Multifaceted antimicrobial stewardship (AMS) interventions including: antibiotic guidance, reviews of antibiotic use using audits, education, patient facing materials, and self-assessment, are successful in improving antimicrobial use. We aimed to measure the self-reported AMS activity of staff completing a self-assessment tool (SAT). The Royal College of General Practitioners (RCGP)/Public Health England (PHE) SAT enables participants considering an AMS eLearning course to answer 12 short questions about their AMS activities. Questions cover guidance, audit, and reflection about antibiotic use, patient facing materials, and education. Responses are recorded digitally. Data were collated, anonymised, and exported into Microsoft Excel. Between November 2014 and June 2016, 1415 users completed the SAT. Ninety eight percent reported that they used antibiotic guidance for treating common infections and 63% knew this was available to all prescribers. Ninety four percent of GP respondents reported having used delayed prescribing when appropriate, 25% were not using Read codes, and 62% reported undertaking a practice-wide antibiotic audit in the last two years, of which, 77% developed an audit action plan. Twenty nine percent had undertaken other antibiotic-related clinical courses. Fifty six percent reported sharing patient leaflets covering infection. Many prescribers reported undertaking a range of AMS activities. GP practice managers should ensure that all clinicians have access to prescribing guidance. Antibiotic audits should be encouraged to enable GP staff to understand their prescribing behaviour and address gaps in good practice. Prescribers are not making full use of antibiotic prescribing-related training opportunities. Read coding facilitates more accurate auditing and its use by all clinicians should be encouraged. Antimicrobial Stewardship in Primary Care collaboration came together with the aim of developing an antimicrobial stewardship (AMS) toolkit. The group worked with general practitioners (GPs), educators, and community medicines managers to assess relevant guidelines and develop AMS materials. Within a series of workshops they agreed upon the content of a toolkit to support appropriate antibiotic prescribing . This weTARGET stands for Treat Antibiotics Responsibly, Guidance, Education, Tools. Many of the materials are based on the Theory of Planned Behaviour  and togewww.elearning.rcgp.org.uk).Based on the Antimicrobial Assessment Toolkit (ASAT) for secondary care ,4,5, a cThis study aims to understand the AMS activity of primary health care professionals completing the eLearning SAT. Results will be used to inform the future development and promotion of AMS activities and tools by the RCGP and Public Health England (PHE).Between November 2014 and June 2016, 2248 users accessed the eModule Antibiotic Resistance in Primary Care that is linked to the SAT. Forty percent of these (897/2248) completed the whole eModule and 63% (1415/2248) completed the SAT. Of these completing the SAT, 92% (1308/1415) went on to complete the module after the SAT. One CPD  point is available upon completing the module, although it is not compulsory to complete the SAT in order to receive the certificate.Of those that completed the tool, 91% (1286/1415) were from England, 4% (56/1415) Scotland, 4% (51/1415) Wales and 1% (14/1415) Northern Ireland. Forty eight percent of the English respondents (620/1286) were from the Midlands and 17% (221/1286) were from one CCG in England. Nineteen percent were from the South (excluding London), 19.3% from the North, and 13.1% from London. The SAT was completed by at least 1 person in every health board or CCG, excluding six health boards in Scotland and one CCG in England. The profession of the respondents can be seen in Of those completing the SAT, 96% (1362/1415) were based in general practice, 2% (27/1415) were from an out of hours setting, and the remainder were based either in a hospital, pharmacy, or other workplace. Eighty five percent of respondents (1207/1415) were GPs and 7% (97/1415) were nurses. Two percent (28/1415) were pharmacists. Results are reported as “all respondents” when there are no differences between responders and reported separately when there are differences.Almost all respondents  and 100% of nurses reported that they used antibiotic guidance when considering how to treat common infections. Sixty three percent (896/1415) knew that antibiotic guidance was made available to all temporary prescribers in their practice such as locums, trainees, maternity cover, etc. However, nine percent (122/1415) reported that the guidance was not made available to temporary prescribers and a further 28% (397/1415) did not know whether this was the case.Ninety four percent of GP respondents (1188/1255) and 85% of other respondents (136/160) reported that they used delayed/back-up antibiotic prescribing as appropriate. Seventy five percent of all primary healthcare professionals that completed the tool (1057/1415) said that they recorded clinical indication using Read codes.p < 0.001).Overall, less than half of the respondents  reported undertaking a practice-wide antibiotic audit in the last two years. This percentage has increased over time from 30% in November 2014 to 60% in May 2016 . ProportThirty one percent of respondents (432/1415) were