FUTURE OF MICROVASCULAR RESEARCH:​

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FUTURE OF MICROVASCULAR RESEARCH
EXPERIMENTAL AND COMPUTATIONAL ADVANCES
An Academic presentation by Dr. Nancy Agnes,
Head, Technical Operations, Pubrica Group
www.pubrica.com Email sales_at_pubrica.com
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Introduction
The microcirculation is constantly changing as
people grow and adapt, both in health and
sickness, while maintaining tissue health and
homeostasis. Microcirculation is the end point
of the circulatory system, which consists of a
network of microvessels that transport oxygen and
nutrients, meanwhile eliminating waste items from
organ tissues. Microcirculation helps blood
transport and intercellular signaling in response
to local demands, as well as redistributing
hydraulic loads and promoting inflammatory
processes 1. Recent advancements on both
experimental techniques and computational
modeling open new avenues for the understanding
of microvascular physiology and pathology by
developing mathematical modeling. This article
will explore more on emerging trends and
technologies on microvascular functions.
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Background Significance

• Microvascular dysfunction is defined as a
  structural and functional remodeling of the
  microcirculation resulting in disturbance of
  autoregulation of blood flow due either to
  dysfunctional coronary vasodilator capacity or
  increased reactivity to microvascular
  vasoconstriction 2.

• Microvascular dysfunction can result in various
  diseases such as diabetes, hypertension, and
  cardiovascular disorders. Structural as well as
  functional abnormalities in these blood vessels
  result in endothelial dysfunction and
  abnormalities within the myocardium with its
  effects on the intramural microvasculature 2.

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• To address the developing issues related to
  microvascular dysfunction and other microvascular
  complications such as Type 2 Diabetes Mellitus,
  understanding the function of microvascular is
  vital. It helps to develop effective treatment or
  therapeutic strategies. Despite the traditional
  methods such as animal model and histological
  validations, it is essential to discover new
  innovative strategies to overcome limitations in
  these traditional methods 3 4.

• However, some of the latest technological
  innovations, such as advanced imaging techniques,
  microfluidics, and computational modeling, have
  potentially enhanced our understanding related to
  microvascular dynamics. Employing mathematical
  models can accelerate the physiological
  understanding the underlying issues and help in
  finding quantities, which is difficult in
  experimental model 1. Thus, it will be possible
  to use both experimental and computational
  approaches, which will provide a better
  understanding of microvascular dynamics to pave
  the way for innovative therapies and diagnostics.

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Current State of Microvascular Research

• The traditional approaches in the study of
  microvascular function mainly rely on imaging and
  invasive techniques. Unfortunately, such
  techniques usually lack details of microvascular
  dynamics. The use of non-invasive imaging
  techniques, including computed tomography (CT),
  magnetic resonance imaging (MRI), and positron
  emission tomography (PET), has increased
  resolution but cannot be used for widespread
  application because the technical costs of
  acquisition and exposure to radiation are too
  high.

• The study of microvascular function is at a very
  crossroad, since common existing imaging and
  intrusive techniques fail to provide a complete
  dynamic of microvasculature. Non-invasive
  techniques such as CT, MRI, and PET are promising
  but limited by high costs along with radiation
  exposure, making it hard for broad applications.
  Pubrica offers research services encompassing
  advanced data analysis, computational modeling,
  and manuscript support, enabling you to take your
  microvascular research to new heights and
  overcome such challenges.

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Emerging Trends and Technologies
High-Resolution Imaging
Newer imaging techniques such asmultiphoton
microscopy (two-photon microscopy) and optical
coherence tomography (OCT) help the researchers
to visualize microvascular structures and
functions in high precision. OCT provides
detailed retina images that help to detect subtle
changes in retinal thickness and morphology. It
is widely used in clinical practices in detecting
and monitoring DR (diabetic retinopathy) and DME
(diabetic macular edema) 5. On the other hand,
microvascular morphological properties such as
diameter, segment length, and tortuosity can be
extracted using a two-photon microscopic
technique employing a deep-learning algorithm
6. In addition, non-invasive techniques such as
computed tomography (CT), magnetic resonance
imaging (MRI) and positron emission tomography
(PET) are also used in evaluating microvascular
function.
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Microfluidics

