In situ Forming Hyperbranched PEG—Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties
The rapidly increasing resistance of bacteria to currently approved antibiotic drugs makes surgical interventions and the treatment of bacterial infections increasingly difficult. In recent years, complementary strategies to classical antibiotic therapy have, therefore, gained importance. One of the...
Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/a4ca70823b9b4af8a9d46977e2efd765 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:a4ca70823b9b4af8a9d46977e2efd765 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:a4ca70823b9b4af8a9d46977e2efd7652021-11-16T13:54:29ZIn situ Forming Hyperbranched PEG—Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties2296-418510.3389/fbioe.2021.742135https://doaj.org/article/a4ca70823b9b4af8a9d46977e2efd7652021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fbioe.2021.742135/fullhttps://doaj.org/toc/2296-4185The rapidly increasing resistance of bacteria to currently approved antibiotic drugs makes surgical interventions and the treatment of bacterial infections increasingly difficult. In recent years, complementary strategies to classical antibiotic therapy have, therefore, gained importance. One of these strategies is the use of medicinal honey in the treatment of bacterially colonized wounds. One of the several bactericidal effects of honey is based on the in situ generation of hydrogen peroxide through the activity of the enzyme glucose oxidase. The strategy underlying this work is to mimic this antibacterial redox effect of honey in an injectable, biocompatible, and rapidly forming hydrogel. The hydrogel was obtained by thiol–ene click reaction between hyperbranched polyethylene glycol diacrylate (HB PEGDA), synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization, and thiolated hyaluronic acid (HA-SH). After mixing 500 µL HB PEGDA (10%, w/w) and 500 µL HA-SH (1%, w/w) solutions, hydrogels formed in ∼60 s (HB PEGDA/HA-SH 10.0–1.0), as assessed by the tube inverting test. The HB PEGDA/HA-SH 10.0–1.0 hydrogel (200 µL) was resistant to in vitro dissolution in water for at least 64 days, absorbing up to 130 wt% of water. Varying glucose oxidase (GO) amounts (0–500 U/L) and constant glucose content (2.5 wt%) were loaded into HB PEGDA and HA-SH solutions, respectively, before hydrogel formation. Then, the release of H2O2 was evaluated through a colorimetric pertitanic acid assay. The GO content of 250 U/L was selected, allowing the formation of 10.8 ± 1.4 mmol H2O2/L hydrogel in 24 h, under static conditions. The cytocompatibility of HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with different GO activities (≤ 500 U/L) at a constant glucose amount (2.5 wt%) was investigated by in vitro assays at 24 h with L929 and HaCaT cell lines, according to DIN EN ISO 10993-5. The tests showed cytocompatibility for GO enzyme activity up to 250 U/L for both cell lines. The antibacterial activity of HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with increasing amounts of GO was demonstrated against various gram-positive bacteria (S. aureus and S. epidermidis), antibiotic-resistant gram-positive bacteria (MRSA and MRSE), gram-negative bacteria (P. aeruginosa, E. coli, and A. baumanii), and antibiotic-resistant gram-negative strains (P. aeruginosa and E. coli) using agar diffusion tests. For all gram-positive bacterial strains, increasing efficacy was measured with increasing GO activity. For the two P. aeruginosa strains, efficacy was shown only from an enzyme activity of 125 U/L and for E. coli and A. baumanii, efficacy was shown only from 250 U/L enzyme activity. HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with ≤250 U/L GO and 2.5 wt% glucose are promising formulations due to their fast-forming properties, cytocompatibility, and ability to produce antibacterial H2O2, warranting future investigations for bacterial infection treatment, such as wound care.Jeddah Marie VasquezJeddah Marie VasquezJeddah Marie VasquezAyesha IdreesAyesha IdreesIrene CarmagnolaAa SigenAa SigenSean McMahonSean McMahonLennart MarlinghausGianluca CiardelliUdo GreiserHongyun TaiWenxin WangWenxin WangJochen SalberValeria ChionoFrontiers Media S.A.articleantibacterialhyaluronic acidhyperbranched PEGthiol-ene click chemistryhoney-mimetic hydrogeldressingBiotechnologyTP248.13-248.65ENFrontiers in Bioengineering and Biotechnology, Vol 9 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
antibacterial hyaluronic acid hyperbranched PEG thiol-ene click chemistry honey-mimetic hydrogel dressing Biotechnology TP248.13-248.65 |
| spellingShingle |
antibacterial hyaluronic acid hyperbranched PEG thiol-ene click chemistry honey-mimetic hydrogel dressing Biotechnology TP248.13-248.65 Jeddah Marie Vasquez Jeddah Marie Vasquez Jeddah Marie Vasquez Ayesha Idrees Ayesha Idrees Irene Carmagnola Aa Sigen Aa Sigen Sean McMahon Sean McMahon Lennart Marlinghaus Gianluca Ciardelli Udo Greiser Hongyun Tai Wenxin Wang Wenxin Wang Jochen Salber Valeria Chiono In situ Forming Hyperbranched PEG—Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties |
| description |
