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.

Calcium silicate-based cement has garnered huge interest in recent years, due to its versatility and potential in mass fabrication of a variety of bioceramics. For this study, the main objective was to fabricate functionalized calcium silicate (CS) powder integrated with a simple bio-inspired surface modification using polydopamine (PDA), to regulate cellular behaviors such as cellular adhesion, and subsequently cell differentiation and proliferation. For this study, scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) techniques were used to analyze the chemical compositions and observe the surface characteristics of our PDA coated CS cements. Such modifications were found to enhance Wharton Jelly’s mesenchymal stem cells (WJMSC) in various ways. Firstly, PDA-coated CS cements were found to significantly enhance cell adhesion with higher expressions of cell adhesion markers, such as focal adhesion kinase and integrins. This was further supported by morphology analysis of the cells. This enhanced cell adhesion, in turn, led to significantly higher secretion of extracellular matrix (ECM) proteins, such as collagen I and fibronectin, which directly promoted cell attachments and proliferation. In our osteogenesis assays, it was found that secretion and expression of osteogenesis related genes and proteins were significantly higher and were dependent on the PDA content. Therefore, these results demonstrated that such simple bio-inspired modification techniques of synthetic degradable CS cements can be applied as a future modification, to modify and convert inert surfaces of synthetic bone grafts to enhance and modulate the cell behaviors of WJMSCs. This in turn can be used as a potential alternative for further bioengineering research.

According to the Centers for Disease Control and Prevention, tooth caries is a common problem affecting 9 out of every 10 adults worldwide. Dentin regeneration has since become one of the pressing issues in dentistry with tissue engineering emerging as a potential solution for enhancing dentin regeneration. In this study, we fabricated cell blocks with human dental pulp stem cells (hDPSCs)-laden alginate/fish gelatin hydrogels (Alg/FGel) at the center of the cell block and human umbilical vascular endothelial cells (HUVEC)-laden Si ion-infused fish gelatin methacrylate (FGelMa) at the periphery of the cell block. 1H NMR and FTIR results showed the successful fabrication of Alg/FGel and FGelMa. In addition, Si ions in the FGelMa were noted to be bonded via covalent bonds and the increased number of covalent bonds led to an increase in mechanical properties and improved degradation of FGelMa. The Si-containing FGelMa was able to release Si ions, which subsequently significantly not only enhanced the expressions of angiogenic-related protein, but also secreted some cytokines to regulate odontogenesis. Further immunofluorescence results indicated that the cell blocks allowed interactions between the HUVEC and hDPSCs, and taken together, were able to enhance odontogenic-related markers’ expression, such as alkaline phosphatase (ALP), dentin matrix phosphoprotein-1 (DMP-1), and osteocalcin (OC). Subsequent Alizarin Red S stain confirmed the benefits of our cell block and demonstrated that such a novel combination and modification of biomaterials can serve as a platform for future clinical applications and use in dentin regeneration.