Cuahtecontzi Delint, Rosalia and Ishak, Mohd I. and Tsimbouri, Penelope M. and Jayawarna, Vineetha and Burgess, Karl V.E. and Ramage, Gordon and Nobbs, Angela H. and Damiati, Laila and Salmeron-Sanchez, Manuel and Su, Bo and Dalby, Matthew (2024) Nanotopography influences host-pathogen quorum sensing and facilitates selection of bioactive metabolites in mesenchymal stromal cells and pseudomonas aeruginosa co-cultures. ACS Applied Materials and Interfaces, 16 (33). pp. 43374-43386. ISSN 1944-8244

Abstract

Orthopedic implant-related bacterial infections and resultant antibiotic-resistant biofilms hinder implant–tissue integration and failure. Biofilm quorum sensing (QS) communication determines the pathogen colonization success. However, it remains unclear how implant modifications and host cells are influenced by, or influence, QS. High aspect ratio nanotopographies have shown to reduce biofilm formation of Pseudomonas aeruginosa, a sepsis causing pathogen with well-defined QS molecules. Producing such nanotopographies in relevant orthopedic materials (i.e., titanium) allows for probing QS using mass spectrometry-based metabolomics. However, nanotopographies can reduce host cell adhesion and regeneration. Therefore, we developed a polymer (poly(ethyl acrylate), PEA) coating that organizes extracellular matrix proteins, promoting bioactivity to host cells such as human mesenchymal stromal cells (hMSCs), maintaining biofilm reduction. This allowed us to investigate how hMSCs, after winning the race for the surface against pathogenic cells, interact with the biofilm. Our approach revealed that nanotopographies reduced major virulence pathways, such as LasR. The enhanced hMSCs support provided by the coated nanotopographies was shown to suppress virulence pathways and biofilm formation. Finally, we selected bioactive metabolites and demonstrated that these could be used as adjuncts to the nanostructured surfaces to reduce biofilm formation and enhance hMSC activity. These surfaces make excellent models to study hMSC–pathogen interactions and could be envisaged for use in novel orthopedic implants.

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Cuahtecontzi Delint, Rosalia
Author

Cuahtecontzi Delint, Rosalia and Ishak, Mohd I. and Tsimbouri, Penelope M. and Jayawarna, Vineetha and Burgess, Karl V.E. and Ramage, Gordon and Nobbs, Angela H. and Damiati, Laila and Salmeron-Sanchez, Manuel and Su, Bo and Dalby, Matthew (2024) Nanotopography influences host-pathogen quorum sensing and facilitates selection of bioactive metabolites in mesenchymal stromal cells and pseudomonas aeruginosa co-cultures. ACS Applied Materials and Interfaces, 16 (33). pp. 43374-43386. ISSN 1944-8244

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Ishak, Mohd I.
Author

Cuahtecontzi Delint, Rosalia and Ishak, Mohd I. and Tsimbouri, Penelope M. and Jayawarna, Vineetha and Burgess, Karl V.E. and Ramage, Gordon and Nobbs, Angela H. and Damiati, Laila and Salmeron-Sanchez, Manuel and Su, Bo and Dalby, Matthew (2024) Nanotopography influences host-pathogen quorum sensing and facilitates selection of bioactive metabolites in mesenchymal stromal cells and pseudomonas aeruginosa co-cultures. ACS Applied Materials and Interfaces, 16 (33). pp. 43374-43386. ISSN 1944-8244

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Tsimbouri, Monica P.
Author

Cuahtecontzi Delint, Rosalia and Ishak, Mohd I. and Tsimbouri, Penelope M. and Jayawarna, Vineetha and Burgess, Karl V.E. and Ramage, Gordon and Nobbs, Angela H. and Damiati, Laila and Salmeron-Sanchez, Manuel and Su, Bo and Dalby, Matthew (2024) Nanotopography influences host-pathogen quorum sensing and facilitates selection of bioactive metabolites in mesenchymal stromal cells and pseudomonas aeruginosa co-cultures. ACS Applied Materials and Interfaces, 16 (33). pp. 43374-43386. ISSN 1944-8244

