3D Matrices for Enhanced Encapsulation and Controlled Release of Anti-Inflammatory Bioactive Compounds in Wound Healing

Current trends in the development of wound dressings are oriented towards the use of biopolymer-based materials, due to their unique properties such as non-toxicity, hydrophilicity, biocompatibility and biodegradability, properties that have advantageous therapeutic characteristics. In this regard, the present study aims to develop hydrogels based on cellulose and dextran (CD) and to reveal their anti-inflammatory performance. This purpose is achieved by incorporating plant bioactive polyphenols (PFs) in CD hydrogels. The assessments include establishing the structural characteristics using attenuated total reflection Fourier transformed infrared (ATR-FTIR) spectroscopy, the morphology by scanning electron microscopy (SEM), the swelling degree of hydrogels, the PFs incorporation/release kinetics and the hydrogels’ cytotoxicity, together with evaluation of the anti-inflammatory properties of PFs-loaded hydrogels. The results show that the presence of dextran has a positive impact on the hydrogel’s structure by decreasing the pore size at the same time as increasing the uniformity and interconnectivity of the pores. In addition, there is an increased degree of swelling and of the encapsulation capacity of PFs, with the increase of the dextran content in hydrogels. The kinetics of PFs released by hydrogels was studied according to the Korsmeyer–Peppas model, and it was observed that the transport mechanisms depend on hydrogels’ composition and morphology. Furthermore, CD hydrogels have been shown to promote cell proliferation without cytotoxicity, by successfully culturing fibroblasts and endothelial cells on CD hydrogels (over 80% viability). The anti-inflammatory tests performed in the presence of lipopolysaccharides demonstrate the anti-inflammatory properties of the PFs-loaded hydrogels. All these results provide conclusive evidence on the acceleration of wound healing by inhibiting the inflammation process and support the use of these hydrogels encapsulated with PFs in wound healing applications.

[1]  M. Raucci,et al.  Advances in the Physico-Chemical, Antimicrobial and Angiogenic Properties of Graphene-Oxide/Cellulose Nanocomposites for Wound Healing , 2023, Pharmaceutics.

[2]  L. Grøndahl,et al.  Evaluation of techniques used for visualisation of hydrogel morphology and determination of pore size distributions , 2023, Materials Advances.

[3]  J. Kaur,et al.  "RECENT APPROACHES TO THE SYNTHESIS OF HYDROGELS FROM LIGNOCELLULOSIC BIOMASS: A REVIEW " , 2022, Cellulose Chemistry and Technology.

[4]  Rongying Ou,et al.  Polysaccharide-Based Hydrogels for Wound Dressing: Design Considerations and Clinical Applications , 2022, Frontiers in Bioengineering and Biotechnology.

[5]  P. Taboada,et al.  Development of functional hybrid scaffolds for wound healing applications , 2022, iScience.

[6]  Xiao–kun Ouyang,et al.  Polyphenol-based hydrogels: Pyramid evolution from crosslinked structures to biomedical applications and the reverse design , 2022, Bioactive materials.

[7]  M. L. Kori,et al.  Fabrication and Evaluation of Carboxy Methyl Cellulose Anchored Dextran Bioinspired Hydrogel for Effective Delivery of Piroxicam , 2022, Indian Journal of Pharmaceutical Sciences.

[8]  M. Xie,et al.  Applications of infrared spectroscopy in polysaccharide structural analysis: Progress, challenge and perspective , 2021, Food chemistry: X.

[9]  S. Kamel,et al.  Biocompatible hydrogel based on aldehyde-functionalized cellulose and chitosan for potential control drug release , 2021 .

[10]  M. Kopjar,et al.  Hydrogels: Characteristics and Application as Delivery Systems of Phenolic and Aroma Compounds , 2021, Foods.

[11]  M. Dinu,et al.  New cellulose-collagen-alginate materials incorporated with quercetin, anthocyanins and lipoic acid. , 2021, International journal of biological macromolecules.

[12]  Christopher S. Chen,et al.  Reconstituting the dynamics of endothelial cells and fibroblasts in wound closure , 2021, APL bioengineering.

[13]  Zhipeng Gu,et al.  Polyphenol scaffolds in tissue engineering. , 2021, Materials horizons.

[14]  D. Ciolacu,et al.  Cellulose-Based Hydrogels as Sustained Drug-Delivery Systems , 2020, Materials.

[15]  Elham M. A. Dannoun,et al.  Tea from the drinking to the synthesis of metal complexes and fabrication of PVA based polymer composites with controlled optical band gap , 2020, Scientific Reports.

[16]  E. Silina,et al.  The Effect of Inflammation on the Healing Process of Acute Skin Wounds Under the Treatment of Wounds with Injections in Rats , 2020, Journal of experimental pharmacology.

[17]  A. Tabernero,et al.  Microbial Exopolysaccharides as Drug Carriers , 2020, Polymers.

[18]  Karina Cesca,et al.  STUDY OF MELANOMA CELL BEHAVIOR IN VITRO IN COLLAGEN FUNCTIONALIZED BACTERIAL NANOCELLULOSE HYDROGELS , 2020 .

[19]  B. Kaczmarek Tannic Acid with Antiviral and Antibacterial Activity as A Promising Component of Biomaterials—A Minireview , 2020, Materials.

