CLARISSA CIARLANTINI

Dottoressa di ricerca

ciclo: XXXVI


supervisore: Antonella Piozzi

Titolo della tesi: DEVELOPMENT OF BIOACTIVE POLYMER SYSTEMS FOR MEDICAL APPLICATIONS

There are currently numerous opportunities and challenges in the development and characterization of biomaterials. In the medical field, the functions required for biomaterials are multiple. They can be exploited, for example, to improve joint capacity, to control blood flow, in the filling of cavities (in the context of cosmetic surgery), for the distribution of drugs or other bioactive molecules and are widely used in the regeneration of tissues. To allow the realization of all these applications, biomaterials can be modelled in different geometries. For example, three-dimensional porous architectures, used as supports for tissue regeneration (scaffolds) or in the release of active components or target molecules (nano-/micro-particles), as well as flat structures (film) for wound healing or drug delivery can be manufactured. In addition, to be successfully applied in the biomedical field, biomaterials must be biodegradable, biocompatible, and bioactive. Among various biomaterials which can be used in the medical application, polysaccharides play a crucial role thanks to their intrinsic biodegradability and biocompatibility. However, they alone do not possess sufficient bioactivity to produce biomedical devices. Furthermore, they are characterized by poor control of the degradation phase, low mechanical strength, and poor dimensional stability in an aqueous environment. Hence the need to submit these materials to chemical or physical modification processes or to cross-linking to obtain matrices with enhanced chemical-physical and biological properties. In this research, bioactive and/or biomimetic polymeric systems were developed for biomedical applications. In particular, porous scaffolds based on chitosan-alginate polyelectrolyte complexes (PECs) were fabricated by freeze-drying method and then crosslinked with Ca2+ ions. Various chitosan-alginate (CS-AL) molar ratios were used to obtain PECs with different structural and mechanical properties. FTIR and TGA analyses indicated the CS:AL molar ratio of 1:2.3 was more effective in PEC formation. This CS1-AL2.3 scaffold possessed the best mechanical properties and good pore morphology. The crosslinking process led to a less porous structure and a significant increase in the elastic modulus. To make matrix bioactive, the CS1-AL2.3 system was chemically modified with 3,4-dihydroxyhydrocinnamic acid (HCAF) and then crosslinked with Ca2+. The functionalization degree of the scaffold was approximately 12%, while its antioxidant properties increased by 3 orders of magnitude compared to the non-functionalized matrix. The introduction of sulphonic groups into the bioactive scaffold made the structure more porous and hydrophilic and promoted the penetration and proliferation of fibroblasts into the scaffold. Porous scaffolds can also be fabricated using other techniques including electrospinning. The electrospinning technique produces fibers with a thickness that varies from nanometers to several micrometers depending on the electrospinning conditions. In this work, electrospinning was used to fabricate biomimetic scaffolds based on polyelectrolyte complexes constituted by chitosan (CS) and alginate (AL) or CS and hyaluronic acid (HA), using polyvinyl alcohol (PVA) as a fluid viscosity modulating agent. To improve the dimensional stability of the systems in an aqueous medium, the electrospun scaffolds were cross-linked first by physical crosslinking, performed using freeze-thaw processes, and then chemically with EDC:NHS reagents. The matrices containing collagen showed high thermal and structural stability. In particular, the most promising CS-AL-PVA15-COL0.7 matrix possessed the best degree of pore interconnection associated with mechanical properties suitable for tissue engineering application. In the case of HA-based electrospun matrices, scaffolds with more homogeneous fibers and larger pore sizes were obtained compared to the matrices containing collagen. However, these matrices were characterized by lower mechanical resistance and dimensional stability in an aqueous environment. The CS-HA0.5-PVA15 matrix appeared to have the best compromise between mechanical properties and degree of pore interconnection. As for the cell viability test, the selected biomimetic electrospun scaffolds demonstrated no obvious toxic effects in the first 24 h. However, among the developed electrospun scaffolds, only CS-AL-PVA15-COL0.7 and CS-HA0.5-PVA15 could have potential for tissue engineering applications, especially for tendon regeneration. Wound healing is a complex biological process related to the regeneration of damaged tissue. Generally, dressings are used to promote the healing process of wounds. Recently, the design of polymeric systems capable of releasing bioactive molecules (antioxidants, anti-inflammatories or drugs) has been taken into consideration. Polysaccharides have attracted much attention for wound dressing fabrication thanks to their excellent characteristics, including their similarity to the extracellular matrix. CS has been shown to have good performance on the regeneration of skin tissue due to its ability to promote the formation of granulation tissue. At this aim, bioactive dressings were developed by chemical and physical modification of chitosan with GMA and GLY, respectively. It was evidenced that after functionalization with GMA the swelling properties of CS decreased while the mechanical ones improved in terms of elasticity thanks to the subsequent introduction of GLY, used as a plasticizer. It was verified that the most suitable GLY concentration to obtain wound healing dressings with good elongation at break, WVTR and wettability values was 20% (w/w). After the cross-linking reaction with EGDMA, carried out at different crosslinker concentrations, an increase in the elastic modulus and a decrease in the elasticity of the matrices were observed. However, it was possible to obtain matrices with contact angle and WVTR values which satisfied the fundamental requirements for obtaining wound dressings only when an EGDMA concentration of 0.05 mM was used. To avoid possible inflammatory reactions during the wound healing phase and improve the antimicrobial properties of the obtained devices, an antioxidant molecule, 3,4 hydroxycinnamic acid (HCAF), capable of limiting oxidative stress phenomena was introduced by using two different procedures (chemical and physical introduction). Thermal and mechanical analysis confirmed the formation of a more cohesive network which limited the plasticizing effect of the GLY, particularly when HCAF was chemically bound. Despite both membranes maintaining good values of elongation at break and water absorption, the imbibed one showed a lower EC50 value, indicating the greater possibility of HCAF to interact with DPPH radicals. Preliminary antimicrobial tests showed the effectiveness against S. Aureus of the dressing alone containing the antioxidant physically bound (CS_GMA_GLY20_HCAF_0.05).

