Xingyou Hu

PLGA/HA biomaterials have been widely applied in tissue engineering and regenerative medicine for decades. In bone regeneration, PLGA/HA has been fabricated into films and porous scaffolds and further functionalized with bioactive peptides to enhance angiogenesis and osteogenic differentiation. GFOGER, a collagen-derived motif recognized by integrin α2β1, provides specific adhesion cues that regulate the attachment and osteogenic commitment of bone marrow mesenchymal stromal cells (BMSCs). In this study, we fabricated a PLGA/HA electrospun scaffold and functionalized its surface with GFOGER peptide. The scaffold's surface morphology, chemical composition, wettability, and structural properties were characterized using scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, and contact angle analysis. Cytocompatibility was verified by MTT assay, demonstrating the suitability of the scaffold for cell culture. Importantly, BMSCs cultured on PLGA/HA/GFOGER scaffolds exhibited enhanced osteogenic differentiation, as evidenced by the upregulation of Runx2, BMP2, and OCN. These findings support the potential of PLGA/HA/GFOGER composite scaffolds as promising biomaterials for bone regeneration applications.

Background: Cosmc (C1GalT1C1) mutation could cause aberrant O-glycosylation and result in expression of Tn antigen on the surface of tumor cells (Tn⁺ cells), which is associated with the metastasis and prognosis of cancer progression. Mesenchymal stem cells (MSCs) could participate in immunoregulation, tissue damage repair, and tumor inhibition and be seen as an ideal candidate for tumor therapy due to their inherent capacity to migrate to tumor sites. However, their therapeutic effectiveness in different tumors is inconsistent and still controversial. Of note, emerging data reveal that side population (SP) cells have a stronger multilineage developmental potential than main population cells and can function as stem/progenitor cells. The effect of SP cells derived from MSCs on the biological behaviors and the O-glycosylation status of tumor cells remains unclear. Methods: SP cells were isolated from human umbilical cord MSCs (hUCMSCs) and human placenta MSCs (hPMSCs). Tn⁺ cells (LS174T-Tn⁺ and HT-29-Tn⁺ cells) and matching Tn⁻ cells (LS174T-Tn⁻ and HT-29-Tn⁻ cells) were isolated from human colorectal cancer cell (CRC) lines LS174T and HT-29 by immune magnetic beads. The proliferation, migration, apoptosis, Tn antigen expression, and O-glycome in Tn⁺ and Tn⁻ CRC cells before and after co-cultured with SP-MSCs were detected using real-time cell Analysis (RTCA), flow cytometry (FCM), and cellular O-glycome reporter/amplification (CORA), respectively. Cosmc protein and O-glycosyltransferase (T-synthase and C3GnT) activity in CRC cells were, respectively, assessed using western blotting and fluorescence method. Results: Both SP cells derived from hUCMSCs and hPMSCs could inhibit proliferation and migration, promote apoptosis of CRC cells, significantly reduce Tn antigen expression on Tn⁺ CRC cells, generate new core 1-, 2-, and 3-derived O-glycans, increase T-synthase and C3GnT activity, and elevate the levels of Cosmc and T-synthase protein. Conclusion: SP-hUCMSCs and SP-hPMSCs could inhibit proliferation and migration and promote apoptosis of Tn⁺ CRC cells via increasing O-glycosyltransferase activity to modify O-glycosylation status, which further adds a new dimension to the treatment of CRC.

Biomaterials have been widely used as substitutes for diseased tissue in surgery and have gained great success and attention. At present, the biocompatibility of biomaterials such as PET woven fabrics is often evaluated both in vitro and in vivo. However, the current experimental methods cannot reveal the relationship between material surfaces and cell adhesion, and few research works have focused on the mechanisms of how the surface morphology of biomaterials affects cell adhesion and proliferation. Thus, it is meaningful to find out how the altered surfaces could affect cell adhesion and growth. In this study, we employed Ar low-temperature plasma treatment technology to create nano-grooves on the warp yarn of PET woven fabrics and seeded human umbellar vein endothelial cells (HUVEC) on these fabrics. We then assessed the O-glycan and N-glycan profiles of the cells grown on different structures of the polyester woven fabrics. The result showed that the surface morphology of polyester woven fabrics could affect the O-glycan profile but not the N-glycan profile of cultured HUVEC. Taken together, the study describes the effects of the surface morphology of biomaterial on the biosynthesis of cellular glycans and may provide new insights into the design and manufacture of biomaterials used as blood vessels based on the expression profiles of O-glycans on cultured cells.

