# Engineered osteogenic growth factors for targeted stimulation of bone regeneration

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2022 · $197,277

## Abstract

PROJECT SUMMARY
Bone is one of the most commonly transplanted human tissues, second only to blood. Each year, there are over
2 million bone graft procedures performed worldwide, with an estimated financial burden of $5 billion. The
demand for bone transplants greatly outstrips the supply of available tissue, and the gap continues to widen due
to factors such as rising obesity rates and increasing life expectancy. Stem cell-based bone tissue engineering
scaffolds have emerged as a promising and sustainable alternative to natural bone grafts, but clinical
advancement of this approach has been limited. A major translational barrier for bone tissue engineering has
been poor osteogenic induction and vascularization. This limitation can be addressed through the delivery of
growth factors, which provide critical biochemical cues that support regeneration. However, growth factor
administration is complicated by the pleiotropic effects of these molecules, which hinder efficacy and can lead to
harmful toxicities or development of conditions such as cancer, vascular diseases, and fibrotic disorders.
We propose to overcome the challenges associated with growth factor administration by developing a novel
system for targeted protein delivery that will enable safe and effective incorporation of growth factors into bone
tissue engineering platforms. Leveraging innovative strategies in molecular engineering, we will re-design a
homodimeric pro-osteogenic and pro-angiogenic growth factor ligand/receptor pair to exclusively interact with
one another and not with any other proteins in the body. This “orthogonal” growth factor ligand/receptor pair will
be biophysically characterized and functionally validated in 2D and 3D human stem cell models to demonstrate
potent and specific delivery of pro-regenerative signals to engineered cells. We will subsequently evaluate the
therapeutic potential for our engineered orthogonal growth factor ligand/receptor pair in craniofacial bone repair
by systemically administering the orthogonal ligand concurrently with implantation of orthogonal receptor-
expressing stem cells embedded in a biomaterial scaffold into a critical-size mouse calvarial defect model.
Successful completion of the impactful objectives laid out in our proposal will represent a tremendous advance
in the field of molecular therapeutic design that will have resounding effects throughout the regenerative
engineering space. In addition to the important translational implications for our work in the development of next
generation bone repair platforms, our versatile approach can be readily extended to other growth factor systems
as well as a vast array of other ligand/receptor interactions for a broad scope of medical applications. Our
interdisciplinary team of experts in protein engineering, computational design, bone tissue regeneration, and
preclinical stem cell therapy models is uniquely poised to pioneer a new design paradigm for developing targeted
growth facto...

## Key facts

- **NIH application ID:** 10459814
- **Project number:** 1R21DE031436-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Warren L Grayson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $197,277
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459814

## Citation

> US National Institutes of Health, RePORTER application 10459814, Engineered osteogenic growth factors for targeted stimulation of bone regeneration (1R21DE031436-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10459814. Licensed CC0.

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