[20]  Zhen Liu,et al.  Soft Actuated Hybrid Hydrogel with Bioinspired Complexity to Control Mechanical Flexure Behavior for Tissue Engineering , 2020, Nanomaterials.

[21]  I. Manduteanu,et al.  Molecular mechanisms involved in high glucose‐induced valve calcification in a 3D valve model with human valvular cells , 2020, Journal of cellular and molecular medicine.

[22]  Hao Hu,et al.  Rational design and latest advances of polysaccharide-based hydrogels for wound healing. , 2020, Biomaterials science.

[23]  Xu Song,et al.  Resveratrol inhibits LPS-induced inflammation through suppressing the signaling cascades of TLR4-NF-κB/MAPKs/IRF3 , 2019, Experimental and therapeutic medicine.

[24]  B. Simionescu,et al.  CELLULOSE-BASED HYDROGELS IN TISSUE ENGINEERING APPLICATIONS , 2019 .

[25]  Hongcan Shi,et al.  Preparation of cellulose nanocrystal/oxidized dextran/gelatin (CNC/OD/GEL) hydrogels and fabrication of a CNC/OD/GEL scaffold by 3D printing , 2019, Journal of Materials Science.

[26]  H. Ferfera-Harrar,et al.  Eco-friendly porous carboxymethyl cellulose/dextran sulfate composite beads as reusable and efficient adsorbents of cationic dye methylene blue. , 2019, International journal of biological macromolecules.

[27]  K. Tasanen,et al.  Toward understanding scarless skin wound healing and pathological scarring , 2019, F1000Research.

[28]  C. Matar,et al.  The Immunomodulatory and Anti-Inflammatory Role of Polyphenols , 2018, Nutrients.

[29]  R. Adnan,et al.  Magnetic nanocellulose alginate hydrogel beads as potential drug delivery system. , 2018, International journal of biological macromolecules.

[30]  A. Almutairi,et al.  Inflammation-Responsive Drug-Conjugated Dextran Nanoparticles Enhance Anti-Inflammatory Drug Efficacy. , 2018, ACS applied materials & interfaces.

[31]  N. Stevulova,et al.  Characterization of Cellulosic Fibers by FTIR Spectroscopy for Their Further Implementation to Building Materials , 2018 .

[32]  Andrei Jitianu,et al.  Dextran hydrogels by crosslinking with amino acid diamines and their viscoelastic properties. , 2018, International journal of biological macromolecules.

[33]  A. Khademhosseini,et al.  Polyphenol uses in biomaterials engineering. , 2018, Biomaterials.

[34]  G. Dodi,et al.  Biosynthesis of dextran by Weissella confusa and its In vitro functional characteristics. , 2018, International journal of biological macromolecules.

[35]  D. Rana,et al.  Jute cellulose nano-fibrils/hydroxypropylmethylcellulose nanocomposite: A novel material with potential for application in packaging and transdermal drug delivery system , 2018 .

[36]  B. Nyström,et al.  Effects of chain length of the cross-linking agent on rheological and swelling characteristics of dextran hydrogels. , 2018, Carbohydrate polymers.

[37]  Shin-Ping Lin,et al.  Novel dextran modified bacterial cellulose hydrogel accelerating cutaneous wound healing , 2017, Cellulose.

[38]  C. Chuah,et al.  Enhancement of Curcumin Bioavailability Using Nanocellulose Reinforced Chitosan Hydrogel , 2017, Polymers.

[39]  G. Dodi,et al.  EFFECTS OF CULTURE MEDIUM COMPOSITION ON BIOSYNTHESIS OF EXOPOLYSACCHARIDES , 2017 .

[40]  T. Budtova,et al.  Physically and chemically cross-linked cellulose cryogels: Structure, properties and application for controlled release. , 2016, Carbohydrate polymers.

[41]  B. Hinz The role of myofibroblasts in wound healing. , 2016, Current research in translational medicine.

[42]  T. Klein,et al.  Evaluation of the impact of freezing preparation techniques on the characterisation of alginate hydrogels by cryo-SEM , 2016 .

[43]  V. V. Padma,et al.  Wound dressings – a review , 2015, BioMedicine.

[44]  J. Ostrowska-Czubenko,et al.  pH-responsive hydrogel membranes based on modified chitosan: water transport and kinetics of swelling , 2015, Journal of Polymer Research.

[45]  A. Molinaro,et al.  Structural analysis and characterization of dextran produced by wild and mutant strains of Leuconostoc mesenteroides. , 2014, Carbohydrate polymers.

[46]  L. Godbout,et al.  Cellulose - Fundamental Aspects , 2013 .

[47]  Matheus Poletto,et al.  Structural Characteristics and Thermal Properties of Native Cellulose , 2013 .

[48]  Jeremy J Mao,et al.  Engineering dextran-based scaffolds for drug delivery and tissue repair. , 2012, Nanomedicine.

[49]  M. Cazacu,et al.  New cellulose–lignin hydrogels and their application in controlled release of polyphenols , 2012 .

[50]  J. Garai,et al.  Influence of dextran-70 on systemic inflammatory response and myocardial ischaemia-reperfusion following cardiac operations , 2007, Critical care.

[51]  Dong Il Yoo,et al.  FTIR analysis of cellulose treated with sodium hydroxide and carbon dioxide. , 2005, Carbohydrate research.

[52]  J. Dordick,et al.  Enzymatic synthesis of dextran-containing hydrogels. , 2002, Biomaterials.