Saturday, August 23, 2025 8/23/2025

Manipulation of Host Tissue to Induce a Hierarchical Microvasculature

Award Number: R01HL167939
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Manipulation of Host Tissue to Induce a Hierarchical Microvasculature - Abstract Reconstructive surgeons are tasked with the restoration of soft tissue loss irrespective of etiology. Over the past two decades, hydrogel scaffolds have become a vital platform for tissue revascularization and surgical repair. However, their slow and random vascularization upon implantation often precipitates failure and precludes true tissue regeneration and function. Native microvascular networks are characterized by organized tree-like branching patterns that originate from large feeding vessels. Our objective is to utilize complementary regenerative strategies based upon rigorous preliminary data that enables the rapid development of this hierarchical microvasculature. To achieve our objective, we recently developed an innovative microsurgical tactic termed vascular micropuncture (MP). In this method, small perforations are created using a needle in the recipient vasculature to facilitate cellular extravasation and angiogenesis, without causing thrombosis or significant hemorrhage. Such induced angiogenesis can be used to randomly vascularize an adjacently placed hydrogel scaffold, leading to perfusion within 24 h and a doubling of neovascularization. With this compelling result, we propose to advance the MP method using an emerging in situ microengineering technology. We have developed granular hydrogel scaffolds (GHS) based on an extracellular matrix mimetic material with controlled microporosity that improves cell infiltration and guides vascular network formation both in vitro and in vivo. Our hypothesis is that customized GHS can be synergistically used with MP to hasten and precisely guide hierarchical microvascular development. To test this hypothesis, we will focus on the following three independent specific aims: 1) To design and optimize GHS to guide microvascular development, 2) To evaluate the effect of MP characteristics to hasten microvascular development and 3) To evaluate the coupling effects of MP and GHS to hasten and precisely guide hierarchical microvascular development. The successful completion of these studies should markedly improve the vascularization of scaffolds used in soft tissue reconstructive surgery. Also, it sets the platform for further investigation in building a hierarchical microvasculature that is cornerstone to blood flow regulation, oxygen diffusion, and immune cell modulation. Consequently, our novel approach holds immense potential for broadly advancing regenerative medicine.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $760,025 )
2025	2025	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Cardiovascular Diseases Research	002	3	8/15/2025	NON-COMPETING CONTINUATION	$755,271
2025	2024	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Cardiovascular Diseases Research	001	2	6/4/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Cardiovascular Diseases Research	000	2	6/4/2025	SUPPLEMENT FOR EXPANSION	$4,754
														Subtotal = $760,025

Issue Date FY: 2024 ( Subtotal = $932,422 )
2024	2024	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Cardiovascular Diseases Research	001	2	5/15/2024	SUPPLEMENT FOR EXPANSION	$78,750
2024	2024	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Cardiovascular Diseases Research	000	2	4/27/2024	NON-COMPETING CONTINUATION	$703,351
2024	2024	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Cardiovascular Diseases Research	003	2	9/18/2024	SUPPLEMENT FOR EXPANSION	$87,800
2024	2024	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Cardiovascular Diseases Research	002	2	6/19/2024	NON-COMPETING CONTINUATION	$62,521
														Subtotal = $932,422

Issue Date FY: 2023 ( Subtotal = $857,943 )
2023	2023	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Cardiovascular Diseases Research	000	1	4/30/2023	NEW	$800,971
2023	2023	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Cardiovascular Diseases Research	001	1	9/19/2023	SUPPLEMENT FOR EXPANSION	$56,972
														Subtotal = $857,943

Grand Total All Awards = $2,550,390

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Manipulation of Host Tissue to Induce a Hierarchical Microvasculature

Award Number: R01HL167939

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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