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  • 1.
    Basu, Alex
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Ion-Crosslinked Nanocellulose Hydrogels for Advanced Wound Care Applications2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    A current trend in the field of wound care is the development of wound healing materials that are designed to address specific types of wounds or underlying pathologies to achieve improved healing. At the same time, there is a societal drive to replace synthetic materials with renewable alternatives. The work presented in this thesis was therefore carried out to investigate the use of wood nanocellulose, produced from the world’s most abundant biopolymer, cellulose, in advanced wound care applications.

    Wood-based nanofibrillated cellulose (NFC) was chemically functionalized and crosslinked using calcium to obtain a self-standing hydrogel. The NFC hydrogel was evaluated in terms of its physicochemical properties, biocompatibility, blood interactions, bacterial interactions, in vivo wound healing ability and, finally, as a protein carrier. Parallel with the assessment of the NFC hydrogel, modified versions of the material were tested to investigate the tunability of the above-mentioned characteristics.

    The ability of the hydrogel to maintain a moist wound bed was demonstrated. Evaluation of the biocompatibility showed that the material was cytocompatible and did not trigger inflammatory mechanisms. Furthermore, the NFC hydrogel supported cell proliferation, and was shown to possess hemostatic properties. It was also discovered that the material had a slight bacteriostatic effect and the ability to act as a barrier against bacteria. When tested in vivo, the hydrogel was found to significantly improve wound healing.

    Modifications through the incorporation of additives to the hydrogel matrix, as well as exchange of the crosslinking ion, were shown to influence the biological response to the material. Moreover, the results presented here demonstrate the possibility of using the NFC hydrogel as a protein carrier; the easily adjustable charge property being identified as a central parameter for manipulation to regulate the release profile.

    In conclusion, this work has demonstrated the extensive wound healing ability of the calcium-crosslinked NFC hydrogel, and represents an important milestone in the research on NFC towards advanced wound care applications. It is expected that the easily modifiable nature of the material can be exploited to further develop the NFC hydrogel to suit the treatment needs for a broad range of wound types.

    Delarbeten
    1. On the use of ion-crosslinked nanocellulose hydrogels for wound healing solutions: Physicochemical properties and application-oriented biocompatibility studies
    Öppna denna publikation i ny flik eller fönster >>On the use of ion-crosslinked nanocellulose hydrogels for wound healing solutions: Physicochemical properties and application-oriented biocompatibility studies
    Visa övriga...
    2017 (Engelska)Ingår i: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 174, s. 299-308Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Calcium ion-crosslinked nanofibrillated cellulose (NFC) hydrogels were investigated as potential materials for wound healing dressings. The physicochemical properties of the hydrogels were examined by rheology and water retention tests. Skin cells and monocytes were selected for application-oriented bio-compatibility studies. The NFC hydrogels presented entangled fibrous networks and solid-like behavior. Water retention tests showed the material's potential to maintain a suitable moist environment for different type of wounds. The hydrogels did not affect dermal fibroblasts monolayer cultures upon directcontact, as cell monolayers remained intact after application, incubation and removal of the materials. Inflammatory response studies with blood-derived mononuclear cells revealed the inert nature of the hydrogels in terms of cytokine secretion and reactive oxygen species production. Results highlight the great potential of ion-crosslinked NFC hydrogels for the development of advanced wound dressings, where further functionalization of the material could lead to improved properties towards the healing of specific wound types.

    Nyckelord
    Nanofibrillated cellulose, Inflammation, Fibroblasts, Mononuclear cells
    Nationell ämneskategori
    Nanoteknik
    Forskningsämne
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-332126 (URN)10.1016/j.carbpol.2017.06.073 (DOI)000407696800032 ()28821071 (PubMedID)
    Forskningsfinansiär
    Forskningsrådet Formas
    Tillgänglig från: 2017-10-24 Skapad: 2017-10-24 Senast uppdaterad: 2018-10-12Bibliografiskt granskad
    2. Hemocompatibility of Ca2+-Crosslinked Nanocellulose Hydrogels: Toward Efficient Management of Hemostasis
    Öppna denna publikation i ny flik eller fönster >>Hemocompatibility of Ca2+-Crosslinked Nanocellulose Hydrogels: Toward Efficient Management of Hemostasis
    2017 (Engelska)Ingår i: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 17, nr 11, artikel-id 1700236Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The present work investigates Ca2+-crosslinked nanofibrillated cellulose hydrogels as potential hemostatic wound dressings by studying core interactions between the materials and a central component of wounds and wound healing—the blood. Hydrogels of wood-derived anionic nanofibrillated cellulose (NFC) and NFC hydrogels that incorporate kaolin or collagen are studied in an in vitro whole blood model and with platelet-free plasma assays. The evaluation of thrombin and factor XIIa formation, platelet reduction, and the release of activated complement system proteins, shows that the NFC hydrogel efficiently triggered blood coagulation, with a rapid onset of clot formation, while displaying basal complement system activation. By using the NFC hydrogel as a carrier of kaolin, the onset of hemostasis is further boosted, while the NFC hydrogel containing collagen exhibits blood activating properties comparable to the anionic NFC hydrogel. The herein studied NFC hydrogels demonstrate great potential for being part of advanced wound healing dressings that can be tuned to target certain wounds (e.g., strongly hemorrhaging ones) or specific phases of the wound healing process for optimal wound management.

