Introduction: Search for
alternatives in the health area, new technologies and concepts help to set up
dimensions of the clinical situation, and priorities for investigation. The
field of tissue engineering substitutes aims to mimic the extracellular matrix
structurally and physiologically to replace or improve functions of the failing
organ.
Objective: Provide a brief
summary of the current achievements of technology in organ transplantation.
Method: This is a
narrative review based on sources of primary and secondary evidence from a
bibliographic survey.
Results: In clinical
practice, various strategies are available or developed from advantages and
disadvantages techniques.
Conclusion: Similar to
native tissues, sophisticated biomaterial designs are making compliance simpler
in a dynamic system, aiming a personalized way.
Keywords: Prostheses and
implants, Biomedical technology, Bioartificial organs, Biocompatible materials
INTRODUCTION
According to the World Health Organization (WHO)’s
definition, “health is a state of complete physical, mental and social
well-being and not merely the absence of disease or infirmity” [1]. It
emphasizes the need for governmental agencies to elaborate on public health
policies that responsibility to care about the welfare aspects [1,2]. Based on
the foregoing analysis, the worldwide confronted with a shift resulting from
globalization and challenges of a new knowledge-driven economy; cultural and
community life; religion; morbidity and mortality due to the high prevalence of
co-morbidities in a permanently evolving process of society [1-3].
In 2016 the average life expectancy at birth of
the global population was 72.0 years [4,5]. Currently, quality of life is an
important concern and it will dictate how these people will achieve the
‘elderly’ [6,7]. Reiterating that the organism has a limit to regenerate
itself, loss of functionality through pathological changes or trauma reflects
upon high-cost therapy and the population dependence on health services [8-10].
An example is organ transplantation, indicated to diseases sometimes refractory
to treatment, which impacts the patients’ routine and requires constant changes
in their daily life. Nevertheless, the shortage of donors for transplantation
therapy is a serious worldwide issue and the number of patients on waiting
lists increases [11-14].
The Brazilian Association of Organ Transplants
(ABTO), a civil non-profit entity, shows that donation's rate practically
stagnated (decrease of 0.6%) compared to the first semester in 2018 [12].
Moreover, some situations that are characterized by key limitations like cold
ischemia time and pre-existing physical conditions may affect the survival of
the transplanted organ [15].
Considering the biochemical and cellular phenomena
to restore the body integrity in a dynamic system [8,16,17]; inter and
multidisciplinary intervention correlates the scientific and technological
environment by bioengineers supplying cell products that should face a
personalized medicine [18-20].
One might hope by several strategies now available
to be used for replacing or improve failing organs function (biodegradable or
bioresorbable substrate) with specific physical characteristics according to
clinical demand [18,20-26]. Attachment cells, growth, proliferation and
differentiation in modifiable surface materials by functional reactions
establish the bioactivity [22-24,26].
Others biotechnological
tools to fabricate donor tissue or organs are being developed or tested for
approval (e.g. tissue-engineered substitutes; molecular diagnosis; genomics, etc.) [21,27-31]. Once, mechanical
properties closer to those of natural, as well as attractive
cost-effectiveness, safer products, restriction of animal experiments and
effective drugs for research are desired [20,24,29,32-34].
Motivated by these considerations, in this
narrative review we will provide a brief summary of current achievements in the
field of organ transplantation technology, establishing the dimension and
priorities for investigation.
METHOD
This is a narrative review that was based on
primary and secondary evidence sources from bibliographic surveys. As Cochrane
Library; Web of Science; MEDLINE from the National Library of Medicine of the
United States of America via PubMed; databases of Latin American and Caribbean
Literature in Health Sciences (Lilacs); SciVerse Scopus and Scientific
Electronic Library Online (Scielo) by the Portal of Bases in Health Sciences
(VHL).
The Health Sciences Descriptors (DeCS) used in
English were: Prostheses and Implants; Biomedical Technology; Bioartificial
Organs; Biocompatible Materials. The Boolean Operator “AND” was used. Articles
with relevant and current rationale available in full were established as
inclusion criteria. Duplicated articles (more than one database searched) and
those that did not contemplate the subject matters were excluded.
