The introduction of photopolymerizable, resin-based composite (RBC) fillings has in many ways advanced the field of restorative dentistry, both in terms of patient experience and clinical practice. However, the prevalence of secondary caries associated with RBCs, which most often occur along restoration margins, remains a significant challenge to address; the majority of RBCs require a replacement within 8–12 years [1], [2], [3]. Given the location of failure being isolated to restoration margins, it is clear that the weak point of this biomaterial system lies at the adhesion between exposed dentin and the restoration system, and thus this adhesive interface must be well-understood to advance technologies that address these failures.

The adhesive interface which binds exposed dentin and enamel to the bulk RBC typically consists of a photopolymerized, methacrylate polymer network that is formed in situ. Ideally, this photopolymerized network would infiltrate into the exposed dentin, thus surrounding collagen fibrils with a stable, robust network. Typical methacrylate constituents utilized in adhesive networks include hydrophilic monomers such as hydroxyethyl methacrylate (HEMA) which ensures the optimal wetting of the dentin surface and facilitates the infiltration of the adhesive resin into the collagen fibrils [4]. There are also more hydrophobic crosslinkers including urethane dimethacrylate (UDMA) and bisphenol a-glycidyl methacrylate (BisGMA) which increase the rigidity of the formed adhesive material. Acidic monomers such as bis[2-(methacryloyloxy)ethyl] phosphate (2MP) and 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) are often incorporated (in self-etch and universal systems) to afford simultaneous etching of the exposed dentin during adhesive application [5], [6], [7]. Lastly, methacrylate monomers are often diluted with a (co)solvent such as water, ethanol, acetone or a mixture thereof. The cosolvent is typically evaporated by air-drying prior to light exposure and curing [8], [9]. The addition of cosolvent improves the wetting properties of the formulation, facilitates penetration of the adhesive into dentin, and prevents exposed collagen fibrils from becoming over-dried and collapsing [8], [10]. In self-etch adhesives, water promotes the ionization of the organic acidic monomers in order to provide adequate acidic etching.

However, prior works demonstrate that cosolvents cannot be completely removed prior to light-curing, and 12 to 14 wt% remains during the polymerization [8], [11]. In addition, free water also exists from collagen fibrils and dentin tubules [12]. The presence of these residual solvents, both from the adhesive formulation and the oral environment, is considered a challenge as it contributes to heterogeneity and potential phase separation of the formed adhesive network during application and subsequent photopolymerization. Phase separation between different (co)monomers and solvents has been observed, particularly in self-etch dental adhesives, over the past 20 years [13], [14], [15], [16] and is cited as a critical factor to address for adhesive integrity and durability [15], [17], [18]. The most critical consequence of adhesive phase separation is that hydrophilic, loosely-crosslinked domains rich in HEMA form, which are ultimately more susceptible to water uptake and subsequent hydrolytic degradation.

Given the established connection between adhesive phase separation and adhesive failure, understanding phase separation during an in situ polymerization procedure is necessary to continue engineering novel, robust adhesives. Often, the fraction of HEMA employed as a comonomer in the adhesive formulation is cited as a determinant of phase separation [13] as well as the presence of residual hydrophilic solvents [1], [15]. Unfortunately, while these two factors are cited frequently in the research literature, their role in driving or preventing phase separation is not well understood and many contradictory reports have been published. Being hydrophilic in nature, some studies cite HEMA as being an agent that enhances solubility of adhesive constituents (cosolvent and hydrophobic co-monomers), thus preventing macroscopic phase separation [13], [18], [19], [20]. Subsequent studies conclude that while a sufficiently large content of HEMA may compatibilize adhesive constituents, there is a noticeable decrease in adhesive performance attributed to increased water uptake via osmosis [21]. Furthermore, studies in different application fields which have an explicit objective of developing phase-separated polymeric materials have often relied on the copolymerization of HEMA with other (meth)acrylate constituents [22], [23], [24] at levels similar to those employed in dental adhesives. This highlights how our assumption that HEMA serves as a compatibilizer between adhesive resin constituents, thus improving adhesive network performance, is incomplete.

With the combined observations of overwhelming failure at adhesive margins and the prevalence of adhesive materials to phase separate, it is evident that this phase separation and subsequent heterogeneity must be well-understood to engineer adhesive materials that can persist in an oral environment and withstand evolving conditions. While in the field of dental materials phase separation is associated with decreased performance [15], engineered heterogeneity via phase separation in polymeric materials can be leveraged for enhanced performance in other application fields. This includes the development of gels and elastomers [25], [26], membranes [27], electronic materials [28], and coatings [29], [30]. In these examples, the parameter space where improvements are conferred to a material is often narrow and therefore it must be understood how constituents (co-monomers, solvents, etc.) contribute to heterogeneity and phase structure. This will inform future adhesive developments and application protocols.

With this in mind, the aims of this study were: (1) to determine how phase structure is influenced by monomer constituents and cosolvent fraction in a model adhesive system; and (2) to identify the driving forces for the formation of heterogeneity and phase separation in dental adhesive resins. We utilize a combination of in situ (e.g., during polymerization) and post-polymerization characterization techniques. The tested hypothesis was that the degree of heterogeneity and proclivity for phase separation would increase with increasing cosolvent fraction, and also with increasing C/H ratio (hydrophobic crosslinkers to hydrophilic HEMA). In testing this hypothesis, the work described here informs how heterogeneity and phase structure within an adhesive network evolves during polymerization and as a function of adhesive formulation composition.