# Environmentally-responsive, layer-by-layer coatings for the on-demand delivery of therapeutic growth factors and antibiotics to repair craniomaxillofacial bone defects

> **NIH NIH F32** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $14,838

## Abstract

Craniomaxillofacial (CMF) surgery is required to address congenital birth defects and traumatic injuries to the
face and jaw. CMF reconstruction is one of the most challenging areas for bone regeneration, as it requires
modulated repair that leads to tissue regeneration while maintaining or recapitulating facial structure. Moreover,
these facial bone reconstructions often suffer from bacterial infections that stall the healing process. Many
different polymeric scaffold materials that exhibit degradability and minimal toxicity have been developed as
bone void fillers to promote tissue regeneration in large CMF bone defects, but in general these materials do not
intrinsically promote new bone growth or protect against infection. To this end, polymeric scaffold implants coated
with electrostatic layer-by-layer (LbL) assemblies of polyelectrolyte polymers, pro-healing growth factor proteins,
and antibiotics that can enhance bone regeneration have been developed. However, current polyelectrolyte-
based constructs are engineered to degrade by non-specific hydrolysis and are minimally-responsive to the rate
of tissue repair and bone regeneration or bacterial infection. Consequently, there is a need for LbL systems that
better deliver therapies over the entire lifetime of the bone healing process and can respond to differential healing
rates and flare-ups of bacterial infection. This project seeks to develop biomaterial implants coated with
drug-loaded, environmentally-responsive LbL nanofilms that will selectively release drug payloads to
generate a more robust healing response in infected, critically-sized CMF bone defects. Cell-responsive
constructs can selectively release pro-healing therapeutics in response to new tissue growth or infection, thus
creating a material scaffold system that can deliver reparative drugs “on-demand”. It is predicted that more
specifically controlling the release of therapeutic molecules from implanted materials will prolong the effective
drug delivery window by conserving the drug only until it is needed, thereby increasing the relative efficiency of
the treatment in vivo. Therefore, LbL coatings that are specifically degraded by cell-generated reactive oxygen
species (ROS) and matrix metalloproteinase (MMP) enzymes, signals both associated with bone healing, will be
created to specifically release pro-healing growth factors to improve the healing of CMF injuries. Once these
responsive growth factor release systems are optimized, they will be combined with antibiotic-containing LbL
coatings that selectively release their drug payload in response to bacterial infection. This work is anticipated to
establish an effective platform for promoting cell-mediated drug delivery in LbL systems and has the potential to
improve treatment outcomes in both CMF repair and across a variety of applications in regenerative medicine.

## Key facts

- **NIH application ID:** 9927495
- **Project number:** 5F32DE027877-03
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** John Robert Martin
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $14,838
- **Award type:** 5
- **Project period:** 2018-06-01 → 2020-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927495

## Citation

> US National Institutes of Health, RePORTER application 9927495, Environmentally-responsive, layer-by-layer coatings for the on-demand delivery of therapeutic growth factors and antibiotics to repair craniomaxillofacial bone defects (5F32DE027877-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9927495. Licensed CC0.

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