title: Tolerogenic responses of CD206+, CD83+, FOXP3+, and CTLA-4 to sericin/polyvinyl alcohol/glycerin scaffolds relevant to IL-33 and HSP60 activity.
abstract: Silk sericin-releasing (sericin/polyvinyl alcohol (PVA)/glycerin) scaffolds have been designed for wound dressing applications using different fabrication techniques that influence scaffold antigenicity. The immunological tolerance of scaffolds depends on the balance of immunogenic and tolerogenic responses modulated by dendritic cells (DCs). An in vivo skin implantation model was used to compare the tolerogenic effect of sericin/PVA/glycerin scaffolds prepared by freeze-drying versus salt-leaching techniques, using an Allevyn® scaffold as a control. Immunohistochemical and histopathological studies were performed to evaluate tolerogenic DCs (CD206+), immunogenic DCs (CD83+), regulatory T-cells (FOXP3+ and CTLA-4), a proinflammatory cytokine (interleukin 33: IL-33), a stress marker (heat shock protein 60; HSP60), histopathological changes and related inflammatory cells. It was found that both sericin/PVA/glycerin scaffolds were tolerogenic and induced early activated Treg functions, while the Allevyn® scaffold was immunogenic. However, the tolerance of the freeze-dried sericin/PVA/glycerin scaffolds was not as consistent as the salt-leached sericin/PVA/glycerin scaffolds, indicated by the low level of CTLA-4 expression. This was probably due to molecular cross-linking and the morphological and mechanical properties of the freeze-drying technique, which would enhance the immune response. Severe inflammatory responses (including mast cell degranulation and foreign body giant cell accumulation) and histopathological changes (including fat infiltration and fibrosis formation) were mainly found with the Allevyn® scaffold, presumably from its architecture and chemical composition, especially polyurethane. The up-regulation of IL-33 and HSP60 with the Allevyn® scaffold was correlated with the inflammatory and pathological levels. Our findings suggested that salt-leached sericin/PVA/glycerin scaffolds were tolerogenic, induced a low inflammatory response and were appropriate for wound dressing applications.
authors: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Ratchawithi Road, Ratchathewi, Bangkok, Thailand. am_sumate@hotmail.com.
authors: Sumate
authors: S
authors: Ampawong
authors: Bioactive Resources for Innovative Clinical Applications Research Unit and Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, PhayaThai Road, Phatumwan, Bangkok, Thailand. aramwit@gmail.com.
authors: Pornanong
authors: P
authors: Aramwit
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001672:Biocompatible Materials / Q000737:chemistry*; D060908:CTLA-4 Antigen / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D005990:Glycerol / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007136:Immunoglobulins / Q000276:immunology; D007150:Immunohistochemistry; D000067596:Interleukin-33 / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology; D008422:Materials Testing; D008562:Membrane Glycoproteins / Q000276:immunology; D024101:Mitochondrial Proteins / Q000276:immunology; D011142:Polyvinyl Alcohol; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000276:immunology; D047030:Sericins / Q000276:immunology; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D001672:Biocompatible Materials; D060908:CTLA-4 Antigen; D018834:Chaperonin 60; D051858:Forkhead Transcription Factors; D005990:Glycerol; D007136:Immunoglobulins; D000067596:Interleukin-33; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011142:Polyvinyl Alcohol; D011956:Receptors, Cell Surface; D047030:Sericins; D000097802:CD83 Antigen; C500522:Foxp3 protein, rat; C557067:Hspd1 protein, rat; C553108:Il33 protein, rat