• This technique helps to develop more
  physiologically relevant blood vessel models to
  produce continuously perfused, multi-cellular,
  long-term cultures to overcome the limitations of
  2D models. Further, this microfluidic system
  utilizes sub-millimeter-sized channels to
  accurately control extremely small amounts of
  fluid in the order of 10-9 to 10-18 7.
• Further, as an ideal platform, microfluidics
  technology helps in bridging the gap between
  simple, low-cost 2D in vitro models and complex,
  expensive in vivo models 8. It helps in
  developing high-throughput biological modeling of
  microvasculature by reducing the consumption of
  expensive reagents and precious cells.
• In the development of microfluidic systems,
  organ-on-a-chip models are one of the significant
  innovations that replicate the microenvironment
  of the microvasculature, allowing for more
  precise disease modeling and drug testing 9.
  Further, these models have specifically proven
  valuable in investigating complex diseases like
  diabetes and cancer caused by microvascular
  dysfunction.

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3D Bioprinting of Vascular Networks
Improvements in 3D bioprinting technology have
enabled the creation of bioengineered tissues
with intrinsically integrated functional
microvascular networks 9. These technologies
can create innovation in tissue engineering and
regenerative medicine, leading to new ways to
treat cardiovascular disease.
Omics Technologies
Currently, the availability of single-cell RNA
sequencing and multi-omics techniques enables the
researchers to tackle a much greater level of
detail for microvascular heterogeneity. This
allows us to understand how microvascular
function varies by tissue type and disease state
10. Further, the emerging methodologies in
genomic and proteomic analyses provide promising
opportunities for early detection of
microvascular complications in patients with type
2 Diabetes mellitus 11. However, further
research is essential to address challenges, and
refined methodologies can produce effective
results in clinical settings.
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Computational Modeling

• Computer modeling can be a useful adjunct to
  hypothesis testing, making predictions and
  providing quantitative insight into vascular
  regulation dynamics that cannot be accessed
  directly during in vivo experimentation 1.
  Computational modeling helps the researchers to
  investigate the mechanics of the delicate system
  while minimizing using animals in experiments
  9. The research simulates microvascular flow
  dynamics by using advanced computational
  techniques, such as finite element analysis and
  agent-based modeling, to forecast the responses
  such systems would exhibit to pathological
  conditions.

• In a study, Solovyev et al. (2013) defined a
  hybrid model, combining a lumped model for blood
  flow with an agent-based model of skin injury, to
  evaluate the role of blood flow on the
  development of pressure ulcers in spinal-cord
  injury patients 1. Complex constitutive models
  can be used to determine hemodynamic features and
  wall properties of vessel reflecting
  physiological and pathological conditions like
  aging or hypertension. Similarly, blood flow
  variables can be computed using numerical
  analysis techniques such as finite differences,
  finite elements, and finite volumes 1. It can
  be extended to large vessel networks by imposing
  mass and momentum conservation. 

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Machine Learning and AI
The integration of machine learning and
artificial intelligence (AI) into microvascular
research can pave the way for innovation in
predictive modeling. AI helps in analyzing
patterns in large volumes of datasets, which
provide a clear understanding of microvascular
behavior under different physiological conditions.
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Novel Therapeutic Approaches
Therapeutic strategies that are targeted at
microvasculature, such as by using angiogenesis
inhibitors or pro-angiogenic therapies, may open
new horizons in the treatment of diseases
associated with dysfunctional microvascular
function 12. Similarly, the use of
microvascular biomarkers does hold promise for
advancing personalized medicine.
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Future Directions
S.NO Future Direction Scope References
1 Development of Biomimetic Microvascular Models Establish models of human microvascular behaviour using in vitro microfluidic systems. 13
2 Integration of AI in Computational Modeling Utilize machine learning algorithms to predict microvascular responses based on large datasets. Further, integrating nanotechnology and AI into microvascular leads to the development of more sophisticated models capable of predicting microvascular function in real-time. 12
3 Personalised medicine By leveraging computational models and experimental data, researchers can create individualized treatment plans that optimize microvascular function for each patient 1
4 Enhanced Biomarker Discovery Use omics technologies to identify new biomarkers of microvascular dysfunction. Further, developing advanced technologies enable researchers to get clear understanding of microvascular complications. 5
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Conclusion
The emergence of new trends in experimental and
computational approaches is rapidly evolving
towards the understanding of the function of
micro vessels. Combining these methodologies will
make possible to the development of novel
therapies and improvement in the clinical
management of diseases involving dysfunction of
the microvascular system. As this field
progresses, interdisciplinary collaboration will
be useful in unlocking the full potential of
these new technologies.
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References

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