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Publications (112)
This paper presents a study on cold microdrawing of pure magnesium for biomedical applications, where hollow sinking drawing of microtubes of 820 µm diameter and wall thickness around 100 µm was used, varying drawing speeds to achieve a significant reduction in cross-sectional area in a single pass. Results showed an improved surface finish with re...
This study evaluates the morpho-functional modifications that characterize meniscal development from neonatal to adult dogs. Even if menisci are recognized as essential structures for the knee joint, poor information is available about their morphogenesis, in particular in dog models. Menisci from a group of Dobermann Pinchers aged 0, 10, 30 days,...
The mechanisms of deep-hole microdrilling of pure Mg material were experimentally studied in order to find a suitable setup for a novel intraocular drug delivery device prototyping. Microdrilling tests were performed with 0.20 mm and 0.35 mm microdrills, using a full factorial design in which cutting speed vc and feed fz were varied over two levels...
The constantly increasing incidence of coronary artery disease worldwide makes necessary to set advanced therapies and tools such as tissue engineered vessel grafts (TEVGs) to surpass the autologous grafts [(i.e., mammary and internal thoracic arteries, saphenous vein (SV)] currently employed in coronary artery and vascular surgery. To this aim, in...
3D-Bioprinting leads to the realization of tridimensional customized constructs to reproduce the biological structural complexity. The new technological challenge focuses on obtaining a 3D structure with several distinct layers to replicate the hierarchical organization of natural tissues. This work aims to reproduce large blood vessel substitutes...
Tissue engineering (TE) combines scaffolds, cells, and chemical and physical cues to replace biological tissues [...]
The analysis of the morphological, structural, biochemical, and mechanical changes of the Extracellular Matrix (ECM), which occur during meniscus development, represents the goal of the present study. Medial fully developed menisci (FD, 9-month-old pigs), partially developed menisci (PD, 1-month-old piglets), and not developed menisci (ND, from sti...
RetinaIn the present study, we present a strategy to develop a 3R-compliant in vitro retina model to study age-related macular degeneration pathways.
The menisci of the knee are complex fibro-cartilaginous tissues that play important roles in load bearing, shock absorption, joint lubrication, and stabilization. The objective of this study was to evaluate the interaction between the different meniscal tissue components (i.e., the solid matrix constituents and the fluid phase) and the mechanical r...
Optic nerve and retinal diseases such as age-related macular degeneration and inherited retinal dystrophies (IRDs) often cause permanent sight loss. Currently, a limited number of retinal diseases can be treated. Hence, new strategies are needed. Regenerative medicine and especially tissue engineering have recently emerged as promising alternatives...
Cell's microenvironment has been shown to exert influence on cell behavior. In particular, matrix-cell interactions strongly impact cell morphology and function. The purpose of this study was to analyze the influence of different culture substrate materials on phenotype and functional properties of lung epithelial adenocarcinoma (A549) cells. A549...
Glaucoma is the second cause of irreversible blindness in the world. Intraocular pressure (IOP) is a recognized major risk factor for the development and progression of glaucomatous damage. Goldmann applanation tonometry (GAT) is internationally accepted as the gold standard for the measurement of IOP. The purpose of this study was to search for co...
Aim
To evaluate quantitatively the effects of the Epi-Off-CXL irradiance dose on the stromal stiffening of pig corneas.
Setting
Laboratory of Biological structures (LaBS), Politecnico di Milano, Milano, Italy.
Methods
Inflation tests have been carried on 90 excised and de-epithelized pig corneas, monitoring the change of configuration of the corn...
Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly worldwide. So far, the etiology and the progression of AMD are not well known. Animal models have been developed to study the mechanisms involved in AMD; however, according to the “Three Rs” principle, alternative methods have been investigated. Here we presen...
Magnesium is an essential element for the ocular functions and used for the realization of medical devices due to its low corrosion resistance, bioresorbable nature and biocompatibility. Wet age-related macular degeneration is one of the main causes of blindness with patients treated by intravitreal injections of inhibitor drugs. According to the n...
Experimental inflation tests, conducted on 90 pig corneas before and after corneal collagen crosslinking (CXL) treatment, are simulated with the finite element method. The experimental sample consists of five groups of corneas treated with different UV-A irradiation times (2.5, 5, 10, 15, and 20 min) at constant irradiance 9 mW/cm². The linear elas...
Artificial substrates supporting the healing of skin wounds require specific structural and chemical architectures that promote a recapitulation of the complexity of the native organ. Bottom-up fabrication technologies are emerging as effective strategies to fine tune biochemical, morphological, and structural features intended for regenerative app...
