Nitric Oxide generating coating alters hematoma structure and soft tissue healing

Introduction: Peri-implantitis remains a major clinical problem due to the challenges in soft tissue integration on implants surfaces. During tissue healing processes, hematoma formation is the initial response to implant surfaces, which serves as a reservoir for growth factors and provides a natural scaffold for cell infiltration. However, little information is available regarding whether altering hematoma properties can benefit soft tissue healing and tissue integration. This study aims to modulate hematoma properties to create a friendly microenvironment for a strong soft tissue seal on implant surfaces. Methods: We developed a polydopamine (PDAM) based coating capable of well-controlled nitric oxide (NO) generation by applying the copper (Cu) dose gradient. The incorporated copper with progressive raw concentrations of 10, 50 and 250µg/mL in the coating (PDAM@Cu coatings) served as a catalyst and reacted with endogenous NO donors in the blood. The resulting influence on clot structure and tissue healing microenvironment were analyzed along with its impact on the migration and proliferation of human gingival fibroblasts (HGFs). Results: It was noted that NO generation rates could be controlled using Cu from the coatings as a catalyst. As a result of this, the clot formation, structural properties, clot degradation, and growth factor release could be manipulated. Consequently, the NO generating surfaces of PDAM@Cu coating yielded a desired porous structure in clots and growth factor release profile, especially of platelet derived growth factors such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). The NO generating surfaces of PDAM@Cu coating subsequently allowed increased migration and proliferation of HGFs. Conclusion: In this study, we developed a novel NO-generating strategy to regulate hematoma properties and growth factors release. The optimized coating could provide a favourable micro-environment for soft tissue healing and prompt cell migration and proliferation of HGFs. Therefore, PDAM surface modification with incorporation of Cu as a catalyst for NO generation could induce a functional implant surface for soft tissue integration.