# Endothelial cell specification at the osteogenic and angiogenic interface in cranial bone tissue engineering

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $551,455

## Abstract

Abstract
Repair and reconstruction of bone loss due to tumor resection, trauma and infection remains a significant
clinical challenge. Worldwide, autografts or allografts are used in approximately 3 million orthopaedic
procedures annually, of which 6% are craniomaxillofacial in nature. Bone tissue engineering has been hailed
as the ultimate solution for replacing bone autograft in repair of bone defects. However, the long-term success
of bone tissue engineering is impeded by inadequate vascularization of the engineered construct. The current
lack of progress in vascularization of tissue engineered scaffold is attributed to our incomplete understanding
of angiogenesis and vascular beds in bone repair and regeneration. A functional blood vessel network consists
of arteries, veins and a capillary interface that connects arterial and venous microvessels for proper vascular
perfusion. While the specification of arterial and venous endothelium has been well studied during early
embryonic development, the postnatal regulation of arterial and venous expansion and specification at capillary
level during repair and regeneration is poorly understood. A series of recent studies have suggested that
hypoxia affects the endothelial cell (EC) specification at the osteogenic and angiogenic interface in
development and aging. Genetic manipulation of the hypoxia inducible factor 1 (HIF-1) pathway markedly
affects the formation of specific subsets of capillary vessels, termed Type H (CD31highEmcnhigh) vessels that
couple to OSX+ osteoblasts at the long bone metaphysis. To gain a better understanding of the critical role of
hypoxia at the osteogenic and angiogenic interface in repair and regeneration, we established a series of novel
imaging approaches that permit high resolution, quantitative, and functional analyses of capillary vessels that
couple to Col (I) 2.3 GFP+ osteoblasts at a cranial bone defect site. Utilizing these novel imaging approaches in
a layer-by-layer enabled, nanofiber-mediated cranial defect repair model, we demonstrate that osteogenesis-
dependent angiogenesis consists of morphologically and functionally distinct CD31+Emcn+ and CD31+Emcn-
vessels. Examination of blood vessel type distribution and bone regeneration demonstrates differential
angiogenic responses and contrasting distributions of CD31+Emcn+ and CD31+Emcn- vessels associated with
Col I (2.3) GFP+ osteoblasts, new bone and non-bone forming tissue, suggesting that EC specification at the
capillary level is a key component of osteogenesis-dependent angiogenesis in bone repair and regeneration.
Based on these findings, we propose to examine the effects of hypoxia on EC specification and the impact of
dysregulation of EC specification on bone formation during cranial defect repair and regeneration. Three
complementary Aims will combine imaging, genetic and engineering approaches to defining the osteogenesis-
dependent EC specification and the role of hypoxia in repair and regeneration. ...

## Key facts

- **NIH application ID:** 10028453
- **Project number:** 1R01DE029790-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** XINPING ZHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $551,455
- **Award type:** 1
- **Project period:** 2020-09-03 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10028453

## Citation

> US National Institutes of Health, RePORTER application 10028453, Endothelial cell specification at the osteogenic and angiogenic interface in cranial bone tissue engineering (1R01DE029790-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10028453. Licensed CC0.

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