The purpose of this study is to investigate the effect of vitreous sloshing induced by saccades on the intravitreal delivery of large molecule drugs. The vitreous body was considered in its age-related liquefaction condition. Fluid dynamics and large molecule distribution were described by the coupling of mass conservation's and Fick's laws with co...
Bioreactors are powerful tools for in vitro development of engineered substitutes through controlled biological, physical, and mechanical culture conditions: bioreactor technology allows a closer in vitro replication of native tissues. One of bioreactors applications is the design of in vitro 3D tissue models as a bridge between 2D and in vivo mode...
Joint motion and postnatal stress of weight bearing are the principal factors that determine the phenotypical and architectural changes that characterize the maturation process of the meniscus. In this study, the effect of compressive forces on the meniscus will be evaluated in a litter of 12 Dobermann Pinschers, of approximately 2 months of age, e...
Tendon tissue ruptures often require the replacement of damaged tissues. The use of auto- or allografts is notoriously limited due to the scarce supply and the high risks of immune adverse reactions. To overcome these limitations, tissue engineering (TE) has been considered a promising approach. Among several biomaterials, decellularized xenografts...
Impact statement:
The importance of the present study is linked to how the contact forces act on the knee meniscus in particular, considering the femoral condyles and tibial plateau: this can be useful as a base for the ultimate creation of tissue-engineered biphasic scaffolds, which can mimic the native tissue complex, for meniscal repair or rege...
One of the main ocular diseases is age-related macular degeneration, actually treated with antibodies injections into the eye. This problem has been faced by computational approaches, taking into account either the influence of the tissues surrounding the vitreous, or the saccades. The aim of this work is to propose a combined fluid dynamic model o...
Nowadays, intravitreal injections are the gold standard for the treatment of age-related macular degeneration (AMD). The prediction of the transport mechanism for the injected anti vascular endothelial growth factor (anti-VEGF) is needed in order to understand its distribution and consumption after each injection. Thus, this study aims at implement...
Introduction:
An innovative approach to the treatment of tendon injury or degeneration is given by engineered grafts, made available through the development of bioreactors that generate tendon tissue in vitro, by replicating in vivo conditions. This work aims at the design of a bioreactor capable of applying a stimulation of cyclic strain on cell...
Animal‐derived pericardium is the elective tissue employed in manufacturing heart valve prostheses. The preparation of this tissue for biological valves production consists in fixation with aldehydes, which reduces, but not eliminates, the xenoantigens and the donor cellular material. As a consequence, especially in patients below 65‐70 years of ag...
The aim of this study was to evaluate the effect of an in vitro mechanical stimulation by the use of a bioreactor on an engineered tendon for 7 and 14 days and to analyze the effect of the use of different cell sources: tenocytes, dermal fibroblasts or Adipose-Derived Stem Cells (ASCs), isolated from pig tissues. Histology showed a re-organization...
Background: Aldehyde-fixed pericardium is commonly used in valve implant manufacturing. Despite its wide employment, this tissue undergoes chronic rejection that limits implant performance and durability. In this work, we employed a method to engineer a leaflet-like tissue by seeding aortic valve interstitial cells (VIC) into fixative-free decellul...
In the last few years, the demand for tissue substitutes has increased and decellularized matrices has been widely proposed in the medical field to restore severe damages thanks to high biocompatibility and biomechanical properties similar to the native tissues. However, biological grafts represent a potential source of contamination and disease tr...
Objectives:
Serious and even fatal consequences of disk batteries ingestion in children are well known. Among other applications, disk batteries are currently utilized to power small toys, from which they can be unexpectedly extracted and swallowed.
Methods:
We tested a new cell intended for little toys (Green Cell - GC), after 6 and 12 hour of...
In the last years, several tissue engineering techniques have been applied to develop different kinds of osteochondral substitutes to overcome the scarce reparative properties of this tissue. The aim of this study was to generate and compare three biphasic scaffolds in an osteochondral lesion in a large-animal model. A critical osteochondral defect...
Tendon ruptures and/or large losses remain to be a great clinical challenge and often require full replacement of the damaged tissue. The use of auto- and allografts or engineered scaffolds is an established approach to restore severe tendon injuries. However, these grafts are commonly related to scarce biocompatibility, site morbidity, chronic inf...
The architecture and dynamic physical environment of tissues can be recreated in-vitro by combining 3D porous scaffolds and bioreactors able to apply controlled mechanical stimuli on cells. In such systems, the entity of the stimuli and the distribution of nutrients within the engineered construct depend on the micro-structure of the scaffolds. In...
