Artificial Organ Engineering

271 Pages·2017·6.68 MB·English

by  Maria Cristina Annesini

Maria Cristina Annesini · Luigi Marrelli
Vincenzo Piemonte · Luca Turchetti
Artificial
Organ
Engineering
fi
Arti cial Organ Engineering
Maria Cristina Annesini Luigi Marrelli
(cid:129)
Vincenzo Piemonte Luca Turchetti
(cid:129)
fi
Arti cial Organ Engineering
123
Maria Cristina Annesini Vincenzo Piemonte
Department ofChemical Engineering Faculty of Engineering
MaterialsandEnvironment University “Campus Bio-medico”of Rome
University “La Sapienza”of Rome Rome
Rome Italy
Italy
Luca Turchetti
Luigi Marrelli ENEA- Italian National Agency for New
Faculty of Engineering Technologies, EnergyandSustainable
University “Campus Bio-medico”of Rome EconomicDevelopment
Rome Rome
Italy Italy
ISBN978-1-4471-6442-5 ISBN978-1-4471-6443-2 (eBook)
DOI 10.1007/978-1-4471-6443-2
LibraryofCongressControlNumber:2014936613
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Introduction
The history of medicine has always been characterized by the attempt to treat a
wide range of diseases, some very serious and with high mortality, and others
debilitating and detrimental for the quality of life of patients. With the increase of
life expectancy, organ failure has become quite common, making the problem of
degenerationofsomebodyparts(organs,jointsetc)increasinglycritical.Therefore,
the possibility of replacing these parts, represents an interesting opportunity for
increasing life duration and improving its quality.
Substitutionofapartofthehumanbodycanbeachievedbytransplantationfrom
a human or animal donor. Tissues for transplantation can be obtained from the
recipient’s own body (autotransplantation). Tissues or organs can be taken from a
different living or dead compatible human donor (allotransplantation) or from an
animal (xenotransplantation). Unfortunately, while the population of patients
requiring organs continues to increase, the lack of an adequate number of donors,
along with biological and ethical problems connected with allotransplantation and
xenotransplantation,makesorgantransplantationstillinadequateandthenumberof
patients on the waiting lists is growing rapidly. A possible alternative to trans-
plantation consists in the use of artificial and bio-artificial organs. The availability
ofdevicesable tosubstitute,oratleastsupport,damagedvitalfunctionscanallow
the patient to be kept alive a long time or, at least, until either a transplantation is
possible or the physiological activity of the native organ is restored. Furthermore,
artificialorgansplayakeyroleinenhancingapatient’squalityoflife.However,the
currentstateofdevelopmentinthefieldsofbiotechnologyandbioengineeringdoes
not allow all organs and tissues to be available.
At present, several extracorporeal artificial assist devices are available and in
use, such as the artificial kidney, whereas only few implantable devices are
approved for clinical use. In the last decades, biomedical engineering has made
greatstridesinthisfieldwiththesupportofnanotechnology,microelectronics,and
biology and with the significant contribution of the fundamentals of chemical
engineeringsuchasthermodynamics,kinetics,andtransportphenomena;therefore,
we can imagine that in the future, the number of miniature artificial organs for
permanent implantation will increase. A comprehensive definition considers
v
vi Introduction
artificial organs “any equipment, device, or material, directly or indirectly inter-
faced with living tissue and used to substitute, partly or entirely, or to strengthen
functions of a natural organ or of any other part of the body badly working or
lacking.” This definition, drawn from a conference of the National Institute of
Health, considers as artificial organs both devices performing physical–chemical
functions (such as artificial kidney, blood oxygenator, and artificial liver.) and
electromechanical devices (such as pacemakers, heart valves, artificial hands, and
orthopedicprostheses)oraestheticparts(suchasmammaryprostheses).Adifferent
approach distinguishes between artificial (and bio-artificial) organs and prostheses,
defining the former as devices substituting or supporting any physical–chemical
function of the body and the latter as devices designed only for mechanical or
electromechanical functions.
Theearliestartificialorgansweremostlybasedonmechanicaltechnologies.The
first artificial kidney, which marks the beginning of artificial organ history, was
basicallyabloodfilteraimedatremovingwastematerial fromthebody.Likewise,
artificial hearts and ventricular assist devices (VADs) were all based on pump and
valvetechnology.However,biomedicalresearchershavequicklyrealizedthatmost
human organs cannot be substituted by artificial ones mimicking only their
mechanical functions. Endocrine organs, for example, are exceedingly complex in
their functions to be artificially reproduced at the present state of scientific and
technological knowledge. A typical case is represented by the liver, which carries
out many biological functions, among which blood detoxification and synthesis of
biomolecules essential in metabolism are only the most well-known.