carrying out self-reported good practice in antibiotic prescribing as defined by the tool, answering yes to all five questions in this section .Thirty two percent of respondents (453/1415) indicated that they or their practice were already fulfilling all the components relating to local leadership of AMS, particularly action plans resulting from antibiotic audits .p < 0.001). Two thirds of all respondents  reported that they analysed and discussed antibiotic prescribing at least once a year; 62% (871/1415) reported that their practice kept a written record and action plan resulting from antibiotic audits.Of those that reported undertaking a practice-wide antibiotic audit in the last two years, 84% (639/757) also said that they analysed and discussed antibiotic prescribing at their practice in comparison to local indicators at least once a year. Seventy seven percent (584/757) also kept a written surgery action plan resulting from audits.Only 8% of respondents reported that their practices (110/1415) were already fulfilling the four key criteria of an antibiotic aware practice . Twenty p < 0.001 vs. 54% of the other professionals). Two thirds of all respondents had a practice strategy to avoid patients re-consulting to obtain antibiotics. Most  had not undertaken any antibiotic-related prescribing clinical courses but the reflective notes did suggest that many intended to undertake further online training as part of their personal development plan. This is illustrated by the following quotes:Seventy one percent of respondents (1009/1415) reported using patient focused strategies to highlight the importance of responsible antibiotic use, such as videos and posters in clinical and waiting areas. Just over half of respondents  indicated that they regularly shared patient information leaflets around infections within consultations. Proportionately more nurse respondents indicated that they did this  had an identified practice lead for stewardship, although just over two thirds (67%) analysed and discussed antibiotic prescribing in comparison to local indicators at least once a year. The least popular stewardship activity was participation in antibiotic-related prescribing clinical courses, with less than a third reporting to having done this.We have noted some positive examples of sharing information with patients: over 70% of respondents are using posters and videos to highlight the importance of responsible antibiotic use. However, only just over one half of respondents regularly shared any kind of patient information leaflets; it is not known which leaflets were shared.A key strength of this work is the large sample of 1415 GP staff from CCGs and health boards across the U.K., over the course of 18 months and providing a self-reported view of both individual and practice AMS activity. However, this is also a limitation as this represents around 2% of the total GP population in the U.K.  and the As respondents completed an anonymised form they were not influenced by their team or by an interviewer and therefore were free to record activity in a reflective manner. It is therefore unlikely that respondents were influenced by observer bias and were more likely to provide an accurate reflection of their AMS. Conversely, this makes it difficult to analyse the responses in relation to objective measures such as prescribing rates. It is also impossible to provide follow up questions to respondents, e.g., to find out more about their reported AMS activities.The proportion reporting they use delayed/back-up prescribing when appropriate was high, at 94% of GPs. This high percentage could also be because we had an “antibiotic interested” sample, or that the term “appropriate” was interpreted differently by respondents. In another U.K. study , only haThe wording of the questions within the SAT does not enable us to explore exact detail of AMS activities within each section. For example, the question about delayed prescribing doesn’t ask when they used this strategy or how, and therefore is limiting. It would be useful to add open questions about the different AMS strategies used. Similarly, we only have limited information on the Read coding activity. We do not know, for example, the quality of the Read coding that is conducted.In this sample, 77% of those that had conducted an antibiotic audit had developed a surgery action plan as a result of the audit. It has been argued that audits are not effective at changing behaviour if the audits are not complete, if re-auditing is not carried out, or if the audits do not lead to a firm action plan with the aim of quality improvement . In thisA 2014/15 survey of CCGs exploring local implementation of national AMS toolkits found that 84% of responding CCGs had implemented AMS antibiotic audits in GP practices . HoweverA Patients Association report released in 2016  reportedIn 2016, almost three quarters of GPs were familiar with the NICE  Antimicrobial Stewardship Guideline ,12 and aThe sample used in this study is arguably a favourable representation of AMS activity, therefore the reality of nationwide stewardship activities is likely to be less than reported here. Despite this, the findings highlight important areas for improvement in this sample and beyond. This study shows that antibiotic guidance, the bedrock of AMS, is being widely implemented. However, GP