A novel three-dimensional bi-component substitute made of collagen type I and hydroxyapatite (HA) was tested for the repair of osteochondral lesions in a swine model. This scaffold was assembled by a newly developed method that guarantees the strict integration between the organic and the inorganic parts, mimicking the biological tissue between the...
Atherosclerosis and its complications still represent the leading cause of death in the developed countries. While autologous blood vessels may be regarded as the best solution for peripheral and coronary bypass, they are unavailable in most patients. Even though tissue engineering techniques are often applied to the development of small-diameter v...
In cardiac tissue engineering, the use of bioreactors
is fundamental for applying controlled mechanical stimuli on the
cells and recreate a physiological environment for cardiomyocytes
cultures. This work is focused on an innovative Sensorized
Squeeze PRessure (S2PR) bioreactor, able to apply a periodic
contactless hydrodynamic pressures on 3D poro...
Purpose:
Mechanical properties of the extra-cellular matrix (ECM) such as stiffness mediate cell signaling, proliferation, migration, and differentiation. Within this context, we developed a method to estimate in vitro the stress-strain field induced by contraction of cardiovascular progenitor cells on substrates of controlled stiffness.
Methods:...
To withstand the high probability of success, the growing diffusion of laser surgery for the correction of visual defects, corneal surgeons are regarding with interest numerical tools able to provide reliable predictions of the intervention outcomes. The main obstacle to the definition of a predictive numerical instrument is the objective difficult...
An experimental program has been carried out in order to investigate the mechanical behavior of porcine corneas. We report the results of inflation tests on the whole cornea and uniaxial tests on excised corneal strips, performed on 51 fresh porcine eyes. Uniaxial tests have been performed on specimens cut from previously inflated corneas. The corn...
A eukaryotic cell attaches and spreads on substrates, whether it is the extracellular matrix naturally produced by the cell itself, or artificial materials, such as tissue-engineered scaffolds. Attachment and spreading require the cell to apply forces in the nN range to the substrate via adhesion sites, and these forces are balanced by the elastic...
The present work is aimed at the design and fabrication of microfluidic devices for pharmacological in-vitro tests on cells as a tool for individuating the concentration range in which the drug effectiveness is guaranteed, with particular attention to anti-osteoporotic therapies with strontium ranelate. The microsystem consists of a microchannels n...
Over the last twenty years major advancements have taken place in the design of medical devices and personalized therapies. They have paralleled the impressive evolution of three-dimensional, non invasive, medical imaging techniques and have been continuously fuelled by increasing computing power and the emergence of novel and sophisticated softwar...
The aim of this study was to investigate the effect of different pattern of spontaneous breathing on the respiratory mechanics and on the integrity of the pulmonary extracellular matrix.
Experiments were performed on adult healthy rats in which different spontaneously breathing pattern was elicited through administration of two commonly used anaest...
The role of the mechanical properties of the initial lymphatic wall and of the surrounding tissue in supporting lymph formation and/or progression was studied in six anaesthetized, neuromuscularly blocked and mechanically ventilated rats. After mid-sternal thoracotomy, submesothelial initial lymphatics were identified on the pleural diaphragmatic s...
Research in tissue engineering has been focused on articular cartilage repair for more than a decade. Some pioneristic studies involved the use of hydrogels such as alginate and fibrin glue which still possess valuable potential for cartilage regeneration. One of the main issues in cartilage tissue engineering is represented by the ideal maturation...
The aim of this study was to investigate the in vitro effect of different concentrations of blood on the morphological and biochemical properties of engineered cartilage. Previous studies have demonstrated a negative effect of blood on native cartilage; however, the effect of the contact of blood on engineered cartilage is unclear.
Articular chondr...
A finite elements model of an interdigitated microsensor has been used to investigate the sensitivity of the sensor to the detection and the quantification of cells flowing in a test chamber. In particular the sensitivity of the sensor towards the geometry of sensors and the presence of a cell flowing through the channels was evaluated; several sen...
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and
Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early
dhildhood mortality and growth failure data and their association with maternal
The field of mechanobiology has grown tremendously in the past few decades, and it is now well accepted that dynamic stresses and strains can impact cell and tissue organization, cell-cell and cell-matrix communication, matrix remodeling, cell proliferation and apoptosis, cell migration, and many other cell behaviors in both physiological and patho...
Menisci represent fundamental structures for the maintenance of knee homeostasis, playing a key role in knee biomechanics. However, their intrinsic regenerative potential is poor. As a consequence, when a lesion occurs and the meniscus is partially removed by surgery, knee mechanics is subject to dramatic changes. These have been demonstrated to le...
