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1.
Bioact Mater ; 16: 173-186, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35386316

RESUMO

Multifunctional scaffolds with host defense peptides designed for regenerative endodontics are desirable nanobiotechnological tools for dentistry. Here, different scaffolds were tested for use during the pulp revascularization process, including poly(vinyl alcohol)-PVA hydrogels or resins, collagen hydrogels and poly(vinyl alcohol) PVA/Chitosan (PVA/CS) nanofibers. Based on time to degradation (21 days), nanofibers were chosen to be incorporated with ciprofloxacin and IDR-1002 (each at 50 mg/g). Nanofibers containing ciprofloxacin and IDR-1002 had anti-biofilm activity against Enterococcus faecalis, Staphylococcus aureus and a multispecies oral biofilm, besides anti-inflammatory activities. The in vivo subcutaneous tissue response to tooth fragments filled with nanofibers demonstrated a pulp-like tissue formation, when compared to empty teeth fragments. Thus, we designed a strong antimicrobial, immunomodulatory and regenerative candidate for pulp revascularization and regeneration procedures.

2.
J Med Chem ; 63(21): 12921-12928, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33126797

RESUMO

Therapeutic options to treat multidrug resistant bacteria, especially when present in biofilms, are limited due to their high levels of antibiotic resistance. Here, we report the anti-biofilm and immunomodulatory activities of the host defense peptide (HDP)-mimicking ß-peptide polymer (20:80 Bu:DM) and investigated its activity in vivo. The polymer outperformed antibiotics in the removal and reduction of the viability of established biofilms, achieving a maximum activity of around 80% reduction in viability. Interestingly the polymer also exhibited HDP-like immunomodulation in inducing chemokines and anti-inflammatory cytokines and suppressing lipopolysaccharide-induced proinflammatory cytokines. When tested in a murine, high-density skin infection model using P. aeruginosa LESB58, the polymer was effective in diminishing abscess size and reducing bacterial load. This study demonstrates the dual functionality of HDP-mimicking ß-peptide polymers in inhibiting biofilms and modulating innate immunity, as well as reducing tissue dermonecrosis.


Assuntos
Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Biofilmes/efeitos dos fármacos , Polímeros/química , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Citocinas/farmacologia , Modelos Animais de Doenças , Humanos , Imunidade Inata/efeitos dos fármacos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Peptidomiméticos , Polímeros/farmacologia , Polímeros/uso terapêutico , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Dermatopatias/tratamento farmacológico , Dermatopatias/microbiologia , Dermatopatias/patologia
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