Biocompatible Multifunctional Polymeric Material for Mineralized Tissue Adhesion

Abstract

This study develops a biocompatible multifunctional thiol-ene resin system for adhesion to dentin mineralized tissue. Adhesive resins maintain the strength and longevity of dental composite restorations through chemophysical bonding to exposed dentin surfaces after cavity preparations. Monomers of conventional adhesive systems may result in inhomogeneous polymer networks and the release of residual monomers that cause cytotoxicity. In this study, a one-step multifunctional polymeric resin system by incorporating trimethylolpropane triacrylate (TMPTA) and bis[2-(methacryloyloxy)ethyl] phosphate (BMEP) is developed to enhance both mechanical properties and adhesion to dentin. Molecular dynamics simulations identify an optimal triacylate:trithiol ratio of 2.5:1, which is consistent with rheological and mechanical tests that yield a storage modulus of ≈30 MPa with or without BMEP. Shear bond tests demonstrate that the addition of BMEP significantly improves dentin adhesion, achieving a shear bond strength of 10.8 MPa, comparable to the commercial primer Clearfil SE Bond. Nanoindentation modulus mapping characterizes the hybrid layer and mechanical gradient of the adhesive resin system. Further, the triacrylate-BMEP resin shows biocompatibility with dental pulp cells and fibroblasts in vitro. These findings suggest that the triacrylate-trithiol crosslinking and chemophysical bonding of BMEP provide enhanced bond strength and biocompatibility for dental applications.

Keywords: dentin adhesion; molecular dynamics simulation; nanoindentation; thiol‐ene polymerization; triacrylate resin.

Figure 5

Biocompatibility of resin systems with and without BMEP on hDPSCs. a) Fluorescence imaging (scale bar 200 µm) of hDPSCs after 24 h culture in original condition (100% concentration) media compared to negative control, stained for nuclei (blue) and F‐actin (green). b) Relative cell viability, compared to negative control, and c) cell counts of hDPSCs after 24 h culture in condition media. Condition media are diluted with DMEM to a total concentration of 100%, 50%, and 25% of the original condition media. n = 3 biological replicates, error bars represent SD.

Figure 1

Illustration of TMPTA‐TMPMP resin‐dentin dual adhesion mechanisms. a) Overall schematic of resin with Trimethylolpropane triacrylate (TMPTA) and Trimethylolpropane tris(3‐mercaptopropionate) (TMPMP) as monomers, Bis[2‐(methacryloyloxy)ethyl] phosphate (BMEP) as the primer, and 2,2‐Dimethoxy‐2‐phenylacetophenone (DMPA) as the photoinitiator. b) Demonstration of both physical and chemophysical interlocks between resin and dentin through crosslinked polymers and chelation reactions involving BMEP.

Figure 2

Molecular dynamics simulations and comparative modulus and shrinkage analysis for resin systems with varying compositions of TMPTA and TMPMP. a) Illustration of TMPTA‐TMPMP crosslinking in resin. b) Molecular dynamics simulation results of potential energy and axis‐binding energy profile for TMPTA and TMPMP reacting under different ratios. U – potential energy; S – screening material, TMPMP; B – base material, TMPTA. c,d) Summary plots for (c) axis‐binding energy difference and (d) potential energy difference between U_BS and U_SS or U_BB for different TMPTA: TMPMP ratios. e) Storage modulus and loss modulus of resin plotted as a function of: TMPTA: TMPMP ratios, acrylate concentration, and thiol concentration. f) Shrinkage of resin under different TPMTA: TMPMP ratios.

Figure 3

Comparative adhesion, storage modulus and shrinkage analysis of the resin‐dentin interface and resin systems with and without BMEP. a) Illustration of the resin‐dentin interface. b) SEM (left) and EDS (right) images of the dentin interface (resin applied perpendicular to dentinal tubules) with the resin tag exposed. (Yellow: sulfur). c) SEM images of the dentin interface (resin applied parallel to tubules) without resin tag under 200 and 50 µm scale. d) Shear test demonstration for adhesion situation between resin and dentin sample (contact area = 2.1 mm²), and e) corresponding shear strength statistical results for resins and the commercial primer Clearfil SE Bond (Brown–Forsythe and Welch Test, sample size n = 15). f) Statistical results of two resin systems about storage modulus and shrinkage percentage (unpaired t‐test, sample size n = 3).

Figure 4

Nanomechanical analysis of the resin‐dentin adhesive interface. a) Illustration of two interlocking mechanisms on the resin‐dentin interface. b) Nanoindentation mapping array (10 sperate indentation lines * 20 indentation tests), c) modulus results for resin with (red) and without (black) BMEP, plots for (d) sigmoidal fitting results (blue curves), e) corresponding summary table (E: modulus, R²: the coefficient of determination), and f) comparison on HL's sum of residual (SS_res). g) Weighted k‐means clustering results (dentin region – orange, hybrid layer (HL) region – grey, resin region – blue), and h) corresponding summary table (x_{HL_start/ end}: hybrid layer region starting/ ending position, d: thickness). All the results demonstrated here represent the aggregate outcomes derived from the analysis of all ten individual indentation line tests.