| | - Moema Hausen
- Department of Physiological Sciences, Faculty of Medical Sciences and Health, Pontifical Catholic University of São Paulo (PUC/SP), Joubert Wey, 290, Sorocaba, 18030-070, Brazil
| | - Rodrigo Gomes
- Department of Physiological Sciences, Faculty of Medical Sciences and Health, Pontifical Catholic University of São Paulo (PUC/SP), Joubert Wey, 290, Sorocaba, 18030-070, Brazil.,Postgraduate Program in Biotechnology and Environmental Monitoring, Federal University of São Carlos (UFSCar), Sorocaba, Brazil
| | - Eliana Duek
- Department of Physiological Sciences, Faculty of Medical Sciences and Health, Pontifical Catholic University of São Paulo (PUC/SP), Joubert Wey, 290, Sorocaba, 18030-070, Brazil.,Postgraduate Program in Biotechnology and Environmental Monitoring, Federal University of São Carlos (UFSCar), Sorocaba, Brazil
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Pearce HA, Kim YS, Diaz-Gomez L, Mikos AG. Tissue Engineering Scaffolds. Biomater Sci 2020. [DOI: 10.1016/b978-0-12-816137-1.00082-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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17
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Brown JL, Laurencin CT. Bone Tissue Engineering. Biomater Sci 2020. [DOI: 10.1016/b978-0-12-816137-1.00085-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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18
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Li Y, Pavanram P, Zhou J, Lietaert K, Taheri P, Li W, San H, Leeflang M, Mol J, Jahr H, Zadpoor A. Additively manufactured biodegradable porous zinc. Acta Biomater 2020; 101:609-623. [PMID: 31672587 DOI: 10.1016/j.actbio.2019.10.034] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 10/16/2019] [Accepted: 10/24/2019] [Indexed: 12/24/2022]
Abstract
Additively manufacturing (AM) opens up the possibility for biodegradable metals to possess uniquely combined characteristics that are desired for bone substitution, including bone-mimicking mechanical properties, topologically ordered porous structure, pore interconnectivity and biodegradability. Zinc is considered to be one of the promising biomaterials with respect to biodegradation rate and biocompatibility. However, no information regarding the biodegradability and biocompatibility of topologically ordered AM porous zinc is yet available. Here, we applied powder bed fusion to fabricate porous zinc with a topologically ordered diamond structure. An integrative study was conducted on the static and dynamic biodegradation behavior (in vitro, up to 4 weeks), evolution of mechanical properties with increasing immersion time, electrochemical performance, and biocompatibility of the AM porous zinc. The specimens lost 7.8% of their weight after 4 weeks of dynamic immersion in a revised simulated body fluid. The mechanisms of biodegradation were site-dependent and differed from the top of the specimens to the bottom. During the whole in vitro immersion time of 4 weeks, the elastic modulus values of the AM porous zinc (E = 700-1000 MPa) even increased and remained within the scope of those of cancellous bone. Indirect cytotoxicity revealed good cellular activity up to 72 h according to ISO 10,993-5 and -12. Live-dead staining confirmed good viability of MG-63 cells cultured on the surface of the AM porous zinc. These important findings could open up unprecedented opportunities for the development of multifunctional bone substituting materials that will enable reconstruction and regeneration of critical-size load-bearing bone defects. STATEMENT OF SIGNIFICANCE: No information regarding the biodegradability and biocompatibility of topologically ordered AM porous zinc is available. We applied selective laser melting to fabricate topologically ordered porous zinc and conducted a comprehensive study on the biodegradation behavior, electrochemical performance, time-dependent mechanical properties, and biocompatibility of the scaffolds. The specimens lost 7.8% of their weight after4 weeks dynamic biodegradation while their mechanical properties surprisingly increased after 4 weeks. Indirect cytotoxicity revealed good cellular activity up to 72 h. Intimate contact between MG-63 cells and the scaffolds was also observed. These important findings could open up unprecedented opportunities for the development of multifunctional bone substituting materials that mimic bone properties and enable full regeneration of critical-size load-bearing bony defects.
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Wang L, Wu S, Cao G, Fan Y, Dunne N, Li X. Biomechanical studies on biomaterial degradation and co-cultured cells: mechanisms, potential applications, challenges and prospects. J Mater Chem B 2019; 7:7439-7459. [PMID: 31539007 DOI: 10.1039/c9tb01539f] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2025]
Abstract
Biomechanics contains a wide variety of research fields related to biology and mechanics. Actually, to better study or develop a tissue-engineered system, it is now widely recognized that there is no complete nor meaningful study without considering biomechanical factors and the cell response or adaptation to biomechanics. In that respect, this review will focus on not only the influence of biomechanics in biomaterial degradation and co-cultured cells, based on current major frontier research findings, but also the challenges and prospects in biomechanical research. Particularly, through the elaboration of certain typical forces affecting biomaterial degradation and celluar functions, this paper tries to reveal the possible mechanisms, and thus provide ideas on how to design or optimize co-culture systems and apply external forces for proper cell and tissue engineering. Furthermore, while emphasizing the importance of the mechanical control of the cell phenotype and fate, it is expected that these achievements can pave the way to materials-based therapies for different pathological conditions, including diagnosis and treatment of cancer.
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Affiliation(s)
- Lu Wang
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. and Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100083, China
| | - Shuai Wu
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.
| | - Guangxiu Cao
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. and Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100083, China
| | - Yubo Fan
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. and Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100083, China
| | - Nicholas Dunne
- Centre for Medical Engineering Research, School of Mechanical and Manufacturing Engineering, Dublin City University, Stokes Building, Collins Avenue, Dublin 9, Ireland
| | - Xiaoming Li
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. and Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100083, China
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20
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Li Y, Jahr H, Pavanram P, Bobbert FSL, Paggi U, Zhang XY, Pouran B, Leeflang MA, Weinans H, Zhou J, Zadpoor AA. Additively manufactured functionally graded biodegradable porous iron. Acta Biomater 2019; 96:646-661. [PMID: 31302295 DOI: 10.1016/j.actbio.2019.07.013] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 07/03/2019] [Accepted: 07/09/2019] [Indexed: 11/28/2022]
Abstract
Additively manufactured (AM) functionally graded porous metallic biomaterials offer unique opportunities to satisfy the contradictory design requirements of an ideal bone substitute. However, no functionally graded porous structures have ever been 3D-printed from biodegradable metals, even though biodegradability is crucial both for full tissue regeneration and for the prevention of implant-associated infections in the long term. Here, we present the first ever report on AM functionally graded biodegradable porous metallic biomaterials. We made use of a diamond unit cell for the topological design of four different types of porous structures including two functionally graded structures and two reference uniform structures. Specimens were then fabricated from pure iron powder using selective laser melting (SLM), followed by experimental and computational analyses of their permeability, dynamic biodegradation behavior, mechanical properties, and cytocompatibility. It was found that the topological design with functional gradients controlled the fluid flow, mass transport properties and biodegradation behavior of the AM porous iron specimens, as up to 4-fold variations in permeability and up to 3-fold variations in biodegradation rate were observed for the different experimental groups. After 4 weeks of in vitro biodegradation, the AM porous scaffolds lost 5-16% of their weight. This falls into the desired range of biodegradation rates for bone substitution and confirms our hypothesis that topological design could indeed accelerate the biodegradation of otherwise slowly degrading metals, like iron. Even after 4 weeks of biodegradation, the mechanical properties of the specimens (i.e., E = 0.5-2.1 GPa, σy = 8-48 MPa) remained within the range of the values reported for trabecular bone. Design-dependent cell viability did not differ from gold standard controls for up to 48 h. This study clearly shows the great potential of AM functionally graded porous iron as a bone substituting material. Moreover, we demonstrate that complex topological design permits the control of mechanical properties, degradation behavior of AM porous metallic biomaterials. STATEMENT OF SIGNIFICANCE: No functionally graded porous structures have ever been 3D-printed from biodegradable metals, even though biodegradability is crucial both for full tissue regeneration and for the prevention of implant-associated infections in the long term. Here, we present the first report on 3D-printed functionally graded biodegradable porous metallic biomaterials. Our results suggest that topological design in general, and functional gradients in particular can be used as an important tool for adjusting the biodegradation behavior of AM porous metallic biomaterials. The biodegradation rate and mass transport properties of AM porous iron can be increased while maintaining the bone-mimicking mechanical properties of these biomaterials. The observations reported here underline the importance of proper topological design in the development of AM porous biodegradable metals.
