title: Biocomposites of copper-containing mesoporous bioactive glass and nanofibrillated cellulose: Biocompatibility and angiogenic promotion in chronic wound healing application.
abstract: Biocomposites of copper-containing mesoporous bioactive glass (Cu-MBG) and nanofibrillated cellulose (NFC) were designated as potential dressing material for chronic wound healing. The phase composition and mesoporous micro-structure of the synthesized Cu-MBGs were elaborately characterized by combining several techniques, including TEM, SEM, XRD, SXAS and N2physisorption. High bioactivity of the Cu-MBG was confirmed in stimulated body fluids in vitro. A controlled dissolution of Cu from the glass suggests Cu-MBG a suitable source for Cu release in wound healing dressings. Depending on the content of Cu-MBG in the composite formulation, the composites were fabricated as membranes and aerogels. In biocompatibility assessment of the composites, a dose-dependent cytotoxicity of Cu2+on 3T3 fibroblasts was found. Importantly, a critical biological level of Cu2+below 10mg/L was suggested for the survival and growth of 3T3 fibroblasts. The Cu2+released from the composite aerogel of NFC and Cu-MBG showed a profound angiogenic effect in the 3D spheroid culture system of human umbilical vein endothelial cells. Moreover, the angiogenic gene expression of 3T3 fibroblast was upregulated in the real-time quantitative PCR analysis, which also confirms that the incorporation of Cu-MBG into NFC matrix enhances the proangiogenic potential of the biocomposites. In addition, composites of NFC and Cu-MBG also showed an inhibiting effect on the growth of E. coli.
  
  
  
  To address an urgent need in clinics on developing a new generation of therapeutic dressings with advanced functionalities, this study has exploited the utilization of Cu-containing mesoporous bioactive glass in the nanocellulose matrix to release Cu2+as therapeutic ions for its angiogenic effect on promoting wound healing. This manuscript reports research work on biomaterial design, fabrication development, material characterizations and bioassessments in 2D cellular studies. To utilize nanocellulose derived from the wood resource in biomedical applications is of great significance, due to its vast availability and bioeconomy competence. The use of Cu-containing bioactive glass in tissue engineering scaffolds, including wound healing, is an intriguing research topic, which has been recently discussed in the field of biomaterials. I think that our manuscript title with 'Biocomposites of copper-containing mesoporous bioactive glass and nanofibrillated cellulose: biocompatibility and angiogenic promotion in chronic wound healing application' will make its own contribution on understanding the complex effects of Cu2+on wound-healing-relevant events with acceptable novelty for Acta Biomaterialia.
authors.affiliation: Johan Gadolin Process Chemistry Centre, Åbo Akademi University, FI-20500 Åbo/Turku, Finland. Electronic address: xwang@abo.fi.
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Wang
authors.affiliation: Cell Biology, Biosciences, Faculty of Science and Engineering, Åbo Akademi University & Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland. Electronic address: cfang@abo.fi.
authors.forename: Fang
authors.initials: F
authors.lastname: Cheng
authors.affiliation: Johan Gadolin Process Chemistry Centre, Åbo Akademi University, FI-20500 Åbo/Turku, Finland.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Laboratory of Physical Chemistry, Åbo Akademi University, FI-20500 Åbo/Turku, Finland.
authors.forename: Jan-Henrik
authors.initials: JH
authors.lastname: Smått
authors.affiliation: Johan Gadolin Process Chemistry Centre, Åbo Akademi University, FI-20500 Åbo/Turku, Finland.
authors.forename: David
authors.initials: D
authors.lastname: Gepperth
authors.affiliation: Department of Chemistry, University of Turku, FI-20014 Turku, Finland; Turku University Centre for Materials and Surfaces (MatSurf), Turku, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Lastusaari
authors.affiliation: Johan Gadolin Process Chemistry Centre, Åbo Akademi University, FI-20500 Åbo/Turku, Finland.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Xu
authors.affiliation: Johan Gadolin Process Chemistry Centre, Åbo Akademi University, FI-20500 Åbo/Turku, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Hupa
mesh_terms: D016475:3T3 Cells; D000327:Adsorption; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002482:Cellulose / Q000737:chemistry*; D003300:Copper / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005898:Glass / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D008567:Membranes, Artificial; D051379:Mice; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D009584:Nitrogen / Q000737:chemistry; D016062:Porosity; D017550:Spectroscopy, Fourier Transform Infrared; D014945:Wound Healing / Q000187:drug effects*; D014961:X-Ray Diffraction
chemical_list: D001672:Biocompatible Materials; D008567:Membranes, Artificial; D003300:Copper; D002482:Cellulose; D009584:Nitrogen
keywords: Angiogenesis; Biocomposite; Copper ion; Mesoporous bioactive glass; Nanofibrillated cellulose; Wound healing dressing