4D Printing of Shape-memory Nanocomposite Scaffolds via Digital Light Processing for Bone Tissue Engineering

Additive manufacturing (AM, i.e., 3D printing) has made profound impact in many industries including biomedical. Using smart materials and AM technologies, 4D printing can produce objects whose shape and/or property will change under appropriate stimuli such as temperature. 4D printed structures are important for specific applications. A main focus of 3D/4D printing in biomedicine is at tissue engineering (TE). For 4D printing in TE, smart materials are a key component but currently they are still very limited. Over the past few decades, bone tissue engineering (BTE) has shown its ability to tackle difficult problems in human bone loss that tradition treatments such as autograft or allograft cannot deal with. 4D printed BTE porous scaffolds are needed for minimally invasive surgery for bone regeneration or for regenerating bone in critical-size bone defects of irregular shapes. In this study, using shape-memory and biodegradable poly(D,L-lactide-co-trimethylene carbonate) (PDLLA-co-TMC) polymer, a new osteoconductive and shape-memory nanocomposite, β-tricalcium phosphate (β-TCP)/PDLLA-co-TMC was developed for 4D printing of BTE scaffolds, and digital light processing (DLP) was employed for 4D printing. Using acetone, β-TCP nanoparticle suspensions in PDLLA-co-TMC were made as printing inks. Inks having 5, 10, 15, 20, 25 and 30 vol% of β-TCP, together with PEGDA, free radical inhibitor, photoabsorber and photoinitiator, were DLP-printed into nanocomposite scaffolds of the designed grid structure with square pores; and post-DLP photocuring was conducted. Nanocomposite scaffolds of different pore sizes showed high fidelity to the design. The strength of nanocomposite scaffolds of 400-micron pore size could reach 3.13 MPa, approaching that of human cancellous bone and hence indicating their suitability for BTE. Flat nanocomposite scaffolds could fold quickly into tubular shape in water when temperature changed from 25C to 37C, indicating their good shape-morphing ability. Cytocompatibility assessment using MC3T3-E1 pre-osteoblasts showed good biocompatibility and osteoconductivity of nanocomposite scaffolds.