title: Tendon Regeneration with Tendon Hydrogel-Based Cell Delivery: A Comparison of Fibroblasts and Adipose-Derived Stem Cells.
abstract: BACKGROUND
  Tendon hydrogel is a promising biomaterial for improving repair strength after tendon injury. This study compares the capacity of fibroblasts and adipose-derived stem cells to proliferate, survive, and acquire tenogenic properties when seeded into tendon hydrogel in vitro and in vivo.
  
  
  METHODS
  The effect of cell density on hydrogel contraction was measured macroscopically. To assess tenogenic properties, RNA was isolated from cells seeded in vitro in hydrogel, and tenocyte markers were quantified. To assess in vitro proliferation and survival, MTS and live-dead assays were performed. Finally, to assess the in vivo survival of cells in hydrogel, subcutaneous injections were performed on rats and in vivo imaging was performed.
  
  
  RESULTS
  At 0.5 million cells/ml, both the fibroblasts and adipose-derived stem cells induced minimal hydrogel contraction compared with higher cellular concentrations. Fibroblasts and adipose-derived stem cells seeded at 0.5 million cells/ml in tendon hydrogel up-regulated several tenocyte markers after 1 week. On MTS assay, fibroblasts and adipose-derived stem cells proliferated in hydrogel at similar rates. On live-dead assay, fibroblasts survived longer than adipose-derived stem cells. With use of the in vivo imaging system and histologic evaluation, fibroblasts survived longer than adipose-derived stem cells in hydrogel in vivo.
  
  
  CONCLUSIONS
  Tendon healing is mediated by the proliferation, survival, and tenogenic differentiation of cells at the site of injury. Tendon hydrogel delivering dermal fibroblasts may improve and stimulate this process compared with adipose-derived stem cells. Future studies will be needed to evaluate the effects of this hydrogel-based cell delivery on chronic tendon injuries.
authors.affiliation: Stanford and Palo Alto, Calif.|From the Division of Plastic and Reconstructive Surgery, Stanford Health Care; the Department of Pediatrics, Stanford University School of Medicine; and the Division of Plastic and Reconstructive Surgery, VA Palo Alto Health Care System.
authors.forename: Arhana
authors.initials: A
authors.lastname: Chattopadhyay
authors.affiliation: Stanford and Palo Alto, Calif.|From the Division of Plastic and Reconstructive Surgery, Stanford Health Care; the Department of Pediatrics, Stanford University School of Medicine; and the Division of Plastic and Reconstructive Surgery, VA Palo Alto Health Care System.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Galvez
authors.affiliation: Stanford and Palo Alto, Calif.|From the Division of Plastic and Reconstructive Surgery, Stanford Health Care; the Department of Pediatrics, Stanford University School of Medicine; and the Division of Plastic and Reconstructive Surgery, VA Palo Alto Health Care System.
authors.forename: Michael
authors.initials: M
authors.lastname: Bachmann
authors.affiliation: Stanford and Palo Alto, Calif.|From the Division of Plastic and Reconstructive Surgery, Stanford Health Care; the Department of Pediatrics, Stanford University School of Medicine; and the Division of Plastic and Reconstructive Surgery, VA Palo Alto Health Care System.
authors.forename: Anais
authors.initials: A
authors.lastname: Legrand
authors.affiliation: Stanford and Palo Alto, Calif.|From the Division of Plastic and Reconstructive Surgery, Stanford Health Care; the Department of Pediatrics, Stanford University School of Medicine; and the Division of Plastic and Reconstructive Surgery, VA Palo Alto Health Care System.
authors.forename: Rory
authors.initials: R
authors.lastname: McGoldrick
authors.affiliation: Stanford and Palo Alto, Calif.|From the Division of Plastic and Reconstructive Surgery, Stanford Health Care; the Department of Pediatrics, Stanford University School of Medicine; and the Division of Plastic and Reconstructive Surgery, VA Palo Alto Health Care System.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lovell
authors.affiliation: Stanford and Palo Alto, Calif.|From the Division of Plastic and Reconstructive Surgery, Stanford Health Care; the Department of Pediatrics, Stanford University School of Medicine; and the Division of Plastic and Reconstructive Surgery, VA Palo Alto Health Care System.
authors.forename: Mollie
authors.initials: M
authors.lastname: Jacobs
authors.affiliation: Stanford and Palo Alto, Calif.|From the Division of Plastic and Reconstructive Surgery, Stanford Health Care; the Department of Pediatrics, Stanford University School of Medicine; and the Division of Plastic and Reconstructive Surgery, VA Palo Alto Health Care System.
authors.forename: Chris
authors.initials: C
authors.lastname: Crowe
authors.affiliation: Stanford and Palo Alto, Calif.|From the Division of Plastic and Reconstructive Surgery, Stanford Health Care; the Department of Pediatrics, Stanford University School of Medicine; and the Division of Plastic and Reconstructive Surgery, VA Palo Alto Health Care System.
authors.forename: Elise
authors.initials: E
authors.lastname: Umansky
authors.affiliation: Stanford and Palo Alto, Calif.|From the Division of Plastic and Reconstructive Surgery, Stanford Health Care; the Department of Pediatrics, Stanford University School of Medicine; and the Division of Plastic and Reconstructive Surgery, VA Palo Alto Health Care System.
authors.forename: James
authors.initials: J
authors.lastname: Chang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003584:Cytological Techniques; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D012313:RNA / Q000032:analysis; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000502:physiology*; D012867:Skin / Q000166:cytology; D013234:Stem Cells / Q000166:cytology; D013710:Tendons / Q000166:cytology* / Q000502:physiology*
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D012313:RNA