Project Details
Description
Abstract
This research is significant as it will facilitate a new generation of regenerative scaffolds. Voluminous soft tissue
loss is often encountered after injury, and reconstructive procedures are suboptimal. Over the past two decades,
collagen-based scaffolds have become vital to surgeons by providing a platform for tissue revascularization and
reconstruction. However, their slow random vascularization upon implantation often leads to failure and prevents
true recapitulation of native tissue vascular hierarchy. Thus, scaffolds which could rapidly guide microvascular
development would be exceedingly relevant to replacing ‘like tissue with like tissue’, a hallmark of reconstructive
surgery. This proposal’s objective is to develop a coordinated engineering-surgical approach for rapid and
guided scaffold vascularization. We have developed a novel microsurgical tactic, termed vascular
“micropuncture” (MP), which increases the angiogenic capabilities of the rat recipient macrovasculature to
quickly vascularize an adjacently placed bulk scaffold. We believe the resulting capillary outgrowth is induced by
the instantaneous extravasation of immune cells, especially macrophages. While this partially expedites
vascularization in an adjacently placed bulk collagen scaffold, the resulting neo-microvasculature has a random
pattern. Currently used bulk scaffolds have nanoscale pores that are orders of magnitude smaller than cell size
and lack interconnectivity. This does not permit for rapid and guided cell infiltration; hence vascularization is slow
and random. To address this, we have pioneered the development of in situ forming extracellular matrix (ECM)-
mimetic granular scaffolds with customizable microarchitectures and cell permeating capabilities. Our preliminary
data suggests that our microporous granular scaffolds are well suited to guide MP-induced vascularization. Our
central hypothesis is that customized microporous granular scaffolds can be used alongside MP to enhance
and guide vascularization. The rationale is that completion of these studies will reveal how to best optimize
complementary tactics for the multifaceted problem of guided engineered tissue vascularization. Our central
hypothesis will be tested by three specific aims: 1) To develop ECM-mimetic in situ forming microporous granular
hydrogel scaffolds that regulate cellular activities pertinent to accelerating angiogenesis in vitro and in vivo; 2)
Controlling scaffold vascularization by varying recipient MP interval and diameter; and 3) Controlling macrophage
infiltration and vascular architecture by scaffold design. We will pursue these aims using innovative
combinatorial techniques from both the surgical and engineering sciences. The expected outcome is a rapidly
vascularized scaffold having a controllable microvascular hierarchy while also creating experimental techniques
at the engineering-microsurgery interface. These results will have a positive impact by laying the foundation in
developing new and translatable reconstructive approaches for large volume tissue loss.
Status | Finished |
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Effective start/end date | 9/16/22 → 9/15/23 |
Funding
- National Institute of Biomedical Imaging and Bioengineering: $801,134.00
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