Publicação
Active Dressings Based On Natural Polymers For Wound Treatment
| Resumo: | The skin is one of the human organs responsible for sensory detection, temperature regulation, and water balance. Skin damage can lead to wounds that if not treated properly may cause serious health complications. The conventional wound healing products, made from non-biodegradable synthetic materials, usually have low biocompatibility and only offer mechanical protection or exudate removal, without actively helping the wound healing process. To address these limitations, developing new natural, biocompatible, biodegradable, and bioactive materials is crucial to create an optimal environment for proper wound regeneration, minimizing any adverse secondary effects. In this context, this dissertation proposes the use of natural polymers (polyhydroxyalkanoate (PHA) and exopolysaccharide (EPS)) to develop porous structures for wound treatment. To achieve this, four biopolymers were produced: the EPS FucoPol and three different types of PHA: (poly(3-hydroxybutyrate) (P(3HB)), poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (P(3HB-co-3HV-co-3HHx) and a medium chain length PHA (mcl-PHA)), characterized by their distinct physical, chemical and functional properties. The PHAs had distinct molecular weights (ranging from 0.4 to 9.2 x105 Da), different crystallinities (from 18.2 to 85.5%), diverse melting points (between 44.9 and 174.2 °C), various glass transition temperatures (from -46 to 4.1 °C), but similar degradation temperatures (around 275 °C). FucoPol was an amorphous exopolysaccharide had a molecular weight of 1.4 x106 Da, was rich in fucose (34.3 mol%) and had a high degradation temperature (240 °C). All the produced biopolymers were non-cytotoxic towards fibroblasts and keratinocytes. The inherent structural properties of PHA polymers, as well as their lack of cytotoxicity, makes them suitable materials to develop porous structures for wound treatment applications. Given this, different PHA porous structures were developed, based on two different strategies: the emulsion templating technique followed by solvent evaporation and the hot-pressing salt leaching method. Generally, the porous structures achieved by these procedures were macroscopically white and opaque, with thicknesses ranging from 160 to 700 μm, and porosity values from 49.8 to 87.1%. The morphological appearance of these structures resembled those of porous scaffolds attained with synthetic polymers, such as, poly(lactic acid) (PLA), poly(caprolactone) (PCL) and poly(ethylene terephthalate) (PET), which are examples of polymers commonly used in wound dressing applications. The PHA scaffolds were shown to be capable of sustaining fibroblast adhesion and proliferation. The adhesion values achieved for all PHA structures ranged from 25% to 46%, where P(3HB) emulsion templated scaffold achieved the highest fibroblast population after 7 days of cell cultivation (311%). PHAs are biocompatible and biodegradable polymers with good structural properties, however, they usually lack biological activity. To confer this bioactivity to the developed scaffolds, FucoPol (a natural bioemulsifier) was added to these structures, due to its proven ability to promote in vitro migration of keratinocytes, which supports its use in wound treatment. The resulting FucoPol:PHA structures were porous materials with improved bioactive properties. FucoPol revealed to improve biological features, increasing fibroblast population values after 7 days from 311% to 325% and from 145% to 340% for P(3HB) and P(3HB-co-3HV-co-3HHx) emulsion templated scaffolds, respectively. This behaviour was also observed in the hot-pressing salt leaching scaffolds with an increase from 178% to 333% for P(3HB) and from 80% to 121% for P(3HB-co-3HV-co-3HHx) porous structures. Some of these proliferation profiles revealed to be superior to the ones described in the literature for scaffolds produced with PCL, poly(urethane) (PU) and chitosan. These results also suggested that the most promising PHA polymer to produce 3D scaffolds was the homopolymer P(3HB), while the emulsion templating technique showed to be the most favourable strategy to produce porous structures. This dissertation revealed that it is possible to achieve porous scaffolds based on two natural polymers (PHA and FucoPol), through two different methods, with biological properties suitable for soft tissue engineering purposes or in skin regeneration for wound treatment applications. |
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| Autores principais: | Pereira, João |
