title: Chondroitin Sulfate Immobilized on a Biomimetic Scaffold Modulates Inflammation While Driving Chondrogenesis.
abstract: Costs associated with degenerative inflammatory conditions of articular cartilage are exponentially increasing in the aging population, and evidence shows a strong clinical need for innovative therapies. Stem cell-based therapies represent a promising strategy for the treatment of innumerable diseases. Their regenerative potential is undeniable, and it has been widely exploited in many tissue-engineering approaches, especially for bone and cartilage repair. Their immune-modulatory capacities in particular make stem cell-based therapeutics an attractive option for treating inflammatory diseases. However, because of their great plasticity, mesenchymal stem cells (MSCs) are susceptible to different external factors. Biomaterials capable of concurrently providing physical support to cells while acting as synthetic extracellular matrix have been established as a valuable strategy in cartilage repair. Here we propose a chondroitin sulfate-based biomimetic scaffold that recapitulates the physicochemical features of the chondrogenic niche and retains MSC immunosuppressive potential in vitro, either in response to a proinflammatory cytokine or in the presence of stimulated peripheral blood mononuclear cells. In both cases, a significant increase in the production of molecules associated with immunosuppression (nitric oxide and prostaglandins), as well as in the expression of their inducible enzymes (iNos, Pges, Cox-2, and Tgf-β). When implanted subcutaneously in rats, our scaffold revealed a reduced infiltration of leukocytes at 24 hours, which correlated with a greater upregulation of genes involved in inflammatory cell apoptotic processes. In support of its effective use in tissue-engineering applications of cartilage repair, the potential of the proposed platform to drive chondrogenic and osteogenic differentiation of MSC was also proven.
  
  
  CONCLUSIONS
  Recently, increasing clinical evidence has highlighted the important role of proinflammatory mediators and infiltrating inflammatory cell populations inducing chronic inflammation and diseases in damaged cartilage. This work should be of broad interest because it proposes an implantable biomimetic material, which holds the promise for a variety of medical conditions that necessitate the functional restoration of damaged cartilage tissue (such as trauma, diseases, deformities, or cancer).
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Corradetti
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Taraballi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA Institute of Science and Technology for Ceramics, National Research Council of Italy, Faenza, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Minardi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Van Eps
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Cabrera
authors.affiliation: Centre for NanoHealth, Swansea University Medical School, Swansea University Bay, Singleton Park, Wales, United Kingdom.
authors.forename: Lewis W
authors.initials: LW
authors.lastname: Francis
authors.affiliation: Centre for NanoHealth, Swansea University Medical School, Swansea University Bay, Singleton Park, Wales, United Kingdom.
authors.forename: Salvatore A
authors.initials: SA
authors.lastname: Gazze
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA Department of Medicine, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA Department of Orthopedics & Sports Medicine, Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: Bradley K
authors.initials: BK
authors.lastname: Weiner
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA ETasciotti@houstonmethodist.org.
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D040761:Biomimetic Materials; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D020219:Chondrogenesis / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D011917:Rats, Inbred Lew; D055153:Stem Cell Niche; D013997:Time Factors; D054457:Tissue Scaffolds
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D002809:Chondroitin Sulfates
keywords: Arthritis; Biomimetic scaffolds; Chondrogenic differentiation; Chondroitin sulfate; Immunosuppression; Mesenchymal stem cells; Tissue engineering