The lack of bone grafts represents a major issue in the orthopedic field, reconstructive surgery, and dentistry. There are several bone conditions that often demand the use of grafts, such as fractures, infections, and bone cancer. The number of bone cancer cases increased in the past few decades and along with it, the need for bone grafting materials. To avoid the use of autografts and allografts there has been an increased interest towards synthetic grafts. This research aims to develop some collagen/hydroxyapatite (Coll/HAp) scaffolds cross-linked with three different agents that could be used in bone tissue engineering (BTE). These scaffolds were obtained with a freeze-drying method after the in situ formation of hydroxyapatite inside the collagen matrix. They were structurally and morphologically characterized and evaluated in terms of antimicrobial activity on