| Assunto: | Poly(hydroxyalkanoate) (PHA) FucoPol Porous scaffold Emulsion templating Hot-pressing salt leaching Tissue engineering |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | The skin is one of the human organs responsible for sensory detection, temperature regulation, and water balance. Skin damage can lead to wounds that if not treated properly may cause serious health complications. The conventional wound healing products, made from non-biodegradable synthetic materials, usually have low biocompatibility and only offer mechanical protection or exudate removal, without actively helping the wound healing process. To address these limitations, developing new natural, biocompatible, biodegradable, and bioactive materials is crucial to create an optimal environment for proper wound regeneration, minimizing any adverse secondary effects. In this context, this dissertation proposes the use of natural polymers (polyhydroxyalkanoate (PHA) and exopolysaccharide (EPS)) to develop porous structures for wound treatment. To achieve this, four biopolymers were produced: the EPS FucoPol and three different types of PHA: (poly(3-hydroxybutyrate) (P(3HB)), poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (P(3HB-co-3HV-co-3HHx) and a medium chain length PHA (mcl-PHA)), characterized by their distinct physical, chemical and functional properties. The PHAs had distinct molecular weights (ranging from 0.4 to 9.2 x105 Da), different crystallinities (from 18.2 to 85.5%), diverse melting points (between 44.9 and 174.2 °C), various glass transition temperatures (from -46 to 4.1 °C), but similar degradation temperatures (around 275 °C). FucoPol was an amorphous exopolysaccharide had a molecular weight of 1.4 x106 Da, was rich in fucose (34.3 mol%) and had a high degradation temperature (240 °C). All the produced biopolymers were non-cytotoxic towards fibroblasts and keratinocytes. The inherent structural properties of PHA polymers, as well as their lack of cytotoxicity, makes them suitable materials to develop porous structures for wound treatment applications. Given this, different PHA porous structures were developed, based on two different strategies: the emulsion templating technique followed by solvent evaporation and the hot-pressing salt leaching method. Generally, the porous structures achieved by these procedures were macroscopically white and opaque, with thicknesses ranging from 160 to 700 μm, and porosity values from 49.8 to 87.1%. The morphological appearance of these structures resembled those of porous scaffolds attained with synthetic polymers, such as, poly(lactic acid) (PLA), poly(caprolactone) (PCL) and poly(ethylene terephthalate) (PET), which are examples of polymers commonly used in wound dressing applications. The PHA scaffolds were shown to be capable of sustaining fibroblast adhesion and proliferation. The adhesion values achieved for all PHA structures ranged from 25% to 46%, where P(3HB) emulsion templated scaffold achieved the highest fibroblast population after 7 days of cell cultivation (311%). PHAs are biocompatible and biodegradable polymers with good structural properties, however, they usually lack biological activity. To confer this bioactivity to the developed scaffolds, FucoPol (a natural bioemulsifier) was added to these structures, due to its proven ability to promote in vitro migration of keratinocytes, which supports its use in wound treatment. The resulting FucoPol:PHA structures were porous materials with improved bioactive properties. FucoPol revealed to improve biological features, increasing fibroblast population values after 7 days from 311% to 325% and from 145% to 340% for P(3HB) and P(3HB-co-3HV-co-3HHx) emulsion templated scaffolds, respectively. This behaviour was also observed in the hot-pressing salt leaching scaffolds with an increase from 178% to 333% for P(3HB) and from 80% to 121% for P(3HB-co-3HV-co-3HHx) porous structures. Some of these proliferation profiles revealed to be superior to the ones described in the literature for scaffolds produced with PCL, poly(urethane) (PU) and chitosan. These results also suggested that the most promising PHA polymer to produce 3D scaffolds was the homopolymer P(3HB), while the emulsion templating technique showed to be the most favourable strategy to produce porous structures. This dissertation revealed that it is possible to achieve porous scaffolds based on two natural polymers (PHA and FucoPol), through two different methods, with biological properties suitable for soft tissue engineering purposes or in skin regeneration for wound treatment applications. |
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