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  • 1.
    Bottier, Mathieu
    et al.
    Eq. 13, Institut Mondor de Recherche Biomédicale, Inserm U955, Créteil, France.
    Peña Fernández, Marta
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Vehicle Engineering and Solid Mechanics, Biomechanics. Zeiss Global Centre, School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth, PO1 3DJ, UK.
    Pelle, Gabriel
    Eq. 13, Institut Mondor de Recherche Biomédicale, Inserm U955, Créteil, France.
    Isabey, Daniel
    Eq. 13, Institut Mondor de Recherche Biomédicale, Inserm U955, Créteil, France.
    Louis, Bruno
    Eq. 13, Institut Mondor de Recherche Biomédicale, Inserm U955, Créteil, France.
    Grotberg, James B
    Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA..
    Filoche, Marcel
    Eq. 13, Institut Mondor de Recherche Biomédicale, Inserm U955, Créteil, France.
    A new index for characterizing micro-bead motion in a flow induced by ciliary beating: Part II, modeling.2017In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 13, no 7, article id e1005552Article in journal (Refereed)
    Abstract [en]

    Mucociliary clearance is one of the major lines of defense of the human respiratory system. The mucus layer coating the airways is constantly moved along and out of the lung by the activity of motile cilia, expelling at the same time particles trapped in it. The efficiency of the cilia motion can experimentally be assessed by measuring the velocity of micro-beads traveling through the fluid surrounding the cilia. Here we present a mathematical model of the fluid flow and of the micro-beads motion. The coordinated movement of the ciliated edge is represented as a continuous envelope imposing a periodic moving velocity boundary condition on the surrounding fluid. Vanishing velocity and vanishing shear stress boundary conditions are applied to the fluid at a finite distance above the ciliated edge. The flow field is expanded in powers of the amplitude of the individual cilium movement. It is found that the continuous component of the horizontal velocity at the ciliated edge generates a 2D fluid velocity field with a parabolic profile in the vertical direction, in agreement with the experimental measurements. Conversely, we show than this model can be used to extract microscopic properties of the cilia motion by extrapolating the micro-bead velocity measurement at the ciliated edge. Finally, we derive from these measurements a scalar index providing a direct assessment of the cilia beating efficiency. This index can easily be measured in patients without any modification of the current clinical procedures.

  • 2. Dall'Ara, Enrico
    Palanca, Marco
    Giorgi, Mario
    Cristofolini, Luca
    Tozzi, Gianluca
    Precision of Digital Volume Correlation approaches for strain analysis in bone imaged with micro-computed tomography at different dimensional levels2017In: Frontiers in MaterialsArticle in journal (Refereed)
  • 3.
    De Mori, Arianna
    et al.
    School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK..
    Peña Fernández, Marta
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Vehicle Engineering and Solid Mechanics, Biomechanics. Zeiss Global Centre, School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth, PO1 3DJ, UK.
    Blunn, Gordon
    School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK..
    Tozzi, Gianluca
    Zeiss Global Centre, School of Engineering, University of Portsmouth, Portsmouth PO1 3DJ, UK..
    Roldo, Marta
    School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK..
    3D Printing and Electrospinning of Composite Hydrogels for Cartilage and Bone Tissue Engineering.2018In: Polymers, ISSN 2073-4360, E-ISSN 2073-4360, Vol. 10, no 3, article id E285Article in journal (Refereed)
    Abstract [en]

    Injuries of bone and cartilage constitute important health issues costing the National Health Service billions of pounds annually, in the UK only. Moreover, these damages can become cause of disability and loss of function for the patients with associated social costs and diminished quality of life. The biomechanical properties of these two tissues are massively different from each other and they are not uniform within the same tissue due to the specific anatomic location and function. In this perspective, tissue engineering (TE) has emerged as a promising approach to address the complexities associated with bone and cartilage regeneration. Tissue engineering aims at developing temporary three-dimensional multicomponent constructs to promote the natural healing process. Biomaterials, such as hydrogels, are currently extensively studied for their ability to reproduce both the ideal 3D extracellular environment for tissue growth and to have adequate mechanical properties for load bearing. This review will focus on the use of two manufacturing techniques, namely electrospinning and 3D printing, that present promise in the fabrication of complex composite gels for cartilage and bone tissue engineering applications.

