Treatment of non-healing wounds represents hitherto a severe dilemma for the healthcare worldwide because of wound failure to recover. The physiological wound healing is in fact a critical process requiring lack of both bacterial contamination and persistent inflammatory events in the damaged site. Despite a broad range of both antimicrobial and anti-inflammatory agents is commercially available, a successful tackling of bacterial infections and chronic inflammation is particularly challenging due to the increase of microbial resistance and remarkable side effects caused by an abuse of drugs. To this end, the development of innovative biomaterials used in combination with alternative agents is very challenging. The goals for the present thesis were to fabricate and characterize in terms of physical, chemical and biological properties, nanoengineered biomaterials to be used in the treatment of severe wounds. The potential use of two polysaccharides, namely chitosan and hyaluronan, and of their derivatives has been investigated. In the Chapter I is described an innovative method for the production of tridimensional hydrogels based on chitosan and on the cross-linker tripolyphosphate (TPP). The possibility to obtain hydrogels with chitosans with different acetylation degree (Fa) and molecular weight (Mw) was tackled. Resulting hydrogels were studied in terms of mechanical properties. Finally, soft-pliable and biocompatible membranes were obtained by freeze-drying. Further analyses are accounted in the Chapter II aiming at deeply investigating on hydrogel-forming process. More in detail, the different affinity of cross-linkers TPP and pyrophosphate (PPi) towards chitosan was explored in diluted solutions. The mechanical behavior of resulting hydrogels was further investigated whereas the polymer distribution within matrices has been assessed by both qualitative and quantitative methods. In the Chapter III the preparation of soft pliable chitosan-based membranes prepared from hydrogels containing antimicrobial silver nanoparticles (AgNPs) stabilized by a lactose-modified chitosan (chitlac) is tackled. A thorough investigation on bactericidal properties of the material revealed the synergistic activity of chitosan and AgNPs to reduce the growth of different bacteria strains and to break apart mature biofilms. Finally, biocompatibility assays on keratinocytes and fibroblasts did not prove any harmful effect on mammalian cells. The anti-inflammatory behavior of the short chain fatty acid butyrate is discussed in the first part of Chapter IV. Such feature was proved to be time- and dose-dependent. To extend on time and to modulate the biological activity of butyrate, chitosan/hyaluronan-based nanoparticles (complexes) were developed. These carriers showed the ability to encapsulate butyrate as payload, an intrinsic scavenging activity, the ability to quickly interact with neutrophils, muco-adhesive properties and lack of cytotoxicity. In the Chapter V it has been reported the biological investigation of a complex between hyaluronan-lipoate and silver ions (named SHLS12). Biological studies showed the ability of SHLS12 to exert a straightforward bactericidal activity against different bacterial strains grown both in sessile and planktonic state. The lack of toxicity was proved towards mammalian cells. By considering its ability to preserve antibacterial properties when exposed to serum proteins, this complex may be considered as a promising biomaterial for the treatment of non-healing wounds.

Novel biomaterials for innovative therapies in the severe wounds treatment / Sacco, Pasquale. - (2016 Apr 07).

Novel biomaterials for innovative therapies in the severe wounds treatment

SACCO, PASQUALE
2016-04-07

Abstract

Treatment of non-healing wounds represents hitherto a severe dilemma for the healthcare worldwide because of wound failure to recover. The physiological wound healing is in fact a critical process requiring lack of both bacterial contamination and persistent inflammatory events in the damaged site. Despite a broad range of both antimicrobial and anti-inflammatory agents is commercially available, a successful tackling of bacterial infections and chronic inflammation is particularly challenging due to the increase of microbial resistance and remarkable side effects caused by an abuse of drugs. To this end, the development of innovative biomaterials used in combination with alternative agents is very challenging. The goals for the present thesis were to fabricate and characterize in terms of physical, chemical and biological properties, nanoengineered biomaterials to be used in the treatment of severe wounds. The potential use of two polysaccharides, namely chitosan and hyaluronan, and of their derivatives has been investigated. In the Chapter I is described an innovative method for the production of tridimensional hydrogels based on chitosan and on the cross-linker tripolyphosphate (TPP). The possibility to obtain hydrogels with chitosans with different acetylation degree (Fa) and molecular weight (Mw) was tackled. Resulting hydrogels were studied in terms of mechanical properties. Finally, soft-pliable and biocompatible membranes were obtained by freeze-drying. Further analyses are accounted in the Chapter II aiming at deeply investigating on hydrogel-forming process. More in detail, the different affinity of cross-linkers TPP and pyrophosphate (PPi) towards chitosan was explored in diluted solutions. The mechanical behavior of resulting hydrogels was further investigated whereas the polymer distribution within matrices has been assessed by both qualitative and quantitative methods. In the Chapter III the preparation of soft pliable chitosan-based membranes prepared from hydrogels containing antimicrobial silver nanoparticles (AgNPs) stabilized by a lactose-modified chitosan (chitlac) is tackled. A thorough investigation on bactericidal properties of the material revealed the synergistic activity of chitosan and AgNPs to reduce the growth of different bacteria strains and to break apart mature biofilms. Finally, biocompatibility assays on keratinocytes and fibroblasts did not prove any harmful effect on mammalian cells. The anti-inflammatory behavior of the short chain fatty acid butyrate is discussed in the first part of Chapter IV. Such feature was proved to be time- and dose-dependent. To extend on time and to modulate the biological activity of butyrate, chitosan/hyaluronan-based nanoparticles (complexes) were developed. These carriers showed the ability to encapsulate butyrate as payload, an intrinsic scavenging activity, the ability to quickly interact with neutrophils, muco-adhesive properties and lack of cytotoxicity. In the Chapter V it has been reported the biological investigation of a complex between hyaluronan-lipoate and silver ions (named SHLS12). Biological studies showed the ability of SHLS12 to exert a straightforward bactericidal activity against different bacterial strains grown both in sessile and planktonic state. The lack of toxicity was proved towards mammalian cells. By considering its ability to preserve antibacterial properties when exposed to serum proteins, this complex may be considered as a promising biomaterial for the treatment of non-healing wounds.
7-apr-2016
MARSICH, ELEONORA
28
2014/2015
Settore FIS/03 - Fisica della Materia
Università degli Studi di Trieste
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2907993
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