## 1 Introduction  
Dental caries remains a prevalent global disease, characterized by bacterial infection and mineral loss of hard dental tissues due to oral biofilm formation [1; 2]. The major risk factors causing dental caries are enamel hypoplasia, eating habits, poor oral hygiene and trouble brushing, caregiver effect, low income, and low level of education [3; 4; 5]. Within carious dentin, two distinct layers play a critical role: the irreparable caries-infected dentin, also known as the outer layer, and the repairable caries-affected dentin (CAD), referred to as the inner layer [6]. Infected dentin exhibits significant decalification, denatured collagen fibers, and disrupted odontoblasts, necessitating removal. In contrast, affected dentin displays minimal demineralization, relatively intact collagen fibers, and lacks bacterial invasion, requiring preservation [7; 8; 6]. Contemporary adhesive systems strive to achieve robust bonding to various tooth substrates, particularly to caries-affected dentin [9]. In the field of dentistry, there has been a paradigm shift towards minimally invasive and preventive approaches, transforming from [PERSON]'s \"extension for prevention\" management to a \"construction with conservation\" mindset [10; 11; 12]. As a result, the search for less invasive yet effective caries excavation techniques has led to the development of minimally invasive methods that aim to remove only the infected dentin while preserving healthy enamel and dentin [13]. These techniques include air abrasion, sono-abrasion, and chemo-mechanical caries removal (CMCR) methods [12; 14; 15]. Chemo-mechanical caries removal (CMCR) is a non-aggressive approach involving the application of a chemical gel that selectively removes soft and necrotic infected dentin using a hand instrument while leaving the affected dentin intact [16]. CMCR agents can be categorized into sodium hypochlorite (NaOCl)-based (e.g., Caridex(r), Carisolv(r)) and enzyme-based (e.g., Carie-Care(tm), Papacarie(r), BRIX3000). Carsolv, a pink gel, contains sodium hypochlorite, amino acids (leucine, lysine, glutamic acid), methylcellulose, and erythrosine, acting by chlorinating and facilitating the removal of denatured collagen. On the other hand, Papacarie is an enzyme-based CMCR agent consisting of papain, a proteolytic enzyme with bactericidal and anti-inflammatory properties [17; 18; 19; 20; 21]. Bonding agents utilized in clinical practice can be classified into etch-and-rinse (ER), self-etch (SE), universal (U), and resin-modified glass ionomer adhesives (RMGIA) [22; 23; 24]. However, bonding to caries-affected dentin (CAD) poses challenges during operative treatment. The morphological alterations in CAD, including reduced mineral content, loss of crystallinity, and organic matrix changes, can impede dentin hybridization and compromise the mechanical performance of bonded restorations. High porosity and exposure of collagen fibers, along with a decrease in surface energy, are seen in the intertubular CAD. Reduction of these mechanical properties significantly influences a decrease of the mean elastic modulus and nano-hardness in CAD when compared to unaltered tissue. The obliteration of tubules can interfere with resin infiltration, at the same time preventing tags during bonding procedures. On the contrary, the lower mineral content of intertubular dentin in CAD permits deeper etching of this substrate [13; 14; 15; 16]. Self-etch adhesives are the latest generation of adhesives. Adhesive frameworks today are either \"etch and rinse\" or \"self-etch\" approaches, which have different mechanisms of action on tooth substrate. Etch and rinse include pre-treatment with phosphoric acid etchant before bonding. Self-etch adhesives are acid-type monomers that perform etching and rinsing at the same time point [25; 26]. They are easy to apply and have fewer clinical steps. Both systems structure mixed layers as resin infiltrates the permeable dentin and enamel [22; 27].