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Affiliation(s)
- Y Li
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628 CD, The Netherlands.
| | - H Jahr
- Department of Anatomy and Cell Biology, University Hospital RWTH Aachen, Aachen 52074, Germany; Department of Orthopedic Surgery, Maastricht UMC+, Maastricht 6202 AZ, The Netherlands
| | - P Pavanram
- Department of Anatomy and Cell Biology, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - F S L Bobbert
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628 CD, The Netherlands
| | - U Paggi
- 3D Systems - LayerWise NV, Grauwmeer 14, Leuven 3001, Belgium; KU Leuven Department of Mechanical Engineering, Kasteelpark Arenberg 44, Leuven 3001, Belgium
| | - X-Y Zhang
- Department of Mechanical Engineering, Tsinghua University, Beijing 10004, China
| | - B Pouran
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628 CD, The Netherlands; Department of Orthopedics, UMC Utrecht, Heidelberglaan 100, Utrecht 3584CX, The Netherlands
| | - M A Leeflang
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628 CD, The Netherlands
| | - H Weinans
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628 CD, The Netherlands; Department of Orthopedics, UMC Utrecht, Heidelberglaan 100, Utrecht 3584CX, The Netherlands
| | - J Zhou
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628 CD, The Netherlands
| | - A A Zadpoor
- Department of Biomechanical Engineering, Delft University of Technology, Delft 2628 CD, The Netherlands
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21
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Patel DK, Lim KT. Biomimetic Polymer-Based Engineered Scaffolds for Improved Stem Cell Function. MATERIALS (BASEL, SWITZERLAND) 2019; 12:E2950. [PMID: 31514460 PMCID: PMC6766224 DOI: 10.3390/ma12182950] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 09/06/2019] [Accepted: 09/09/2019] [Indexed: 12/17/2022]
Abstract
Scaffolds are considered promising materials for tissue engineering applications due to their unique physiochemical properties. The high porosity and adequate mechanical properties of the scaffolds facilitate greater cell adhesion, proliferation, and differentiation. Stem cells are frequently applied in tissue engineering applications due to their excellent potential. It has been noted that cell functions are profoundly affected by the nature of the extracellular matrix (ECM). Naturally derived ECM contains the bioactive motif that also influences the immune response of the organism. The properties of polymer scaffolds mean they can resemble the native ECM and can regulate cellular responses. Various techniques such as electrospinning and 3D printing, among others, are frequently used to fabricate polymer scaffolds, and their cellular responses are different with each technique. Furthermore, enhanced cell viability, as well as the differentiation ability of stem cells on the surface of scaffolds, opens a fascinating approach to the formation of ECM-like environments for tissue engineering applications.
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Affiliation(s)
- Dinesh K Patel
- The Institute of Forest Science, Kangwon National University, Chuncheon-24341, Korea.
| | - Ki-Taek Lim
- Department of Biosystems Engineering, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon-24341, Korea.
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Validation of a novel 3D flow model for the optimization of construct perfusion in radial-flow packed-bed bioreactors (rPBBs) for long-bone tissue engineering. N Biotechnol 2019; 52:110-120. [PMID: 31173925 DOI: 10.1016/j.nbt.2019.06.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Revised: 05/27/2019] [Accepted: 06/02/2019] [Indexed: 12/25/2022]
Abstract
Osteogenic cell culture in three-dimensional (3D) hollow cylindrical porous scaffolds in radial-flow packed-bed bioreactors (rPBBs) may overcome the transport limitations of static and axial perfusion bioreactors in the engineering of long-bone substitutes. Flow models of rPBBs help optimize radial flux distribution of medium and tissue maturation in vitro. Only a 2D model is available for steady flow transport in rPBBs with axisymmetric inlet and outlet accounting for the fluid dynamics of void spaces, assessed against literature information. Here, a novel 3D model is proposed for steady flow transport in the three compartments of rPBBs with a more practical lateral outlet. A 3D model of transient tracer transport was developed based on the flow model to predict bioreactor residence time distribution (RTD). Model-predicted flow patterns were validated in terms of RTD against tracer experiments performed with bioreactor prototypes equipped with commercial scaffolds for bone tissue engineering. Bioreactors were challenged with a step change in entering tracer concentration in an optimized set-up under conditions promoting uniform radial flux distribution and typical shunt flows. Model-predicted RTDs agreed well with those experimentally determined. In conclusion, tracer experiments validate the use of the 3D flow model for optimizing construct perfusion in rPBBs to engineer long-bone substitutes.
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23
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Sarker MD, Naghieh S, Sharma NK, Ning L, Chen X. Bioprinting of Vascularized Tissue Scaffolds: Influence of Biopolymer, Cells, Growth Factors, and Gene Delivery. JOURNAL OF HEALTHCARE ENGINEERING 2019; 2019:9156921. [PMID: 31065331 PMCID: PMC6466897 DOI: 10.1155/2019/9156921] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 02/03/2019] [Indexed: 01/16/2023]
Abstract
Over the past decades, tissue regeneration with scaffolds has achieved significant progress that would eventually be able to solve the worldwide crisis of tissue and organ regeneration. While the recent advancement in additive manufacturing technique has facilitated the biofabrication of scaffolds mimicking the host tissue, thick tissue regeneration remains challenging to date due to the growing complexity of interconnected, stable, and functional vascular network within the scaffold. Since the biological performance of scaffolds affects the blood vessel regeneration process, perfect selection and manipulation of biological factors (i.e., biopolymers, cells, growth factors, and gene delivery) are required to grow capillary and macro blood vessels. Therefore, in this study, a brief review has been presented regarding the recent progress in vasculature formation using single, dual, or multiple biological factors. Besides, a number of ways have been presented to incorporate these factors into scaffolds. The merits and shortcomings associated with the application of each factor have been highlighted, and future research direction has been suggested.
