# Development of affinity-based delivery systems for angiogenic growth factors

> **NIH NIH F31** · UNIVERSITY OF OREGON · 2024 · $48,366

## Abstract

PROJECT SUMMARY
Angiogenesis is a coordinated regenerative process during which the temporally regulated presentation of many
signaling proteins stimulates cellular recruitment, patterning, and morphogenesis. Disruptions in this healing
cascade from chronic diseased tissues or severe injuries can easily impair the natural sequence of protein
presentation, resulting in poor healing outcomes and further propagation of diseased states. The long-term
objective of this research is to develop tunable multi-protein delivery systems capable of phased therapeutic
angiogenic protein delivery to reconstitute and enhance angiogenesis. To achieve this objective, this work will
integrate specific reversible affinity-based interactions between small protein domains called affibodies and
therapeutic angiogenic proteins to temporally regulate multi-protein delivery from hydrogel. Building from the well
characterized roles of vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF2), and platelet
derived growth factor (PDGF) in stimulating the angiogenic cascade, we will sequentially deliver these three
growth factors from this controlled delivery platform. We expect this approach will more accurately recapitulate
the natural, staggered presentation of growth factors seen during natural angiogenic healing responses,
providing the necessary stimuli to enhance the regeneration of healthy mature vasculature. This research will
target two major knowledge gaps: 1) How do affinity-based delivery systems modulate the delivery and bioactivity
of VEGF, FGF-2, and PDGF when released from hydrogels? 2) How is the sequential presentation of VEGF,
FGF-2, and PDGF implicated in mediating angiogenesis? Facilitating this research, we have applied directed
evolution and computational protein design approaches to develop affibodies with high specificity and a broad
range of affinity strengths towards VEGF, FGF-2, and PDGF. Focusing on the implementation of these affibodies
within a hydrogel network, my overarching hypothesis is that temporally regulated sequential delivery of VEGF,
FGF-2, and PDGF will reconstitute the angiogenic cascade. I will test this hypothesis through two specific aims:
1) Develop hydrogels that sequentially release VEGF, FGF-2, and PDGF, 2) Probe how the sequence of VEGF,
FGF-2, and PDGF presentation mediates angiogenesis. Ultimately, we expect to achieve tunable sequential
controlled release of multiple therapeutically relevant angiogenic growth factors from the same delivery vehicle.
Overall, this work will expand our understanding of applying affinity-based protein-protein interactions in hydrogel
as temporally regulated controlled release systems. Moreover, this work will provide new therapeutic approaches
for stimulating revascularization of wounded or diseased tissues.

## Key facts

- **NIH application ID:** 10999212
- **Project number:** 1F31HL176164-01
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** Justin E Svendsen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,366
- **Award type:** 1
- **Project period:** 2024-08-20 → 2027-08-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10999212

## Citation

> US National Institutes of Health, RePORTER application 10999212, Development of affinity-based delivery systems for angiogenic growth factors (1F31HL176164-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10999212. Licensed CC0.

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