    Nyckelord
    biocompatibility, blood coagulation, complement system, nanofibrillated cellulose, wound dressing
    Nationell ämneskategori
    Nanoteknik
    Forskningsämne
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-332127 (URN)10.1002/mabi.201700236 (DOI)000415130800015 ()28941135 (PubMedID)
    Forskningsfinansiär
    Forskningsrådet Formas
    Tillgänglig från: 2017-10-24 Skapad: 2017-10-24 Senast uppdaterad: 2018-10-12Bibliografiskt granskad
    3. Ion-crosslinked wood-derived nanocellulose hydrogels with tunable antibacterial properties: Candidate materials for advanced wound care applications
    Öppna denna publikation i ny flik eller fönster >>Ion-crosslinked wood-derived nanocellulose hydrogels with tunable antibacterial properties: Candidate materials for advanced wound care applications
    Visa övriga...
    2018 (Engelska)Ingår i: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 181, s. 345-350Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Development of advanced dressings with antimicrobial properties for the treatment of infected wounds is an important approach in the fight against evolution of antibiotic resistant bacterial strains. Herein, the effects of ion-crosslinked nanocellulose hydrogels on bacteria commonly found in infected wounds were investigated in vitro. By using divalent calcium or copper ions as crosslinking agents, different antibacterial properties against the bacterial strains Staphylococcus epidermidis and Pseudomonas aeruginosa were obtained. Calcium crosslinked hydrogels were found to retard S. epidermidis growth (up to 266% increase in lag time, 36% increase in doubling time) and inhibited P. aeruginosa biofilm formation, while copper crosslinked hydrogels prevented S. epidermidis growth and were bacteriostatic towards P. aeruginosa (49% increase in lag time, 78% increase in doubling time). The wound dressing candidates furthermore displayed barrier properties towards both S. epidermidis and P. aeruginosa, hence making them interesting for further development of advanced wound dressings with tunable antibacterial properties.

    Nyckelord
    Nanofibrillated cellulose, Biofilm, Wound dressing, Infected wound
    Nationell ämneskategori
    Nanoteknik
    Forskningsämne
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-333382 (URN)10.1016/j.carbpol.2017.10.085 (DOI)000418661000041 ()29253982 (PubMedID)
    Forskningsfinansiär
    Forskningsrådet Formas
    Tillgänglig från: 2017-11-13 Skapad: 2017-11-13 Senast uppdaterad: 2018-10-12Bibliografiskt granskad
    4. In vitro and in vivo evaluation of the wound healing properties of nanofibrillated cellulose hydrogels
    Öppna denna publikation i ny flik eller fönster >>In vitro and in vivo evaluation of the wound healing properties of nanofibrillated cellulose hydrogels
    (Engelska)Ingår i: Artikel i tidskrift (Refereegranskat) Submitted
    Nationell ämneskategori
    Nanoteknik
    Forskningsämne
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-362724 (URN)
    Tillgänglig från: 2018-10-09 Skapad: 2018-10-09 Senast uppdaterad: 2018-10-12
    5. Towards Tunable Protein-Carrier Wound Dressings Based on Nanocellulose Hydrogels Crosslinked with Calcium Ions
    Öppna denna publikation i ny flik eller fönster >>Towards Tunable Protein-Carrier Wound Dressings Based on Nanocellulose Hydrogels Crosslinked with Calcium Ions
    2018 (Engelska)Ingår i: Nanomaterials, E-ISSN 2079-4991, Vol. 8, nr 7, artikel-id 550Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A Ca2+-crosslinked wood-based nanofibrillated cellulose (NFC) hydrogel was investigated to build knowledge toward the use of nanocellulose for topical drug delivery applications in a chronic wound healing context. Proteins of varying size and isoelectric point were loaded into the hydrogel in a simple soaking procedure. The release of the proteins from the hydrogel was monitored and kinetics determining parameters of the release processes were assessed. The integrity of the hydrogel and proteins were also studied. The results showed that electrostatic interactions between the proteins and the negatively-charged NFC hydrogel structure played a central role in the loading process. The release of the proteins were governed by Fickian diffusion. An increased protein size, as well as a positive protein charge facilitated a slower and more sustained release process from the hydrogel matrix. At the same time, the positively-charged protein was shown to increase the post-loading hydrogel strength. Released proteins maintained structural stability and activity, thus indicating that the Ca2+-crosslinked NFC hydrogel could function as a carrier of therapeutic proteins without compromising protein function. It is foreseen that, by utilizing tunable charge properties of the NFC hydrogel, release profiles can be tailored to meet very specific treatment needs.

