# Chitosan Guided Bone Regeneration Membranes for Dual Local Delivery of Simvastatin and Raspberry Ketone

> **NIH NIH R01** · UNIVERSITY OF MEMPHIS · 2020 · $439,015

## Abstract

We propose newly developed electrospun chitosan guided bone regeneration (GBR) membranes for
local delivery of simvastatin (SMV), an alternative to BMP-2, and raspberry ketone (RK), an anti-
inflammatory/pro-healing agent, as a novel adjunctive therapy to heal grafted dental/craniomaxillofacial
defects. GBR membranes are widely used in dental/craniomaxillofacial applications to protect bone
grafted spaces from invasion by soft tissues and by providing an osteogenic environment for enhancing
bone regeneration. Our chitosan GBR membranes overcome limitations of current GBR membranes by
providing predictable degradation, and biomimetic nanofiber structure with an interconnected porosity
that that is cell occlusive but allows exchange of fluids and signals between healing bone and epithelial
compartments. The nanofiber structure also provides high surface area that is advantageous for drug
loading and delivery. Our goal is to synergize our chitosan GBR membranes with local delivery of
RK and SMV, to create novel bioactive GBR membranes that promote healing by stimulating the
transition of the macrophage phenotype from pro-inflammation to pro-healing and promoting
osteogenesis that significantly augments healing of grafted dental/craniomaxillofacial defects,
especially large traumatic defects. Innovation of this work arises from our unique strategies that
stabilize nanofiber structure of the electrospun chitosan and in the local delivery of SMV, an economical
alternative to BMP-2 for stimulating bone formation, and the novel RK compound, to provide anti-
inflammatory/pro-healing characteristics. Delivery of these agents from our GBR membranes will result
in adjunctive implants that afford surgeons flexibility in choice of graft materials to be used with the
GBR membrane in accordance with graft availability, clinician and patient factors, and may serve as a
platform for overcoming inflammation and stimulating healing in other tissue engineering applications.
In this work we will first, investigate individual delivery of RK (aim 1) and SMV (aim 2) from membranes,
and effects on macrophage phenotype and osteogenesis in vitro and in rat calvarial models. We will
then (aim 3) investigate dual release for synergistic/antagonistic effects on cells and healing of grafted
site as compared to commercial GBR membrane in rat models. Finally (aim 4) the dual loaded bioactive
chitosan GBR membranes will be investigated in a pre-clinical porcine model as compared to
commercial devices. This work will have a large impact in augmenting dental/craniomaxillofacial bone
regeneration especially in challenging traumatic bone injuries and lead to improved restoration of facial
esthetics and subsequent dental/craniofacial implant therapies. These membranes may also find
application in augmenting treatments in challenging large segmental orthopedic defects

## Key facts

- **NIH application ID:** 9892879
- **Project number:** 5R01DE026759-04
- **Recipient organization:** UNIVERSITY OF MEMPHIS
- **Principal Investigator:** JOEL D BUMGARDNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $439,015
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892879

## Citation

> US National Institutes of Health, RePORTER application 9892879, Chitosan Guided Bone Regeneration Membranes for Dual Local Delivery of Simvastatin and Raspberry Ketone (5R01DE026759-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9892879. Licensed CC0.

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