# Mechanisms and Application of Micropunctured Induced Angiogenesis for the Rapid Perfusion of Intraoperative Bioprinted Flaps

> **NIH NIH R56** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2021 · $693,843

## Abstract

PROJECT SUMMARY/ABSTRACT
Advances have allowed for the in vitro creation of thin vascularized replacement grafts but lack of a continuous
and anastomosable vasculature limits translation and scale-up of size. There is little knowledge about the utility
of surgical approaches in facilitating prompt inosculation of implanted engineered tissues. Our long-term goal
is to develop surgical strategies which augment the vascular integration of thick engineered flaps; which would
offer more clinical relevance. The objective of this proposal is to define the mechanisms and impact of a
coordinated surgical and additive manufacturing approach for the rapid vascularization of an engineered adipose
flap, which would be applicable for soft tissue reconstruction. We have developed an innovative microsurgical
tactic, termed “vascular micropuncture”, which increases the angiogenic capabilities of the rat recipient
vasculature in order to quickly perfuse an adjacently placed un-anastomosable thin engineered graft. This results
in graft perfusion within 24 hours and a doubling of neovascularization. If combined with standard vascular
interposition conduits (e.g. saphenous vein), which can be used to lengthen the recipient pedicle, it offers an
easily translatable approach for thick flap engineering. Our central hypothesis is that vascular micropuncture
and lengthening of the recipient vasculature can enable direct inosculation and rapid perfusion of a thick adipose
flap that is intraoperatively bioprinted with adipocyte/endothelial progenitor cell spheroids. The rationale is that
completion of these studies will reveal how to best optimize complementary tactics for the inosculation of
concurrently engineered in situ flaps. Our central hypothesis will be tested by three specific aims: 1) Demonstrate
that micropuncture induces angiogenesis by allowing for immediate monocyte/macrophage extravasation; 2)
High-throughput bioprinting and in vitro testing of a hypoxia-resistant vascularized adipose graft; 3) Coordinated
in situ thick flap generation and surgically induced rapid perfusion. We will pursue these aims using novel
combinatorial techniques from both the surgical and engineering sciences, including recently developed
microsurgical and aspiration assisted bioprinting approaches. This proposed research is significant because it
will integrate these advances to intraoperatively assemble and rapidly perfuse a thick engineered flap; a
noteworthy advance from the often-described thin engineered graft. The expected outcome is that mechanisms
of micropunctured induced angiogenesis will be identified and experimental techniques for augmenting
engineered tissue inosculation will be determined. These results will have a positive impact by laying the
foundation in developing new and translatable reconstructive approaches for large volume soft tissue loss.

## Key facts

- **NIH application ID:** 10179655
- **Project number:** 1R56HL157190-01
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** DINO J RAVNIC
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $693,843
- **Award type:** 1
- **Project period:** 2021-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179655

## Citation

> US National Institutes of Health, RePORTER application 10179655, Mechanisms and Application of Micropunctured Induced Angiogenesis for the Rapid Perfusion of Intraoperative Bioprinted Flaps (1R56HL157190-01). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10179655. Licensed CC0.

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