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Affiliation(s)
- M. D. Sarker
- Division of Biomedical Engineering, College of Engineering, University of Saskatchewan, Saskatoon, SK, Canada
| | - Saman Naghieh
- Division of Biomedical Engineering, College of Engineering, University of Saskatchewan, Saskatoon, SK, Canada
| | - N. K. Sharma
- Department of Mechanical Engineering, College of Engineering, University of Saskatchewan, Saskatoon, SK, Canada
| | - Liqun Ning
- Department of Mechanical Engineering, College of Engineering, University of Saskatchewan, Saskatoon, SK, Canada
| | - Xiongbiao Chen
- Division of Biomedical Engineering, College of Engineering, University of Saskatchewan, Saskatoon, SK, Canada
- Department of Mechanical Engineering, College of Engineering, University of Saskatchewan, Saskatoon, SK, Canada
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24
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Ma S, Tang Q, Feng Q, Song J, Han X, Guo F. Mechanical behaviours and mass transport properties of bone-mimicking scaffolds consisted of gyroid structures manufactured using selective laser melting. J Mech Behav Biomed Mater 2019; 93:158-169. [PMID: 30798182 DOI: 10.1016/j.jmbbm.2019.01.023] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 01/28/2019] [Accepted: 01/30/2019] [Indexed: 01/02/2023]
Abstract
Bone scaffolds created in porous structures manufactured using selective laser melting (SLM) are widely used in tissue engineering, since the elastic moduli of the scaffolds are easily adjusted according to the moduli of the tissues, and the large surfaces the scaffolds provide are beneficial to cell growth. SLM-built gyroid structures composed of 316L stainless steel have demonstrated superior properties such as good corrosion resistance, strong biocompatibility, self-supported performance, and excellent mechanical properties. In this study, gyroid structures of different volume fraction were modelled and manufactured using SLM; the mechanical properties of the structures were then investigated under quasi-static compression loads. The elastic moduli and yield stresses of the structures were calculated from stress-strain diagrams, which were developed by conducting quasi-static compression tests. In order to estimate the discrepancies between the designed and as-produced gyroid structures, optical microscopy and micro-CT scanner were used to observe the structures' micromorphology. Since good fluidness is conducive to the transport of nutrients, computational fluid dynamics (CFD) values were used to investigate the pressure and flow velocity of the channel of the three kinds of gyroid structures. The results show that the sizes of the as-produced structures were larger than their computer aided design (CAD) sizes, but the manufacturing errors are within a relatively stable range. The elastic moduli and yield stresses of the structures improved as their volume fractions increased. Gyroid structure can match the mechanical properties of human bone by changing the porosity of scaffold. The process of compression failure showed that 316L gyroid structures manufactured using SLM demonstrated high degrees of toughness. The results obtained from CFD simulation showed that gyroid structures have good fluidity, which has an accelerated effect on the fluid in the middle of the channel, and it is suitable for transport nutrients. Therefore, we could predict the scaffold's permeability by conducting CFD simulation to ensure an appropriate permeability before the scaffold being manufactured. SLM-built gyroid structures that composed of 316L stainless steel were suitable to be designed as bone scaffolds in terms of mechanical properties and mass-transport properties, and had significant promise.
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Affiliation(s)
- Shuai Ma
- State Key Laboratory of Mechanical Transmissions, Chongqing University, Chongqing, China
| | - Qian Tang
- State Key Laboratory of Mechanical Transmissions, Chongqing University, Chongqing, China.
| | - Qixiang Feng
- State Key Laboratory of Mechanical Transmissions, Chongqing University, Chongqing, China
| | - Jun Song
- State Key Laboratory of Mechanical Transmissions, Chongqing University, Chongqing, China
| | - Xiaoxiao Han
- Additive Manufacturing Research Group, Loughborough University, UK
| | - Fuyu Guo
- State Key Laboratory of Mechanical Transmissions, Chongqing University, Chongqing, China
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25
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Vijayakumar V, Samal SK, Mohanty S, Nayak SK. Recent advancements in biopolymer and metal nanoparticle-based materials in diabetic wound healing management. Int J Biol Macromol 2018; 122:137-148. [PMID: 30342131 DOI: 10.1016/j.ijbiomac.2018.10.120] [Citation(s) in RCA: 211] [Impact Index Per Article: 30.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 09/26/2018] [Accepted: 10/14/2018] [Indexed: 01/13/2023]
Abstract
Currently, diabetes mellitus (DM) accelerated diabetic foot ulcer (DFU) remains vivacious health problem related with delayed healing and high amputation rates which leads to enormous clinical obligation. Keeping in view of the foregoing, researchers have been made in their efforts to develop novel materials which accelerate delayed wound healing in the diabetic patient and reduce the adversative influences of DFUs. The most prominent materials used for the wound healing application have biocompatibility, low cytotoxicity, excellent biodegradable properties, and antimicrobial activity properties. Utilization of nanoparticles has emerged as a protruding scientific and technological revolution in controlling DFUs. Biopolymers in combination with bioactive nanoparticles having antimicrobial, antibacterial, and anti-inflammatory properties have great potential in wound care to enhance the healing process of diabetic wound infectious. Combination of antibacterial nanoparticles like silver nanoparticles (AgNPs), gold nanoparticles (AuNPs), copper nanoparticles (CuNPs) etc. with polymeric matrix could efficiently inhibit bacterial growth and at the same time fastens the healing process of a wound. This review briefed the recent development of different natural polymers and antibacterial nanoparticles to mitigate the diabetes mellitus based DFU.
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Affiliation(s)
- Veena Vijayakumar
- School for Advanced Research in Polymers (SARP)-Laboratory for Advanced Research in Polymeric Materials (LARPM), Central Institute of Plastics Engineering and Technology (CIPET), B-25, CNI Complex, Patia, Bhubaneswar, Odisha 751024, India
| | - Sushanta K Samal
- School for Advanced Research in Polymers (SARP)-Laboratory for Advanced Research in Polymeric Materials (LARPM), Central Institute of Plastics Engineering and Technology (CIPET), B-25, CNI Complex, Patia, Bhubaneswar, Odisha 751024, India.
| | - Smita Mohanty
- School for Advanced Research in Polymers (SARP)-Laboratory for Advanced Research in Polymeric Materials (LARPM), Central Institute of Plastics Engineering and Technology (CIPET), B-25, CNI Complex, Patia, Bhubaneswar, Odisha 751024, India
| | - Sanjay K Nayak
- School for Advanced Research in Polymers (SARP)-Laboratory for Advanced Research in Polymeric Materials (LARPM), Central Institute of Plastics Engineering and Technology (CIPET), B-25, CNI Complex, Patia, Bhubaneswar, Odisha 751024, India
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26
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Aidun A, Zamanian A, Ghorbani F. Novel bioactive porous starch-siloxane matrix for bone regeneration: Physicochemical, mechanical, and in vitro
properties. Biotechnol Appl Biochem 2018; 66:43-52. [DOI: 10.1002/bab.1694] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 09/15/2018] [Accepted: 09/25/2018] [Indexed: 12/30/2022]
Affiliation(s)
- Amir Aidun
- National Cell Bank of Iran; Pasteur Institute of Iran; Tehran Iran
- Tissues and Biomaterials Research Group (TBRG); Universal Scientific Education and Research Network (USERN); Tehran Iran
| | - Ali Zamanian
- Biomaterials Research Group; Department of Nanotechnology and Advanced Materials; Materials and Energy Research Center; Tehran Iran
- Skin & Stem cell Research Center; Tehran University of Medical Sciences; Tehran Iran
| | - Farnaz Ghorbani
- Biomaterials Research Group; Department of Nanotechnology and Advanced Materials; Materials and Energy Research Center; Tehran Iran
- Skin & Stem cell Research Center; Tehran University of Medical Sciences; Tehran Iran
- Department of Biomedical Engineering; Tehran Science and Research Branch; Islamic Azad University; Tehran Iran
- Department of Biomaterials; Aprin Advanced Technologies Development Company; Tehran Iran
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27
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Zhao F, van Rietbergen B, Ito K, Hofmann S. Flow rates in perfusion bioreactors to maximise mineralisation in bone tissue engineering in vitro. J Biomech 2018; 79:232-237. [PMID: 30149981 DOI: 10.1016/j.jbiomech.2018.08.004] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 06/28/2018] [Accepted: 08/10/2018] [Indexed: 12/31/2022]
Abstract
In bone tissue engineering experiments, fluid-induced shear stress is able to stimulate cells to produce mineralised extracellular matrix (ECM). The application of shear stress on seeded cells can for example be achieved through bioreactors that perfuse medium through porous scaffolds. The generated mechanical environment (i.e. wall shear stress: WSS) within the scaffolds is complex due to the complexity of scaffold geometry. This complexity has so far prevented setting an optimal loading (i.e. flow rate) of the bioreactor to achieve an optimal distribution of WSS for stimulating cells to produce mineralised ECM. In this study, we demonstrate an approach combining computational fluid dynamics (CFD) and mechano-regulation theory to optimise flow rates of a perfusion bioreactor and various scaffold geometries (i.e. pore shape, porosity and pore diameter) in order to maximise shear stress induced mineralisation. The optimal flow rates, under which the highest fraction of scaffold surface area is subjected to a wall shear stress that induces mineralisation, are mainly dependent on the scaffold geometries. Nevertheless, the variation range of such optimal flow rates are within 0.5-5 mL/min (or in terms of fluid velocity: 0.166-1.66 mm/s), among different scaffolds. This approach can facilitate the determination of scaffold-dependent flow rates for bone tissue engineering experiments in vitro, avoiding performing a series of trial and error experiments.
