Advanced reconfigurable scaffolds fabricated by 4D printing for treating critical-size bone defects of irregular shapes

While scaffold-based tissue engineering has been widely used to treat bone critical-size defects, challenges such as implantation of scaffolds in defects with irregular shapes and implantation of scaffolds through minimally invasive surgery remain in the tissue engineering field. Customized bioactive bone tissue engineering scaffolds with reconfigurable capability for both easy scaffold implantation and perfect shape fitting in irregularly shaped bone defects are therefore needed. Herein, applying 4D printing, photothermal-responsive shape memory bone tissue engineering scaffolds are constructed by incorporating black phosphorus nanosheets and osteogenic peptide into β-tricalcium phosphate/poly(lactic acid-co-trimethylene carbonate) (TCP/P(DLLA-TMC)) nanocomposite scaffolds. When near-infrared irradiation is applied to customized scaffolds on-demand, scaffold temperature rapidly increases to 45 C, enabling scaffold shape reconfiguration for easy scaffold implantation and precise fitting in irregular bone defects. Once the implantation is finished, scaffold temperature rapidly decreases to 37 C and scaffolds display mechanical properties comparable to those of human cancellous bone. The improved osteogenesis in bone defect sites is then initiated through pulsed peptide release from scaffolds. Compact integration of reconfigurable scaffolds in rat cranial bone defects and improved new bone formation are demonstrated through micro-computed tomography and histochemical analyses. This study shows a facile method to clinically treat bone defects of irregular shapes.