Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct 11;10(10):652.
doi: 10.3390/gels10100652.

Shear-Thinning Extrudable Hydrogels Based on Star Polypeptides with Antimicrobial Properties

Dimitrios Skoulas  1 , Muireann Fallon  2 , Katelyn J Genoud  3   4 , Fergal J O'Brien  3   4   5 , Deirdre Fitzgerald Hughes  2 , Andreas Heise  1   4   5
Affiliations

Shear-Thinning Extrudable Hydrogels Based on Star Polypeptides with Antimicrobial Properties

Dimitrios Skoulas et al. Gels. .

Abstract

Hydrogels with low toxicity, antimicrobial potency and shear-thinning behavior are promising materials to combat the modern challenges of increased infections. Here, we report on 8-arm star block copolypeptides based on poly(L-lysine), poly(L-tyrosine) and poly(S-benzyl-L-cysteine) blocks. Three star block copolypeptides were synthesized with poly(S-benzyl-L-cysteine) always forming the outer block. The inner block comprised either two individual blocks of poly(L-lysine) and poly(L-tyrosine) or a statistical block copolypeptide from both amino acids. The star block copolypeptides were synthesized by the Ring Opening Polymerization (ROP) of the protected amino acid N-carboxyanhydrides (NCAs), keeping the overall ratio of monomers constant. All star block copolypeptides formed hydrogels and Scanning Electron Microscopy (SEM) confirmed a porous morphology. The investigation of their viscoelastic characteristics, water uptake and syringe extrudability revealed superior properties of the star polypeptide with a statistical inner block of L-lysine and L-tyrosine. Further testing of this sample confirmed no cytotoxicity and demonstrated antimicrobial activity of 1.5-log and 2.6-log reduction in colony-forming units, CFU/mL, against colony-forming reference laboratory strains of Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, respectively. The results underline the importance of controlling structural arrangements in polypeptides to optimize their physical and biological properties.

Keywords: antimicrobial potency; hydrogels; polypeptides; star polymers.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript or in the decision to publish the results.

Figures

Figure 1
Figure 1
(a) Synthesis of the protected star block copolypeptides by NCA ring-opening polymerization from an 8-arm PPI dendrimer; (b) structures of the deprotected star block copolypeptides (P1–P3); (c) image of the hydrogel obtained from P3.
Figure 2
Figure 2
1H NMR spectrum of deprotected P1 (DMSO-d6) and schematic polymer structure with signal assignments.
Figure 3
Figure 3
(a) Strain-dependent storage G′ and loss G″ moduli for the hydrogels P1, P2 and P3. (b) Frequency-dependent storage G′ and loss G″ moduli for the hydrogels P1, P2 and P3.
Figure 4
Figure 4
Time-dependent storage G′ and loss G″ moduli of the hydrogel P3.
Figure 5
Figure 5
Representative SEM pictures of lyophilized P3 hydrogels.
Figure 6
Figure 6
(a) Percentage of metabolic activity of rat MSCs (n = 3) over 7 days in culture with hydrogel P3 as determined via alamarBlue© (excitation 545 nm and emission at 590 nm). The red line represents the 70% cut-off for cytocompatibility as per the ISO standard. Metabolic activity is presented as mean ± SEM and compared to that of cells not exposed to hydrogels (cells alone); (b) log reduction in colony-forming units (CFU) mL−1 following application of approximately 105 CFU/mL S. aureus (ATCC25923) or E. coli (ATCC25922) to hydrogel P3; (c,d) representative examples of LIVE/DEAD™ fluorescent imaging of rMSCs exposed to the P3 hydrogel after 7 days (scale bars 200 μm); (c) cells not exposed to hydrogel and (d) cells exposed P3 hydrogel.
Figure 7
Figure 7
A cone structure showing high control of hydrogel 3D printing from 3D CAD file to hydrogel construct.
See this image and copyright information in PMC

References

    1. Rice L.B. Progress and challenges in implementing the research on ESKAPE pathogens. Infect. Control Hosp. Epidemiol. 2010;31((Suppl. S1)):S7–S10. doi: 10.1086/655995. - DOI - PubMed
    1. Belanger C.R., Hancock R.E.W. Testing physiologically relevant conditions in minimal inhibitory concentration assays. Nat. Protoc. 2021;16:3761–3774. doi: 10.1038/s41596-021-00572-8. - DOI - PubMed
    1. Jacquet R., LaBauve A.E., Akoolo L., Patel S., Alqarzaee A.A., Fok Lung T.W., Poorey K., Stinear T.P., Thomas V.C., Meagher R.J., et al. Dual gene expression analysis identifies factors associated with Staphylococcus aureus virulence in diabetic mice. Infect. Immun. 2019;87:e00163-19. doi: 10.1128/IAI.00163-19. - DOI - PMC - PubMed
    1. Geisinger E., Isberg R.R. Interplay between antibiotic resistance and virulence during Disease promoted by multidrug-resistant bacteria. J. Infect. Dis. 2017;215:S9–S17. doi: 10.1093/infdis/jiw402. - DOI - PMC - PubMed
    1. de Macedo G.H.R.V., Costa G.D.E., Oliveira E.R., Damasceno G.V., Mendonça J.S.P., Silva L.S., Chagas V.L., Bazán J.M.N., Aliança A.S.S., de Miranda R.C.M., et al. Interplay between eskape pathogens and immunity in skin infections: An overview of the major determinants of virulence and antibiotic resistance. Pathogens. 2021;10:148. doi: 10.3390/pathogens10020148. - DOI - PMC - PubMed

LinkOut - more resources