  • 4. Lu, Xuekun
    et al.
    Peña Fernández, Marta
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Vehicle Engineering and Solid Mechanics, Biomechanics. Zeiss Global Centre, School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth, PO1 3DJ, UK.
    Bradley, Robert S
    Rawson, Shelley D
    O'Brien, Marie
    Hornberger, Benjamin
    Leibowitz, Marty
    Tozzi, Gianluca
    Withers, Philip J
    Anisotropic crack propagation and deformation in dentin observed by four-dimensional X-ray nano-computed tomography.2019In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 96, p. 400-411, article id S1742-7061(19)30464-7Article in journal (Refereed)
    Abstract [en]

    Understanding the cracking behaviour of biological composite materials is of practical importance. This paper presents the first study to track the interplay between crack initiation, microfracture and plastic deformation in three dimensions (3D) as a function of tubule and collagen fibril arrangement in elephant dentin using in situ X-ray nano-computed tomography (nano-CT). A nano-indenter with a conical tip has been used to incrementally indent three test-pieces oriented at 0°, 45° and 70° to the long axis of the tubules (i.e. radial to the tusk). For the 0° sample two significant cracks formed, one of which linked up with microcracks in the axial-radial plane of the tusk originating from the tubules and the other one occurred as a consequence of shear deformation at the tubules. The 70° test-piece was able to bear the greatest loads despite many small cracks forming around the indenter. These were diverted by the microstructure and did not propagate significantly. The 45° test-piece showed intermediate behaviour. In all cases strains obtained by digital volume correlation were well in excess of the yield strain (0.9%), indeed some plastic deformation could even be seen through bending of the tubules. The hoop strains around the conical indenter were anisotropic with the smallest strains correlating with the primary collagen orientation (axial to the tusk) and the largest strains aligned with the hoop direction of the tusk. STATEMENT OF SIGNIFICANCE: This paper presents the first comprehensive study of the anisotropic nature of microfracture, crack propagation and deformation in elephant dentin using time-lapse X-ray nano-computed tomography. To unravel the interplay of collagen fibrils and local deformation, digital volume correlation (DVC) has been applied to map the local strain field while the crack initiation and propagation is tracked in real time. Our results highlight the intrinsic and extrinsic shielding mechanisms and correlate the crack growth behavior in nature to the service requirement of dentin to resist catastrophic fracture. This is of wide interest not just in terms of understanding dentin fracture but also can extend beyond dentin to other anisotropic structural composite biomaterials such as bone, antler and chitin.

  • 5.
    Peña Fernández, Marta
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Vehicle Engineering and Solid Mechanics, Biomechanics. Zeiss Global Centre, School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth, PO1 3DJ, UK.
    Bodey, Andrew (Contributor)
    Parwani, Rachna
    Blunn, Gordon
    Barber, Asa
    Tozzi, Gianluca
    Full-field strain analysis of bone-biomaterial systems produced by osteoregenerative biomaterials after in vivo service in an ovine model2019In: ACS Biomaterials Science and EngineeringArticle in journal (Refereed)
  • 6.
    Peña Fernández, Marta
    et al.
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Vehicle Engineering and Solid Mechanics, Biomechanics. Zeiss Global Centre, School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth, PO1 3DJ, UK.
    Barber, A H
    Blunn, G W
    Tozzi, G
    Optimization of digital volume correlation computation in SR-microCT images of trabecular bone and bone-biomaterial systems.2018In: Journal of Microscopy, ISSN 0022-2720, E-ISSN 1365-2818, Vol. 272, no 3, p. 213-228Article in journal (Refereed)
    Abstract [en]