The lymphatic system originates from the interstitial tissue with initial lymphatic capillaries, whose wall is devoid of smooth muscle cells. In these vessels, lymph formation and progression is sustained by cyclic tissue stresses transmitted to the vessel lumen according to the mechanical properties of the vessel walls, which are at present still...
Poly(lactide-co-glycolide) (PLGA) scaffolds have been successfully used in bone tissue engineering, with or without hydroxyapatite (HA) and with a macroporosity given either by simple PLGA sphere packaging and/or by leaching out NaCl. The objective of this work was the optimization of the design parameters for bone tissue engineering scaffolds made...
Active regulation of dendritic cells (DC) by the lymphatics is just beginning to be explored [1]. The importance of interstitial flow on CCR7 signaling has recently been demonstrated for breast cancer cells [2], which likely mimic DCs to home to lymph nodes. Both lymphatics and DCs secrete the CCR7 ligands CCL19 (which is not matrix-binding) and CC...
Osteoarthritis (OA) is a disease affecting articular cartilage and the underlying bone, resulting from many biological and mechanical interacting factors which change the extracellular matrix (ECM) and cells and lead to increasing levels of cartilage degeneration, like softening, fibrillation, ulceration and cartilage loss. The early diagnosis of t...
The use of autologous chondrocytes seeded onto a biological scaffold represents a current valid tool for cartilage repair. However, the effect of the contact of blood to the engineered construct is unknown. The aim of this work was to investigate in vitro the effect of blood on the morphological, biochemical and biomechanical properties of engineer...
Computational models, developed to study abdominal aortic aneurysm (AAA) biomechanics, demonstrated that the presence of an intraluminal thrombus (ILT) can significantly alter the wall stress distribution in the degenerated vessel wall [1,2]. ILT is a soft hydrated tissue constituted of 90% of water. The solid porous matrix is made of a fibrin latt...
Experimental tests, such as the confined and unconfined compression and the indentation tests, are traditionally used to determine the poroelastic properties of hydrated soft tissues (HSTs). The purpose of this study was to quantitatively evaluate the reliability of H(A) and K values as identified from experimental confined test data, estimating th...
Interstitial fluid flow has been shown to affect the organization and behavior of cells in 3D environments in vivo and in vitro, yet the forces driving such responses are not clear. Due to the complex architecture of the extracellular matrix (ECM) and the difficulty of measuring fluid flow near cells embedded in it, the levels of shear stress exper...
Natural cartilage remodels both in vivo and in vitro in response to mechanical stresses, hence mechanical stimulation is believed to be a potential tool to modulate extra-cellular matrix synthesis in tissue-engineered cartilage. Fluid-induced shear is known to enhance chondrogenesis in engineered cartilage constructs. The quantification of the hydr...
Bioreactors allowing direct-perfusion of culture medium through tissue-engineered constructs may overcome diffusion limitations associated with static culturing, and may provide flow-mediated mechanical stimuli. The hydrodynamic stress imposed on cells within scaffolds is directly dependent on scaffold microstructure and on bioreactor configuration...
The mechanisms underlying the ability of articular cartilage to withstand and distribute the loads applied across diarthrodial joints have been widely studied. Experimental tests have been done under several configurations to reveal the tissue response to mechanical stimuli, and theoretical models have been developed for the interpretation of the e...
Bioreactors allowing culture medium perfusion overcome diffusion limitations associated with static culturing and provide flow-mediated mechanical stimuli. The hydrodynamic stress imposed to cells will depend not only on the culture medium flow rate, but also on the scaffold three-dimensional (3D) micro-architecture. We developed a CFD model of the...
Bioreactors allowing direct perfusion of culture medium through tissue-engineered constructs may overcome diffusion limitations associated with static culturing, and may provide flow-mediated mechanical stimuli. The hy-drodynamic stress imposed on cells in these systems will depend not only on the culture medium flow rate but also on the scaffold t...
Bioreactors allowing culture medium perfusion overcome diffusion limitations associated with static culturing, and provide
flow-mediated mechanical stimuli. Currently, one of the main issues in bioreactors design is to build a set up which may provide
the required nutrients, optimizing the mechanical stimulation on the cells. However, in most of th...
Cell organization is largely orchestrated by extracellular gradients of morphogenetic proteins. VEGF, an essential factor for capillary formation, is stored in the extracellular matrix, but the mechanisms by which it and other matrix-bound morphogens are mobilized to form spatial gradients are poorly understood. Here, we suggest an efficient mechan...
The function of articular cartilage is to support and distribute loads and to provide lubrication in the diarthrodial joints. Cartilage function is described by proper mechanical and rheological properties, strain and depth-dependent, which are not completely assessed. Unconfined and confined compression are commonly used to evaluate the Young's mo...