    Ort, förlag, år, upplaga, sidor
    MDPI, 2018
    Nyckelord
    nanofibrillated cellulose, ion-crosslinked, drug delivery, wound healing, chronic wounds
    Nationell ämneskategori
    Nanoteknik
    Forskningsämne
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-362722 (URN)10.3390/nano8070550 (DOI)000442523100101 ()30036970 (PubMedID)
    Forskningsfinansiär
    Forskningsrådet Formas, 942-2015-475
    Tillgänglig från: 2018-10-09 Skapad: 2018-10-09 Senast uppdaterad: 2018-10-30Bibliografiskt granskad
  • 2.
    Basu, Alex
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Celma, Gunta
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Ferraz, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    In Vitro and in Vivo Evaluation of the Wound Healing Properties of Nanofibrillated Cellulose Hydrogels2018Ingår i: ACS Applied Bio MaterialsArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Current trends in wound care research move toward the development of wound healing dressings designed to treat different types of wounds (e.g., burns and chronic wounds) and toward tailoring treatments for different stages of the wound healing process. In this context, the development of advanced nanotherapeutic materials is highlighted as a promising strategy to efficiently control specific phases of the wound healing process. Here, Ca2+-cross-linked wood-derived nanofibrillated cellulose (NFC) hydrogels are evaluated as wound healing dressings. In vitro biocompatibility assays were performed to study the interaction of the NFC hydrogels with cellular processes that are tightly related to wound healing. Moreover, an in vivo dermo-epidermic full thickness wound healing model in rat was used to uncover the wound healing ability of the Ca2+-cross-linked NFC hydrogels. The in vitro experiments showed that the NFC hydrogels were able to support fibroblast and keratinocyte proliferation. A potential effect of the hydrogels on triggering keratinocyte differentiation was furthermore proposed. In vivo, the NFC hydrogels stimulated healing without causing any adverse local tissue effects, potentially owing to their moisture-donating properties and the herein discussed aiding effect of the Ca2+-cross-linker on epidermal generation. Thus, this work extensively demonstrates the wound healing ability of NFC hydrogels and presents an important milestone in the research on NFC toward advanced wound healing applications.

  • 3.
    Basu, Alex
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Ferraz, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Ion-crosslinked nanocellulose hydrogels for biomedical applications2015Konferensbidrag (Refereegranskat)
  • 4.
    Basu, Alex
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Ferraz, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Nanofibrillated cellulose hydrogels for wound healing solutions: the status quo and future prospects2015Ingår i: Uppsala Biomaterials Conference 2015, 2015Konferensbidrag (Refereegranskat)
  • 5.
    Basu, Alex
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Heitz, Karen
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Welch, Ken
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Ferraz, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Ion-crosslinked wood-derived nanocellulose hydrogels with tunable antibacterial properties: Candidate materials for advanced wound care applications2018Ingår i: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 181, s. 345-350Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Development of advanced dressings with antimicrobial properties for the treatment of infected wounds is an important approach in the fight against evolution of antibiotic resistant bacterial strains. Herein, the effects of ion-crosslinked nanocellulose hydrogels on bacteria commonly found in infected wounds were investigated in vitro. By using divalent calcium or copper ions as crosslinking agents, different antibacterial properties against the bacterial strains Staphylococcus epidermidis and Pseudomonas aeruginosa were obtained. Calcium crosslinked hydrogels were found to retard S. epidermidis growth (up to 266% increase in lag time, 36% increase in doubling time) and inhibited P. aeruginosa biofilm formation, while copper crosslinked hydrogels prevented S. epidermidis growth and were bacteriostatic towards P. aeruginosa (49% increase in lag time, 78% increase in doubling time). The wound dressing candidates furthermore displayed barrier properties towards both S. epidermidis and P. aeruginosa, hence making them interesting for further development of advanced wound dressings with tunable antibacterial properties.