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Affiliation(s)
- Feihu Zhao
- Orthopaedic Biomechanics Group, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
| | - Bert van Rietbergen
- Orthopaedic Biomechanics Group, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
| | - Keita Ito
- Orthopaedic Biomechanics Group, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands; Department of Orthopaedics, UMC Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands
| | - Sandra Hofmann
- Orthopaedic Biomechanics Group, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands; Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands.
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Babaliari E, Petekidis G, Chatzinikolaidou M. A Precisely Flow-Controlled Microfluidic System for Enhanced Pre-Osteoblastic Cell Response for Bone Tissue Engineering. Bioengineering (Basel) 2018; 5:bioengineering5030066. [PMID: 30103544 PMCID: PMC6164058 DOI: 10.3390/bioengineering5030066] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Revised: 08/03/2018] [Accepted: 08/09/2018] [Indexed: 12/27/2022] Open
Abstract
Bone tissue engineering provides advanced solutions to overcome the limitations of currently used therapies for bone reconstruction. Dynamic culturing of cell-biomaterial constructs positively affects the cell proliferation and differentiation. In this study, we present a precisely flow-controlled microfluidic system employed for the investigation of bone-forming cell responses cultured on fibrous collagen matrices by applying two flow rates, 30 and 50 μL/min. We characterized the collagen substrates morphologically by means of scanning electron microscopy, investigated their viscoelastic properties, and evaluated the orientation, proliferation and osteogenic differentiation capacity of pre-osteoblastic cells cultured on them. The cells are oriented along the direction of the flow at both rates, in contrast to a random orientation observed under static culture conditions. The proliferation of cells after 7 days in culture was increased at both flow rates, with the flow rate of 50 μL/min indicating a significant increase compared to the static culture. The alkaline phosphatase activity after 7 days increased at both flow rates, with the rate of 30 μL/min indicating a significant enhancement compared to static conditions. Our results demonstrate that precisely flow-controlled microfluidic cell culture provides tunable control of the cell microenvironment that directs cellular activities involved in bone regeneration.
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Affiliation(s)
- Eleftheria Babaliari
- Department of Materials Science and Technology, University of Crete, Crete 70013, Greece.
- Foundation for Research and Technology-Hellas (FORTH), Institute of Electronic Structure and Laser (IESL), Crete 70013, Greece.
| | - George Petekidis
- Department of Materials Science and Technology, University of Crete, Crete 70013, Greece.
- Foundation for Research and Technology-Hellas (FORTH), Institute of Electronic Structure and Laser (IESL), Crete 70013, Greece.
| | - Maria Chatzinikolaidou
- Department of Materials Science and Technology, University of Crete, Crete 70013, Greece.
- Foundation for Research and Technology-Hellas (FORTH), Institute of Electronic Structure and Laser (IESL), Crete 70013, Greece.
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29
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Perez JR, Kouroupis D, Li DJ, Best TM, Kaplan L, Correa D. Tissue Engineering and Cell-Based Therapies for Fractures and Bone Defects. Front Bioeng Biotechnol 2018; 6:105. [PMID: 30109228 PMCID: PMC6079270 DOI: 10.3389/fbioe.2018.00105] [Citation(s) in RCA: 243] [Impact Index Per Article: 34.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 07/09/2018] [Indexed: 12/25/2022] Open
Abstract
Bone fractures and segmental bone defects are a significant source of patient morbidity and place a staggering economic burden on the healthcare system. The annual cost of treating bone defects in the US has been estimated to be $5 billion, while enormous costs are spent on bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. Autologous bone grafts represent the gold standard for the treatment of bone defects. However, they are associated with variable clinical outcomes, postsurgical morbidity, especially at the donor site, and increased surgical costs. In an effort to circumvent these limitations, tissue engineering and cell-based therapies have been proposed as alternatives to induce and promote bone repair. This review focuses on the recent advances in bone tissue engineering (BTE), specifically looking at its role in treating delayed fracture healing (non-unions) and the resulting segmental bone defects. Herein we discuss: (1) the processes of endochondral and intramembranous bone formation; (2) the role of stem cells, looking specifically at mesenchymal (MSC), embryonic (ESC), and induced pluripotent (iPSC) stem cells as viable building blocks to engineer bone implants; (3) the biomaterials used to direct tissue growth, with a focus on ceramic, biodegradable polymers, and composite materials; (4) the growth factors and molecular signals used to induce differentiation of stem cells into the osteoblastic lineage, which ultimately leads to active bone formation; and (5) the mechanical stimulation protocols used to maintain the integrity of the bone repair and their role in successful cell engraftment. Finally, a couple clinical scenarios are presented (non-unions and avascular necrosis—AVN), to illustrate how novel cell-based therapy approaches can be used. A thorough understanding of tissue engineering and cell-based therapies may allow for better incorporation of these potential therapeutic approaches in bone defects allowing for proper bone repair and regeneration.
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Affiliation(s)
- Jose R Perez
- Department of Orthopedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Dimitrios Kouroupis
- Department of Orthopedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL, United States.,Diabetes Research Institute & Cell Transplant Center, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Deborah J Li
- Department of Orthopedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Thomas M Best
- Department of Orthopedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Lee Kaplan
- Department of Orthopedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Diego Correa
- Department of Orthopedics, UHealth Sports Medicine Institute, Miller School of Medicine, University of Miami, Miami, FL, United States.,Diabetes Research Institute & Cell Transplant Center, Miller School of Medicine, University of Miami, Miami, FL, United States
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Li W, Yang X, Feng S, Yang S, Zeng R, Tu M. The fabrication of biomineralized fiber-aligned PLGA scaffolds and their effect on enhancing osteogenic differentiation of UCMSC cells. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2018; 29:117. [PMID: 30027312 DOI: 10.1007/s10856-018-6114-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 06/19/2018] [Indexed: 06/08/2023]
Abstract
The key factor of scaffold design for bone tissue engineering is to mimic the microenvironment of natural bone extracellular matrix (ECM) and guide cell osteogenic differentiation. The biomineralized fiber-aligned PLGA scaffolds (a-PLGA/CaPs) was developed in this study by mimicking the structure and composition of native bone ECM. The aligned PLGA fibers was prepared by wet spinning and then biomineralized via an alternate immersion method. Introduction of a bioceramic component CaP onto the PLGA fibers led to changes in surface roughness and hydrophilicity, which showed to modulate cell adhesion and cell morphology of umbilical cord mesenchymal stem cells (UCMSCs). It was found that organized actin filaments of UCMSCs cultured on both a-PLGA and a-PLGA/CaP scaffolds appeared to follow contact guidance along the aligned fibers, and those cells grown on a-PLGA/CaP scaffolds exhibited a more polarized cellular morphology. The a-PLGA/CaP scaffold with multicycles of mineralization facilitated the cell attachment on the fiber surfaces and then supported better cell adhesion and contact guidance, leading to enhancement in following proliferation and osteogenic differentiation of UCMSCs. Our results give some insights into the regulation of cell behaviors through design of ECM-mimicking structure and composition and provide an alternative wet-spun fiber-aligned scaffold with HA-mineralized layer for bone tissue engineering application.