    A micromechanical characterization of biomaterials for bone tissue engineering is essential to understand the quality of the newly regenerated bone, enabling the improvement of tissue regeneration strategies. A combination of microcomputed tomography in conjunction with in situ mechanical testing and digital volume correlation (DVC) has become a powerful technique to investigate the internal deformation of bone structure at a range of dimensional scales. However, in order to obtain accurate three-dimensional strain measurement at tissue level, high-resolution images must be acquired, and displacement/strain measurement uncertainties evaluated. The aim of this study was to optimize imaging parameters, image postprocessing and DVC settings to enhance computation based on 'zero-strain' repeated high-resolution synchrotron microCT scans of trabecular bone and bone-biomaterial systems. Low exposures to SR X-ray radiation were required to minimize irradiation-induced tissue damage, resulting in the need of advanced three-dimensional filters on the reconstructed images to reduce DVC-measured strain errors. Furthermore, the computation of strain values only in the hard phase (i.e. bone, biomaterial) allowed the exclusion of large artefacts localized in the bone marrow. This study demonstrated the suitability of a local DVC approach based on synchrotron microCT images to investigate the micromechanics of trabecular bone and bone-biomaterial composites at tissue level with a standard deviation of the errors in the region of 100 microstrain after a thorough optimization of DVC computation. LAY DESCRIPTION: Understanding the quality of newly regenerated bone after implantation of novel biomaterials is essential to improve bone tissue engineering strategies and formulation of biomaterials. The relationship between microstructure and mechanics of bone has been previously addressed combining microcomputed tomography with in situ mechanical testing. The addition of an image-based experimental technique such as digital volume correlation (DVC) allows to characterize the deformation of materials in a three-dimensional manner. However, in order to obtain accurate information at the micro-scale, high-resolution images, obtained for example by using synchrotron radiation microcomputed tomography, as well as optimization of the DVC computation are needed. This study presents the effect of different imaging parameters, image postprocessing and DVC settings for as accurate investigation of trabecular bone structure and bone-biomaterial interfaces. The results showed that when appropriate image postprocessing and DVC settings are used DVC computation results in very low strain errors. This is of vital importance for a correct understanding of the deformation in bone-biomaterial systems and the ability of such biomaterials in producing new bone comparable with the native tissue they are meant to replace.

  • 7.
    Peña Fernández, Marta
    et al.
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Vehicle Engineering and Solid Mechanics, Biomechanics. Zeiss Global Centre, School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth, PO1 3DJ, UK.
    Black, Cameron
    Dawson, Jon
    Gibbs, David
    Kanczler, Janos
    Oreffo, Richard O C
    Tozzi, Gianluca
    Exploratory Full-Field Strain Analysis of Regenerated Bone Tissue from Osteoinductive Biomaterials.2020In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 13, no 1, article id E168Article in journal (Refereed)
    Abstract [en]

    Biomaterials for bone regeneration are constantly under development, and their application in critical-sized defects represents a promising alternative to bone grafting techniques. However, the ability of all these materials to produce bone mechanically comparable with the native tissue remains unclear. This study aims to explore the full-field strain evolution in newly formed bone tissue produced in vivo by different osteoinductive strategies, including delivery systems for BMP-2 release. In situ high-resolution X-ray micro-computed tomography (microCT) and digital volume correlation (DVC) were used to qualitatively assess the micromechanics of regenerated bone tissue. Local strain in the tissue was evaluated in relation to the different bone morphometry and mineralization for specimens (n = 2 p/treatment) retrieved at a single time point (10 weeks in vivo). Results indicated a variety of load-transfer ability for the different treatments, highlighting the mechanical adaptation of bone structure in the early stages of bone healing. Although exploratory due to the limited sample size, the findings and analysis reported herein suggest how the combination of microCT and DVC can provide enhanced understanding of the micromechanics of newly formed bone produced in vivo, with the potential to inform further development of novel bone regeneration approaches.

