# Vascularization of critical-sized craniomaxillofacial defects

> **NIH NIH R56** · OLD DOMINION UNIVERSITY · 2021 · $58,190

## Abstract

Project Summary
Lack of proper vascularization leads to the ultimate failure in treatment of critical-sized craniomaxillofacial
defects. The large size of the defect obstructs penetration of blood components from the surrounding
environment into the inner parts of the defect, and thus hinders vascularity. In such situations, vascular
endothelial growth factor (VEGF) is the most effective factor that can reestablish the oxygen supply to tissues.
While applying external VEGF is a key means for blood vessel formation in critical-sized defects, its slight
uncontrolled administration is risky and can be tumorigenic. Thus, conventional methods cannot be used for
encapsulation and delivery of VEGF. In this proposal, we will develop a new on-chip method for delivery of VEGF
with precise and sustained release capabilities using a microfluidic platform. Our novel design allows making
monodispersed particles in a highly controllable and reproducible manner, providing us with the ability to fine-
tune the size, microstructure, loading capacity and release rate of particles, in addition to balancing the pH and
maintaining the VEGF bioactivity. Release of VEGF must not be only controlled and sustained, but also highly
localized in the region of the defect as moving the VEGF-loaded particles into unwanted areas is not favorable
and can be risky. Thus, in another strategy, the VEGF-loaded particles will be immobilized onto a new 3D-printed
scaffold specifically designed for critical-sized defects. The design of this novel scaffold (filed for patent) is
inspired by reinforced concrete, in which reinforcing Rebars are embedded in the host material to enhance the
mechanical properties of the scaffold (100-375 times improvement). In other words, it is a hybrid scaffold, made
of two components: 1) Skeleton Rebars: non-porous and slowly-biodegradable constituent undertaking
mechanical necessities of the scaffold, and 2) Host Component: porous and rapidly-biodegradable constituent
undertaking biological necessities of the scaffold. Although the mechanical strength of Rebars is the property
that makes the scaffold appropriate for critical-sized defects, another functionality of the Rebar, which is its slow
degradability (6 months), makes the design a perfect choice for the VEGF delivery purpose. Rebars will provide
us with the opportunity to immobilize VEGF-loaded particles on a solid surface and not let the particles move
elsewhere. The immobilization process itself is a new method developed in our lab that can firmly attach these
particles to the rebars of the scaffolds. The VEGF-loaded scaffold will undergo a detailed in vitro analysis and
release adjustment inside a bioreactor, which can mimic the body condition. The VEGF release profiles will be
adjusted to reach the target value (1.2 ng/ml per day per cm3 of scaffold), and the comprehensive in vitro analyses
will evaluate the osteogenesis and angiogenesis characters of the construct. The optimized VEGF-loaded scaf...

## Key facts

- **NIH application ID:** 11248620
- **Project number:** 7R56DE029191-02
- **Recipient organization:** OLD DOMINION UNIVERSITY
- **Principal Investigator:** Lobat Tayebi
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $58,190
- **Award type:** 7
- **Project period:** 2021-09-02 → 2025-09-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11248620

## Citation

> US National Institutes of Health, RePORTER application 11248620, Vascularization of critical-sized craniomaxillofacial defects (7R56DE029191-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11248620. Licensed CC0.

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