Biofunctionalization of zirconia with cell-adhesion peptides via polydopamine crosslinking for soft tissue engineering: effects on the biological behaviors of human gingival fibroblasts and oral bacteria

Abstract

Rapid soft tissue integration is essential for long-term dental implant success. Zirconia is increasingly used as an abutment material owing to its excellent aesthetic properties and biocompatibility; however, it is bioinert, and tissue integration is poor. We developed a feasible surface modification method, exploiting the reactivity of polydopamine (PDA) films to immobilize cell-adhesion peptides (Arg-Gly-Asp, RGD) onto zirconia abutment surfaces. Further, we evaluated the effect thereof on human gingival fibroblast (HGF) behavior and oral bacterial adhesion, which influence the peri-implant soft tissue seal. HGF responses to linear KGGRGDSP and cyclic RGDfK sequences were compared. PDA deposition and covalent coupling of RGD were verified by X-ray photoelectron spectroscopy and fluorescence microscopy. The biological behaviors of HGFs on the modified zirconia; i.e., adhesion, spreading, proliferation, gene and protein expression, were elucidated. Biofunctionalization of zirconia with the adhesion peptides significantly enhanced the biological activities of HGFs. Cyclic RGD induced slightly improved cell attachment, spreading, and proliferation, but similar cell differentiation when compared to linear RGD peptides. To assess their antimicrobial properties, the different substrates were exposed to cultures of the early colonizer Streptococcus mutans or the periodontal pathogen Porphyromonas gingivalis, and bacterial adhesion was evaluated by scanning electron microscopy and live/dead staining.PDA and PDA-RGD coatings decreased zirconia surface colonization by both bacterial species to similar extents. Thus, PDA-RGD-functionalized zirconia modulates specific HGF responses, while maintaining the antimicrobial activity of the PDA coating. The selective bio-interaction pattern of this surface modification holds great promise for improving soft-tissue integration around zirconia abutments in clinical applications.

Biofunctionalization of Dental Abutment Surfaces by Crosslinked ECM Proteins Strongly Enhances Adhesion and Proliferation of Gingival Fibroblasts

“…[ 37 ] Moreover, an immobilized biomolecule such as RGD must withstand the contractile forces during cellular attachment otherwise these forces can redistribute weakly absorbed ligands on the surface, possibly leading to weak fibrillar adhesion. [ 6 ]…”

“…[37] Moreover, an immobilized biomolecule such as RGD must withstand the contractile forces during cellular attachment otherwise these forces can redistribute weakly absorbed ligands on the surface, possibly leading to weak fibrillar adhesion. [6] The wettability of native and modified surfaces was determined by measurements of the water droplet contact angles (Figure 4F). The surface wettability values of native Y-TZP and Ti6Al4V were located at 63.6 ± 1.1 and 69.8 ± 0.9, respectively.…”

“…[46,47] In findings similar to ours here, Yang et al showed that the application of RGD sequences on zirconia significantly enhances the biological activities of HGFs. [6] Jian et al demonstrated that titanium surfaces with a microgroove structure modified with fibronectin significantly enhanced cell adhesion, proliferation of HGFs, and cell orientation along these structures. [48] However, fibronectin was connected to silanized titanium surfaces without using a crosslinker.…”

“…The soft tissue barrier, the so‐called biological width around natural teeth, is usually ≈2 mm whereas the width around implants is generally 3–4 mm. [ 1 ] This enables bacteria such as Streptococcus oralis to more easily enter this gap and compete with host cells to cover the implant, which is described in literature as a “race for the surface.” [ 6–8 ] As soon as pathogens cover the implant surface, a plaque biofilm will form that protects bacteria from displacement through host cells. [ 9 ] Consequently, the penetration of bacteria into the implant/tissue interface can cause an accelerated destruction of the epithelial and connective tissue due to biofilm formation [ 1,6 ] and further lead to periimplant bone destruction.…”

Harnessing biomolecules for bioinspired dental biomaterials

“…199 Other work has immobilized linear and cyclized RGD on zirconia and showed enhanced spreading, proliferation, and focal adhesion formation from gingival fibroblasts. 200 The growing demand of zirconia implants, and the prevalence of restorative abutment made of this tough and aesthetic ceramic, motivates future development of biomolecule coatings for them. [201][202][203][204] 3.1.1.2 Laminin-derived peptides.…”