While blood detoxification can be fairly performed by the use of membranes,
synthesis mechanisms and other hepatic functions are still far from being repro-
ducedbyanartificialliver.Today,manyartificialdevicesareroughsimplifications
ofthebiologicaloriginalandareabletoreproduceonlysomeofthevitalfunctions.
For these reasons, biomedical research has concentrated its efforts on the devel-
opment of hybrid systems, coupling biological and artificial components. These
devices, named bio-artificial organs, usually contain a bioreactor where cells or a
tissue of the organ to be substituted carry out the functions of the native organ.
Besides artificial and bio-artificial organs, a third approach, named neo-organs, is
now emerging. This approach is closely connected with tissue engineering and is
based on growing, over suitable biodegradable supports (scaffold), cells of the
tissue to be produced or stem cells. Tissues with various three-dimensional struc-
tures can be currently produced with this technique. Very good results have been
obtained in the production of bone and skin tissue, to be used in case of burns.
Research is in progress in the field of nerves, muscles, and blood vessels.
As for market scenarios, according to a recent report published by the
Transparency Market Research1, the world market of artificial organs, including
1http://www.transparencymarketresearch.com
Artificialvitalorgansandmedicalbionicsmarket(artificialheart,kidney,liver,pancreasand
lungs,earbionics,visionbionics,exoskeletons,bioniclimbs,brainbionicsandcardiacbionics)—
GlobalIndustryanalysis,size,share,growth,trendsandforecast,2012–2018.
Introduction vii
prostheses,isexpectedtogrowatacompoundannualgrowthrate(CAGR)of9.2%.
Sincein2011theartificialvitalorgansandmedicalbionicsmarketwereevaluatedat
aboutUS$17.5billion,theaboveCAGRvaluegivesaforecastofUS$32.3billion
in2018.Itisasubstantialandcontinuouslydevelopingmarketthathasapreeminent
importance in technologically advanced countries, especially in the field of new
devices.Theglobalmarketofartificialorgansisledbytheartificialkidney,which
made up 48 % of the global market in 2010. Its use is highly recommended as a
short-/medium-termtreatment,especiallywhenusedasasupportwhilewaitingfora
kidney transplant. Industrial research is focused on the development of better
membranes and on more efficient and cheaper production technology. Recently,
promising steps forward have been taken in the field of artificial and bio-artificial
livers. Devices such as MARS (Molecular Adsorbent Recirculating System) and
ELAD are quite largelyusedto provide for the detoxifyingneedsofthe organism.
A bio-artificial liver could also provide the metabolic functions of natural liver. In
coming years, technological advancements are expected in the field of an implan-
tablebio-artificialpancreaswithremarkablelucrative prospectsconnectedwiththe
current spreading of diabetes mellitus. Besides the improvement in safety and effi-
cacy,anaspecttobetakenintoaccountisthereductionofproductionandoperation
costs of present and future devices, in order to make them affordable for a greater
numberofpeople,especiallyindevelopingcountries.Formostofthesepeople,the
dialysis treatment, diffusely used in advanced countries, is still a dream barred by
povertyconditions.
A very important issue to be taken into account in the development and pro-
duction of artificial organs concerns materials (biomaterials) to be used in contact
with the tissues of the human body. These materials play a fundamental role in
making a medical device safe for human use. The main requirement for a bioma-
terialisbiocompatibility,i.e.,thepropertyofnotcausingtoxicordamagingeffects
on biological systems and not activating the immune system. However, it is
importanttonote that biocompatibility isnota propertyof thematerial alone, asit
dependsonthepositioninwhichthematerialisusedorimplantedandonthetime
of exposure to the biologic matter. From this point of view, it is possible that a
material can be considered as biocompatible if used in extracorporeal devices, but
not for internal use. Furthermore, biocompatibility is affected by the production
processofthematerialanditsstateofcleaningandsterilization.Theassessmentof
biocompatibility is regulated by ISO 10993 standards, which describe tests to be
performed,invitrooronanimals,dependingonthecategoryofcontactwithhuman
body. These tests, which must be carried out in specialized laboratories, concern
toxicity, carcinogenicity, hemocompatibility, etc., and are sometimes very expen-
sive(upto100,000€).Besidesbiocompatibility,othermoreconventionalproperties
of a material to be used in artificial organs are mechanical strength and durability.
