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This bedside-to-bench study aimed to systematically investigate the value of applying BMP2-loaded calcium phosphate cement (BMP2-CPC) in the restoration of large-scale alveolar bone defects. Compared to deproteinized bovine bone (DBB), BMP2-CPC was shown to be capable of inducing a favorable pattern of bone regeneration and bone remodeling accompanied by active osteoclastogenesis and optimized biomaterial resorption when applied in reconstructive periodontally accelerated osteogenic orthodontics (PAOO) surgery. To verify the regulatory role of osteoclasts in the BMP2-CPC-induced pattern of bone regeneration, in vitro and in vivo studies were designed to elucidate the underlying mechanism. Our results revealed that osteoclasts played a multifaceted role (facilitating osteogenesis, bone remodeling and biomaterial resorption) in the BMP2-CPC-induced bone regeneration. Osteoclasts contributed to the osteogenic differentiation of mesenchymal stem cells (MSCs) by secreting calcium ions, CTHRC1 and PDGF-B. Moreover, the increased osteoclasts promoted the remodeling of new bone and BMP2-CPC resorption, leading to a harmonized replacement of biomaterials with mature bone. In conclusion, the in vitro and in vivo experimental results corresponded with the clinical results and showed the optimized properties of BMP2-CPC in activating osteoclast-driven bone regeneration and remodeling, thus indicating the highly promising prospects of BMP2-CPC as an ideal therapeutic for alveolar bone defects.

To develop a biodegradable membrane with guided bone regeneration (GBR), a Mg-2.0Zn-1.0Gd alloy (wt.%, MZG) membrane with Ca-P coating was designed and fabricated in this study. The microstructure, hydrophilicity, in vitro degradation, cytotoxicity, antibacterial effect and in vivo regenerative performance for the membrane with and without Ca-P coating were evaluated. After coating, the membrane exhibited an enhance hydrophilicity and corrosion resistance, showed good in vitro cytocompatibility upon MC3T3E-1 cells, and exhibited excellent antibacterial effect against E. coli, Staphylococcus epidermis and Staphylococcus aureus, simultaneously. In vivo experiment using the rabbit calvarial defect model confirmed that Ca-P coated MZG membrane underwent progressive degradation without inflammatory reaction and significantly improved the new bone formation at both 1.5 and 3 months after the surgery. All the results strongly indicate that MZG with Ca-P coating have great potential for clinical application as GBR membranes.

User-generated contents (UGCs) on social media are a valuable source of emergency information (EI) that can facilitate emergency responses. However, the tremendous amount and heterogeneous quality of social media UGCs make it difficult to extract truly useful EI, especially using pure machine learning methods. Hence, this study proposes a machine learning and rule-based integration method (MRIM) and evaluates its EI classification performance and determinants. Through comparative experiments on microblog data about the “July 20 heavy rainstorm in Zhengzhou” posted on China’s largest social media platform, we find that the MRIM performs better than pure machine learning methods and pure rule-based methods, and that its performance is influenced by microblog characteristics such as the number of words, exact address and contact information, and users’ attention. This study demonstrates the feasibility of integrating machine learning and rule-based methods to mine the text of social media UGCs and provides actionable suggestions for emergency information management practitioners.

In this study, we proposed BMP2-incorporated calcium phosphate cement (BMP2-CPC), for application in guided bone regeneration (GBR) and compared the experimental bone restoration performance and clinical alveolar bone reconstruction outcome of BMP2-CPC with those of deproteinized bovine bone (DBB). The animal study indicated that, compared to DBB, which induced the slow ingrowth of new bone, BMP2-CPC induced numerous small growth centers for bone regeneration and facilitated a significant amount of bone regeneration in rabbit calvarial bone defects. Fewer residual graft particles remained in the BMP2-CPC-treated defects than in the DBB-treated defects. The clinical study indicated that BMP2-CPC was similar to DBB in remedying alveolar bone insufficiency and maintaining implant stability. In conclusion, the results of this present study indicate that compared to DBB, BMP2-CPC can significantly enhance in vivo bone regeneration and remodeling in rabbit calvarial bone defects and shows preliminary support on its clinical application in GBR surgeries.