Produzione scientifica

11573/1705924 - 2024 - Design of bioactive and biomimetic scaffolds based on chitosan-alginate polyelectrolyte complexes for tissue engineering
Ciarlantini, C; Francolini, I; Silvestro, I; Mariano, A; Scotto D'abusco, A; Piozzi, A. - 01a Articolo in rivista
rivista: CARBOHYDRATE POLYMERS (Elsevier Science Limited:Oxford Fulfillment Center, PO Box 800, Kidlington Oxford OX5 1DX United Kingdom:011 44 1865 843000, 011 44 1865 843699, EMAIL: asianfo@elsevier.com, tcb@elsevier.co.UK, INTERNET: http://www.elsevier.com, http://www.elsevier.com/locate/shpsa/, Fax: 011 44 1865 843010) pp. 1-16 - issn: 0144-8617 - wos: WOS:001137783100001 (2) - scopus: 2-s2.0-85179884648 (3)

11573/1701220 - 2024 - Development of antioxidant and antimicrobial membranes based on functionalized and crosslinked chitosan for tissue regeneration
Ciarlantini, Clarissa; Lacolla, Elisabetta; Francolini, Iolanda; Fernández-García, Marta; Muñoz-Núñez, Carolina; Muñoz-Bonilla, Alexandra; Piozzi, Antonella - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel (Matthaeustrasse 11) : Molecular Diversity Preservation International MDPI) pp. 1-26 - issn: 1661-6596 - wos: WOS:001172262500001 (0) - scopus: 2-s2.0-85185898835 (0)

11573/1683616 - 2023 - Rice husk ash as a green feedstock for the extraction of nano-silica and its application in the synthesis of an efficient solid biocatalyst
Chiappini, Viviana; Scuto, Francesca Romana; Ciarlantini, Clarissa; Piozzi, Antonella; Girelli, Anna Maria - 04f Poster
congresso: 15th Mediterranean Congress of Chemical Engineering (Barcelona (Spain))
libro: 15th Mediterranean Congress of Chemical Engineering - ()

