_applied sciences_  
_Systematic Review_  
Effect of the Incorporation of Compounds into Digitally Manufactured Dental Materials--A Systematic Review  
**[PERSON] 1**, [PERSON] 2, [PERSON] 3,4,+ and [PERSON] 5,+  
Footnote †: margin: _Appl. Sci._**2024,** _14, 2931.  
particularly in the fabrication of removable dentures, and this fabrication process involves methods of subtraction and addition [5]. The most common CAD-CAM manufacturing technique in the addition method is rapid prototyping, and in the subtraction method, it is milling. Rapid prototyping uses 3D printing techniques in which the resin is applied layer by layer and then polymerized with various light sources such as visible, ultraviolet and laser light. CAD-CAM milling, on the other hand, is a manufacturing process in which a pre-polymerized resin plate is subtracted [6].  
Three-dimensional printing, especially stereolithography (SLA) and the digital light process (DLP), are widely used techniques. SLA is an additive manufacturing technique used for both polymeric and ceramic materials, especially for personalized orthodontic appliances. Compared to the other 3D printing techniques, the SLA process provides better results in terms of surface finish, higher mechanical strength, and greater geometric precision [6]. However, this method also has some disadvantages, as it cannot be sterilized by heat and is a very expensive technology used only for light-cured liquid polymers [7]. The advantages of DLP technology include high precision, smooth surface, fast execution, and lower cost, but it has the same disadvantages as stereolithography [8; 9].  
Polymethyl methacrylate (PMMA) is a synthetic polymer that is part of most acrylic resins. PMMA has long been used for the fabrication of dentures as it has numerous advantages: Ease of fabrication and repair, good patient acceptance, low cost, biocompatibility, odor and taste neutrality, and good esthetic properties [5]. However, it also has some disadvantages, such as low wear resistance, allergic reactions due to the release of monomers into the oral cavity, and, above all, a high susceptibility to microbial and fungal contamination [4; 10; 11; 12].  
In view of these problems associated with the use of PMMA, the incorporation of compounds into CAD-CAM dental materials is increasingly being investigated to improve the mechanical properties and, above all, to prevent the development of microorganisms. Some examples of compounds with antimicrobial properties are zinc dioxide nanoparticles [13], graphene nanoplatelets [14], silver-reinforced mesoporous silica nanoparticles [15], titanium dioxide [16], cellulose-silver nanocrystals [17], ceramic nitrides [18], zwitterionic materials [19], chlorhexidine [20; 21; 22; 23; 24], andtocopherol [25].  
In dentistry, new CAD-CAM materials have also been developed that combine the properties of ceramics with those of resins. One example of this type of material is the infiltrated polymeric ceramic network [10]. Examples of other materials currently under investigation are nano-ceramic resins, which consist of 80% zirconia and silica clusters, and lithium disilicate ceramics, which consist of 40% lithium metasilicate crystals [26].  
The aim of this systematic review was to analyze whether the compounds incorporated into the acrylic resins produced by CAD-CAM can improve their performance, i.e., surface and mechanical properties; their effectiveness of antimicrobial activity; and to ensure safety through cytotoxicity and genotoxicity tests.