RESULTS/DISCUSSION
Importance
of the microenvironment
Difficulty in technical skill, ethical questions,
and financing constraints still needed to be overcome [21,31,35,36]. To
identify ways to simplify clinical practice through, effective and resolute
care, has motivating scientists to achieve functionality model in a highly
dynamic entity over the years [9].
The extracellular matrix (ECM) composed by
multi-component structural elements (e.g. collagens, laminins, entactin,
glycoproteins, elastic fibers, etc.), provide mechanical support to the
resident cells, stability, a shape of tissues besides participating in their
performance (tissue development, turnover and regeneration) [8].
Herewith, the homeostasis requires constant
physical and chemical adaptations from cells residing in living systems [8].
And understanding human physiology as the components, structures and their
interactions influence the environment’s manufacture [8,26,32,37].
To advance knowledge of sophisticated
laboratory-grown, three-dimensional (3D) cultures with specific micro
architectural features become a viable alternative to improve the interaction
of adhered cells from different transplant techniques [20,27,32,38-41].
The scaffold constitutes in controlled
morphologies of interconnected pore networks construction at various scales
(nano, micro and macro) and different distribution, which affects the final
application at post-injury to physical integrity [32].
Aiming to functional performance to handle the
tackle of practical failures such as inadequate vascularization, it is
important to select the most suitable material for the guide’s supporting
substructure. If so, those variables need to be identified in the scaffold
because they impact on mechanical properties during cell invasion and remodeling
expressed in vitro [42-45].
Tissue
engineered
There are valuable tools in tissue restoration for
patient survival: I) allografts, also known as allogenic, homologous grafts or
homografts; II) xenografts, heterografts or xenogenic grafts; and III) alloplastic
grafts or synthetic grafts [20]. Regardless of the case, immunosuppressant
medications are needed, even with their side effects [46].
Concerning item III, biomaterials have their
compositions explored to act cooperatively or synergistically to the organism
[19,20,26]. Confirming the growth of some products in the public and private
health care organizations, which were approved by Food and Drug Administration
(FDA) [10,23,47-49].
These biomaterials are defined as “a substance
that is able, or has been engineered, to take a form which, alone or as part of
a complex system, is used to direct, by control of interactions with components
of living systems, the course of any therapeutic or diagnostic procedure, in
human or veterinary medicine” [19]. However, thus with biological evaluation
through material-tissue tests interaction in risk management established by the
International Organization for Standardization of the Manufacture of Medical
Devices [23], the immune response is one of the determinants of rejection [46].
Research endeavors make worldwide progress with an
ingenious structural project that can include many substances and applications
in different forms (foams, fibers, membranes, hydrocolloids, and hydrogels) for
better settings [27]. Several biomaterials are used with a concept of
organotypic models to acquire bottom-up or top-down approaches [30,50,51]. Some
of them are discussed below.
Cells: The mergers of
omics technologies in vitro
engineered substitutes establish models for research and applications around
the world [52,53]. Understanding the multipotent stem cell and its biology
behavior, allow us to evolve a noninvasive and accurate method of diagnosis or
therapy [54].
Furthermore, the stem cells can proliferate
themselves for many generations and differentiating into multi-lineage cells.
Readily being used, induced pluripotent stem cells (iPS cells or iPSCs) are
reprogrammed from adult cells to create living neo-tissues in vitro as a strategy to reproduce biological function [55-57].
Another possibility is mesenchymal stem cells
(MSCs) that can differentiate into a variety of cell types. Moreover, the
multilineage potential, immunomodulation by express cell surface markers, and
anti-inflammatory molecules make it an interesting tool in chronic diseases and
clinical trials [54,56,57].
In addition, soft-tissue grafts have shown
improvement in clinical outcomes. Abundant adipose tissue-derived stem cells
(ADSCs) sources as a form of cell-based therapy are still discussed in
regenerative medicine and became a topic of growing interesting [58,59].
Scaffold: Temporary to
permanent substitutes materials with different characteristics allow for a
diversified design [20]. It may consist of natural microstructures (e.g.
polysaccharides: chitosan, alginate, cellulose and others; proteins: collagen,
gelatin, fibrin and others), polymers (e.g. Polyglycolide (PGA) and its
compounds, Polycaprolactone (PCL), Polylactide (PLA) and others) or hybrid
approaches [29,43,55,60,61].
