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

Abstract

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.

4D biofabrication via instantly generated graded hydrogel scaffolds

“…Compared with 3D scaffolds, 4D scaffolds with the ability to reconfigure their shapes during culture show huge potential for morphodynamic tissue engineering. Hydrogels that harness non-uniform swelling [ 43 , 54 , [56] , [57] , [58] ], post-programmed anisotropic internal strains [ 59 , 60 ], or cell contractile forces [ [61] , [62] , [63] ] can accomplish this task. However, in addition to the stringent requirements regarding material cytocompatibility, the fabrication process, and imposed stimulation, complexity in fabrication and lack of controllability present a significant impedance to 4D tissue engineering.…”

Multi‐Dimensional Printing for Bone Tissue Engineering

“…Wang et al reported a shape memory bone scaffold based on -TCP/poly(lactic acid-co-trimethylene carbonate) (TCP/P(DLLA-TMC)), which was further modified with osteogenic peptide and black phosphorous nanosheets. [167] The black phosphorous nanosheets provided photothermal-responsive features, enabling the scaffolds to undergo shape reconfiguration. The mechanical strength of the scaffolds was also changed after printing and NIR irradiation, making it more similar to native human cancellous bone.…”

Current Application of Beta-Tricalcium Phosphate in Bone Repair and Its Mechanism to Regulate Osteogenesis

“…Wang et al constructed β-TCP-based nanocomposite scaffolds by incorporating black phosphorus nanosheets and osteogenic peptide into β-TCP/poly (lactic acid-co-trimethylene carbonate) (TCP/P (DLLA-TMC)) by 4D printing. The shape of the 4D-printed scaffolds can be reconfigured to adjust precise fitting in irregular bone defects when the scaffold temperature rapidly increases to 45°C (Wang et al, 2020b). To date, the β-TCP-based 4D printed products have rarely been reported in bone tissue engineering, however, these materials have substantial potential as bone substitutes although further research is warranted.…”