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Affiliation(s)
- Wenqiang Li
- Department of Material Science and Engineering, Jinan University, Guangzhou, 510632, People's Republic of China
- Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Jinan University, Guangzhou, 510632, People's Republic of China
| | - Xiaohui Yang
- Department of Material Science and Engineering, Jinan University, Guangzhou, 510632, People's Republic of China
- Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Jinan University, Guangzhou, 510632, People's Republic of China
| | - Shanbao Feng
- Department of Material Science and Engineering, Jinan University, Guangzhou, 510632, People's Republic of China
- Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Jinan University, Guangzhou, 510632, People's Republic of China
| | - Shenyu Yang
- Department of Material Science and Engineering, Jinan University, Guangzhou, 510632, People's Republic of China
- Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Jinan University, Guangzhou, 510632, People's Republic of China
| | - Rong Zeng
- Department of Material Science and Engineering, Jinan University, Guangzhou, 510632, People's Republic of China
- Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Jinan University, Guangzhou, 510632, People's Republic of China
| | - Mei Tu
- Department of Material Science and Engineering, Jinan University, Guangzhou, 510632, People's Republic of China.
- Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Jinan University, Guangzhou, 510632, People's Republic of China.
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31
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Ashraf R, Sofi HS, Malik A, Beigh MA, Hamid R, Sheikh FA. Recent Trends in the Fabrication of Starch Nanofibers: Electrospinning and Non-electrospinning Routes and Their Applications in Biotechnology. Appl Biochem Biotechnol 2018; 187:47-74. [PMID: 29882194 DOI: 10.1007/s12010-018-2797-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Accepted: 05/25/2018] [Indexed: 01/11/2023]
Abstract
Electrospinning a versatile and the most preferred technique for the fabrication of nanofibers has revolutionized by opening unlimited avenues in biomedical fields. Presently, the simultaneous functionalization and/or post-modification of as-spun nanofibers with biomolecules has been explored, to serve the distinct goals in the aforementioned field. Starch is one of the most abundant biopolymers on the earth. Besides, being biocompatible and biodegradable in nature, it has unprecedented properties of gelatinization and retrogradation. Therefore, starch has been used in numerous ways for wide range of applications. Keeping these properties in consideration, the present article summarizes the recent expansion in the fabrication of the pristine/modified starch-based composite scaffolds by electrospinning along with their possible applications. Apart from electrospinning technique, this review will also provide the comprehensive information on various other techniques employed in the fabrication of the starch-based nanofibers. Furthermore, we conclude with the challenges to be overcome in the fabrication of nanofibers by the electrospinning technique and future prospects of starch-based fabricated scaffolds for exploration of its applications.
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Affiliation(s)
- Roqia Ashraf
- Department of Nanotechnology, University of Kashmir, Srinagar, Jammu and Kashmir, 190006, India
| | - Hasham S Sofi
- Department of Nanotechnology, University of Kashmir, Srinagar, Jammu and Kashmir, 190006, India
| | - Aijaz Malik
- Center of Data Mining and Biomedical Informatics, Faculty of Medical technology, Mahidol University, Salaya, 73170, Thailand
| | - Mushtaq A Beigh
- Department of Nanotechnology, University of Kashmir, Srinagar, Jammu and Kashmir, 190006, India
| | - Rabia Hamid
- Department of Nanotechnology, University of Kashmir, Srinagar, Jammu and Kashmir, 190006, India.,Department of Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, 190006, India
| | - Faheem A Sheikh
- Department of Nanotechnology, University of Kashmir, Srinagar, Jammu and Kashmir, 190006, India.
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Kang YG, Wei J, Shin JW, Wu YR, Su J, Park YS, Shin JW. Enhanced biocompatibility and osteogenic potential of mesoporous magnesium silicate/polycaprolactone/wheat protein composite scaffolds. Int J Nanomedicine 2018; 13:1107-1117. [PMID: 29520139 PMCID: PMC5833793 DOI: 10.2147/ijn.s157921] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Successful bone tissue engineering using scaffolds is primarily dependent on the properties of the scaffold, including biocompatibility, highly interconnected porosity, and mechanical integrity. METHODS In this study, we propose new composite scaffolds consisting of mesoporous magnesium silicate (m_MS), polycaprolactone (PCL), and wheat protein (WP) manufactured by a rapid prototyping technique to provide a micro/macro porous structure. Experimental groups were set based on the component ratio: (1) WP0% (m_MS:PCL:WP =30:70:0 weight per weight; w/w); (2) WP15% (m_MS:PCL:WP =30:55:15 w/w); (3) WP30% (m_MS:PCL:WP =30:40:30 w/w). RESULTS Evaluation of the properties of fabricated scaffolds indicated that increasing the amount of WP improved the surface hydrophilicity and biodegradability of m_MS/PCL/WP composites, while reducing the mechanical strength. Moreover, experiments were performed to confirm the biocompatibility and osteogenic differentiation of human mesenchymal stem cells (MSCs) according to the component ratio of the scaffold. The results confirmed that the content of WP affects proliferation and osteogenic differentiation of MSCs. Based on the last day of the experiment, ie, the 14th day, the proliferation based on the amount of DNA was the best in the WP30% group, but all of the markers measured by PCR were the most expressed in the WP15% group. CONCLUSION These results suggest that the m_MS/PCL/WP composite is a promising candidate for use as a scaffold in cell-based bone regeneration.
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Affiliation(s)
- Yun Gyeong Kang
- School of Biomedical Engineering, Inje University, Gimhae, Republic of Korea
| | - Jie Wei
- Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, China
| | - Ji Won Shin
- School of Biomedical Engineering, Inje University, Gimhae, Republic of Korea
| | - Yan Ru Wu
- Department of Health Science and Technology, Inje University, Gimhae, Republic of Korea
| | - Jiacan Su
- Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Young Shik Park
- School of Biological Science, Inje University, Gimhae, Republic of Korea
| | - Jung-Woog Shin
- School of Biomedical Engineering, Inje University, Gimhae, Republic of Korea
- Department of Health Science and Technology, Inje University, Gimhae, Republic of Korea
- Cardiovascular and Metabolic Disease Center/Institute of Aged Life Redesign/UHARC, Inje University, Gimhae, Republic of Korea
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33
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Canadas RF, Marques AP, Reis RL, Oliveira JM. Bioreactors and Microfluidics for Osteochondral Interface Maturation. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1059:395-420. [PMID: 29736584 DOI: 10.1007/978-3-319-76735-2_18] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The cell culture techniques are in the base of any biology-based science. The standard techniques are commonly static platforms as Petri dishes, tissue culture well plates, T-flasks, or well plates designed for spheroids formation. These systems faced a paradigm change from 2D to 3D over the current decade driven by the tissue engineering (TE) field. However, 3D static culture approaches usually suffer from several issues as poor homogenization of the formed tissues and development of a necrotic center which limits the size of in vitro tissues to hundreds of micrometers. Furthermore, for complex tissues as osteochondral (OC), more than recovering a 3D environment, an interface needs to be replicated. Although 3D cell culture is already the reality adopted by a newborn market, a technological revolution on cell culture devices needs a further step from static to dynamic already considering 3D interfaces with dramatic importance for broad fields such as biomedical, TE, and drug development. In this book chapter, we revised the existing approaches for dynamic 3D cell culture, focusing on bioreactors and microfluidic systems, and the future directions and challenges to be faced were discussed. Basic principles, advantages, and challenges of each technology were described. The reported systems for OC 3D TE were focused herein.
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Affiliation(s)
- Raphaël F Canadas
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Barco, Guimarães, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Alexandra P Marques
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Barco, Guimarães, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.,The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
| | - Rui L Reis
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Barco, Guimarães, Portugal. .,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. .,The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal.
| | - J Miguel Oliveira
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Barco, Guimarães, Portugal.,ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.,The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
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Waghmare VS, Wadke PR, Dyawanapelly S, Deshpande A, Jain R, Dandekar P. Starch based nanofibrous scaffolds for wound healing applications. Bioact Mater 2017; 3:255-266. [PMID: 29744465 PMCID: PMC5935783 DOI: 10.1016/j.bioactmat.2017.11.006] [Citation(s) in RCA: 88] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 11/03/2017] [Accepted: 11/21/2017] [Indexed: 01/11/2023] Open
Abstract
Starch is an attractive polymer for wound healing applications because of its wide availability, low cost, biocompatibility, biodegradability and wound-healing property. Here, we have fabricated starch-based nanofibrous scaffolds by electrospinning for wound healing applications. The diameter of the optimized nanofibers was determined by field emission scanning electron microscopy (FE-SEM) and was found to be in the range of 110–300 nm. The mechanical strength (0.5–0.8 MPa) of the nanofibrous scaffolds was attuned using polyvinyl alcohol (plasticizer) and glutaraldehyde (crosslinking agent), to impart them with sufficient durability for skin tissue engineering. Absence of negative interactions between the polymers was confirmed by Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), differential scanning microscopy (DSC) and thermal gravimetric analysis (TGA). Cellular assays with L929 mouse fibroblast cells indicated the ability of the scaffolds to promote cellular proliferation, without exhibiting any toxic effect to the cells. Thus, the nanofibrous scaffolds demonstrated potential for wound healing applications.