Parathyroid hormone (PTH) is a critical regulator of bone remodeling. Intermittent administration of PTH (1-34) stimulates osteogenesis and promote bone formation, however, the possible targets and underlying mechanisms have not been fully elucidated yet. In this study, functional links between PTH and Foxc1, a transcription factor reported to play a predominant role in regulating bone development and formation, were indicated. We determined the effect of Foxc1 on osteogenic differentiation in vitro and bone regeneration in vivo under the induction of intermittent PTH, and further explored its possible targets. We found that the expression level of Foxc1 was upregulated during osteogenic induction by intermittent PTH treatment and the elevated expression of Foxc1 induced by intermittent PTH treatment was inhibited by PTH1R silencing, while rescued by PTH supplement. By Foxc1 gain- and loss- of-function experiments in MC3T3-E1 cells, we demonstrated that Foxc1 could promote osteogenic differentiation induced by intermittent PTH treatment in vitro. Moreover, immunofluorescence analysis indicated the nuclear co-localization of Foxc1 with Runx2, while luciferase-reporter and chromatin immunoprecipitation analysis further confirmed that Foxc1 could directly bind to the P1 promoter region of Runx2, which plays an essential role in osteogenic differentiation and bone mineralization. Meanwhile, we also revealed that Foxc1 could promote bone regeneration induced by intermittent PTH treatment in vivo. Taken together, this study revealed the role and mechanism of Foxc1 in osteogenic differentiation in vitro and bone regeneration in vivo in response of intermittent PTH treatment.

This study aimed to explore the in vitro and in vivo roles of macrophages in the osteogenesis stimulated by BMP2-CPC. In vitro, the alteration of macrophage polarization and cytokine secretion induced by BMP2-CPC or CPC was investigated. The influence of conditioned medium derived from BMP2-CPC- or CPC-stimulated macrophages on the migration and osteogenic differentiation of MSCs were evaluated. The in vivo relationship between macrophage polarization and osteogenesis was examined in a rabbit calvarial defect model. The in vitro results indicated that BMP2-CPC and CPC induced different patterns of macrophage polarization and subsequently resulted in distinct patterns of cytokine expression and secretion. Conditioned medium derived from BMP2-CPC- or CPC-stimulated macrophages both exhibited apparent osteogenic effect on MSCs. Notably, BMP2-CPC induced more M2-phenotype polarization and higher expression of anti-inflammatory cytokines and growth factors than did CPC, which led to the better osteogenic effect of conditioned medium derived from BMP2-CPC-stimulated macrophages. The rabbit calvarial defect model further confirmed that BMP2-CPC facilitated more bone regeneration than CPC did by enhancing M2-phenotype polarization in local macrophages and then alleviating inflammatory reaction. In conclusion, this study revealed that the favorable immunoregulatory property of BMP2-CPC contributed to the strong osteogenic capability of BMP2-CPC by modulating macrophage polarization.

This study is aimed at determining the optimal sinus augmentation approach considering the poor bone condition in the zone of atrophic posterior maxilla. A series of simplified maxillary segment models varying in residual bone height (RBH) and bone quality were established. A 10 mm standard implant combined with two types of maxillary sinus augmentation methods was applied with the RBH, which was less than 10 mm in the maxilla. The maximal equivalent von Mises (EQV) stress in residual bone was evaluated. Bone quality had an enormous impact on the stress magnitude of supporting bone. Applying sinus augmentation combined with grafts was suitable for stress distribution, and high-stiffness graft performed better than low-stiffness one. For 7 mm and 5 mm atrophic maxilla, nongrafted maxillary sinus augmentation was feasible in D3 bone. Poor bone quality was a negative factor for the implant in the region of atrophic posterior maxilla, which could be improved by grafts. Meanwhile, the choice of maxillary sinus augmentation approaches should be determined by the RBH and quality.

Crowdsourcing some of the emergency information management (EIM) tasks to the general public has been proven to be effective during emergency events. In order to speed up the diffusion of EIM crowdsourcing tools and quickly gather more participants, this research proposed a solution that takes full advantages of mobile social media platform and its users. Specifically, a mobile crowdsourcing tool named CrowdEIM was designed based on WeChat open platform, and the paper prototypes were evaluated through user study. The findings indicated that the functions of CrowdEIM were clear and easy-to-use. However, there are also some features need to be improved, especially the classification and display of emergency information.

