The
broad objective of this Bioengineering Research
Grant is to study biomechanical interactions
of angiogenic microvessels with the extracellular
matrix (ECM) on the microscale level. We will
answer the following questions:
- How does angiogenesis influence global
and local ECM material properties and ultrastructure?
- Is local angiogenic sprouting correlated
with the stress state as predicted by computational
mechanical modeling, MMP expression and
ECM ultrastructure?
- Does mechanical conditioning of vascularized
constructs influence angiogenic sprouting?
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To answer
these questions, we develop and apply
novel experimental and computational
techniques to study a 3D in vitro angiogenesis
model. In the first specific aim, we
develop techniques to simulate the microscale
biomechanical behavior of vascularized
collagen gels using the Material Point
Method (MPM), using volumetric confocal
images as the basis for generating the
geometry of the computational domain.
In Aim 2, methods are developed to
non-destructively measure collagen gel
ultrastructure, microvessel geometry
and emission spectra using spectrofluorimetry
and multiphoton fluorescence microscopy.
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In Aims 3 and 4, these highly novel approaches
are combined with traditional approaches for
experimental measurements of biomechanical
behavior, gene expression and protein expression
to examine the mechanisms that are responsible
for alterations in ECM material properties
during angiogenesis.
Finally, we examine the effects
of mechanical conditioning on microvessel
sprouting and growth. The proposed experiments
will provide an information base on the magnitudes
and frequencies of forces that most influence
the angiogenic vessel. A better understanding
of the relationship between angiogenic vessels,
the surrounding ECM structure, and the mechanics
of the tissue undergoing angiogenesis will
provide the basis for improved control of
tissue vascularization in both native tissues
(e.g., repairing ischemic tissue) and tissue
engineered constructs.
View collagen polymerization
video.
View 3D data stack video.
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