TABLE 2.

Selected upregulated genes in MSCs cultured on Ti-AM + Bru compared to Ti-AM under osteogenic conditions, with their biological roles and potential contributions to early osseointegration.

Gene	Role	Pro-osteointegrative role in early phase
BMP2	Promotes osteogenic differentiation and bone formation. Crucial for osseointegration	Upregulation of BMP2 indicates activation of osteogenesis, stimulating the differentiation of MSCs into osteoblasts and initiating bone formation at the implant site, which is essential for successful osseointegration
FZD3	Involved in wnt signaling pathway, essential for osteoblast differentiation and bone formation	Upregulation of FZD3 activates the wnt pathway, which is essential for osteoblast differentiation and the promotion of bone regeneration around the Implant, aiding in early osteointegration
SMURF2	Regulates osteoblast differentiation and bone homeostasis, modulating osteogenesis	Upregulation of SMURF2 supports the regulation of osteoblast differentiation, ensuring proper bone formation and remodeling, which is critical for implant stabilization and osseointegration
IL8	Pro-inflammatory cytokine involved in immune cell recruitment and inflammation at the implant site	Upregulation of IL8 contributes to the inflammatory phase by attracting immune cells to the implant site, which helps in tissue repair and infection control. While inflammation is necessary for healing, its resolution is also crucial for osteointegration
OAS1	Part of the immune response, involved in antiviral defense and modulating inflammation	Upregulation of OAS1 activates the innate immune system to protect the implant site, while also controlling inflammation, creating a balanced environment that supports tissue healing and osseointegration
IFIT1	Interferon-induced gene, involved in immune modulation and the antiviral response	Upregulation of IFIT1 enhances the immune response to defend against potential infection at the implant site, while promoting immune regulation to ensure that inflammation does not hinder the osteointegration process
NDUFA9	Part of mitochondrial complex I, involved in cellular energy production necessary for cell proliferation and differentiation	Upregulation of NDUFA9 supports increased energy production, which is vital for cell proliferation and osteoblast differentiation during the early stages of bone healing and implant integration
MTHFD2L	Involved in folate metabolism, crucial for cell division, DNA synthesis, and overall cell function	Upregulation of MTHFD2L facilitates the necessary metabolic processes for cell proliferation and differentiation, ensuring that osteoblasts are able to efficiently form new bone around the implant
SCL20A1	Phosphate transporter essential for bone mineralization, contributing to bone formation around the implant	Upregulation of SLC20A1 enables efficient phosphate transport, which is critical for bone mineralization, promoting the formation of a mineralized bone matrix at the implant site, a key part of osseointegration