Extrusion-based 3D bioprinting of cell-laden hydrogels is a potential technology for regenerative medicine, which enables the fabrication of constructs with spatially defined cell distribution. However, the limited assessment of rheological behaviors of hydrogel before printing is still a major issue for the advancement of 3D bioprinting. In this work, we systematically investigated the rheological behaviors (i.e. viscosity, storage modulus (G’), and loss modulus (G”)) of alginate/gelatin composite hydrogels first for 3D printing complex constructs. The rheological studies revealed that viscosity of alginate/gelatin hydrogels is temperature-dependent and shear thinning. Sol-gel transition (intersection of G’ and G”) study provided indication for printing temperature, which are in the range of 18.8 °C (H2/7.5) to 24.5 °C (H2/24.5). The alginate (2 wt%) /gelatin (15 wt%) composite hydrogel sample was chosen to print the constructs and subsequent bioprinting. Complex constructs (i.e. nose and ear) were obtained with high printing resolution (151 ± 13.04 μm) in a low temperature (4 °C) chamber and crosslinking with 2 wt% CaCl2 subsequently without extra supports. Human amniotic epithelial cells (AECs) showed superior potential to differentiate into epithelial cells, while Wharton’s jelly derived mesenchymal stem cells (WJMSCs) showed a superior angiogenic potential and fibroblastic phenotype. For the in vitro study, AECs and WJMSCs as seed cells, encapsulated in alginate/gelatin composite hydrogels, were bioprinted to form biomimetic bilayered membranous construct. High cell viability (> 95%) were observed up to 6 days after printing. The presented 3D bioprinting of human AECs and WJMSCs-laden alginate/gelatin composite hydrogels provides promising potentials for future skin tissue engineering.

Crowdsourcing certain emergency information management (EIM) tasks to the general public has been proven to be effective during emergencies. To accelerate the diffusion of EIM crowdsourcing tools and quickly attract more participants, this work proposes a solution that takes full advantage of mobile social media platforms and their users. Specifically, a mobile crowdsourcing tool called CrowdEIM was designed and implemented based on the WeChat Official Accounts Platform. Formative studies were conducted to help design and evaluate a graphical mock-up, and summative evaluations were applied to investigate the effectiveness and usability of the runnable prototype. The findings indicate that EIM crowdsourcing tools based on mobile social media platforms are more likely to be disseminated and can provide more accurate and understandable emergency information, and that only those tools with simple operations can be widely accepted in emergency situations. Although limited to the WeChat platform, the CrowdEIM solution is expected to offer some valuable suggestions for the emergency management practitioners, and help explore more possibilities for the use of mobile social media during emergencies.

Single shear tests performed to study the debonding between the concrete and the FRP plate of 2 mm thickness are presented. Specimens with five different bond lengths have been tested. In order to investigate the debonding mechanism and measure the complete strain distribution, digital image correlation (DIC) method was applied. The shear stress and slip distribution curves were calculated from the strain distribution functions fitted from measured strain data. Based on the features of the shear stress transfer zone under different load levels, the whole loading process has been divided into four stages: (1) elastic stage; (2) cracking stage; (3) debonding stage; (4) failure stage. According to the relationship between the relative bearing capacity and bond length, a concept of efficient bond length was suggested. A bi-linear bond stress-slip model was calibrated by the constitutive parameters of the experimental shear stress-slip curves. Based on the bi-linear bond stress-slip relationship, a numerical model of FRP plate-concrete interface was built using the bonded-particle model (BPM) and the debonding process was numerically analyzed. The numerical results present good agreement with the experimental results in the load-slip response and the shear stress distribution along the bond length. The comparison between the experimental and the numerical results shows that BPM can effectively simulate the debonding process of the FRP plate-concrete interface.

Maintenance and recycling of a product often requires its disassembly. To have a successful disassembly process, it essentially asks for a comprehensive study of disassembly constraints. Related studies have revealed that precedence constraints offer important information to remove the infeasible disassembly plans to attain practical and feasible ones. Standard connectors play an important role to fasten two or more components together. By analyzing the disassembly knowledge and experiences of connectors, it is possible to derive precedence constraint directly. In this paper, different approaches for disassembly precedence constraint generation are first reviewed. Then, a novel connector-knowledge-based approach is presented for automatic generation of disassembly precedence constraints. As a preliminary research, threaded fasteners and keys are analyzed and corresponding precedence rules are extracted. By integrating this novel knowledge-based reasoning (KR) with the geometric reasoning approach, both approaches are utilized to their best advantages. Necessary disassembly constraint information can be automatically generated with less computational complexity. A typical shaft assembly in a gear reducer is selected as the case study to illustrate the proposed approach. The result has shown that this KR approach is simple and efficient in generating reasonable disassembly constraints.

In order to analyze disassembly related properties at design stages, CAD implementations require disassembly constraint modelling (DCM) functionalities to be integrated with CAD design processes. This paper presents a prototype of object-oriented CAD integration for DCM. Based on previous works, an object-oriented approach is proposed to define software modules and objects for disassembly constraint generation and representation. The prototype is implemented as an embedded application on the API platform of commercial CAD software. Hence it provides a tight and seamless integration, which can not only utilize the CAD model information directly, but also aid an on-going design process. This integration makes it possible for designers to optimize their design work for disassembly properties, such as ease of disassembly, at design stages. The case study on a widely used shaft assembly has demonstrated the simplism and effectiveness of the prototype for DCM functionalities.