Antimicrobial and enzyme-responsive multi-peptide surfaces for bone-anchored devices

Nicholas G. Fischer, Xi Chen, Kristina Astleford-hopper, Jiahe He, Alex F. Mullikin, Kim C. Mansky, Conrado Aparicio

Research output: Contribution to journalArticlepeer-review

Abstract

Functionalization of dental and orthopedic implants with multiple bioactivities is desirable to obtain surfaces with improved biological performance and reduced infection rates. While many approaches have been explored to date, nearly all functionalized surfaces are static, i.e., non-responsive to biological cues. However, tissue remodeling necessary for implant integration features an ever-changing milieu of cells that demands a responsive biomaterial surface for temporal synchronization of interactions between biomaterial and tissue. Here, we successfully synthesized a multi-functional, dynamic coating on titanium by co-immobilizing GL13K antimicrobial peptide and an MMP-9 – a matrix metalloproteinase secreted by bone-remodeling osteoclasts – responsive peptide. Our co-immobilized peptide surface showed potent anti-biofilm activity, enabled effective osteoblast and fibroblast proliferation, and demonstrated stability against a mechanical challenge. Finally, we showed peptide release was triggered for up to seven days when the multi-peptide coatings were cultured with MMP-9-secreting osteoclasts. Our MMP-9 cleavable peptide can be conjugated with osteogenic or immunomodulatory motifs for enhanced bone formation in future work. Overall, we envisage our multifunctional, dynamic surface to reduce infection rates of percutaneous bone-anchored devices via strong anti-microbial activity and enhanced tissue regeneration via temporal synchronization between biomaterial cues and tissue responses.

Original languageEnglish (US)
Article number112108
Pages (from-to)112108
JournalMaterials Science and Engineering C
Volume125
DOIs
StatePublished - Jun 1 2021

Bibliographical note

Funding Information:
The authors would like to thank Dr. Jessica Jurovich, Dr. Christine B. Lung, and Professor Sven-Ulrik Gorr at the University of Minnesota for their training and support on experimental tasks for cell culturing, enzyme release, and antimicrobial characterization, respectively. We would also thank Professor Louis Mansky at the University of Minnesota for providing access to the multi-mode microplate reader. This project was supported by the Office of the Vice-president for Research at the University of Minnesota (Project #55466 of the Grant-in-Aid of Research, Artistry and Scholarship Program; CA), National Institute of Dental & Craniofacial Research (Grants R90DE023058 (XC) and T90DE0227232 (NGF and KA), and the Summer Dental Students Research Program of the University of Minnesota School of Dentistry (AFM). XC and NGF were also partially supported by a 3M Science and Technology Fellowship. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from the NSF through the MRSEC (Award Number DMR-2011401 ) and the NNCI (Award Number ECCS-2025124 ) programs. Figures were created with BioRender ( biorender.com ).

Publisher Copyright:
© 2021 Elsevier B.V.

Keywords

  • Antimicrobial
  • Antimicrobial peptide
  • Implant
  • MMP
  • Multifunctional surface
  • Osteoclasts
  • Stimuli-responsive

How much support was provided by MRSEC?

  • Shared

Reporting period for MRSEC

  • Period 2

PubMed: MeSH publication types

  • Journal Article

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