  • 8.
    Peña Fernández, Marta
    et al.
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Vehicle Engineering and Solid Mechanics, Biomechanics. Zeiss Global Centre, School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth, PO1 3DJ, UK.
    Cipiccia, Silvia
    Dall'Ara, Enrico
    Bodey, Andrew J
    Parwani, Rachna
    Pani, Martino
    Blunn, Gordon W
    Barber, Asa H
    Tozzi, Gianluca
    Effect of SR-microCT radiation on the mechanical integrity of trabecular bone using in situ mechanical testing and digital volume correlation.2018In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 88, p. 109-119, article id S1751-6161(18)30763-XArticle in journal (Refereed)
    Abstract [en]

    The use of synchrotron radiation micro-computed tomography (SR-microCT) is becoming increasingly popular for studying the relationship between microstructure and bone mechanics subjected to in situ mechanical testing. However, it is well known that the effect of SR X-ray radiation can considerably alter the mechanical properties of bone tissue. Digital volume correlation (DVC) has been extensively used to compute full-field strain distributions in bone specimens subjected to step-wise mechanical loading, but tissue damage from sequential SR-microCT scans has not been previously addressed. Therefore, the aim of this study is to examine the influence of SR irradiation-induced microdamage on the apparent elastic properties of trabecular bone using DVC applied to in situ SR-microCT tomograms obtained with different exposure times. Results showed how DVC was able to identify high local strain levels (> 10,000 µε) corresponding to visible microcracks at high irradiation doses (~ 230 kGy), despite the apparent elastic properties remained unaltered. Microcracks were not detected and bone plasticity was preserved for low irradiation doses (~ 33 kGy), although image quality and consequently, DVC performance were reduced. DVC results suggested some local deterioration of tissue that might have resulted from mechanical strain concentration further enhanced by some level of local irradiation even for low accumulated dose.

  • 9.
    Peña Fernández, Marta
    et al.
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Vehicle Engineering and Solid Mechanics, Biomechanics. Zeiss Global Centre, School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth, PO1 3DJ, UK.
    Dall'Ara, Enrico
    Kao, Alexander P
    Bodey, Andrew J
    Karali, Aikaterina
    Blunn, Gordon W
    Barber, Asa H
    Tozzi, Gianluca
    Preservation of Bone Tissue Integrity with Temperature Control for In Situ SR-MicroCT Experiments.2018In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 11, no 11, article id E2155Article in journal (Refereed)
    Abstract [en]

    Digital volume correlation (DVC), combined with in situ synchrotron microcomputed tomography (SR-microCT) mechanics, allows for 3D full-field strain measurement in bone at the tissue level. However, long exposures to SR radiation are known to induce bone damage, and reliable experimental protocols able to preserve tissue properties are still lacking. This study aims to propose a proof-of-concept methodology to retain bone tissue integrity, based on residual strain determination using DVC, by decreasing the environmental temperature during in situ SR-microCT testing. Compact and trabecular bone specimens underwent five consecutive full tomographic data collections either at room temperature or 0 °C. Lowering the temperature seemed to reduce microdamage in trabecular bone but had minimal effect on compact bone. A consistent temperature gradient was measured at each exposure period, and its prolonged effect over time may induce localised collagen denaturation and subsequent damage. DVC provided useful information on irradiation-induced microcrack initiation and propagation. Future work is necessary to apply these findings to in situ SR-microCT mechanical tests, and to establish protocols aiming to minimise the SR irradiation-induced damage of bone.

  • 10.
    Peña Fernández, Marta
    et al.
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Vehicle Engineering and Solid Mechanics, Biomechanics. Zeiss Global Centre, School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth, PO1 3DJ, UK.
    Hoxha, Dorela
    Chan, Oliver
    Mordecai, Simon
    Blunn, Gordon W.
    Tozzi, Gianluca
    Centre of Rotation of the Human Subtalar Joint Using Weight-Bearing Clinical Computed Tomography2020In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 10, article id 1035Article in journal (Refereed)
    Abstract [en]

