Min Wang1,Xiaodie Chen1,Jiahui Lai1
The University of Hong Kong1
Min Wang1,Xiaodie Chen1,Jiahui Lai1
The University of Hong Kong1
Porous scaffolds are fabricated for regenerating human body tissues and hance scaffold materials must have good biocompatibility and should degrade during the formation of new tissue in the <i>in vivo</i> environment. Many natural biomaterials possess excellent biological properties and cell affinity, which is beneficial for interactions between cells and these materials and stimulates cell growth and differentiation. Gelatin methacryloyl (GelMA), a photopolymerizable hydrogel composed of natural gelatin functionalized with methacrylic anhydride, preserves the functional amino acid sequence of gelatin (such as arginine-glycine-aspartic acid (RGD) sequence) and can promote cell adhesion and proliferation, which makes it very attractive for tissue engineering. 3D printing has been increasingly used to make tissue engineering scaffolds owing to its many advantages. However, 3D printed structures maintain static shapes during their application time and hence cannot accurately imitate the dynamic nature of tissues. Ideally, shapes, properties and/or functions of tissue engineered products should evolve in the dynamic tissue regeneration process. Therefore, 4D printing, which integrates time with 3D printing, has been developed to fabricate dynamic structures that change the shape, properties and/or functions over time under appropriate stimulus/stimuli such as temperature, pH, humidity, light, electricity, magnetic field, acoustics, or a combination of these stimuli. Currently, 4D printed GelMA scaffolds do not generate sufficient internal force for shape morphing when they are exposed to water. Blending GelMA with a synthetic shape-memory polymer is an effective way to overcome the problem. Poly(D,L-lactide-co-trimethylene carbonate) (PDLLA-<i>co</i>-TMC) is a popular shape-memory polymer in the biomedical field, and structures made of PDLLA-<i>co</i>-TMC with the PDLLA to TMC ratio of 80:20 respond to body temperature. With the addition of PDLLA-<i>co</i>-TMC, GelMA/PDLLA-<i>co</i>-TMC scaffolds may have sufficient internal force for changing the shape. In this study, shape morphing scaffolds with improved flexibility were fabricated via 4D printing using GelMA and PDLLA-<i>co</i>-TMC (80:20) blends. 4D printing involved four steps: (1) pure GelMA and GelMA/PDLLA-<i>co</i>-TMC blends at 1:1, 1:2 and 1:3 blend ratios were printed into planar structures; (2) the planar structures were shaped into tubes by using a glass rod at 80 °C; (3) the tubular structures were flattened at 25 °C; (4) the flattened scaffolds could self-fold into tubular structures at 37 °C within a minute in an aqueous environment. The influence of polymer blend ratio on printability and shape memory was investigated and compared with pure GelMA. The mechanical properties of pure GelMA and GelMA/PDLLA-<i>co</i>-TMC blends were studied. The cell viability on 4D printed GelMA/PDLLA-<i>co</i>-TMC scaffolds were compared. It was found that the addition of PDLLA-<i>co</i>-TMC into GelMA improved material flexibility, stretchability, and shape memory ability while maintaining the biocompatibility. The satisfactory performance of 4D printed GelMA/PDLLA-<i>co</i>-TMC scaffolds has made them promising for tissue engineering applications.