Starch based nanofibrous by electrospinning for wound healing applications. Starch based nanofibrous was characterized by FE-SEM, ATR-FTIR, DSC and TGA techniques. Starch based nanofibrous scaffolds have promoted fibroblast (L929 mouse) cellular proliferation.
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Affiliation(s)
- Vijaya Sadashiv Waghmare
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400019, India
| | - Pallavi Ravindra Wadke
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400019, India
| | - Sathish Dyawanapelly
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400019, India.,Department of Chemical Engineering, Institute of Chemical Technology, Matunga, Mumbai 400019, India
| | - Aparna Deshpande
- Department of Physics, Indian Institute of Science Education and Research (IISER), Pashan, Pune 411008, India
| | - Ratnesh Jain
- Department of Chemical Engineering, Institute of Chemical Technology, Matunga, Mumbai 400019, India
| | - Prajakta Dandekar
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400019, India
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Zhao F, Vaughan TJ, Mc Garrigle MJ, McNamara LM. A coupled diffusion-fluid pressure model to predict cell density distribution for cells encapsulated in a porous hydrogel scaffold under mechanical loading. Comput Biol Med 2017; 89:181-189. [DOI: 10.1016/j.compbiomed.2017.08.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Revised: 07/28/2017] [Accepted: 08/02/2017] [Indexed: 12/19/2022]
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Meyers EA, Kessler JA. TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function. Cold Spring Harb Perspect Biol 2017; 9:cshperspect.a022244. [PMID: 28130363 DOI: 10.1101/cshperspect.a022244] [Citation(s) in RCA: 133] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Signaling by the transforming growth factor β (TGF-β) family is necessary for proper neural development and function throughout life. Sequential waves of activation, inhibition, and reactivation of TGF-β family members regulate numerous elements of the nervous system from the earliest stages of embryogenesis through adulthood. This review discusses the expression, regulation, and function of TGF-β family members in the central nervous system at various developmental stages, beginning with induction and patterning of the nervous system to their importance in the adult as modulators of inflammatory response and involvement in degenerative diseases.
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Affiliation(s)
- Emily A Meyers
- Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611
| | - John A Kessler
- Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611
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Flow velocity-driven differentiation of human mesenchymal stromal cells in silk fibroin scaffolds: A combined experimental and computational approach. PLoS One 2017; 12:e0180781. [PMID: 28686698 PMCID: PMC5501602 DOI: 10.1371/journal.pone.0180781] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 06/21/2017] [Indexed: 12/24/2022] Open
Abstract
Mechanical loading plays a major role in bone remodeling and fracture healing. Mimicking the concept of mechanical loading of bone has been widely studied in bone tissue engineering by perfusion cultures. Nevertheless, there is still debate regarding the in-vitro mechanical stimulation regime. This study aims at investigating the effect of two different flow rates (vlow = 0.001m/s and vhigh = 0.061m/s) on the growth of mineralized tissue produced by human mesenchymal stromal cells cultured on 3-D silk fibroin scaffolds. The flow rates applied were chosen to mimic the mechanical environment during early fracture healing or during bone remodeling, respectively. Scaffolds cultured under static conditions served as a control. Time-lapsed micro-computed tomography showed that mineralized extracellular matrix formation was completely inhibited at vlow compared to vhigh and the static group. Biochemical assays and histology confirmed these results and showed enhanced osteogenic differentiation at vhigh whereas the amount of DNA was increased at vlow. The biological response at vlow might correspond to the early stage of fracture healing, where cell proliferation and matrix production is prominent. Visual mapping of shear stresses, simulated by computational fluid dynamics, to 3-D micro-computed tomography data revealed that shear stresses up to 0.39mPa induced a higher DNA amount and shear stresses between 0.55mPa and 24mPa induced osteogenic differentiation. This study demonstrates the feasibility to drive cell behavior of human mesenchymal stromal cells by the flow velocity applied in agreement with mechanical loading mimicking early fracture healing (vlow) or bone remodeling (vhigh). These results can be used in the future to tightly control the behavior of human mesenchymal stromal cells towards proliferation or differentiation. Additionally, the combination of experiment and simulation presented is a strong tool to link biological responses to mechanical stimulation and can be applied to various in-vitro cultures to improve the understanding of the cause-effect relationship of mechanical loading.
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38
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Diekjürgen D, Grainger DW. Polysaccharide matrices used in 3D in vitro cell culture systems. Biomaterials 2017; 141:96-115. [PMID: 28672214 DOI: 10.1016/j.biomaterials.2017.06.020] [Citation(s) in RCA: 85] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Revised: 06/14/2017] [Accepted: 06/19/2017] [Indexed: 12/22/2022]
Abstract
Polysaccharides comprise a diverse class of polymeric materials with a history of proven biocompatibility and continual use as biomaterials. Recent focus on new matrices appropriate for three-dimensional (3D) cell culture offers new opportunities to apply polysaccharides as extracellular matrix mimics. However, chemical and structural bases for specific cell-polysaccharide interactions essential for their utility as 3-D cell matrices are not well defined. This review describes how these naturally sourced biomaterials satisfy several key properties for current 3D cell culture needs and can also be synthetically modified or blended with additional components to tailor their cell engagement properties. Beyond their benign interactions with many cell types in cultures, their economical and high quality sourcing, optical clarity for ex situ analytical interrogation and in situ gelation represent important properties of these polymers for 3D cell culture applications. Continued diversification of their versatile glycan chemistry, new bio-synthetic sourcing strategies and elucidation of new cell-specific properties are attractive to expand the polysaccharide polymer utility for cell culture needs. Many 3D cell culture priorities are addressed with the portfolio of polysaccharide materials available and under development. This review provides a critical analysis of their properties, capabilities and challenges in 3D cell culture applications.
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Affiliation(s)
- Dorina Diekjürgen
- Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112-5820, USA
| | - David W Grainger
- Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112-5820, USA; Department of Bioengineering, University of Utah, Salt Lake City, UT, 84112-5820, USA.
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Migration and Proliferative Activity of Mesenchymal Stem Cells in 3D Polylactide Scaffolds Depends on Cell Seeding Technique and Collagen Modification. Bull Exp Biol Med 2016; 162:120-126. [PMID: 27882461 DOI: 10.1007/s10517-016-3560-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Indexed: 10/20/2022]
Abstract
We analyzed viability of mesenchymal stem cells seeded by static and dynamic methods to highly porous fibrous 3D poly-L-lactide scaffolds with similar physical and chemical properties, but different spatial organization modified with collagen. Standard collagen coating promoted protein adsorption on the scaffold surface and improved adhesive properties of 100 μ-thick scaffolds. Modification of 600-μ scaffolds with collagen under pressure increased proliferative activity of mesenchymal stem cells seeded under static and dynamic (delivery of 100,000 cells in 10 ml medium in a perfusion system at a rate of 1 ml/min) conditions by 47 and 648%, respectively (measured after 120-h culturing by MTT test). Dynamic conditions provide more uniform distribution of collagen on scaffold fibers and promote cell penetration into 3D poly-L-lactide scaffolds with thickness >600 μ.