Donnelly, Hannah and Ross, Ewan and Xiao, Yinbo and Hermantara, Rio and Taqi, Aqeel and Doherty-Boyd, W. Sebastian and Cassels, Jennifer and Tsimbouri, Penelope M. and Dunne, Karen M. and Hay, Jodie and Cheng, Annie and Meek, R.M. Dominic and Jain, Nikhil and West, Christopher and Wheadon, Helen and Michie, Alison M. and Peault, Bruno and West, Adam G. and Salmeron-Sanchez, Manuel and Dalby, Matthew J. (2024) Bioengineered niches that recreate physiological extracellular matrix organisation to support long-term haematopoietic stem cells. Nature Communications, 15: 5791. ISSN 2041-1723

Doherty-Boyd, W. Sebastian and Tsimbouri, Monica P. and Donnelly, Hannah and Dalby, Matthew J. (2024) Building bones for blood and beyond: the growing field of bone marrow niche model development. Experimental Hematology, 135: 104232. ISSN 0301-472X

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Jayawarna, Vineetha
Author

Cuahtecontzi Delint, Rosalia and Ishak, Mohd I. and Tsimbouri, Penelope M. and Jayawarna, Vineetha and Burgess, Karl V.E. and Ramage, Gordon and Nobbs, Angela H. and Damiati, Laila and Salmeron-Sanchez, Manuel and Su, Bo and Dalby, Matthew (2024) Nanotopography influences host-pathogen quorum sensing and facilitates selection of bioactive metabolites in mesenchymal stromal cells and pseudomonas aeruginosa co-cultures. ACS Applied Materials and Interfaces, 16 (33). pp. 43374-43386. ISSN 1944-8244

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Burgess, Karl
Author

Cuahtecontzi Delint, Rosalia and Ishak, Mohd I. and Tsimbouri, Penelope M. and Jayawarna, Vineetha and Burgess, Karl V.E. and Ramage, Gordon and Nobbs, Angela H. and Damiati, Laila and Salmeron-Sanchez, Manuel and Su, Bo and Dalby, Matthew (2024) Nanotopography influences host-pathogen quorum sensing and facilitates selection of bioactive metabolites in mesenchymal stromal cells and pseudomonas aeruginosa co-cultures. ACS Applied Materials and Interfaces, 16 (33). pp. 43374-43386. ISSN 1944-8244

Delaney, Christopher and Short, Bryn and Rajendran, Ranjith and Kean, Ryan and Burgess, Karl and Williams, Craig and Munro, Carol A. and Ramage, Gordon (2023) An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype. Biofilm, 5: 100112. ISSN 2590-2075

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Ramage, Gordon
Author

Allkja, Jontana and Bakri, Ahmed and Short, Bryn and Gilmour, Andrew and Brown, Jason L. and Bal, Abhijit M. and Newby, Kelly J.M. and Jenkins, Toby and Short, Rob D. and Williams, Craig and Ramage, Gordon (2025) Investigating the prevalence of fungi in diabetic ulcers: an under-recognised contributor to polymicrobial biofilms. APMIS: Journal of Pathology, Microbiology and Immunology, 133 (4): e70025. ISSN 0903-4641

Ware, Alicia and Johnston, William and Delaney, Christopher and Butcher, Mark C. and Ramage, Gordon and Price, Lesley and Butcher, John and Kean, Ryan (2025) Dry surface biofilm formation by Candida auris facilitates persistence and tolerance to sodium hypochlorite. APMIS: Journal of Pathology, Microbiology and Immunology, 133 (4): e70022. ISSN 0903-4641

Abduljalil, Hafsa and Alshanta, Om Alkhir and Chougule, Safa and Butcher, Mark and Short, Bryn and Mclean, William and Parry, Neil and O'Keeffe, Joanne and Ramage, Gordon (2025) Lactams exhibit potent antifungal activity against monospecies and multispecies interkingdom biofilms on a novel hydrogel skin model. APMIS: Journal of Pathology, Microbiology and Immunology, 133 (1): e13510. ISSN 0903-4641

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Nobbs, Angela H.
Author

Cuahtecontzi Delint, Rosalia and Ishak, Mohd I. and Tsimbouri, Penelope M. and Jayawarna, Vineetha and Burgess, Karl V.E. and Ramage, Gordon and Nobbs, Angela H. and Damiati, Laila and Salmeron-Sanchez, Manuel and Su, Bo and Dalby, Matthew (2024) Nanotopography influences host-pathogen quorum sensing and facilitates selection of bioactive metabolites in mesenchymal stromal cells and pseudomonas aeruginosa co-cultures. ACS Applied Materials and Interfaces, 16 (33). pp. 43374-43386. ISSN 1944-8244

