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Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration, blood vessels invasion and transport of nutrient and waste. However, efforts and understanding of the interconnectivity of porous Mg is limited due to the diverse architectures of pore struts and pore size distribution of Mg scaffold systems. In this work, biomimetic hierarchical porous Mg scaffolds with tailored interconnectivity as well as pore size distribution were prepared by template replication of infiltration casting. Mg scaffold with better interconnectivity showed lower mechanical strength. Enlarging interconnected pores would enhance the interconnectivity of the whole scaffold and reduce the change of ion concentration, pH value and osmolality of the degradation microenvironment due to the lower specific surface area. Nevertheless, the degradation rates of five tested Mg scaffolds were no different because of the same geometry of strut unit. Direct cell culture and evaluation of cell density at both sides of four typical Mg scaffolds indicated that cell migration through hierarchical porous Mg scaffolds could be enhanced by not only bigger interconnected pore size but also larger main pore size. In summary, design of interconnectivity in terms of pore size distribution could regulate mechanical strength, microenvironment in cell culture condition and cell migration potential, and beyond that it shows great potential for personalized therapy which could facilitate the regeneration process.

Understanding the interaction of T-cell receptor (TCR) with major histocompatibility-peptide (MHC-peptide) complex is extremely important in human immunotherapy and vaccine development. However, due to the limited available data, the performance of existing models for predicting the interaction of T-cell receptors (TCR) with major histocompatibility-peptide complexes is still unsatisfactory. Deep learning models have been applied to prediction tasks in various fields and have achieved better results compared with other traditional models. In this study, we leverage the gMLP model combined with attention mechanism to predict the interaction of MHC-peptide and TCR. Experiments show that our model can predict TCR-peptide interactions accurately and can handle the problems caused by different TCR lengths. Moreover, we demonstrate that the models trained with paired CDR3β-chain and CDR3α-chain data are better than those trained with only CDR3β-chain or with CDR3α-chain data. We also demonstrate that the hybrid model has greater potential than the traditional convolutional neural network.

Inspired by the process of bone reconstruction, porous scaffolds with robust osteogenesis and biodegradability would provide an ideal bone substitute for clinical practice. In this study, a novel porous Mg–Nd–Zn–Zr (JDBM) alloy scaffold coated with brushite (i.e., DCPD), denoted as JDBM-DCPD, is fabricated using a special patent template technique, which forms the main spherical pores (400–450 μm) and smaller pores (150–250 μm) interconnected between the adjacent main pores, facilitating nutrient penetration and cell in-growth, exhibiting sufficient mechanical properties. In vitro results demonstrate that JDBM-DCPD scaffolds promote cell in-growth and osteogenic differentiation, which significantly enhance mineralization, osteogenesis and angiogenesis-related genes expression when cultured with bone marrow mesenchymal stem cells. After implanting in vivo, JDBM-DCPD scaffolds effectively stimulate angiogenesis, osteogenesis, and remodeling with the degradation of JDBM-DCPD, and perfectly repair large bone defect in rat and rabbit models. Results from the present study provide the solid evidence that porous biodegradable Mg-based scaffolds whose pore structure can be precisely regulated by a spacer-selection technique may be a promising tissue engineering scaffolds for large bone defect repair clinically, free from any extra growth factors and live cells, such advances will make scaffold-based bone tissue repair safer, more convenient and more cost-effective. Keywords: Biodegradable Mg–Nd–Zn–Zr alloy scaffold, DCPD coating, Osteogenesis, Angiogenesis, Bone tissue engineering