    Accurate in vivo quantifcation of subtalar joint kinematics can provide important information for the clinical evaluation of subtalar joint function; the analysis of outcome of surgical procedures of the hindfoot; and the design of a replacement subtalar joint prosthesis. The objective of the current study was to explore the potential of full weight-bearing clinical computed tomography (CT) to evaluate the helical axis and centre of rotation of the subtalar joint during inversion and eversion motion. A subject specifc methodology was proposed for the defnition of the subtalar joint motion combining threedimensional (3D) weight-bearing imaging at diferent joint positions with digital volume correlation (DVC). The computed subtalar joint helical axis parameters showed consistency across all healthy subjects and in line with previous data under simulated loads. A sphere ftting approach was introduced for the computation of subtalar joint centre of rotation, which allows to demonstrate that this centre of rotation is located in the middle facet of the subtalar joint. Some translation along the helical axis was also observed, refecting the elasticity of the soft-tissue restraints. This study showed a novel technique for non-invasive quantitative analysis of bone-to-bone motion under full weight-bearing of the hindfoot. Identifying diferent joint kinematics in patients with ligamentous laxity and instability, or in the presence of stifness and arthritis, could help clinicians to defne optimal patient-specifc treatments.

  • 11.
    Peña Fernández, Marta
    et al.
    KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Vehicle Engineering and Solid Mechanics, Biomechanics. Zeiss Global Centre, School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth, PO1 3DJ, UK.
    Witte, F
    Tozzi, G
    Applications of X-ray computed tomography for the evaluation of biomaterial-mediated bone regeneration in critical-sized defects.2019In: Journal of Microscopy, ISSN 0022-2720, E-ISSN 1365-2818Article in journal (Refereed)
    Abstract [en]

    Bone as such displays an intrinsic regenerative potential following fracture; however, this capacity is limited with large bone defects that cannot heal spontaneously. The management of critical-sized bone defects remains a major clinical and socioeconomic need with osteoregenerative biomaterials constantly under development aiming at promoting and enhancing bone healing. X-ray computed tomography (XCT) has become a standard and essential tool for quantifying structure-function relationships in bone and biomaterials, facilitating the development of novel bone tissue engineering strategies. This paper presents recent advancements in XCT analysis of biomaterial-mediated bone regeneration. As a noninvasive and nondestructive technique, XCT allows for qualitative and quantitative evaluation of three-dimensional (3D) scaffolds and biomaterial microarchitecture, bone growth into the scaffold as well as the 3D characterisation of biomaterial degradation and bone regeneration in vitro and in vivo. Furthermore, in combination with in situ mechanical testing and digital volume correlation (DVC), XCT demonstrated its potential to better understand the bone-biomaterial interactions and local mechanics of bone regeneration during the healing process in relation to the regeneration achieved in vivo, which will likely provide valuable knowledge for the development and optimisation of novel osteoregenerative biomaterials. LAY DESCRIPTION: Bone, being a dynamically adaptable material, displays excellent regenerative properties following fracture. However, the self-healing capacity of bone becomes more difficult with large bone defects. Those defects are common and occur in many clinical situations; hence, biomaterials are mostly used to restore both bone structure and function in the defect site. X-ray computed tomography (XCT) is a powerful tool to evaluate bone regeneration in critical-sized defects after the implantation of biomaterials, allowing to an improved understanding of the regeneration process following different bone tissue engineering approaches. This paper focuses on recent advancements in XCT analysis to characterise biomaterial-mediated bone regeneration in critical-sized defects. XCT supports three-dimensional (3D) analysis of biomaterials, scaffolds and regenerated bone microarchitecture, as well as bone ingrowth into the scaffold. As a nondestructive technique, XCT allows for a 3D characterisation of biomaterial degradation and bone regeneration over time. In addition, XCT combined with in situ mechanical experiments and digital volume correlation (DVC) provides a 3D evaluation and quantification of bone-biomaterial interactions and deformation mechanisms during the regeneration process. This remains essential for the development and enhancement of novel biomaterials able to produce bone that is comparable with the native tissue they aim to replace.

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