See full publications list
Damiati, Laila
Author

Cuahtecontzi Delint, Rosalia and Ishak, Mohd I. and Tsimbouri, Penelope M. and Jayawarna, Vineetha and Burgess, Karl V.E. and Ramage, Gordon and Nobbs, Angela H. and Damiati, Laila and Salmeron-Sanchez, Manuel and Su, Bo and Dalby, Matthew (2024) Nanotopography influences host-pathogen quorum sensing and facilitates selection of bioactive metabolites in mesenchymal stromal cells and pseudomonas aeruginosa co-cultures. ACS Applied Materials and Interfaces, 16 (33). pp. 43374-43386. ISSN 1944-8244

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Salmeron-Sanchez, Manuel
Author

Cuahtecontzi Delint, Rosalia and Ishak, Mohd I. and Tsimbouri, Penelope M. and Jayawarna, Vineetha and Burgess, Karl V.E. and Ramage, Gordon and Nobbs, Angela H. and Damiati, Laila and Salmeron-Sanchez, Manuel and Su, Bo and Dalby, Matthew (2024) Nanotopography influences host-pathogen quorum sensing and facilitates selection of bioactive metabolites in mesenchymal stromal cells and pseudomonas aeruginosa co-cultures. ACS Applied Materials and Interfaces, 16 (33). pp. 43374-43386. ISSN 1944-8244

Donnelly, Hannah and Ross, Ewan and Xiao, Yinbo and Hermantara, Rio and Taqi, Aqeel and Doherty-Boyd, W. Sebastian and Cassels, Jennifer and Tsimbouri, Penelope M. and Dunne, Karen M. and Hay, Jodie and Cheng, Annie and Meek, R.M. Dominic and Jain, Nikhil and West, Christopher and Wheadon, Helen and Michie, Alison M. and Peault, Bruno and West, Adam G. and Salmeron-Sanchez, Manuel and Dalby, Matthew J. (2024) Bioengineered niches that recreate physiological extracellular matrix organisation to support long-term haematopoietic stem cells. Nature Communications, 15: 5791. ISSN 2041-1723

See full publications list
Su, Bo
Author

Cuahtecontzi Delint, Rosalia and Ishak, Mohd I. and Tsimbouri, Penelope M. and Jayawarna, Vineetha and Burgess, Karl V.E. and Ramage, Gordon and Nobbs, Angela H. and Damiati, Laila and Salmeron-Sanchez, Manuel and Su, Bo and Dalby, Matthew (2024) Nanotopography influences host-pathogen quorum sensing and facilitates selection of bioactive metabolites in mesenchymal stromal cells and pseudomonas aeruginosa co-cultures. ACS Applied Materials and Interfaces, 16 (33). pp. 43374-43386. ISSN 1944-8244

See full publications list
Dalby, Matthew J.
Author

Cuahtecontzi Delint, Rosalia and Ishak, Mohd I. and Tsimbouri, Penelope M. and Jayawarna, Vineetha and Burgess, Karl V.E. and Ramage, Gordon and Nobbs, Angela H. and Damiati, Laila and Salmeron-Sanchez, Manuel and Su, Bo and Dalby, Matthew (2024) Nanotopography influences host-pathogen quorum sensing and facilitates selection of bioactive metabolites in mesenchymal stromal cells and pseudomonas aeruginosa co-cultures. ACS Applied Materials and Interfaces, 16 (33). pp. 43374-43386. ISSN 1944-8244

Donnelly, Hannah and Ross, Ewan and Xiao, Yinbo and Hermantara, Rio and Taqi, Aqeel and Doherty-Boyd, W. Sebastian and Cassels, Jennifer and Tsimbouri, Penelope M. and Dunne, Karen M. and Hay, Jodie and Cheng, Annie and Meek, R.M. Dominic and Jain, Nikhil and West, Christopher and Wheadon, Helen and Michie, Alison M. and Peault, Bruno and West, Adam G. and Salmeron-Sanchez, Manuel and Dalby, Matthew J. (2024) Bioengineered niches that recreate physiological extracellular matrix organisation to support long-term haematopoietic stem cells. Nature Communications, 15: 5791. ISSN 2041-1723

Doherty-Boyd, W. Sebastian and Tsimbouri, Monica P. and Donnelly, Hannah and Dalby, Matthew J. (2024) Building bones for blood and beyond: the growing field of bone marrow niche model development. Experimental Hematology, 135: 104232. ISSN 0301-472X

See full publications list
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