Dual-nozzle 3D-printed calcium sulfate/ polylactic acid scaffold incorporating linezolid microspheres for effective repair of femoral condyle defects in rats

Abstract

Large, complex bone defects pose a significant clinical challenge. Conventional bone grafting approaches cannot simultaneously achieve tissue regeneration and infection prevention, resulting in impaired healing outcomes and prolonged treatment cycles. Existing therapeutic strategies lack integrated solutions capable of concurrently providing infection prevention and osteogenesis promotion within a single platform. This study developed a novel multifunctional composite scaffold using dual-nozzle three-dimensional printing technology to simultaneously achieve infection prevention and accelerated bone regeneration. Linezolid-loaded polylactic-co-glycolic acid microspheres (LMS) were uniformly dispersed within the pores of calcium sulfate/polylactic acid (CS/PLA) scaffolds to successfully construct the composite scaffold. In vitro characterization revealed uniform distribution of microspheres within the scaffold pores, with the fabricated CS/PLA-LMS demonstrating excellent biocompatibility and mechanical properties, achieving an elastic modulus of 87 MPa. Furthermore, the composite scaffold effectively inhibited Staphylococcus aureus activity in vitro. In vivo rat femoral condyle defect model revealed that the composite scaffold significantly enhanced bone formation compared to blank controls. Additionally, bone volume fraction increased by 3.2 times, and trabecular spacing decreased by 50%, with mechanistic analysis indicating activation of the phosphoinositide 3-kinase-protein kinase B signaling pathway. The integrated design successfully prevented infection-related complications while promoting robust osteogenesis, offering a clinically relevant solution for treating complex bone defects where infection prevention and regenerative capacity are primary therapeutic concerns.  

Keywords

Bone defect repair / Dual-nozzle three-dimensional printing / Calcium sulfate / Linezolid microspheres

Funding

This study was supported by the Taishan Scholar Project of Shandong Province, China (No.tstp 20250511).

Conflict of Interest

The authors declare that they have no conflict of interest.

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