title: Human stem cell decorated nanocellulose threads for biomedical applications.
abstract: Upon surgery, local inflammatory reactions and postoperative infections cause complications, morbidity, and mortality. Delivery of human adipose mesenchymal stem cells (hASC) into the wounds is an efficient and safe means to reduce inflammation and promote wound healing. However, administration of stem cells by injection often results in low cell retention, and the cells deposit in other organs, reducing the efficiency of the therapy. Thus, it is essential to improve cell delivery to the target area using carriers to which the cells have a high affinity. Moreover, the application of hASC in surgery has typically relied on animal-origin components, which may induce immune reactions or even transmit infections due to pathogens. To solve these issues, we first show that native cellulose nanofibers (nanofibrillated cellulose, NFC) extracted from plants allow preparation of glutaraldehyde cross-linked threads (NFC-X) with high mechanical strength even under the wet cell culture or surgery conditions, characteristically challenging for cellulosic materials. Secondly, using a xenogeneic free protocol for isolation and maintenance of hASC, we demonstrate that cells adhere, migrate and proliferate on the NFC-X, even without surface modifiers. Cross-linked threads were not found to induce toxicity on the cells and, importantly, hASC attached on NFC-X maintained their undifferentiated state and preserved their bioactivity. After intradermal suturing with the hASC decorated NFC-X threads in an ex vivo experiment, cells remained attached to the multifilament sutures without displaying morphological changes or reducing their metabolic activity. Finally, as NFC-X optionally allows facile surface tailoring if needed, we anticipate that stem-cell-decorated NFC-X opens a versatile generic platform as a surgical bionanomaterial for fighting postoperative inflammation and chronic wound healing problems.
authors.affiliation: Department of Applied Physics, Aalto University (formerly Helsinki University of Technology), P.O. Box 15100, FI-00076 AALTO, Espoo, Finland.
authors.forename: Henrikki
authors.initials: H
authors.lastname: Mertaniemi
authors.affiliation: Division of Pharmaceutical Biosciences, Centre of Drug Research, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, P.O. Box 56, FI-00014, Helsinki, Finland; Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, 162-8666, Tokyo, Japan. Electronic address: carmen.escobedo-lucea@helsinki.fi.
authors.forename: Carmen
authors.initials: C
authors.lastname: Escobedo-Lucea
authors.affiliation: Division of Pharmaceutical Biosciences, Centre of Drug Research, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, P.O. Box 56, FI-00014, Helsinki, Finland; Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, 162-8666, Tokyo, Japan.
authors.forename: Andres
authors.initials: A
authors.lastname: Sanz-Garcia
authors.affiliation: Division of Pharmaceutical Biosciences, Centre of Drug Research, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, P.O. Box 56, FI-00014, Helsinki, Finland.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gandía
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, P.O. Box 220, FI-00029 HUS, Helsinki, Finland; Department of Engineering Design and Production, Aalto University, P.O. Box 14300, FI-00076 AALTO, Espoo, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Mäkitie
authors.affiliation: Department of Engineering Design and Production, Aalto University, P.O. Box 14300, FI-00076 AALTO, Espoo, Finland.
authors.forename: Jouni
authors.initials: J
authors.lastname: Partanen
authors.affiliation: Department of Applied Physics, Aalto University (formerly Helsinki University of Technology), P.O. Box 15100, FI-00076 AALTO, Espoo, Finland. Electronic address: olli.ikkala@aalto.fi.
authors.forename: Olli
authors.initials: O
authors.lastname: Ikkala
authors.affiliation: Division of Pharmaceutical Biosciences, Centre of Drug Research, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, P.O. Box 56, FI-00014, Helsinki, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Yliperttula
mesh_terms: D001458:Bandages; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D002482:Cellulose / Q000737:chemistry* / Q000648:ultrastructure; D006801:Humans; D008422:Materials Testing; D045164:Mesenchymal Stem Cell Transplantation / Q000295:instrumentation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D013718:Tensile Strength; D054457:Tissue Scaffolds; D014945:Wound Healing / Q000502:physiology*
chemical_list: D002482:Cellulose
keywords: Cellulose nanofibrils; Mesenchymal stem cells; Surgical applications; Undifferentiated stem cells; Wet strength; Wound healing