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Technologies for Emerging Infectious Diseases

Technologies for Emerging Infectious Diseases Undergraduate Fire Talks

Advancing Polymer-Coated Gelatin Nanoparticles as an Antibiotic-Free Treatment for Staphylococcus epidermidis Infections

Saturday, October 11, 2025

8:30 AM - 8:40 AM PDT

Location: Room 26B

Presenting Author(s)

Julia C. Patterson

Undergraduate Student Researcher
Brown University
Stewartsville, New Jersey, United States

Co-Author(s)

Julia C. Patterson

Undergraduate Student Researcher
Brown University
Stewartsville, New Jersey, United States
Zhaowei Jiang, Ph.D.

Visiting Scholar
Brown University
Providence, Rhode Island, United States
Alec Mccall, BSE

Graduate Student Researcher
Brown University
North Providence, Rhode Island, United States
Yingying Wang, PhD

Postdoctoral Researcher
Brown University
Providence, Rhode Island, United States
Anita Shukla, PhD

Elaine I. Savage Professor of Engineering
Brown University
Providence, Rhode Island, United States

Last Author(s)

Anita Shukla, PhD

Elaine I. Savage Professor of Engineering
Brown University
Providence, Rhode Island, United States

Primary Investigator(s)

Anita Shukla, PhD

Elaine I. Savage Professor of Engineering
Brown University
Providence, Rhode Island, United States

Introduction: : Staphylococcus epidermidis, a major healthcare-associated bacterium, commonly causes biofilm infections on implanted medical devices like catheters and prostheses. Biofilm infections are extremely difficult to eradicate, often requiring device removal and replacement, which increases both cost and patient morbidity1. Biofilms exhibit resistance and tolerance to antibiotics, complicating treatment and contributing to the growing concern of antimicrobial resistance. These concerns necessitate the development of new approaches to prevent these infections. Nanotechnology offers a promising solution through targeted delivery of antimicrobial agents with enhanced therapeutic efficacy. Building on our previous work with polymer-decorated gelatin nanoparticles (P-GNPs) that inhibit S. epidermidis growth, we now investigated their efficacy in ex vivo settings and as a metal implant coating. We hypothesized that P-GNPs can effectively prevent S. epidermidis adhesion and hence biofilm formation on both biological surfaces and metal implants, providing a robust antibiotic-free strategy to combat device-associated infections.

Materials and

Methods: : The pH-responsive copolymer, methoxy PEG-benzoic-imine-branched polyethyleneimine (PEG-b-i-bPEI), was first synthesized and characterized as reported2. Gelatin nanoparticles (GNPs) were synthesized via a desolvation method and cross-linked with glutaraldehyde3. PEG-b-i-PEI copolymer was conjugated to the GNPs via a 1-ethyl-3-(3-dimethylamino)propyl carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) coupling reaction, forming the P-GNPs (Figure 1a)2. To test the potential human skin applicability, a sterile 8-mm porcine skin biopsy was used and placed on Baird-Parker agar plates. The skin samples were pre-treated with P-GNPs, inoculated with S. epidermidis, gently washed with 1× phosphate buffered saline (PBS), and incubated at 37◦C. After 24 hours, the samples were homogenized in 1× PBS (Figure 1b). To test the P-GNPs as a prophylactic implant coating, titanium composite squares with an average surface area of 19.4 mm2 were obtained and plasma-etched to enhance electrostatic interactions between the P-GNPs and metal surface. The metal squares were incubated with 200 or 600 µg/mL of P-GNP solution for 3 hours, and then allowed to dry on an agar plate for 1 hour(Figure 1c). S. epidermidis were seeded at a final concentration of 1×106 CFU/mL in their exponential growth phase onto the surface of the implant model, and washed with 1× PBS 2 hours post-incubation to mimic bacteria adhesion conditions. The samples were incubated for 24 hours with static incubation at 37◦C and then homogenized in 1× PBS. Anti-bacterial adhesion efficacy was evaluated using 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5- carboxanilide (XTT) assay and colony-forming unit (CFU) counting to evaluate cell metabolic activity and growth.

Results, Conclusions, and Discussions:: In this work, we engineered P-GNPs, an antibiotic-free nanoparticle technology, that demonstrated robust prophylactic antibiofilm properties against S. epidermidis on both porcine skin and metal implant models. XTT studies performed demonstrated nearly complete loss of cell viability when 200 µg/mL P-GNP were added to the porcine skin. This nearly complete inhibition of S. epidermidis biofilm formation indicates the success of the NPs in inhibiting bacterial adhesion ex vivo (Figure 1d). To confirm these results over time, CFU counting exhibited a 3-log decrease in CFUs from the ex vivo skin samples after incubation (Figure 1e). These promising ex vivo results suggest potential efficacy for future human skin applications when the formulation is translated to the healthcare setting. Similarly, the metal implant model results indicated that 200 µg/mL of P-GNP is needed to inhibit approximately 100% of the S. epidermidis biofilm (Figure 1f). The CFU counting results confirmed the significant inhibition of S. epidermidis biofilm with an approximate 5-log reduction achieved at a P-GNP concentration of 200 µg/mL (Figure 1g). The XTT assay and CFU enumeration indicated that no statistically significant differences in biofilm inhibition occurred at higher concentrations (600 µg/mL) of P-GNP treatment, confirming that 200 µg/mL was an optimal concentration for effective biofilm prevention. These findings highlight the potential of the P-GNPs as a prophylactic treatment to be coated onto metal implants, effectively inhibiting the development and growth of S. epidermidis biofilm. Collectively, these results establish P-GNPs as a promising antibiotic-free nanotechnology platform for preventing S. epidermidis biofilm formation in both dermatological and implant applications, offering a potential paradigm shift in prophylactic infection control strategies.

Acknowledgements and/or References (Optional): : Acknowledgments
We gratefully acknowledge financial support from the Office of Naval Research (N00014-22-1-2336) and a Brown University Undergraduate Teaching and Research Award. We thank Professor Robert Hurt at Brown University for the use of his Zetasizer.

References
1. Paul D. Fey and Michael E. Olson. Current concepts in biofilm formation of Staphylococcus epidermidis. Future
Microbiology, 5(6):917–933, June 2010.
2. Nayeleh Deirram, Changhe Zhang, Sarah S. Kermaniyan, Angus P. R. Johnston, and Georgina K. Such. pH-Responsive
Polymer Nanoparticles for Drug Delivery. Macromolecular Rapid Communications, 40(10):e1800917, May 2019.
3. Yingying Wang and Anita Shukla. Bacteria-responsive biopolymer-coated nanoparticles for biofilm penetration and eradication. Biomaterials Science, 10(11):2831–2843, 2022.