α-Cyclodextrin mediated 3D printed ceramic/polymer composite scaffolds for immunomodulation and osteogenesis in bone defect repair.

Bone tissue engineering scaffolds for bone defect treatment face numerous challenges, including mechanical mismatches and the lack of immune microenvironment modulation, often leading to implant failure. In this study, an innovative drug-loaded bioinspired ceramic/polymer composite scaffold was designed and fabricated using extrusion-based 3D printing technology, incorporating α-cyclodextrin (αCD) in a novel approach to improve interfacial compatibility and drug-loading efficiency. Hydroxyapatite (HA), the main component of natural bone, was employed as the inorganic phase to mimic the mineral structure of bone tissue. Sodium alginate (SA), a natural polymer, served as the organic phase, imparting mechanical strength and flexibility to the scaffold. To enhance phase compatibility, polyethylene glycol (PEG) was grafted onto the HA surface, and αCD was spontaneously threaded onto the PEG chains to form poly(pseudo)rotaxane structures. This approach further improved the mechanical performance of the scaffold. Additionally, melatonin (MT) was incorporated into the scaffold to enhance its osteogenic, anti-inflammatory, and antioxidant functions. To address MT's poor water solubility and bioavailability, αCD was utilized to encapsulate MT, enabling efficient and sustained release. The scaffold's physical and chemical properties, in vitro mineralization ability, biological functions, and in vivo performance in a rat calvarial defect model were systematically evaluated. Results demonstrated that the scaffold exhibited excellent biocompatibility, promoted osteogenesis, and provided antioxidant and anti-inflammatory effects, making it a promising and efficient solution for bone defect repair.