Vascular diseases are the most prevalent cause of ischemic necrosis of tissue and organ, which even result in dysfunction and death. Vascular regeneration or artificial vascular graft, as the conventional treatment modality, has received keen attentions. However, small-diameter (diameter < 4 mm) vascular grafts have a high risk of thrombosis and intimal hyperplasia (IH), which makes long-term lumen patency challengeable. Endothelial cells (ECs) form the inner endothelium layer, and are crucial for anti-coagulation and thrombogenesis. Thus, promoting in situ endothelialization in vascular graft remodeling takes top priority, which requires recruitment of endothelia progenitor cells (EPCs), migration, adhesion, proliferation and activation of EPCs and ECs. Chemotaxis aimed at ligands on EPC surface can be utilized for EPC homing, while nanofibrous structure, biocompatible surface and cell-capturing molecules on graft surface can be applied for cell adhesion. Moreover, cell orientation can be regulated by topography of scaffold, and cell bioactivity can be modulated by growth factors and therapeutic genes. Additionally, surface modification can also reduce thrombogenesis, and some drug release can inhibit IH. Considering the influence of macrophages on ECs and smooth muscle cells (SMCs), scaffolds loaded with drugs that can promote M2 polarization are alternative strategies. In conclusion, the advanced strategies for enhanced long-term lumen patency of vascular grafts are summarized in this review. Strategies for recruitment of EPCs, adhesion, proliferation and activation of EPCs and ECs, anti-thrombogenesis, anti-IH, and immunomodulation are discussed. Ideal vascular grafts with appropriate surface modification, loading and fabrication strategies are required in further studies.

Angiogenesis is closely coupled with osteogenesis and has equal importance. Thus, promoting angiogenesis during the bone repair process is vital for ideal bone regeneration. As important mediators of cell-cell communication and biological homeostasis, mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been proved to be highly involved in bone and vascular regeneration. Because hypoxia microenvironment promotes the proangiogenic activity of MSCs, in the present study, we investigate the effect and underlying molecular mechanisms of sEVs from hypoxia-preconditioned MSCs (hypo-sEVs) on angiogenesis and develop an effective strategy to promote vascularized bone regeneration. Compared to sEVs from normoxia MSCs (nor-sEVs), hypo-sEVs promoted the proliferation, migration, and angiogenesis of HUVECs and ultimately enhanced bone regeneration and new blood vessel reconstruction in a critical-size calvarial bone defect model. miRNA sequence and the verified results showed that miR-210-3p in hypo-sEVs was increased via HIF-1α under hypoxia. The upregulated miR-210-3p in hypo-sEVs promoted angiogenesis by downregulating EFNA3 expression and enhancing the phosphorylation of the PI3K/AKT pathway. Thus, this study suggests a successful strategy to enhance vascularized bone regeneration by utilizing hypo-sEVs via the miR-210-3p/EFNA3/PI3K/AKT pathway. STATEMENT OF SIGNIFICANCE: Considering the significance of vascularization in ideal bone regeneration, strategies to promote angiogenesis during bone repair are required. Hypoxia microenvironment can promote the proangiogenic potential of mesenchymal stem cells (MSCs). Nonetheless, the therapeutic effect of small extracellular vesicles (sEVs) from hypoxia-preconditioned MSCs on cranio-maxillofacial bone defect remains unknown, and the underlying mechanism is poorly understood. This study shows that hypo-sEVs significantly enhance the proliferation, migration, and angiogenesis of HUVECs as well as promote vascularized bone formation. Moreover, this work indicates that HIF-1α can induce overexpression of miR-210-3p under hypoxia, and miR-210-3p can hinder EFNA3 expression and subsequently activate the PI3K/AKT pathway. The application of hypo-sEVs provides a facile and promising strategy to promote vascularized bone regeneration in a critical-size bone defect model.

Periodontitis is considered to be the main cause of tooth loss, which affects about 15% of the adult population around the world. Scaling and root-planning are the conventional treatments utilized to remove the contaminated tissue and bacteria, but eventually lead to the formation of a poor connection-long junctional epithelium. Therefore, regenerative therapies, such as guided tissue/bone regeneration (GTR/GBR) for periodontal regeneration have been attempted. GTR membranes, acting as scaffolds, create three-dimensional (3D) environment for the guiding of cell attachment, proliferation and differentiation, and play a significant role in periodontal regeneration. Nano-composite scaffolds based on electrospun nanofibers have gained great attention due to their ability to emulate natural extracellular matrix (ECM) that affects cell survival, attachment and reorganization. Promoted protein absorption, cellular reactions, activation of specific gene expression and intracellular signaling, and high surface area to volume ratio are also important properties of nanofibrous scaffolds. Moreover, several bioactive components, such as bioceramics and functional polymers can be easily blended into nanofibrous matrixes to regulate the physical-chemical-biological properties and regeneration abilities. Simultaneously, functional growth factors, proteins and drugs are also incorporated to regulate cellular reactions and even modify the local inflammatory microenvironment, which benefit periodontal regeneration and functional restoration. Herein, the progress of nano-composite electrospun fibers for periodontal regeneration is reviewed, including fabrication methods, compound types and processes, and surface modifications, etc. Significant proof-of-concept examples are utilized to illustrate the results of material characteristics, cellular interactions and periodontal regenerations. Finally, the existing limitations of nano-composite electrospun fibers and the development tendencies in future are also discussed.

Background: Preoperative planning of orthognathic surgery is indispensable for achieving ideal surgical outcome regarding the occlusion and jaws' position. However, orthognathic surgery planning is sophisticated and highly experience-dependent, which requires comprehensive consideration of facial morphology and occlusal function. This study aimed to investigate a robust and automatic method based on deep learning to predict reposition vectors of jawbones in orthognathic surgery plan. Methods: A regression neural network named VSP transformer was developed based on Transformer architecture. Firstly, 3D cephalometric analysis was employed to quantify skeletal-facial morphology as input features. Next, input features were weighted using pretrained results to minimize bias resulted from multicollinearity. Through encoder-decoder blocks, ten landmark-based reposition vectors of jawbones were predicted. Permutation importance (PI) method was used to calculate contributions of each feature to final prediction to reveal interpretability of the proposed model. Results: VSP transformer model was developed with 383 samples and clinically tested with 49 prospectively collected samples. Our proposed model outperformed other four classic regression models in prediction accuracy. Mean absolute errors (MAE) of prediction were 1.41 mm in validation set and 1.34 mm in clinical test set. The interpretability results of the model were highly consistent with clinical knowledge and experience. Conclusions: The developed model can predict reposition vectors of orthognathic surgery plan with high accuracy and good clinically practical-effectiveness. Moreover, the model was proved reliable because of its good interpretability.

Osteoporosis, one of the most serious and common complications of diabetes, has affected the quality of life of a large number of people in recent years. Although there are many studies on the mechanism of diabetic osteoporosis, the information is still limited and there is no consensus. Recently, researchers have proven that osteoporosis induced by diabetes mellitus may be connected to an abnormal iron metabolism and ferroptosis inside cells under high glucose situations. However, there are no comprehensive reviews reported. Understanding these mechanisms has important implications for the development and treatment of diabetic osteoporosis. Therefore, this review elaborates on the changes in bones under high glucose conditions, the consequences of an elevated glucose microenvironment on the associated cells, the impact of high glucose conditions on the iron metabolism of the associated cells, and the signaling pathways of the cells that may contribute to diabetic bone loss in the presence of an abnormal iron metabolism. Lastly, we also elucidate and discuss the therapeutic targets of diabetic bone loss with relevant medications which provides some inspiration for its cure.