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Design and characterization of a supramolecular hydrogel containing nanoparticles with antioxidant and antibacterial properties to treat chronic wounds

Giuliana Orlandini

Design and characterization of a supramolecular hydrogel containing nanoparticles with antioxidant and antibacterial properties to treat chronic wounds.

Rel. Clara Mattu, Gianluca Ciardelli, Monica Boffito. Politecnico di Torino, Corso di laurea magistrale in Ingegneria Biomedica, 2022

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Chronic wound (CW) treatment represents one of the main challenges of modern medicine. As CWs result from a variety of causes, their treatment is particularly difficult and can adversely affect patient’s life. A serious obstacle to CW treatment is represented by bacterial resistance to antibiotics. This thesis aimed at the design of a hydrogel intended to be placed in contact with the bed of CWs to stimulate wound remission, without the use of antibiotics. To obtain this result, an injectable supramolecular (SM) polyurethane (PU) hydrogel was loaded with antioxidant and antibacterial nanoparticles (NPs). The NPs were obtained by combining two plant- derived polyphenolic compounds with antioxidant properties, lignin, and tannic acid. The project focused on the optimization of a green synthesis exploiting the enzymatic activity of laccase to promote lignin phenolation, fundamental to strongly increase NP antioxidant properties. As a result, phenolated lignin NPs (PheLig NPs) were obtained. The NPs were then enriched with a metalloproteinase (MMP) inhibitor to promote an active targeting of the MMPs that are commonly overexpressed in CWs. To this aim, L-tyrosine hydroxamate (LTH) was conjugated to PheLig NPs via enzymatic reaction obtaining LTH-PheLig NPs. Finally, Co was loaded in the NPs via redox reaction, to confer bactericidal properties, obtaining Co-LTH-PheLig NPs. All the synthesized NPs were characterized in term of average dimension, PdI and zeta potential. LTH-PheLig NPs had similar size and zeta potential compared to PheLig NPs, while Co-LTH-PheLig NPs resulted in a smaller average dimension. LTH conjugation increased NP antioxidant properties, as demonstrated by the myeloperoxidase residual activity measured after incubation with NPs. Co inclusion was proved via Inductively Coupled Plasma Spectroscopy . In addition, NP inhibitory effects over bacterial growth as well as their antibacterial properties were measured. Finally, viability tests were conducted on fibroblasts and keratinocytes. PheLig NPs and LTH-PheLig NPs showed good cytocompatibility and inhibitory effects over bacterial growth, but lower bactericidal effects compared to Co-PheLig NPs. Co inclusion increased NP cytotoxicity. However, Co-PheLig NPs showed good bactericidal and antioxidant effects at lower concentration. NPs were then loaded within an injectable SM network based on two PUs (CHP407 and SHF68) and α-cyclodextrins. NP loading increased system stability, as demonstrated by rheological tests. This is probably related to new crosslinking points occurring between NP phenolic groups and SHF68 primary amines. Finally release studies showed a quite linear and controlled kinetics, with no burst release. The overall system showed no swelling behaviour but a weight loss over time proportional to the fluids the system was put in contact with. This is due to an exchange of fluids between the environment inside and outside the hydrogel: the greater the volume of fluid with which the system was in contact, the greater the flow rate. Overall, the developed formulations are potential promising platforms for wound healing applications although further investigations are necessary. Possible future research perspectives could be the optimisation of the NPs content within the system to achieve a good compromise between biocompatibility and release kinetics, as well as the characterisation of the system in contact with human exudate.

Relators: Clara Mattu, Gianluca Ciardelli, Monica Boffito
Academic year: 2022/23
Publication type: Electronic
Number of Pages: 112
Corso di laurea: Corso di laurea magistrale in Ingegneria Biomedica
Classe di laurea: New organization > Master science > LM-21 - BIOMEDICAL ENGINEERING
Aziende collaboratrici: Universitat Politècnica de Catalunya
URI: http://webthesis.biblio.polito.it/id/eprint/25764
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