# Multivalent Presentation of Growth Factors Regulates Cellular Responses

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $324,009

## Abstract

Millions of Americans and people worldwide suffer bone diseases due to injuries, bone defects,
and spinal defects, and therefore are in great need of effective treatments to regenerate bone
and promote bone growth. Among treatments being explored in modern medicine,
administration of growth factors that prompt our own body to regrow bone represents an
attractive direction due to its non-invasiveness and utilization of our own cells, including bone-
forming stem cells. Such treatment with bone growth factors has been approved by the FDA
and is successfully used in clinics, however a recognized drawback of this treatment is that the
administration of extremely high doses of very pure growth factor inevitably causes severe side
effects in some patients. Our team believes current high doses are not necessary, with better
tactics to present growth factors to cells, e.g. 5 growth factors bound together as a well-defined
cluster versus 1000 individual growth factor molecules swimming around the cells. With this
research, we hope to develop more effective ways to present growth factors than the current
approach of injecting high dosage. Our approach is inspired by the way nature itself
‘administers’ these growth factors, which is always in combination with other proteins that
provide the necessary context and help fine-tune cellular responses. This proposal builds on
our discovery that COMP, a protein originally isolated from cartilage, can bind to multiple bone
growth factors all at once. We plan to study how the COMP binds to growth factors, how many
growth factors each COMP can carry (1 to 10), and which of the situations work best towards
bone regeneration. We believe our results shall demonstrate that this multi-valent binding
provides a new platform to present the growth factors to stem cells, to which cells respond with
dramatically enhanced activities including robust bone formation and growth. The results from
this investigation shall greatly enhance our current understanding of how bone growth factors
regulate bone formation at the cellular level, and bring us a giant step closer to non-invasive and
stem cell based therapy for bone regeneration.

## Key facts

- **NIH application ID:** 10173645
- **Project number:** 5R01AR070239-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Dominik R Haudenschild
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $324,009
- **Award type:** 5
- **Project period:** 2017-04-10 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10173645

## Citation

> US National Institutes of Health, RePORTER application 10173645, Multivalent Presentation of Growth Factors Regulates Cellular Responses (5R01AR070239-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10173645. Licensed CC0.

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