11573/1685487 - 2023 - Rice husk ash as a green feedstock for the extraction of nano-silica and its application in the synthesis of an efficient solid biocatalyst
Chiappini, Viviana; Scuto, Francesca Romana; Ciarlantini, Clarissa; Piozzi, Antonella; Girelli, Anna Maria - 04d Abstract in atti di convegno
congresso: 15th Mediterranean Congress of Chemical Engineering (Barcelona (Spain))
libro: 15th Mediterranean Congress of Chemical Engineering - ()

11573/1693004 - 2023 - Development of magnetic molecular imprinted polymer systems for biomedical applications
Ciarlantini, Clarissa; Carnevale, Giorgia; Lacolla, Elisabetta; Francolini, Iolanda; Piozzi, Antonella - 04d Abstract in atti di convegno
congresso: Autumn Meeting for Young Chemists in Biomedical Sciences (Firenze)
libro: Book of abstract-AMYC BIOMED - ()

11573/1693242 - 2023 - Development of antioxidant wound dressings based on functionalized and crosslinked chitosan
Ciarlantini, Clarissa; Lacolla, Elisabetta; Francolini, Iolanda; Piozzi, Antonella - 04d Abstract in atti di convegno
congresso: Macrogiovani (Catania)
libro: Book of abstract-Macrogiovani - ()

11573/1693248 - 2023 - Development of antioxidant wound dressings based on functionalized and crosslinked chitosan
Ciarlantini, Clarissa; Lacolla, Elisabetta; Francolini, Iolanda; Piozzi, Antonella - 04d Abstract in atti di convegno
congresso: 8th EPNOE International Polysaccharides Conference (Graz)
libro: Book of abstract-8th EPNOE International Polysaccharides Conference - ()

11573/1693005 - 2023 - Development of polysaccharide-based nano-systems containing lactoferrin for treatment of respiratory infections
Lacolla, Elisabetta; Marcucci, Arianna; Ciarlantini, Clarissa; Francolini, Iolanda; Bigioni, Irene; Mariano, Alessia; Scotto D'abusco, Anna; De Berardis, Barbara; Marchetti, Magda; Superti, Fabiana; Piozzi, Antonella - 04d Abstract in atti di convegno
congresso: Autumn Meeting for Chemists in Biomedical Sciences (Firenze; Italia)
libro: Book of Abstract_AMYC BIOMED 2023 - ()

11573/1685488 - 2023 - Design of a 3D Amino-Functionalized Rice Husk Ash Nano-Silica/Chitosan/Alginate Composite as Support for Laccase Immobilization
Scuto, Francesca Romana; Ciarlantini, Clarissa; Chiappini, Viviana; Pietrelli, Loris; Piozzi, Antonella; Girelli, Anna M. - 01a Articolo in rivista
rivista: POLYMERS (Basel : Molecular Diversity Preservation International) pp. 3127- - issn: 2073-4360 - wos: WOS:001036415500001 (1) - scopus: 2-s2.0-85166177719 (2)

11573/1663203 - 2022 - Molecularly Imprinted Polymers Based on Chitosan for 2,4-Dichlorophenoxyacetic Acid Removal
Silvestro, Ilaria; Fernández-García, Marta; Ciarlantini, Clarissa; Francolini, Iolanda; Girelli, Anna Maria; Piozzi, Antonella - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel (Matthaeustrasse 11) : Molecular Diversity Preservation International MDPI) pp. - - issn: 1661-6596 - wos: WOS:000881255600001 (4) - scopus: 2-s2.0-85141796192 (6)

11573/1576678 - 2021 - Chitosan–graphene oxide composite membranes for solid-phase extraction of pesticides
Silvestro, I.; Ciarlantini, C.; Francolini, I.; Tomai, P.; Gentili, A.; Dal Bosco, C.; Piozzi, A. - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel (Matthaeustrasse 11) : Molecular Diversity Preservation International MDPI) pp. 1-17 - issn: 1661-6596 - wos: WOS:000690556100001 (21) - scopus: 2-s2.0-85111719012 (22)

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