title: Gingival Mesenchymal Stem Cell (GMSC) Delivery System Based on RGD-Coupled Alginate Hydrogel with Antimicrobial Properties: A Novel Treatment Modality for Peri-Implantitis.
abstract: OBJECTIVE
  Peri-implantitis is one of the most common inflammatory complications in dental implantology. Similar to periodontitis, in peri-implantitis, destructive inflammatory changes take place in the tissues surrounding a dental implant. Bacterial flora at the failing implant sites resemble the pathogens in periodontal disease and consist of Gram-negative anaerobic bacteria including Aggregatibacter actinomycetemcomitans (Aa). Here we demonstrate the effectiveness of a silver lactate (SL)-containing RGD-coupled alginate hydrogel scaffold as a promising stem cell delivery vehicle with antimicrobial properties.
  
  
  METHODS
  Gingival mesenchymal stem cells (GMSCs) or human bone marrow mesenchymal stem cells (hBMMSCs) were encapsulated in SL-loaded alginate hydrogel microspheres. Stem cell viability, proliferation, and osteo-differentiation capacity were analyzed.
  
  
  RESULTS
  Our results showed that SL exhibited antimicrobial properties against Aa in a dose-dependent manner, with 0.50 mg/ml showing the greatest antimicrobial properties while still maintaining cell viability. At this concentration, SL-containing alginate hydrogel was able to inhibit Aa growth on the surface of Ti discs and significantly reduce the bacterial load in Aa suspensions. Silver ions were effectively released from the SL-loaded alginate microspheres for up to 2 weeks. Osteogenic differentiation of GMSCs and hBMMSCs encapsulated in the SL-loaded alginate microspheres were confirmed by the intense mineral matrix deposition and high expression of osteogenesis-related genes.
  
  
  CONCLUSIONS
  Taken together, our findings confirm that GMSCs encapsulated in RGD-modified alginate hydrogel containing SL show promise for bone tissue engineering with antimicrobial properties against Aa bacteria in vitro.
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, CA.|Restorative Dentistry Department, School of Dentistry, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Ivana M A
authors.initials: IM
authors.lastname: Diniz
authors.affiliation: Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania.
authors.forename: Chider
authors.initials: C
authors.lastname: Chen
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, CA.|Laboratory for Immunoregulation and Tissue Engineering (LITE), Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, CA.
authors.forename: Sahar
authors.initials: S
authors.lastname: Ansari
authors.affiliation: Laboratory for Immunoregulation and Tissue Engineering (LITE), Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, CA.
authors.forename: Homayoun H
authors.initials: HH
authors.lastname: Zadeh
authors.affiliation: Department of Oral and Maxillofacial Medicine, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Moshaverinia
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, CA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chee
authors.affiliation: Restorative Dentistry Department, School of Dentistry, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Márcia M
authors.initials: MM
authors.lastname: Marques
authors.affiliation: Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania.
authors.forename: Songtao
authors.initials: S
authors.lastname: Shi
authors.affiliation: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry of USC, University of Southern California, Los Angeles, CA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moshaverinia
mesh_terms: D000464:Alginates; D000890:Anti-Infective Agents; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D059630:Mesenchymal Stem Cells; D010012:Osteogenesis; D057873:Peri-Implantitis / Q000628:therapy*
chemical_list: D000464:Alginates; D000890:Anti-Infective Agents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: Alginate hydrogel; antimicrobial properties; bone regeneration; mesenchymal stem cell; silver