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Application of Antimicrobial Peptides on the development of antibiotic-free wound care dressings
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Orientador(es)
Resumo(s)
Chronic wounds infections (CWI) are a rising global problem, being responsible for
considerable morbidity and decreased life quality. Resulting from microorganism colonization
and biofilm establishment, CWI occur in patients with underlying pathologies
that hinder wound healing. Current therapies have proven to be insufficient, with the
rise and dissemination of antibiotic-resistant microorganisms.
Herein, a new antibiotic-free chitosan-based dressing material with antimicrobial
peptides (AMPs) was developed to mitigate CWI. AMPs are small peptides with broad
spectrum of activity and low propensity for inducing resistance. Unfortunately, AMPs
are easily degraded in vivo and can self-aggregate. Hence, covalent immobilization may
be an efficient strategy to improve bioavailability.
In this context, Dhvar5 (LLLFLLKKRKKRKY) was covalently immobilized onto chitosan
through the highly efficient photoinitiated thiol-norbornene “click” chemistry.
Dhvar5 is a synthetic AMP derived from histatin-5 with promising antimicrobial activity.
Chitosan is a biopolymer amenable to functionalization with antimicrobial, hemostatic
and prohealing properties.
To allow the chemistry, chitosan was functionalized with a norbornene group (Nor-
Chit). Dhvar5 modified with a spacer and a cysteine either at N- or C-terminal, was
used to chemoselectively immobilize the AMP. The immobilization was confirmed by
Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. Proteolytic
stability of the immobilized AMP was investigated with trypsin by a competitive
assay with N- -benzoylarginine ethylester. However, the results were inconclusive due
to a pH mismatch.
NorChit-Dhvar5 coatings were produced by spin-coating, to assess its potential in
attributing antimicrobial properties to wound dressings. NorChit-Dhvar5 coatings were
characterized by ellipsometry and water contact angle, and its antimicrobial efficacy was
evaluated against Staphylococcus epidermidis using a LIVE/DEAD Bacterial Viability Kit.
Both NorChit-Dhvar5 (Nt and Ct) coatings revealed improved antimicrobial activity in
comparison to chitosan, with lower adhered live bacteria percentages ( 75%). NorChit-
Dhvar5 (Nt) also presented lower number of total adhered bacteria (less 35%). Therefore,
NorChit-Dhvar5 represent promising biomaterial for future antimicrobial wound dressing
development.
Descrição
Palavras-chave
chronic wounds infection antimicrobial peptides chitosan click chemistry thiol-norbornene