The Amniotic Membrane (AM) is a great potential
for grafting material [20]. Either directly or following decellularized ECM
scaffolds [62], they are used for the treatment of corneal defects, diabetic
foot ulcers, severe skin burns and specialties of periodontics and implant surgery
[20,63,64].
Another therapeutic possibility is porcine small
intestinal submucosa (SIS). This material consists of about 90% collagen,
exhibits growth factors and adhesion peptide sequences. Considering an
important component of the epithelial basement membrane that facilitates
integration with tissue [20,65,66].
Techniques: Structuring an
integrated and functional graft by association materials, tailored surface,
predictable performance for optimizing properties in their final applications
makes futuristic technologies even closer to reality [21,32,67,68].
The bioreactor provides strategies for cell
seeding of scaffolds [67,69,70] and based on the advantages and disadvantages
of the various techniques applied, we have some examples:
·
Fiber-Assisted Molding (FAM): It establishes a method to fabricate microgrooves and study cells in
complex helical and curved structures (e.g. intestine, esophagus, and heart),
creating unconventional geometric volumes, which are assembled and remodeled
during growth [71].
·
Rotary Jet-Spinning: By building anisotropic arrays, presenting as advantages reduced
commercial cost, high rate of production, and uniaxially aligned nanofiber
structures for polymers allow a contributor to fiber formation and its
application in tissue engineering [72,73].
·
Bioprinting: Recently,
‘time’ is integrated at the evolution of 3D to 4D for complex bioconstructs.
One of the possibilities is through ‘smart materials’ in a dynamic system
whereas the external stimuli can change their reshape and function. And others
by improving the bio-ink that is manufactured layer-by-layer in a static and
inanimate situation, limited by the diameter of the syringe needle and by some
polymers of liquid character. Some biomedical applications are transplantation and
drug screening [74-77].
Nanotechnology: With nano and
micro particles, multiple functions became possible [78].
·
Prevention: To
understand the patient-specific basis of disease, the varied practical
applications stimulate access to before inaccessible areas. Some
characteristics have been observed at the nanoscale like anisotropic
properties, concentration polarization, charge exclusion, and streaming current
phenomena which are exploring and can contribute in a positive form [78,79].
·
Diagnosis: Some nanoparticles
can serve as imaging agents due to their features contrast. Such as
nanoparticles with metallic components used as a biosensor, assisting in image
diagnosis and improving the clinical practices [78,79].
·
Treat diseases: Through
targeted drug delivery systems (TTDS) make compliance simpler and can
considerably improve therapeutic efficacy with more controlled side effects by
harnessing various routes of administration. For example, nanorobots that have
the ability to manipulate environments and biological matter [39]. Enable a
treatment for cancer, the performance of vitreoretinal microsurgery at ocular
sites or on-demand release of specific chemokines at sites of injury [78,79].
Moreover, a nano-fluidic system like biochip is capable of replicating
functions of organs from biomarkers with a combination of bioactive agents
carrying microparticles [51,80]. And nano-membranes in a sustained delivery
system (e.g. alkaloids, flavonoids, essential oils and so on), incorporation of
nanosizing with the medicinal plants or into nanostructures that can optimize
wound management [78,79,81].
In tissue engineering, nanomaterials are able to
enhance cell growth and function. A nanocomposite polymer can include bioactive
properties for better results in transplant therapies [30,79].
TRENDS
IN MODERN BIOLOGY
Exceeding the requirements of biocompatibility
issues and highlights regenerative and restorative concept of compositional and
functional structure, biomimicry, a term in biomaterials science that recently gained
traction, can be defined as “new science that studies nature’s models and then
imitates or takes inspiration from these designs and processes to solve human
problems” [82,83].
In an artificial niche inspired by tissue-specific
niches, it attempts to provide a high-performance material [51,83,84]. Based on
the fact that requires complex design, a multi-layer scaffold bioinspired
approach is the alternative most promising guided regeneration [27,85].
CONCLUSION
The aim of maintaining, enhance or restore tissues
and organs into the dynamic landscape – that represents tissue physiology –
through advances in synthetic technology and biological science by structural,
chemical and physical insights, will yield functional biomaterial designs in
the near future upon medical application.
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