# A pH-Responsive Smart Copolymer For Selective Removal of Cariogenic Oral Biofilms

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $234,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Controlling cariogenic biofilms is the key for prevention of dental caries. However, it is a significant challenge to
disrupt robust extracellular polymeric substances (EPS) matrix structures or kill embedded bacteria.
Therapeutic treatments using chemical or physical means inadequately control cariogenic biofilms and fail to
reduce caries risk. To address this problem, we propose a completely novel removal strategy by transforming
biofilms from sticky into brittle, not dependent on enzymatic or chemical degradation of EPS. We have
designed a low molecular weight cationic methacrylate polymer that can penetrate into a biofilm matrix and
bind to the anionic biofilm biopolymers by electrostatic interactions. This action can crosslink the biofilm matrix,
preventing structural re-arrangement of the EPS matrix under stress, and thus it causes cohesive failure and
untimely biofilm removal. Strikingly, our study demonstrated that the polymer removed 60% of Streptococcus
mutans biofilm biomass by using hydrodynamic cycles for 30 sec, while chlorhexidine and cationic surfactant
(CTAB) failed to remove the same biofilms. In this study, we will extend our approach to address the unmet
challenge of targeting cariogenic biofilms. We hypothesize that pH-responsive smart polymers can be
designed to switch from neutral to cationic states by acidic pH, and thus their anti-biofilm and bactericidal
activities can be triggered only in the acidic microenvironment of cariogenic biofilms, but not in neutral healthy
biofilms. To test this hypothesis, we will design and develop a random copolymer with an equal number of
cationic ammonium and anionic carboxylic groups, that switches from neutral charge to cationic at the pH of
4.5 due to the protonation of carboxylic groups. The significance of this study is to design and develop a highly
effective, safe, and straightforward anti-biofilm approach, as compared to current inadequate treatments using
chemical and biological agents. The innovation of this study is the combination of mechanisms that target the
inherent physicochemical (acidic microenvironment) and mechanical (viscoelasticity) properties of a biofilm
matrix to achieve selective and effective removal of cariogenic biofilms. In Aim 1, we will evaluate the acid-
triggered bactericidal activity of copolymer against planktonic oral bacteria. In Aim 2, we will evaluate its
efficacy and selectivity to remove acidogenic biofilms and kill embedded bacteria by using saliva-derived
biofilm models. The proposed approach has the significant potential of reducing the risk of disease for
individuals at risk of tooth decay improving the lives of millions of people.

## Key facts

- **NIH application ID:** 10057697
- **Project number:** 1R21DE029248-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Kenichi Kuroda
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,000
- **Award type:** 1
- **Project period:** 2020-08-10 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057697

## Citation

> US National Institutes of Health, RePORTER application 10057697, A pH-Responsive Smart Copolymer For Selective Removal of Cariogenic Oral Biofilms (1R21DE029248-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10057697. Licensed CC0.

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