Three in One with Dual-Functional Hydrogel of Lactoferrin/NZ2114/LMSH Promoting -Infected Wound Healing

Overview

Journal Antibiotics (Basel)

Specialty Pharmacology

Date 2024 Sep 28

PMID 39335062

Authors

Kun Zhang

Xuanxuan Ma

Da Teng

Ruoyu Mao

Na Yang

Ya Hao

Jianhua Wang

Affiliations

Soon will be listed here.

Abstract

Wound infections caused by often result in localized suppurative lesions that severely impede the healing process, so it is urgent to develop a dress with efficient antimicrobial and pro-healing functions. In this study, the bifunctional injectable hydrogel lactoferrin (Lf)/NZ2114/lithium magnesium silicate hydrogel (LMSH) was first successfully prepared through the electrostatic interaction method. The physical, biological, and efficacy properties are systematically analyzed with good shear-thinning capacity and biocompatibility. More importantly, it inhibits infection and promotes wound healing in a mouse wound infection model after 14 d treatment, and the bactericidal rate and healing rate were over 99.92% and nearly 100%, respectively. Meanwhile, the massive reduction of inflammatory cells, restoration of tissue structure, and angiogenesis in mice showed the anti-inflammatory and pro-healing properties of the hydrogel. The healed wounds showed thickening with more hair follicles and glands, suggesting that the hydrogel Lf/NZ2114/LMSH (Three in One) could be a better dressing candidate for the treatment of -induced wound infections.

References

Ying Y, Huang Z, Tu Y, Wu Q, Li Z, Zhang Y . A shear-thinning, ROS-scavenging hydrogel combined with dental pulp stem cells promotes spinal cord repair by inhibiting ferroptosis. Bioact Mater. 2022; 22:274-290. PMC: 9556860. DOI: 10.1016/j.bioactmat.2022.09.019. View

Elhabal S, Ghaffar S, Hager R, Elzohairy N, Khalifa M, Mohie P . Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: , and studies. Int J Pharm X. 2023; 5:100174. PMC: 9992749. DOI: 10.1016/j.ijpx.2023.100174. View

Velnar T, Bailey T, Smrkolj V . The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res. 2009; 37(5):1528-42. DOI: 10.1177/147323000903700531. View

Krychowiak M, Grinholc M, Banasiuk R, Krauze-Baranowska M, Glod D, Kawiak A . Combination of silver nanoparticles and Drosera binata extract as a possible alternative for antibiotic treatment of burn wound infections caused by resistant Staphylococcus aureus. PLoS One. 2015; 9(12):e115727. PMC: 4281117. DOI: 10.1371/journal.pone.0115727. View

Sherje A, Dravyakar B, Kadam D, Jadhav M . Cyclodextrin-based nanosponges: A critical review. Carbohydr Polym. 2017; 173:37-49. DOI: 10.1016/j.carbpol.2017.05.086. View

Huang Y, Yang N, Teng D, Mao R, Hao Y, Ma X . Antibacterial peptide NZ2114-loaded hydrogel accelerates Staphylococcus aureus-infected wound healing. Appl Microbiol Biotechnol. 2022; 106(9-10):3639-3656. DOI: 10.1007/s00253-022-11943-w. View

Seo J, Shin S, Lee M, Cha J, Min K, Lee S . Injectable hydrogel derived from chitosan with tunable mechanical properties via hybrid-crosslinking system. Carbohydr Polym. 2020; 251:117036. DOI: 10.1016/j.carbpol.2020.117036. View

Yuan N, Xu L, Xu B, Zhao J, Rong J . Chitosan derivative-based self-healable hydrogels with enhanced mechanical properties by high-density dynamic ionic interactions. Carbohydr Polym. 2018; 193:259-267. DOI: 10.1016/j.carbpol.2018.03.071. View

Cui Z, Milani A, Greensmith P, Yan J, Adlam D, Hoyland J . A study of physical and covalent hydrogels containing pH-responsive microgel particles and graphene oxide. Langmuir. 2014; 30(44):13384-93. DOI: 10.1021/la5032015. View

10.

Xiong Y, Hady W, Deslandes A, Rey A, Fraisse L, Kristensen H . Efficacy of NZ2114, a novel plectasin-derived cationic antimicrobial peptide antibiotic, in experimental endocarditis due to methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2011; 55(11):5325-30. PMC: 3195053. DOI: 10.1128/AAC.00453-11. View

11.

Xiong T, Li X, Zhou Y, Song Q, Zhang R, Lei L . Glycosylation-enhanced biocompatibility of the supramolecular hydrogel of an anti-inflammatory drug for topical suppression of inflammation. Acta Biomater. 2018; 73:275-284. DOI: 10.1016/j.actbio.2018.04.019. View

12.

Ramachandran S, Chen S, Etzler F . Rheological characterization of hydroxypropylcellulose gels. Drug Dev Ind Pharm. 1999; 25(2):153-61. DOI: 10.1081/ddc-100102155. View

13.

Yang Y, Zhang C, Bian X, Ren L, Ma C, Xu Y . Characterization of structural and functional properties of soy protein isolate and sodium alginate interpenetrating polymer network hydrogels. J Sci Food Agric. 2023; 103(13):6566-6573. DOI: 10.1002/jsfa.12736. View

14.

Wiegand I, Hilpert K, Hancock R . Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc. 2008; 3(2):163-75. DOI: 10.1038/nprot.2007.521. View

15.

Yang C, Xue R, Zhang Q, Yang S, Liu P, Chen L . Nanoclay cross-linked semi-IPN silk sericin/poly(NIPAm/LMSH) nanocomposite hydrogel: An outstanding antibacterial wound dressing. Mater Sci Eng C Mater Biol Appl. 2017; 81:303-313. DOI: 10.1016/j.msec.2017.08.008. View

16.

Antoshin A, Shpichka A, Huang G, Chen K, Lu P, Svistunov A . Lactoferrin as a regenerative agent: The old-new panacea?. Pharmacol Res. 2021; 167:105564. DOI: 10.1016/j.phrs.2021.105564. View

17.

Li Z, Fan Z, Xu Y, Lo W, Wang X, Niu H . pH-Sensitive and Thermosensitive Hydrogels as Stem-Cell Carriers for Cardiac Therapy. ACS Appl Mater Interfaces. 2016; 8(17):10752-60. PMC: 6410353. DOI: 10.1021/acsami.6b01374. View

18.

MARTIN P, Nunan R . Cellular and molecular mechanisms of repair in acute and chronic wound healing. Br J Dermatol. 2015; 173(2):370-8. PMC: 4671308. DOI: 10.1111/bjd.13954. View

19.

Legrand D . Overview of Lactoferrin as a Natural Immune Modulator. J Pediatr. 2016; 173 Suppl:S10-5. DOI: 10.1016/j.jpeds.2016.02.071. View

20.

Mathew A, Uthaman S, Cho K, Cho C, Park I . Injectable hydrogels for delivering biotherapeutic molecules. Int J Biol Macromol. 2017; 110:17-29. DOI: 10.1016/j.ijbiomac.2017.11.113. View