Sustained slow-release TGF-β3 in a three-dimensional-printed titanium microporous scaffold composite system promotes ligament-to-bone healing

The treatment of tendon/ligament-to-bone injury is a long-standing research challenge in orthopedics and bone tissue engineering. Orderly healing of the fibrocartilage layer and mineralized bone layer is crucial for treating tendon-bone interface injuries. We designed a three-dimensional printed porous titanium scaffold composite system with thermosensitive collagen hydrogel loaded with transforming growth factor β3 (TGF-β3), formulated for the sustained slow release of TGF-β3 at a constant rate. <i>In vitro</i>, the composite system exhibited good biocompatibility and was beneficial for the adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs), which showed high growth activity. Moreover, the composite system promoted the differentiation of BMSCs via osteogenesis and chondrogenesis. <i>In vivo</i>, the composite system provided active substances at the injured site, promoting the repair of the fibrocartilage layer and of the mineralized bone layer at the interface between the ligament and bone. Micro-CT results demonstrated that the complex promotes the osseointegration of titanium scaffolds in bone defects. Hard tissue sections showed that the new bone, ligament, and the titanium alloy scaffold system formed a closely integrated whole; the composite system provided suitable attachment points for ligament growth. Additionally, the biomechanical strength of the tendon interface improved to some extent. Our results indicate that the composite system has potential as a bioactive implant interface for repairing ligament and bone injuries.