Bone is a highly vascularized tissue with a unique and complex structure. Long bone consists of a peripheral cortical shell containing a network of channels for vascular penetration and an inner highly vascularized bone marrow space. Bioprinting is a powerful tool to enable rapid and precise spatial patterning of cells and biomaterials. Here we developed a two-step digital light processing technique to fabricate a bone-mimetic 3D hydrogel construct based on octacalcium phosphate (OCP), spheroids of human umbilical vein endothelial cells (HUVEC), and gelatin methacrylate (GelMA) hydrogels. The bone-mimetic 3D hydrogel construct was designed to consist of a peripheral OCP-containing GelMA ring to mimic the cortical shell, and a central GelMA ring containing HUVEC spheroids to mimic the bone marrow space. We further demonstrate that OCP, which is evenly embedded in the GelMA, stimulates the osteoblastic differentiation of mesenchymal stem cells. We refined the design of a spheroid culture device to facilitate the rapid formation of a large number of HUVEC spheroids, which were embedded into different concentrations of GelMA hydrogels. It is shown that the concentration of GelMA modulates the extent of formation of the capillary-like structures originating from the HUVEC spheroids. This cell-loaded hydrogel-based bone construct with a biomimetic dual ring structure can be potentially used for bone tissue engineering.

Calcium Titanate (CaTiO₃) has been introduced as an attractive biomaterial for the enhancement of calcium phosphate deposition in vivo and in vitro. We hypothesized that CaTiO₃ directly coated on titanium (Ti) by metal-organic chemical vapor deposition (MOCVD) could be a suitable candidate for biocompatible coatings for medical devices, particularly dental implants. To prove this hypothesis, surface characterization, cell culture, and animal study were completed in this study. The result of this study showed that CTO 800, a CaTiO₃ film prepared by heating at 800 °C, had a high hydrophilic surface. Mouse bone marrow stromal ST-2 cells cultured on substrates and CTO 800 exhibited cell differentiation, represented by alkaline phosphatase activity, compared with cells cultured on non-coated Ti and CTO 700 (a CaTiO₃ film prepared by heating at 700 °C). The push-in test value of CTO 800, a parameter that indicates the degree of osseointegration, was significantly higher than that of Ti. Calcium titanate coated on Ti by MOCVD has the potential to accelerate the process of osseointegration; thus, our results support the use of CaTiO₃ coating for biocompatible biomaterial for medical applications, particularly dental implants.

Here we aimed to establish a simple detection method for detecting circulating tumor cells (CTCs) in the blood sample of colorectal cancer (CRC) patients using poly(2-methoxyethyl acrylate) (PMEA)-coated plates. Adhesion test and spike test using CRC cell lines assured efficacy of PMEA coating. A total of 41 patients with pathological stage II–IV CRC were enrolled between January 2018 and September 2022. Blood samples were concentrated by centrifugation by the OncoQuick tube, and then incubated overnight on PMEA-coated chamber slides. The next day, cell culture and immunocytochemistry with anti-EpCAM antibody were performed. Adhesion tests revealed good attachment of CRCs to PMEA-coated plates. Spike tests indicated that ~75% of CRCs from a 10-mL blood sample were recovered on the slides. By cytological examination, CTCs were identified in 18/41 CRC cases (43.9%). In cell cultures, spheroid-like structures or tumor-cell clusters were found in 18/33 tested cases (54.5%). Overall, CTCs and/or growing circulating tumor cells were found in 23/41 CRC cases (56.0%). History of chemotherapy or radiation was significantly negatively correlated with CTC detection (p = 0.02). In summary, we successfully captured CTCs from CRC patients using the unique biomaterial PMEA. Cultured tumor cells will provide important and timely information regarding the molecular basis of CTCs.

Confluent monolayers of human umbilical vein endothelial cells (HUVECs) on a poly(2-methoxyethyl acrylate) (PMEA) antithrombogenic surface play a major role in mimicking the inner surface of native blood vessels. In this study, we extensively investigated the behavior of cell–polymer and cell–cell interactions by measuring adhesion strength using single-cell force spectroscopy. In addition, the attachment and migration of HUVECs on PMEA-analogous substrates were detected, and the migration rate was estimated. Moreover, the bilateral migration of HUVECs between two adjacent surfaces was observed. Furthermore, the outer surface of HUVEC was examined using frequency-modulation atomic force microscopy (FM-AFM). Hydration was found to be an indication of a healthy glycocalyx layer. The results were compared with the hydration states of individual PMEA-analogous polymers to understand the adhesion mechanism between the cells and substrates in the interface region. HUVECs could attach and spread on the PMEA surface with stronger adhesion strength than self-adhesion strength, and migration occurred over the surface of analogue polymers. We confirmed that platelets could not adhere to HUVEC monolayers cultured on the PMEA surface. FM-AFM images revealed a hydration layer on the HUVEC surfaces, indicating the presence of components of the glycocalyx layer in the presence of intermediate water. Our findings show that PMEA can mimic original blood vessels through an antithrombogenic HUVEC monolayer and is thus suitable for the construction of artificial small-diameter blood vessels.

The regulation of adhesion and the subsequent behavior of fibroblast cells on the surface of biomaterials is important for successful tissue regeneration and wound healing by implanted biomaterials. We have synthesized poly(ω-methoxyalkyl acrylate)s (PMCxAs; x indicates the number of methylene carbons between the ester and ethyl oxygen), with a carbon chain length of x = 2–6, to investigate the regulation of fibroblast cell behavior including adhesion, proliferation, migration, differentiation and collagen production. We found that PMC2A suppressed the cell spreading, protein adsorption, formation of focal adhesion, and differentiation of normal human dermal fibroblasts, while PMC4A surfaces enhanced them compared to other PMCxAs. Our findings suggest that fibroblast activities attached to the PMCxA substrates can be modified by changing the number of methylene carbons in the side chains of the polymers. These results indicate that PMCxAs could be useful coating materials for use in skin regeneration and wound dressing applications.