Dental implants, primarily composed of titanium (Ti) and its alloys, are surgically inserted into the jawbone to replace missing teeth, restoring patients' masticatory function and aesthetic appearance. With commendable survival rates, dental implants have become the preferred treatment for partial and complete edentulism (Smeets et al., 2016; Jasser et al., 2021; Andrade et al., 2022; Park et al., 2022; Sartoretto et al., 2023). The success of these implants largely hinges on osseointegration, which establishes a direct structural and functional connection between living bone and the implant's load-bearing Ti surface, involving various biological responses (Jayesh et al., 2015; Radi et al., 2018; Zhao et al., 2022). This process is particularly critical for patients with poor bone density, significant alveolar bone loss, or metabolic bone diseases, where achieving rapid and reliable osseointegration is imperative (Le Guéhennec et al., 2007; Lee et al., 2014).

Originally, dental implants were machined and bioinert, their biocompatibility was attributed to a spontaneously formed oxide layer on the implant's surface (López-Valverde et al., 2020). Modifying the physicochemical properties of Ti implants, using approaches like physicochemical, morphological, and biochemical methods, can further enhance osseointegration by influencing the behavior and function of multiple cells (Puleo et al., 1999; Hung et al., 2016; Asri et al., 2017; Rupp et al., 2018; Mappa et al., 2024). These strategies aim to promote the in-migration of new bone (e.g., osteoconduction), regulate cell types adhering to the implant surface, and induce osteoinduction for new bone differentiation, all while preserving inherent biocompatibility (Stanford, 2008; Kunrath et al., 2021). Despite the promise of nano/microstructures on implant surfaces for promoting surface mineralization and bone regeneration via morphological and physicochemical approaches, insufficient initial adhesion of tissue repair cells due to the absence of cell-specific binding sites has hindered effective tissue repair (Vogler, 2012; Huang et al., 2021; Yang et al., 2021; Mappa et al., 2024). Biochemical surface modifications, involving the immobilization or adsorption of biofunctional molecules, could effectively elicit distinct cell and tissue responses in various gingival cells (Morra et al., 2003; Marín-Pareja et al., 2014; Chen et al., 2023; Cho et al., 2024).

Collagen, particularly type I derived from bovine, porcine, or even human sources plays a crucial role as the predominant protein in bone. It provides tissue strength and structural stability while facilitating osteoblastic cell adhesion, differentiation, and extracellular matrix secretion (Rico-Llanos et al., 2021; Amirrah et al., 2022). Incorporating additional bio-adhesive motifs for integrin binding and positive charge properties onto implant surfaces through collagen immobilization promotes focal adhesion formation and the early adsorption of most negatively charged proteins (Grant et al., 2001; Minardi et al., 2015). These modifications ultimately enhance cell adhesion and support tissue regeneration. Kado et al. (2019) observed a significant enhancement in the adhesion and spreading of human periodontal ligament cells on Ti surfaces modified with type I collagen immobilization, compared to uncoated Ti surfaces. Additionally, Zhao et al. (2022) demonstrated that Ti surfaces with collagen-decorated nanoporous networks significantly regulated angiogenesis and osteogenesis processes, resulting in favorable osseointegration.

The immobilization of collagen on machined Ti surfaces has been shown to significantly enhance the attachment, spreading, proliferation, and differentiation of human bone marrow-derived mesenchymal stem cells (Kado et al., 2012, 2019). However, there was a lack of research focused on bone regeneration and osseointegration during the initial stages of implantation in vivo. Accordingly, the present study aimed to conduct in vivo animal experiments to further investigate the early-stage osseointegration capability of Ti implants with collagen-immobilized surfaces at weeks 2 and 6 post-implantation. Since collagen cannot be produced artificially, it always comes as a tissue extract. This study adopted a commercially available highly purified collagen type I derived from porcine tendon for investigation. The results will offer valuable scientific insights for further developing and refining Ti dental implants.