The purpose of 4D printing is to embed a product design into a deformable smart material using a traditional 3D printer. The 3D printed object can be assembled or transformed into intended designs by applying certain conditions or forms of stimulation such as temperature, pressure, humidity, pH, wind, or light. Simply put, 4D printing is a continuum of 3D printing technology that is now able to print objects which change over time. In previous studies, many smart materials were shown to have 4D printing characteristics. In this paper, we specifically review the current application, respective activation methods, characteristics, and future prospects of various polymeric materials in 4D printing, which are expected to contribute to the development of 4D printing polymeric materials and technology.

Periodontal disease is a chronic disease that can lead to lose teeth and even tooth loss if left untreated. Osteoporosis and periodontal disease share similar characteristics and associated factors. Current regenerative techniques for periodontal diseases are ineffective in restoring complete function and structural integrity of periodontium due to unwanted migration of cells. In this study, we applied the concept of guided tissue regeneration (GTR) and 3D fabricated gingival fibroblast cell-laden collagen/strontium-doped calcium silicate (SrCS) bi-layer scaffold for periodontal regeneration. The results revealed that the bioactive SrCS had a hydroxyapatite formation on its surface after 14 days of immersion and that SrCS could release Sr and Si ions even after 6 months of immersion. In addition, in vitro results showed that the bi-layer scaffold enhanced secretion of FGF-2, BMP-2, and VEGF from human gingival fibroblasts and increased secretion of osteogenic-related proteins ALP, BSP, and OC from WJMSCs. In vivo studies using animal osteoporotic models showed that the 3D-printed cell-laden collagen/SrCS bi-layer scaffold was able to enhance osteoporotic bone regeneration, as seen from the increased Tb.Th and BV/TV ratio and the histological stains. In conclusion, it can be seen that the bi-layer scaffolds enhanced osteogenesis and further showed that guided periodontal regeneration could be achieved using collagen/SrCS scaffolds, thus making it a potential candidate for future clinical applications.

In this study, we synthesized strontium-contained calcium silicate (SrCS) powder and fabricated SrCS scaffolds with controlled precise structures using 3D printing techniques. SrCS scaffolds were shown to possess increased mechanical properties as compared to calcium silicate (CS) scaffolds. Our results showed that SrCS scaffolds had uniform interconnected macropores (~500 µm) with a compressive strength 2-times higher than that of CS scaffolds. The biological behaviors of SrCS scaffolds were assessed using the following characteristics: apatite-precipitating ability, cytocompatibility, proliferation, and osteogenic differentiation of human mesenchymal stem cells (MSCs). With CS scaffolds as controls, our results indicated that SrCS scaffolds demonstrated good apatite-forming bioactivity with sustained release of Si and Sr ions. The in vitro tests demonstrated that SrCS scaffolds possessed excellent biocompatibility which in turn stimulated adhesion, proliferation, and differentiation of MSCs. In addition, the SrCS scaffolds were able to enhance MSCs synthesis of osteoprotegerin (OPG) and suppress macrophage colony-stimulating factor (M-CSF) thus disrupting normal bone homeostasis which led to enhanced bone formation over bone resorption. Implanted SrCS scaffolds were able to promote new blood vessel growth and new bone regeneration within 4 weeks after implantation in critical-sized rabbit femur defects. Therefore, it was shown that 3D printed SrCS scaffolds with specific controllable structures can be fabricated and SrCS scaffolds had enhanced mechanical property and osteogenesis behavior which makes it a suitable potential candidate for bone regeneration.

Vascular endothelial growth factor (VEGF) is one of the most crucial growth factors and an assistant for the adjustment of bone regeneration. In this study, a 3D scaffold is fabricated using the method of fused deposition modeling. Such a fabricated method allows us to fabricate scaffolds with consistent pore sizes, which could promote cellular ingrowth into scaffolds. Therefore, we drafted a plan to accelerate bone regeneration via VEGF released from the hydroxyapatite/calcium sulfate (HACS) scaffold. Herein, HACS will gradually degrade and provide a suitable environment for cell growth and differentiation. In addition, HACS scaffolds have higher mechanical properties and drug release compared with HA scaffolds. The drug release profile of the VEGF-loaded scaffolds showed that VEGF could be loaded and released in a stable manner. Furthermore, initial results showed that VEGF-loaded scaffolds could significantly enhance the proliferation of human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVEC). In addition, angiogenic- and osteogenic-related proteins were substantially increased in the HACS/VEGF group. Moreover, in vivo results revealed that HACS/VEGF improved the regeneration of the rabbit’s femur bone defect, and VEGF loading improved bone tissue regeneration and remineralization after implantation for 8 weeks. All these results strongly imply that the strategy of VEGF loading onto scaffolds could be a potential candidate for future bone tissue engineering.

Although autologous nerve grafting remains the gold standard treatment for peripheral nerve injuries, alternative methods such as development of nerve guidance conduits have since emerged and evolved to counter the many disadvantages of nerve grafting. However, the efficacy and viability of current nerve conduits remain unclear in clinical trials. Here, we focused on a novel decellularized extracellular matrix (dECM) and polydopamine (PDA)-coated 3D-printed poly(ε-caprolactone) (PCL)-based conduits, whereby the PDA surface modification acts as an attachment platform for further dECM attachment. We demonstrated that dECM/PDA-coated PCL conduits possessed higher mechanical properties when compared to human or animal nerves. Such modifications were proved to affect cell behaviors. Cellular behaviors and neuronal differentiation of Schwann cells were assessed to determine for the efficacies of the conduits. There were some cell-specific neuronal markers, such as Nestin, neuron-specific class III beta-tubulin (TUJ-1), and microtubule-associated protein 2 (MAP2) analyzed by enzyme-linked immunosorbent assay, and Nestin expressions were found to be 0.65-fold up-regulated, while TUJ1 expressions were 2.3-fold up-regulated and MAP2 expressions were 2.5-fold up-regulated when compared to Ctl. The methodology of PDA coating employed in this study can be used as a simple model to immobilize dECM onto PCL conduits, and the results showed that dECM/PDA-coated PCL conduits can as a practical and clinically viable tool for promoting regenerative outcomes in larger peripheral nerve defects.