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Antimicrobial quaternary ammonium organosilane cross-linked nanofibrous collagen scaffolds for tissue engineering

Authors Dhand C, Balakrishnan Y, Ong ST, Dwivedi N, Venugopal JR, Harini S, Leung CM, Low KZW, Loh XJ, Beuerman RW, Ramakrishna S, Verma NK, Lakshminarayanan R

Received 13 December 2017

Accepted for publication 3 April 2018

Published 3 August 2018 Volume 2018:13 Pages 4473—4492


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Thomas Webster

Chetna Dhand,1,2,* Yamini Balakrishnan,3,* Seow Theng Ong,4,* Neeraj Dwivedi,5 Jayarama R Venugopal,6 Sriram Harini,1 Chak Ming Leung,3 Kenny Zhi Wei Low,7 Xian Jun Loh,7 Roger W Beuerman,1,2 Seeram Ramakrishna,8 Navin Kumar Verma,1,4 Rajamani Lakshminarayanan1,2

1Anti-Infectives Research Group, Singapore Eye Research Institute, The Academia, Discovery Tower, Singapore; 2Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore; 3Department of Bioengineering, National University of Singapore, Singapore; 4Dermatology and Skin Biology, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 5Department of Electrical and Computer Engineering, National University of Singapore, Singapore; 6Faculty of Industrial Sciences & Technology, Universiti Malaysia Pahang, Gambang, Malaysia; 7Department of Mechanical Engineering, Faculty of Engineering, Center for Nanofibers and Nanotechnology, National University of Singapore, Singapore; 8Soft Materials Department, Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research, Singapore

*These authors contributed equally to this work

Introduction: In search for cross-linkers with multifunctional characteristics, the present work investigated the utility of quaternary ammonium organosilane (QOS) as a potential cross-linker for electrospun collagen nanofibers. We hypothesized that the quaternary ammonium ions improve the electrospinnability by reducing the surface tension and confer antimicrobial properties, while the formation of siloxane after alkaline hydrolysis could cross-link collagen and stimulate cell proliferation.
Materials and methods: QOS collagen nanofibers were electrospun by incorporating various concentrations of QOS (0.1%–10% w/w) and were cross-linked in situ after exposure to ammonium carbonate. The QOS cross-linked scaffolds were characterized and their biological properties were evaluated in terms of their biocompatibility, cellular adhesion and metabolic activity for primary human dermal fibroblasts and human fetal osteoblasts.
Results and discussion: The study revealed that 1) QOS cross-linking increased the flexibility of otherwise rigid collagen nanofibers and improved the thermal stability; 2) QOS cross-linked mats displayed potent antibacterial activity and 3) the biocompatibility of the composite mats depended on the amount of QOS present in dope solution – at low QOS concentrations (0.1% w/w), the mats promoted mammalian cell proliferation and growth, whereas at higher QOS concentrations, cytotoxic effect was observed.
Conclusion: This study demonstrates that QOS cross-linked mats possess anti-infective properties and confer niches for cellular growth and proliferation, thus offering a useful approach, which is important for hard and soft tissue engineering and regenerative medicine.

Keywords: anti-infective wound dressing, cyto-compatible nanofibre, electrospinning, cost-effective cross-linker, tissue regeneration, antimicrobial

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