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40
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Chen C, Mehl BT, Sell SA, Martin RS. Use of electrospinning and dynamic air focusing to create three-dimensional cell culture scaffolds in microfluidic devices. Analyst 2016; 141:5311-20. [PMID: 27373715 PMCID: PMC5007176 DOI: 10.1039/c6an01282e] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Organs-on-a-chip has emerged as a powerful tool for pharmacological and physiological studies. A key part in the construction of such a model is the ability to pattern or culture cells in a biomimetic fashion. Most of the reported cells-on-a-chip models integrate cells on a flat surface, which does not accurately represent the extracellular matrix that they experience in vivo. Electrospinning, a technique used to generate sub-micron diameter polymer fibers, has been used as an in vitro cell culture substrate and for tissue engineering applications. Electrospinning of fibers directly into a fully sealed fluidic channel using a conventional setup has not been possible due to issues of confining the fibers into a discrete network. In this work, a dynamic focusing method was developed, with this approach enabling direct deposition of electrospun fibers into a fully sealed fluidic channel, to act as a matrix for cell culture and subsequent studies under continuous flowing conditions. Scanning electron microscopy of electrospun polycaprolactone fibers shows that this method enables the formation of fibrous layers on the inner wall of a 3D-printed fluidic device (mean fiber size = 1.6 ± 0.6 μm and average pore size = 113 ± 19 μm(2)). Cells were able to be cultured in this 3D scaffold without the addition of adhesion proteins. Media was pumped through the channel at high flow rates (up to 400 μL min(-1)) during a dynamic cell culture process and both the fibers and the cells were found to be strongly adherent. A PDMS fluidic device was also prepared (from a 3D printed mold) and coated with polycaprolactone fibers. The PDMS device enables optical detection and confocal imaging of cultured cells on the fibers. Finally, macrophages were cultured in the devices to study how the fibrous scaffold can affect cell behavior. It was found that under lipopolysaccharide stimulation, macrophages cultured on PCL fibers inside of a channel secreted significantly more cytokines than those cultured on a thin layer of PCL in a channel or directly on the inner channel wall. Overall, this study represents a new approach for in vitro cell studies, where electrospinning can be used to easily and quickly create 3D scaffolds that can improve the culture conditions in microfluidic devices.
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41
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Gatto F, Troncoso OP, Brunetti V, Malvindi MA, Pompa PP, Torres FG, Bardi G. Human monocyte response to Andean-native starch nanoparticles. STARCH-STARKE 2016. [DOI: 10.1002/star.201600105] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Francesca Gatto
- Istituto Italiano di Tecnologia (IIT); Genova Italy
- Department Of Engineering for Innovation; University of Salento; Lecce Italy
| | - Omar P Troncoso
- Department of Mechanical Engineering; Pontificia Universidad Catolica del Peru; Lima Peru
| | - Virgilio Brunetti
- Istituto Italiano di Tecnologia (IIT); Center for Bio-Molecular Nanotechnology@UniLe; Arnesano, Lecce Italy
| | - Maria Ada Malvindi
- Istituto Italiano di Tecnologia (IIT); Center for Bio-Molecular Nanotechnology@UniLe; Arnesano, Lecce Italy
| | | | - Fernando G Torres
- Department of Mechanical Engineering; Pontificia Universidad Catolica del Peru; Lima Peru
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Su WT, Pan YJ. Stem cells from human exfoliated deciduous teeth differentiate toward neural cells in a medium dynamically cultured with Schwann cells in a series of polydimethylsiloxanes scaffolds. J Neural Eng 2016; 13:046005. [DOI: 10.1088/1741-2560/13/4/046005] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Sun H, Wang J, Deng F, Liu Y, Zhuang X, Xu J, Li L. Co‑delivery and controlled release of stromal cell‑derived factor‑1α chemically conjugated on collagen scaffolds enhances bone morphogenetic protein‑2‑driven osteogenesis in rats. Mol Med Rep 2016; 14:737-45. [PMID: 27220358 PMCID: PMC4918613 DOI: 10.3892/mmr.2016.5339] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Accepted: 04/12/2016] [Indexed: 01/03/2023] Open
Abstract
There has been considerable focus in investigations on the delivery systems and clinical applications of bone morphogenetic protein-2 (BMP-2) for novel bone formation. However, current delivery systems require high levels of BMP-2 to exert a biological function. There are several concerns in using of high levels of BMP-2, including safety and the high cost of treatment. Therefore, the development of strategies to decrease the levels of BMP-2 required in these delivery systems is required. In our previous studies, a controlled-release system was developed, which used Traut's reagent and the cross-linker, 4-(N-maleimi-domethyl) cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt (Sulfo-SMCC), to chemically conjugate BMP-2 directly on collagen discs. In the current study, retention efficiency and release kinetics of stromal cell-derived factor-1α (SDF-1α) cross-linked on collagen scaffolds were detected. In addition, the osteogenic activity of SDF-1α and suboptimal doses of BMP-2 cross-linked on collagen discs following subcutaneous implantation in rats were evaluated. Independent two-tailed t-tests and one-way analysis of variance were used for analysis. In the present study, the controlled release of SDF-1α chemically conjugated on collagen scaffolds was demonstrated. By optimizing the concentrations of Traut's reagent and the Sulfo-SMCC cross-linker, a significantly higher level of SDF-1α was covalently retained on the collagen scaffold, compared with that retained using a physical adsorption method. Mesenchymal stem cell homing indicated that the biological function of the SDF-1α cross-linked on the collagen scaffolds remained intact. In rats, co-treatment with SDF-1α and a suboptimal dose of BMP-2 cross-linked on collagen scaffolds using this chemically conjugated method induced higher levels of ectopic bone formation, compared with the physical adsorption method. No ectopic bone formation was observed following treatment with a suboptimal dose of BMP-2 alone. Therefore, the co-delivery of SDF-1α and a suboptimal dose of BMP-2 chemically conjugated on collagen scaffolds for the treatment of bone injuries reduced the level of BMP-2 required, reducing the risks of side effects.
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Affiliation(s)
- Haipeng Sun
- Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Jinming Wang
- Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Feilong Deng
- Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Yun Liu
- Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Xiumei Zhuang
- Department of Oral Implantology, Sun Yat‑Sen Memorial Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Jiayun Xu
- Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
| | - Long Li
- Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
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Diaz-Gomez L, Concheiro A, Alvarez-Lorenzo C, García-González CA. Growth factors delivery from hybrid PCL-starch scaffolds processed using supercritical fluid technology. Carbohydr Polym 2016; 142:282-92. [DOI: 10.1016/j.carbpol.2016.01.051] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Revised: 01/20/2016] [Accepted: 01/23/2016] [Indexed: 12/26/2022]
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Modified chitosan scaffolds: Proliferative, cytotoxic, apoptotic, and necrotic effects on Saos-2 cells and antimicrobial effect on Escherichia coli. J BIOACT COMPAT POL 2016. [DOI: 10.1177/0883911515627471] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Scaffolds used in tissue engineering applications should have high biocompatibility with minimum allergic, toxic, apoptotic, or necrotic effects on the growing cells and newly forming tissue and, if possible, have antimicrobial property to prevent infection at the host site. In this study, novel micro-fibrous chitosan scaffolds, having mineralized bioactive surface to enhance cell adhesion and a model antibiotic (gentamicin) to prevent bacterial attack, were prepared. The effects of the scaffolds on proliferation, viability, apoptosis, and necrosis of Saos-2 cells are reported for the first time. Wet spinning technique was used in the scaffold preparation and biomineralization was achieved by incubating them in five-time concentrated simulated body fluid for 2, 7, or 14 days (coded as CH-BM/2, CH-BM/7, and CH-BM/14, respectively). Gentamicin, an effectively used antibiotic in bone treatments, was loaded by vacuum-pressure cycle. Energy-dispersive X-ray results demonstrated that Ca/P ratio of the mineral phase varies depending on the incubation period. When the scaffolds were cultured with Saos-2 cells, cell adhesion and extracellular matrix formation occurred on all types of scaffolds. Alamar Blue cytotoxicity tests showed correlation among mineral concentration and cytotoxicity where CH-BM/2 had significantly more favorable properties. For all types of scaffolds, apoptosis and necrosis were less than 10%, meaning the samples are biocompatible. Gentamicin-loaded scaffolds showed high antimicrobial efficacy against Escherichia coli. The presence of mineral phase enhanced the adhesive capacity of cells and entrapment efficiency of antibiotic. These results suggest that the bioactive and antimicrobial scaffolds prepared in this study can act as promising matrices in bone tissue engineering applications.