The rapidly increasing resistance of bacteria to currently approved antibiotic drugs makes surgical interventions and the treatment of bacterial infections increasingly difficult. In recent years, complementary strategies to classical antibiotic therapy have, therefore, gained importance. One of these strategies is the use of medicinal honey in the treatment of bacterially colonized wounds. One of the several bactericidal effects of honey is based on the in situ generation of hydrogen peroxide through the activity of the enzyme glucose oxidase. The strategy underlying this work is to mimic this antibacterial redox effect of honey in an injectable, biocompatible, and rapidly forming hydrogel. The hydrogel was obtained by thiol–ene click reaction between hyperbranched polyethylene glycol diacrylate (HB PEGDA), synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization, and thiolated hyaluronic acid (HA-SH). After mixing 500 µL HB PEGDA (10%, w/w) and 500 µL HA-SH (1%, w/w) solutions, hydrogels formed in ∼60 s (HB PEGDA/HA-SH 10.0–1.0), as assessed by the tube inverting test. The HB PEGDA/HA-SH 10.0–1.0 hydrogel (200 µL) was resistant to in vitro dissolution in water for at least 64 days, absorbing up to 130 wt% of water. Varying glucose oxidase (GO) amounts (0–500 U/L) and constant glucose content (2.5 wt%) were loaded into HB PEGDA and HA-SH solutions, respectively, before hydrogel formation. Then, the release of H2O2 was evaluated through a colorimetric pertitanic acid assay. The GO content of 250 U/L was selected, allowing the formation of 10.8 ± 1.4 mmol H2O2/L hydrogel in 24 h, under static conditions. The cytocompatibility of HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with different GO activities (≤ 500 U/L) at a constant glucose amount (2.5 wt%) was investigated by in vitro assays at 24 h with L929 and HaCaT cell lines, according to DIN EN ISO 10993-5. The tests showed cytocompatibility for GO enzyme activity up to 250 U/L for both cell lines. The antibacterial activity of HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with increasing amounts of GO was demonstrated against various gram-positive bacteria (S. aureus and S. epidermidis), antibiotic-resistant gram-positive bacteria (MRSA and MRSE), gram-negative bacteria (P. aeruginosa, E. coli, and A. baumanii), and antibiotic-resistant gram-negative strains (P. aeruginosa and E. coli) using agar diffusion tests. For all gram-positive bacterial strains, increasing efficacy was measured with increasing GO activity. For the two P. aeruginosa strains, efficacy was shown only from an enzyme activity of 125 U/L and for E. coli and A. baumanii, efficacy was shown only from 250 U/L enzyme activity. HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with ≤250 U/L GO and 2.5 wt% glucose are promising formulations due to their fast-forming properties, cytocompatibility, and ability to produce antibacterial H2O2, warranting future investigations for bacterial infection treatment, such as wound care. |
| format |
article |
| author |
Jeddah Marie Vasquez Jeddah Marie Vasquez Jeddah Marie Vasquez Ayesha Idrees Ayesha Idrees Irene Carmagnola Aa Sigen Aa Sigen Sean McMahon Sean McMahon Lennart Marlinghaus Gianluca Ciardelli Udo Greiser Hongyun Tai Wenxin Wang Wenxin Wang Jochen Salber Valeria Chiono |
| author_facet |
Jeddah Marie Vasquez Jeddah Marie Vasquez Jeddah Marie Vasquez Ayesha Idrees Ayesha Idrees Irene Carmagnola Aa Sigen Aa Sigen Sean McMahon Sean McMahon Lennart Marlinghaus Gianluca Ciardelli Udo Greiser Hongyun Tai Wenxin Wang Wenxin Wang Jochen Salber Valeria Chiono |
| author_sort |
Jeddah Marie Vasquez |
| title |
In situ Forming Hyperbranched PEG—Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties |
| title_short |
In situ Forming Hyperbranched PEG—Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties |
| title_full |
In situ Forming Hyperbranched PEG—Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties |
| title_fullStr |
In situ Forming Hyperbranched PEG—Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties |
| title_full_unstemmed |
In situ Forming Hyperbranched PEG—Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties |
| title_sort |
in situ forming hyperbranched peg—thiolated hyaluronic acid hydrogels with honey-mimetic antibacterial properties |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/a4ca70823b9b4af8a9d46977e2efd765 |
| work_keys_str_mv |
AT jeddahmarievasquez insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT jeddahmarievasquez insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT jeddahmarievasquez insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT ayeshaidrees insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT ayeshaidrees insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT irenecarmagnola insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT aasigen insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT aasigen insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT seanmcmahon insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT seanmcmahon insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT lennartmarlinghaus insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT gianlucaciardelli insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT udogreiser insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT hongyuntai insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT wenxinwang insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT wenxinwang insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT jochensalber insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties AT valeriachiono insituforminghyperbranchedpegthiolatedhyaluronicacidhydrogelswithhoneymimeticantibacterialproperties |
| _version_ |
1718426497069350912 |