Acute thrombosis remains the main limitation of small-diameter vascular grafts (inner diameter <6 mm) for bridging and bypassing of small arteries defects and occlusion. The use of hydrogel tubes represents a promising strategy. However, their low mechanical strength and high swelling tendency may limit their further application. In the present study, a hydrogel vascular graft of Ca alginate/polyacrylamide reinforced with a braided fiber strut was designed and fabricated with the assistance of a customized casting mold. Morphology, structure, swellability, mechanical properties, cyto- and hemocompatibility of the reinforced graft were characterized. The results showed that the reinforced graft was transparent and robust, with a smooth surface. Scanning electron microscopic examination confirmed a uniform porous structure throughout the hydrogel. The swelling of the reinforced grafts could be controlled to 100%, obtaining clinically satisfactory mechanical properties. In particular, the dynamic circumferential compliance reached (1.7 ± 0.1)%/100 mmHg for 50–90 mmHg, a value significantly higher than that of expanded polytetrafluoroethylene (ePTFE) vascular grafts. Biological tests revealed that the reinforced graft was non-cytotoxic and had a low hemolysis percentage (HP) corresponding to (0.9 ± 0.2)%. In summary, the braided fiber-reinforced hydrogel vascular grafts demonstrated both physical and biological superiority, suggesting their suitability for vascular grafts.

The cover image is based on the Research Article Use of an in vitro dynamic culture system to assess flow shear forces upon cell adhesion within different structures by Xingyou Hu et al., DOI: 10.1002/jctb.5834. image

BACKGROUND: The perennial problems associated with long‐term patency of small diameter vascular grafts have yet to be satisfactorily resolved. One approach to rectify this problem is a rapid endothelialization on the inner wall of the grafts, which could significantly reduce inflammation or hyperplasia. Two critical factors that can affect this process in vivo include that of the biocompatibility of the materials and adhesion strength of cells on its surfaces. Thus, an important area of investigation involves an evaluation of cell adhesion on biomaterials in a dynamic culture system, but only limited research has been directed at examining the relationship between the shear forces resulting from flow rates and cell adhesion on the surface of materials. In this study, an in vitro dynamic culture system was utilized for use in examining such relationship by changing the flow rates.RESULTS: Cells adherent on monofilaments were dislodged with a shear force of 5.4 dyn, while most cells adherent on multifilaments tolerated shear forces of 7.0 dyn.CONCLUSION: Priority rankings of materials could be generated as a function of the shear forces tested, and the design or application of artificial blood vessel materials for use within specific regions of the body could be optimized. © 2018 Society of Chemical Industry

As a promising agent for biomedical application, collagen has been used as a nanofiber to architecturally mimic its fibrillar structure in Extracellular Matrix (ECM); however, it has to be modified by techniques, such as crosslinking, to overcome its limitations in structural stability along with potential toxicity. Here, we prepared collagen/polyethylene oxide (PEO) nanofibrous membranes with varying crosslinking degrees and their properties, such as water stability, mechanical properties, blood clotting capacity and cytocompatibility, were studied systematically. By investigating the relationship between crosslinking degree and their properties, nanofibrous membranes with improved morphology retention, blood clotting capacity and cytocompatibility have been achieved. The result of circular dichroism measurement demonstrated that a triple helical fraction around 60.5% was retained. Moreover, the electrospun collagen/PEO at crosslinking degrees above 60.6% could maintain more than 72% of its original weight and its nanofibrous morphology under physiological conditions could be well preserved for up to 7 days. Furthermore, the crosslinked collagen/PEO membrane could provide a more friendly and suitable environment to promote cell proliferation, and about 70% of the clot can be formed in 5 min. With its superior performance in water stability, hemostasis and cytocompatibility, we anticipate that this nanofibrous membrane has great potential for wound dressing.

Cadherins are surface glycoproteins on plasma membranes and exist in many forms: T-cadherin, neuronal cadherin (N-cadherin), epithelial cadherin (E-cadherin), and vascular endothelial (VE-cadherin). Cadherins play critical roles in cell–cell interactions and are involved in multiple functions related to cell growth and proliferation. Findings from numerous reports have indicated that VE-cadherin regulates the remodeling, gating, and maturation of vascular vessels. The surface morphology of materials also impacts endothelial cell adhesion. This report is an overview of recent research on the effects of cadherins on cell–cell interactions, along with cell adhesions as examined on different materials. This summary will provide novel insights and approaches for research on cell–cell and cell–material interactions and illuminate some of the mechanisms of cell growth on different materials.