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Diaz-Gomez L, Yang F, Jansen JA, Concheiro A, Alvarez-Lorenzo C, García-González CA. Low viscosity-PLGA scaffolds by compressed CO2foaming for growth factor delivery. RSC Adv 2016. [DOI: 10.1039/c6ra09369h] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Foaming technology using supercritical and compressed fluids has emerged as a promising solution in regenerative medicine for manufacturing porous polymeric scaffolds.
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Affiliation(s)
- L. Diaz-Gomez
- Departamento de Farmacia y Tecnología Farmacéutica
- Facultad de Farmacia
- Universidade de Santiago de Compostela
- E-15782 Santiago de Compostela
- Spain
| | - F. Yang
- Department of Biomaterials
- Radboud University Medical Center
- 6500 HB Nijmegen
- The Netherlands
| | - J. A. Jansen
- Department of Biomaterials
- Radboud University Medical Center
- 6500 HB Nijmegen
- The Netherlands
| | - A. Concheiro
- Departamento de Farmacia y Tecnología Farmacéutica
- Facultad de Farmacia
- Universidade de Santiago de Compostela
- E-15782 Santiago de Compostela
- Spain
| | - C. Alvarez-Lorenzo
- Departamento de Farmacia y Tecnología Farmacéutica
- Facultad de Farmacia
- Universidade de Santiago de Compostela
- E-15782 Santiago de Compostela
- Spain
| | - C. A. García-González
- Departamento de Farmacia y Tecnología Farmacéutica
- Facultad de Farmacia
- Universidade de Santiago de Compostela
- E-15782 Santiago de Compostela
- Spain
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Ding M, Henriksen SS, Theilgaard N, Overgaard S. Assessment of activated porous granules on implant fixation and early bone formation in sheep. J Orthop Translat 2015; 5:38-47. [PMID: 30035073 PMCID: PMC5987005 DOI: 10.1016/j.jot.2015.09.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 08/02/2015] [Accepted: 09/22/2015] [Indexed: 11/19/2022] Open
Abstract
Background/Objective Despite recent progress in regeneration medicine, the repair of large bone defects due to trauma, inflammation and tumor surgery remains a major clinical challenge. This study was designed to produce large amounts of viable bone graft materials in a novel perfusion bioreactor to promote bone formation. Methods Cylindrical defects were created bilaterally in the distal femurs of sheep, and titanium implants were inserted. The concentric gap around the implants was randomly filled either with allograft, granules, granules with bone marrow aspirate (BMA) or bioreactor activated granule (BAG). The viable BAG consisted of autologous bone marrow stromal cells (BMSCs) seeded upon porous scaffold granules incubated in a 3D perfusion bioreactor for 2 weeks prior to surgery. 6 weeks after, the bone formation and early implant fixation were assessed by means of micro-CT, histomorphometry, and mechanical test. Results Microarchitectural analysis revealed that bone volume fraction and trabecular thickness in the allograft were not statistically different than those (combination of new bone and residue of granule) in the other 3 groups. The structure of the allograft group was typically plate-like, while the other 3 groups were combination of plate and rod. Histomorphometry showed that allograft induced significantly more bone and less fibrous tissue in the concentric gap than the other 3 granule groups, while the bone ingrowth to implant porous surface was not different. No significant differences among the groups were found regarding early implant mechanical fixation. Conclusion In conclusion, despite nice bone formation and implant fixation in all groups, bioreactor activated graft material did not convincingly induce early implant fixation similar to allograft, and neither bioreactor nor by adding BMA credited additional benefit for bone formation in this model.
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Affiliation(s)
- Ming Ding
- Orthopaedic Research Laboratory, Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark
- Corresponding author. Orthopaedic Research Laboratory, Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Winsløwparken 15, 3.sal, DK-5000, Odense C, Denmark.
| | - Susan S. Henriksen
- Orthopaedic Research Laboratory, Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark
| | - Naseem Theilgaard
- Danish Technological Institute, Plastics Technology, Taastrup, Denmark
| | - Søren Overgaard
- Orthopaedic Research Laboratory, Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark
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Dini F, Barsotti G, Puppi D, Coli A, Briganti A, Giannessi E, Miragliotta V, Mota C, Pirosa A, Stornelli MR, Gabellieri P, Carlucci F, Chiellini F. Tailored star poly (ε-caprolactone) wet-spun scaffolds for in vivo regeneration of long bone critical size defects. J BIOACT COMPAT POL 2015. [DOI: 10.1177/0883911515597928] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
One of the most challenging requirements of a successful bone tissue engineering approach is the development of scaffolds specifically tailored to individual tissue defects. Besides materials chemistry, well-defined scaffold’s structural features at the micro- and macro-levels are needed for optimal bone in-growth. In this study, polymeric fibrous scaffolds with a controlled internal network of pores and modelled on the anatomical shape and dimensions of a critical size bone defect in a rabbit’s radius model were developed by employing a computer-aided wet-spinning technique. The tailored scaffolds made of star poly(ε-caprolactone) or star poly(ε-caprolactone)–hydroxyapatite composite material were implanted into 20-mm segmental defects created in radial diaphysis of New Zealand white rabbits. Bone regeneration and tissue response were assessed by X-rays and histological analysis at 4, 8 and 12 weeks after surgery. No signs of macroscopic and microscopic inflammatory reactions were detected, and the developed scaffolds showed a good ability to support and promote the bone regeneration process. However, no significant differences in osteoconductivity were observed between star poly(ε-caprolactone) and star poly(ε-caprolactone)–hydroxyapatite scaffolds. Long-term study on implanted star poly(ε-caprolactone) scaffolds confirmed the presence of signs of bone regeneration and remodelling, particularly evident at 24 weeks.
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Affiliation(s)
- Francesca Dini
- Department of Veterinary Sciences, University of Pisa, Pisa, Italy
| | | | - Dario Puppi
- BIOLab Research Group, UdR-INSTM Pisa, Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
| | - Alessandra Coli
- Department of Veterinary Sciences, University of Pisa, Pisa, Italy
| | - Angela Briganti
- Department of Veterinary Sciences, University of Pisa, Pisa, Italy
| | | | | | - Carlos Mota
- BIOLab Research Group, UdR-INSTM Pisa, Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
| | - Alessandro Pirosa
- BIOLab Research Group, UdR-INSTM Pisa, Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
| | | | - Paolo Gabellieri
- Operative Unit of Orthopedic and Traumatology, Hospital of Cecina, Cecina, Italy
| | - Fabio Carlucci
- Department of Veterinary Sciences, University of Pisa, Pisa, Italy
| | - Federica Chiellini
- BIOLab Research Group, UdR-INSTM Pisa, Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
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Díaz-Rodríguez P, Gómez-Amoza JL, Landin M. The synergistic effect of VEGF and biomorphic silicon carbides topography on
in vivo
angiogenesis and human bone marrow derived mesenchymal stem cell differentiation. Biomed Mater 2015; 10:045017. [DOI: 10.1088/1748-6041/10/4/045017] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Zhao F, Vaughan TJ, McNamara LM. Quantification of fluid shear stress in bone tissue engineering scaffolds with spherical and cubical pore architectures. Biomech Model Mechanobiol 2015. [DOI: 10.1007/s10237-015-0710-0] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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