IADR Abstract Archives
MyD88 Mediates Inflammatory and Healing Responses to Classic Titanium-Based Biomaterials
Objectives: Even highly biocompatible materials, such as Titanium-based devices, cause some degree of host response. However, the mechanisms involved in triggering such response as well the exact role of host response in the subsequent healing remain unknown. The aim of this study was to evaluate the role of Myeloid Differentiation Factor 88 (MyD88) signaling molecule, part or CD14/TLR/MyD88 receptor/signaling complex, in the genesis and modulation of inflammatory immune response to a classic biomaterial (Ti).
Methods: Ti-disks were implanted in the subcutaneous tissue of C57BL/6(WT) and MYD88KO mice strains, comparatively evaluated using histomorphometric and molecular (RealTimePCRarray/ELISA) parameter assessments at 1, 3, 7 and 21 days time points.
Results: Ti-disk implantation in WT mice results in the local release of HMGB1 (measured by ELISA), the major endogenous ligand of CD14/TLR/MyD88 complex, followed by a moderate and transitory leukocyte influx, and the inflammatory process resolution in parallel with fibrous connective tissue formation and disks encapsulation. MyD88KO mice presented a significant decrease in inflammatory response and delayed connective tissue capsule formation and maturation as evidenced by histomorphometry. RealTimePCRarray demonstrate that the impaired healing response in the absence of MyD88 was associated with decreased levels of FGF2, TGFb1, VEGFa, Col1a2, MMP2, MMP9, IL1beta, IL6, TNFalpha, CCL2, CCL5, CCL12, CCL20 and CXCL12. Also, the expression of MSCs markers CD106, COT4, NANOG, CD146, NES and CD105 were reduced in MyD88KO mice, suggesting MyD88-mediated host response also contributes to MSCs migration and/or activation after Ti-disks implantation.
Conclusions: MyD88 is a critical mediator of host inflammatory and healing responses to titanium-based biomaterials in subcutaneous tissue compartment.
Methods: Ti-disks were implanted in the subcutaneous tissue of C57BL/6(WT) and MYD88KO mice strains, comparatively evaluated using histomorphometric and molecular (RealTimePCRarray/ELISA) parameter assessments at 1, 3, 7 and 21 days time points.
Results: Ti-disk implantation in WT mice results in the local release of HMGB1 (measured by ELISA), the major endogenous ligand of CD14/TLR/MyD88 complex, followed by a moderate and transitory leukocyte influx, and the inflammatory process resolution in parallel with fibrous connective tissue formation and disks encapsulation. MyD88KO mice presented a significant decrease in inflammatory response and delayed connective tissue capsule formation and maturation as evidenced by histomorphometry. RealTimePCRarray demonstrate that the impaired healing response in the absence of MyD88 was associated with decreased levels of FGF2, TGFb1, VEGFa, Col1a2, MMP2, MMP9, IL1beta, IL6, TNFalpha, CCL2, CCL5, CCL12, CCL20 and CXCL12. Also, the expression of MSCs markers CD106, COT4, NANOG, CD146, NES and CD105 were reduced in MyD88KO mice, suggesting MyD88-mediated host response also contributes to MSCs migration and/or activation after Ti-disks implantation.
Conclusions: MyD88 is a critical mediator of host inflammatory and healing responses to titanium-based biomaterials in subcutaneous tissue compartment.