# Environmentally-responsive, dual-stage microparticle drug depots with healing-driven growth factor delivery for craniofacial bone regeneration

> **NIH NIH R21** · UNIVERSITY OF CINCINNATI · 2022 · $194,993

## Abstract

Craniofacial surgeries and autologous bone grafts are often required to address congenital birth defects and
traumatic injuries to the face and jaw. Local delivery of osteogenic protein growth factors, particularly bone
morphogenetic protein-2 (BMP2), has been shown to promote healing in these injuries. Bone defect treatment
with pro-angiogenic therapies such as vascular endothelial growth factor (VEGF) also improves healing through
improved tissue vascularization; compellingly, emerging evidence indicates that sequential delivery of pro-
angiogenic and pro-osteogenic therapies promotes even more pronounced bone development than sole
administration of either drug. Despite years of effort developing biomaterial systems as localized growth factor
delivery depots for bone regeneration, many of these technologies still fail to completely regenerate orthopedic
tissue primarily due to poor drug pharmacokinetics and premature therapeutic release. It is hypothesized that
directly matching drug delivery kinetics with the rate of tissue growth will significantly improve bone
regeneration in craniofacial defects. Cell-produced signals, particularly reactive oxygen species (ROS), can
be leveraged to produce selective, “healing-responsive” drug release from activatable biomaterial systems.
This proposed work seeks to develop injectable drug carriers that will mediate sequential, localized release of
VEGF and BMP2 upon triggering by cell-generated oxidation during bone regeneration. These responsive
delivery vehicles will be created using ROS-degradable microparticles coated with ROS-degradable layer-by-
layer (LbL) films, thereby combining the strengths of two controlled release technologies (injectable antioxidant
particles, responsive surface coatings) into a single drug delivery platform. The project’s first aim will optimize
these coated microparticles for dual-stage protein release and potent bioactivity upon oxidative triggering, while
the second aim will evaluate VEGF/BMP2-loaded LbL microparticles for in vivo drug release kinetics and bone
regeneration in critically-sized rat skull defects. We anticipate that the ROS-responsive, dually-loaded particles
will promote more robust bone repair than single-drug formulations or conventional, non-responsive microparticle
analogues. In short, the proposal brings together a highly-qualified research team to achieve the overall project
goal of developing and validating a clinically-translatable approach for controlled, on-demand delivery of
regenerative growth factors to foster robust craniofacial bone regeneration.

## Key facts

- **NIH application ID:** 10527614
- **Project number:** 1R21DE031391-01A1
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** John Robert Martin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $194,993
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527614

## Citation

> US National Institutes of Health, RePORTER application 10527614, Environmentally-responsive, dual-stage microparticle drug depots with healing-driven growth factor delivery for craniofacial bone regeneration (1R21DE031391-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10527614. Licensed CC0.

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