This work examines the effect of perfusion on human mature articular chondrocytes cultured on synthetic biodegradable scaffolds (DegraPol). Human chondrocytes were isolated, seeded on the scaffolds and subjected to perfused culture at a flow rate of 0.5 ml/min, corresponding to an average inlet fluid velocity of 44 microm/s, with flow inversion eve...
This report discusses theoretical effects of blood flow pulsatility upon the rate of oxygen transfer in artificial lungs, demonstrates the effects with in vitro tests upon commercial oxygenators, and applies the theory to these oxygenators and to a thoracic artificial lung. Steady flow gas transfer theory is applied to pulsatile flow by using the i...
The permeability of cartilage contributes to many tissue functions, like the transport of nutrients to chondrocytes, the ability to carry high loads, and the maintenance of a lubricating fluid film between opposing articular surfaces. We measured in vitro the permeability of the human lateral tibial plateau cartilage through its depth, by measuring...
Natural cartilage remodels both in vivo and in vitro in response to mechanical forces and hence mechanical stimulation is believed to have a potential as a tool to modulate extra-cellular matrix synthesis in tissue-engineered cartilage. Fluid-induced shear is known to enhance chondrogenesis on animal cells. A well-defined hydrodynamic environment i...
In order to move towards extracorporeal circulation (ECC) automation, a virtual simulation of the process was designed. The ECC model is composed of a virtual patient linked to a virtual ECC circuit. A user interface panel allows to set control parameters for the simulation and to visualize results. It is possible to switch between manual and autom...
A fluid-induced shear is known to enhance chondrogenesis on animal cells. We have developed a computational fluid dynamic model of the flow through chondrocyte seeded scaffolds cultured inside a novel bioreactor in which the culture medium flows through the constructs' microstructure. The median shear stress imposed to the cells in the bioreactor c...
To study pulmonary arteriolar vasomotion in control conditions and in the transition to hydraulic edema, changes in subpleural pulmonary arteriolar diameter and perivascular interstitial volume were evaluated in anesthetized spontaneously breathing rabbits. Images of subpleural pulmonary microvessels were recorded in control conditions and for up t...
Fluid-induced shear is known to enhance chondrogenesis on animal cells. We have developed a computational fluid dynamic model of the flow through chondrocyte seeded scaffolds cultured inside a novel bioreactor in which the culture medium flows through the constructs' microstructure. The median shear stress imposed to the cells in the bioreactor cul...
To study pulmonary arteriolar vasomotion in control conditions and in the transition to hydraulic edema, changes in subpleural pulmonary arteriolar diameter and perivascular interstitial volume were evaluated in anesthetized spontaneously breathing rabbits. Images of subpleural pulmonary microvessels were recorded in control conditions and for up t...
The finite element method (FEM) and molecular modeling of albumin adsorption on pyrolitic carbon for stress assessment were presented. The interaction forces between an albumin helix and the pyrolitic carbon surface were computed from the binding potential energy data. The results showed that the global forces acting on the semi-ellipse, which is t...
Attachment of an artificial lung (AL) to the pulmonary circulation is anticipated to benefit the treatment of acute or chronic pulmonary disease. AL use would be appropriate when conventional ventilation becomes ineffective or damaging. A numerical model has been developed to predict the hemodynamic consequences of different AL attachment modes and...
Whether pulsatile blood flow affects O 2 transfer rate in artificial lungs is controversial. Applying steady flow theory to pulsatile flow using the instantaneous value of flow rate at each time (i.e., quasi-steady transfer) predicts reduced rates of gas transfer, as much as 20 to 30%, for pulsatile flow relative to those at steady flow for the sam...
A thoracic artificial lung (TAL) was designed to treat respiratory insufficiency, acting as a temporary assist device in acute cases or as a bridge to transplant in chronic cases. We developed a computational model of the pulmonary circulatory system with the TAL inserted. The model was employed to investigate the effects of parameter values and fl...
Despite the wide use of hypothermic cardiopulmonary bypass (CPB) during open heart surgery there is little information about the patient metabolism. In particular no complete studies addressed the assessment of the respiratory ratio (RR) during CPB at different core temperatures. Therefore a clinical study was performed in order to evaluate the oxy...
A pulmonary circulation model with hybrid attachment of a thoracic artificial lung (TAL) was developed to investigate effects of TAL design parameters and attachment modes. The developed model can be solved for pressures and flows within the pulmonary circulation and artificial lung, and these can be used to calculate the right heart power (RHP).