  • 6.
    Basu, Alex
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Hong, Jaan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Ferraz, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Hemocompatibility of Ca2+-Crosslinked Nanocellulose Hydrogels: Toward Efficient Management of Hemostasis2017Ingår i: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 17, nr 11, artikel-id 1700236Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The present work investigates Ca2+-crosslinked nanofibrillated cellulose hydrogels as potential hemostatic wound dressings by studying core interactions between the materials and a central component of wounds and wound healing—the blood. Hydrogels of wood-derived anionic nanofibrillated cellulose (NFC) and NFC hydrogels that incorporate kaolin or collagen are studied in an in vitro whole blood model and with platelet-free plasma assays. The evaluation of thrombin and factor XIIa formation, platelet reduction, and the release of activated complement system proteins, shows that the NFC hydrogel efficiently triggered blood coagulation, with a rapid onset of clot formation, while displaying basal complement system activation. By using the NFC hydrogel as a carrier of kaolin, the onset of hemostasis is further boosted, while the NFC hydrogel containing collagen exhibits blood activating properties comparable to the anionic NFC hydrogel. The herein studied NFC hydrogels demonstrate great potential for being part of advanced wound healing dressings that can be tuned to target certain wounds (e.g., strongly hemorrhaging ones) or specific phases of the wound healing process for optimal wound management.

  • 7.
    Basu, Alex
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Lindh, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Ålander, Eva
    Rise Bioeconomy.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Ferraz, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    On the use of ion-crosslinked nanocellulose hydrogels for wound healing solutions: Physicochemical properties and application-oriented biocompatibility studies2017Ingår i: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 174, s. 299-308Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Calcium ion-crosslinked nanofibrillated cellulose (NFC) hydrogels were investigated as potential materials for wound healing dressings. The physicochemical properties of the hydrogels were examined by rheology and water retention tests. Skin cells and monocytes were selected for application-oriented bio-compatibility studies. The NFC hydrogels presented entangled fibrous networks and solid-like behavior. Water retention tests showed the material's potential to maintain a suitable moist environment for different type of wounds. The hydrogels did not affect dermal fibroblasts monolayer cultures upon directcontact, as cell monolayers remained intact after application, incubation and removal of the materials. Inflammatory response studies with blood-derived mononuclear cells revealed the inert nature of the hydrogels in terms of cytokine secretion and reactive oxygen species production. Results highlight the great potential of ion-crosslinked NFC hydrogels for the development of advanced wound dressings, where further functionalization of the material could lead to improved properties towards the healing of specific wound types.

  • 8.
    Basu, Alex
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Ferraz, Natalia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Towards Tunable Protein-Carrier Wound Dressings Based on Nanocellulose Hydrogels Crosslinked with Calcium Ions2018Ingår i: Nanomaterials, E-ISSN 2079-4991, Vol. 8, nr 7, artikel-id 550Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A Ca2+-crosslinked wood-based nanofibrillated cellulose (NFC) hydrogel was investigated to build knowledge toward the use of nanocellulose for topical drug delivery applications in a chronic wound healing context. Proteins of varying size and isoelectric point were loaded into the hydrogel in a simple soaking procedure. The release of the proteins from the hydrogel was monitored and kinetics determining parameters of the release processes were assessed. The integrity of the hydrogel and proteins were also studied. The results showed that electrostatic interactions between the proteins and the negatively-charged NFC hydrogel structure played a central role in the loading process. The release of the proteins were governed by Fickian diffusion. An increased protein size, as well as a positive protein charge facilitated a slower and more sustained release process from the hydrogel matrix. At the same time, the positively-charged protein was shown to increase the post-loading hydrogel strength. Released proteins maintained structural stability and activity, thus indicating that the Ca2+-crosslinked NFC hydrogel could function as a carrier of therapeutic proteins without compromising protein function. It is foreseen that, by utilizing tunable charge properties of the NFC hydrogel, release profiles can be tailored to meet very specific treatment needs.

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