A potent antibiotic-loaded bone-cement implant against staphylococcal bone infections

Sumana Ghosh; Mau Sinha; Ritwik Samanta; Suresh Sadhasivam; Anamika Bhattacharyya; Ashis Nandy; Swamini Saini; Nupur Tandon; Himanshi Singh; Swati Gupta; Anjali Chauhan; Keerthi Kumar Aavula; Sneha Susan Varghese; Pujie Shi; Sudip Ghosh; Mukesh Kumar Garg; Tanmoy Saha; Aparna Padhye; Shamik Ghosh; Hae Lin Jang; Shiladitya Sengupta

doi:10.1038/s41551-022-00950-x

A potent antibiotic-loaded bone-cement implant against staphylococcal bone infections

Nat Biomed Eng. 2022 Oct;6(10):1180-1195. doi: 10.1038/s41551-022-00950-x. Epub 2022 Oct 13.

Authors

Sumana Ghosh^#^{1

2}, Mau Sinha^#^{1

2}, Ritwik Samanta^{1

2}, Suresh Sadhasivam^{1

2}, Anamika Bhattacharyya^{1

2}, Ashis Nandy^{1

2}, Swamini Saini^{1

2}, Nupur Tandon^{1

2}, Himanshi Singh^{1

2}, Swati Gupta^{1

2}, Anjali Chauhan^{1

2}, Keerthi Kumar Aavula^{1

2}, Sneha Susan Varghese³, Pujie Shi^{4

5

6

7}, Sudip Ghosh³, Mukesh Kumar Garg^{1

2}, Tanmoy Saha^{4

5}, Aparna Padhye^{4

5

6

7}, Shamik Ghosh^{8

9}, Hae Lin Jang^{10

11

12}, Shiladitya Sengupta^{13

14}

Affiliations

¹ Vyome Therapeutics Inc., Princeton, NJ, USA.
² Vyome Therapeutics Limited, New Delhi, India.
³ Department of Biotechnology, Indian Institute of Technology, Kharagpur, India.
⁴ Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
⁶ Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Vyome Therapeutics Inc., Princeton, NJ, USA. shamik.ghosh@vyometx.com.
⁹ Vyome Therapeutics Limited, New Delhi, India. shamik.ghosh@vyometx.com.
¹⁰ Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. hjang@bwh.harvard.edu.
¹¹ Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. hjang@bwh.harvard.edu.
¹² Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. hjang@bwh.harvard.edu.
¹³ Center for Engineered Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. ssengupta2@bwh.harvard.edu.
¹⁴ Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA. ssengupta2@bwh.harvard.edu.

^# Contributed equally.

Abstract

New antibiotics should ideally exhibit activity against drug-resistant bacteria, delay the development of bacterial resistance to them and be suitable for local delivery at desired sites of infection. Here, we report the rational design, via molecular-docking simulations, of a library of 17 candidate antibiotics against bone infection by wild-type and mutated bacterial targets. We screened this library for activity against multidrug-resistant clinical isolates and identified an antibiotic that exhibits potent activity against resistant strains and the formation of biofilms, decreases the chances of bacterial resistance and is compatible with local delivery via a bone-cement matrix. The antibiotic-loaded bone cement exhibited greater efficacy than currently used antibiotic-loaded bone cements against staphylococcal bone infections in rats. Potent and locally delivered antibiotic-eluting polymers may help address antimicrobial resistance.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents* / pharmacology
Anti-Bacterial Agents* / therapeutic use
Biofilms
Bone Cements*
Prostheses and Implants
Rats

Substances

Bone Cements
Anti-Bacterial Agents

Grants and funding

R01 CA236702/CA/NCI NIH HHS/United States