For example, a normal heart beats about 40 million times a year. Therefore, parts
of an artificial heart used to pump blood must be made of materials able to work
for a long time without being deformed or broken. Another example refers to
materials used in orthopaedic prostheses, whose average life is about 10–15 years.
viii Introduction
In substituting a natural joint by an artificial one, two mobile parts touching each
other must slide with a low friction coefficient and negligible tear effects. Suitable
biomaterialsmustnotinvolvethereleaseofsmalldebriswithharmfuleffectssince,
besidesweareffects,theyactivatethereactionoftheimmunesystem,whichisoften
coupledwiththereleaseofenzymesthatdestroytheadjoiningtissue.Anadditional
problem connected with the use of biomaterials is the possible formation of bio-
films. These are aggregates of bacteria which stick irreversibly to surfaces making
multilayer settlements incorporated in a porous matrix that shelters the microor-
ganisms from the attack of antibiotics. This problem can appear in catheters, in
contact lenses, and, with serious effects, in heart valves. The formation of biofilms
depends on the physical and chemical properties of the support surface, especially
on its roughness and porosity, and on material hydrophobicity and chemical com-
position.Severalgroupsofscientistsandbioengineersareinvestigatingsolutionsto
prevent the formation of biofilms through specific coatings and surface treatments.
Today,withtheincreasingchemicalandbiologicalknowledge,thepointofviewon
the features of biomaterials is changing. For example, in the past, the greatest
chemicalandbiologicalinactivitywasrequiredforabiomaterial,whilenowseveral
very reactive materials are proving to be more suitable for some biomedical
applications. Some materials, for example, form chemical bonds with the sur-
rounding tissue, increasing the stability of prostheses. Other materials degrade and
can be adsorbed onto the tissue when they are no longer necessary.
Toconclude,itisveryimportanttohighlightthataproperdesignandoperation
of artificial and bio-artificial organs require a deep knowledge offundamentals of
chemical thermodynamics, transport phenomena, and chemical kinetics, besides
anatomy and physiology. Most of the methods used in blood detoxification are
basedonphysicochemicaloperationsaimedatremoving,inashorttime,clinically
important amounts of some substances without appreciable risk for the patient.
Such separation operations are usually performed by selective membranes perme-
able to the toxic substances to be removed and impermeable to the essential
compounds. Understanding of mass transfer across these membranes is therefore
the basis for the design of a hemodialyzer. In hemoperfusion, toxic substances are
removed by adsorption on solid adsorbents and solid–liquid phase equilibrium is
involved. Furthermore, a rheology analysis is usually required in order to avoid
bloodcelldamage.Likewise,theuseofanimalcellsinbio-artificialorgansrequires
theknowledgeofthefundamentalsofbioreactors,oftencoupledwithmassandheat
transfer processes.
The book is divided in two parts: The first one provides a presentation of the
physical fundamentals involved in the technology of artificial and bio-artificial
organs; the second one is devoted to the monographic presentation of the most
important organ support and replacement devices based on mass transfer opera-
tions. More specifically, in the first part, mass transport phenomena are firstly
discussed, from both a local and macroscopic point of view; separation processes
widelyusedinartificialorgans,i.e.,separationbasedontransportthroughselective
membranes and adsorption, are then presented; finally, the fundamentals of
bioreactorengineeringarecovered,focusingontheinteractionbetweenbioreaction
Introduction ix
kineticsandtransportphenomena.Thethreechaptersofthesecondpartaredevoted
todevicesforbloodoxygenation,renalreplacementtherapy,andliversupport.For
each device, a survey of commonly used solutions and the most promising
developments is presented. Mathematical models to assess the performance are
reported as fundamental tools for the quantitative description of clinical devices;
nevertheless,themodelsproposedarekeptsimpletokeepthefocusontheessential
features of each process.
Contents
Part I Fundamentals
1 Diffusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2 A Rigorous Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.3 Diffusivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.4 Local Analysis of Mass Transport Phenomena
and Evaluation of the Concentration Profiles. . . . . . . . . . . . . . . 8
1.5 Diffusion Characteristic Time . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.6 Diffusion and Chemical Reaction. . . . . . . . . . . . . . . . . . . . . . . 11
1.6.1 Diffusion and Reaction in Series . . . . . . . . . . . . . . . . . 12
1.6.2 Diffusion and Reaction in Parallel . . . . . . . . . . . . . . . . 14
1.6.3 Oxygen Transport to Tissue . . . . . . . . . . . . . . . . . . . . 15
1.7 Diffusion and Convection. . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2 Mass Transfer Coefficient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2.2 Definition of Mass Transport Coefficients. . . . . . . . . . . . . . . . . 24
2.3 Evaluation of Mass Transport Coefficient . . . . . . . . . . . . . . . . . 25
2.4 Mass Transfer Between Two Phases. . . . . . . . . . . . . . . . . . . . . 27
3 Membrane Operations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
3.2 Phenomenological Aspects and Definitions . . . . . . . . . . . . . . . . 34
3.2.1 Membrane Types. . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
3.2.2 Membrane Separation Processes. . . . . . . . . . . . . . . . . . 35
3.2.3 Flow Patterns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
3.2.4 Membrane Modules. . . . . . . . . . . . . . . . . . . . . . . . . . 38
3.2.5 Osmosis, Osmotic Pressure,
and Reverse Osmosis. . . . . . . . . . . . . . . . . . . . . . . . . 39
xi