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Silk-Based Therapeutics Targeting Pseudomonas aeruginosa.
J Funct Biomater 2019; 10(3)JF

Abstract

Pseudomonas aeruginosa (P. aeruginosa) infections may lead to severe damage of the cornea, mucosa, and skin. The highly aggressive nature of P. aeruginosa and the rise in multi-drug resistance, particularly in nosocomial settings, lead to an increased risk for permanent tissue damage and potentially death. Thus, a growing need exists to develop alternative treatments to reduce both the occurrence of bacterial infection and biofilm development, as well as pathological progression post-infection. Silk derived from Bombyx mori silkworms serves as a unique biomaterial that is biocompatible with low immunogenicity and high versatility, and thereby ideal for stabilizing therapeutics. In this study, we assessed the cytotoxicity of P. aeruginosa on human corneal stromal stem cells and two mucosal cell lines (Caco-2 and HT29-MTX). To determine whether antibiotic-immobilized scaffolds can serve as alternative therapeutics to free, diffuse forms, we developed novel gentamicin-conjugated silk films as functional scaffolds and compared antimicrobial effects and free gentamicin. The advantages of generating a surface coating with a covalently-bound antibiotic may reduce potential side-effects associated with free gentamicin, as well as limit the diffusion of the drug. Our results suggest that gentamicin conjugated to native silk and carboxyl-enriched silk inhibits P. aeruginosa growth. Development of stabilized antibiotic treatments with surface toxicity selective against bacteria may serve as an alternative approach to treat active infections, as well as potential prophylactic use as coatings in high-risk cases, such as post-surgical complications or prolonged hospitalization.

Authors+Show Affiliations

Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA. tmckay333@gmail.com.Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA. rachael.parker@tufts.edu.Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA. mrgnhawker@gmail.com.Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA. meghan.mcgill@tufts.edu.Department of Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155, USA. david.kaplan@tufts.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31540233

Citation

McKay, Tina B., et al. "Silk-Based Therapeutics Targeting Pseudomonas Aeruginosa." Journal of Functional Biomaterials, vol. 10, no. 3, 2019.
McKay TB, Parker RN, Hawker MJ, et al. Silk-Based Therapeutics Targeting Pseudomonas aeruginosa. J Funct Biomater. 2019;10(3).
McKay, T. B., Parker, R. N., Hawker, M. J., McGill, M., & Kaplan, D. L. (2019). Silk-Based Therapeutics Targeting Pseudomonas aeruginosa. Journal of Functional Biomaterials, 10(3), doi:10.3390/jfb10030041.
McKay TB, et al. Silk-Based Therapeutics Targeting Pseudomonas Aeruginosa. J Funct Biomater. 2019 Sep 13;10(3) PubMed PMID: 31540233.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Silk-Based Therapeutics Targeting Pseudomonas aeruginosa. AU - McKay,Tina B, AU - Parker,Rachael N, AU - Hawker,Morgan J, AU - McGill,Meghan, AU - Kaplan,David L, Y1 - 2019/09/13/ PY - 2019/08/06/received PY - 2019/09/10/revised PY - 2019/09/11/accepted PY - 2019/9/22/entrez KW - Pseudomonas aeruginosa KW - antibiotic KW - scaffold KW - silk JF - Journal of functional biomaterials JO - J Funct Biomater VL - 10 IS - 3 N2 - Pseudomonas aeruginosa (P. aeruginosa) infections may lead to severe damage of the cornea, mucosa, and skin. The highly aggressive nature of P. aeruginosa and the rise in multi-drug resistance, particularly in nosocomial settings, lead to an increased risk for permanent tissue damage and potentially death. Thus, a growing need exists to develop alternative treatments to reduce both the occurrence of bacterial infection and biofilm development, as well as pathological progression post-infection. Silk derived from Bombyx mori silkworms serves as a unique biomaterial that is biocompatible with low immunogenicity and high versatility, and thereby ideal for stabilizing therapeutics. In this study, we assessed the cytotoxicity of P. aeruginosa on human corneal stromal stem cells and two mucosal cell lines (Caco-2 and HT29-MTX). To determine whether antibiotic-immobilized scaffolds can serve as alternative therapeutics to free, diffuse forms, we developed novel gentamicin-conjugated silk films as functional scaffolds and compared antimicrobial effects and free gentamicin. The advantages of generating a surface coating with a covalently-bound antibiotic may reduce potential side-effects associated with free gentamicin, as well as limit the diffusion of the drug. Our results suggest that gentamicin conjugated to native silk and carboxyl-enriched silk inhibits P. aeruginosa growth. Development of stabilized antibiotic treatments with surface toxicity selective against bacteria may serve as an alternative approach to treat active infections, as well as potential prophylactic use as coatings in high-risk cases, such as post-surgical complications or prolonged hospitalization. SN - 2079-4983 UR - https://www.unboundmedicine.com/medline/citation/31540233/Silk-Based_Therapeutics_Targeting_Pseudomonas_aeruginosa DB - PRIME DP - Unbound Medicine ER -