practice managers need to ensure that temporary prescribers have access to this antibiotic prescribing guidance. A quarter of our respondents were not using Read codes and nearly half had not conducted an antibiotic audit. These should be encouraged as they are an effective means of enabling GP staff to understand their prescribing behaviour and address gaps in good practice. Some respondents (17%) had not compared their own prescribing with local indicators. This is now much easier to do and should be encouraged using data on websites such as PrescQIPP , FingertRecent qualitative research relating to the TARGET resources  highlighPrescribers are not making full use of the antibiotic-related prescribing training opportunities that are available online through the TARGET Antibiotics Toolkit and elsewhere, and may need more dedicated time or incentives to be able to do this.The Quality Premium (QP) is a financial incentive intended to reward CCGs for quality improvement. The QP for 2017/18 contains an antibiotic component to reduce total antibiotic prescribing by 1% and broad-spectrum antibiotics by 10%. CCGs  can be rewarded financially for improvement in this respect and it has therefore generated much interest and subsequent AMS activity. Our study highlights an opportunity for CCGs to provide support for regular and appropriate audits, therefore monitoring progress in meeting QP targets.As we have indicated, there is a need for GPs to conduct further antibiotic related training. CCGs should encourage this and use other supporting resources in the TARGET Antibiotics Toolkit. Indeed some are doing so through enhanced payment incentive schemes.It is important to explore in more depth the issues raised by this study, especially now that further antimicrobial stewardship initiatives have been introduced in the UK. Our analysis suggests that there is some good activity underway nationally and further research using an objective methodology is necessary to identify activities within individual CCGs, the extent of activity implementation and adoption, and the overall success of activities in terms of resistance rates and antimicrobial prescribing.PHE promotes TARGET via events and RCGP communications, but rely on CCGs and local teams to promote the resources locally. As we have highlighted, there is a particularly high number of responses in our study from one CCG. Further investigation suggests that this CCG circulates regular newsletters containing information about TARGET. However, we do not know to what extent this is enough to generate a higher level of interest in the SAT nor do we yet have a comprehensive picture of what other CCGs are doing in this respect. Further research examining the exact nature of AMS activities in more detail would also address these issues.The responses to the SAT are recorded digitally on the RCGP server and participants can print their responses and CPD certificate on completion. Data were collated by RCGP Learning between November 2014 and June 2016, anonymized, and exported into Microsoft Excel.Data was cleaned to remove duplicate participants, subsequent attempts, or entries in which no questions were completed. It was then analysed using Microsoft Excel and comparisons were made between different respondents. Chi-squared testing was used to determine if participant type influenced the responses of GPs and “others” . Further testing was carried out for each question on the disproportionately high number of responses that came from a specific CCG to see whether there were significant differences from the main cohort. Any significant differences are reported in our results.Ethical approval was not required for this piece of work as it was a service evaluation and the involved staff and all data obtained was anonymised by the RCGP by removing email addresses and any identifiable information.Our findings suggest that there is scope for improvement in planning and monitoring AMS and associated prescribing activity at a GP practice level. Respondents to the SAT reported undertaking a variety of AMS activities to differing extents. It is important to ensure that all clinicians have access to prescribing guidance to facilitate accurate prescribing. The use of antibiotic audits should be reinforced to enable clinicians to understand their prescribing behaviour, address gaps in good practice and create effective action plans. Prescribers are not making full use of antibiotic prescribing-related training opportunities. Read coding facilitates more accurate auditing and its use by all clinicians should be encouraged.


Multiscale modeling for cement-based materials, such as concrete, is a relatively young subject, but there are already a number of different approaches to study different aspects of these classical materials. In this paper, the parameter-passing multiscale modeling scheme is established and applied to address the multiscale modeling problem for the integrated system of cement paste, mortar, and concrete. The block-by-block technique is employed to solve the length scale overlap challenge between the mortar level (0.1–10 mm) and the concrete level (1–40 mm). The microstructures of cement paste are simulated by the HYMOSTRUC3D model, and the material structures of mortar and concrete are simulated by the Anm material model. Afterwards the 3D lattice fracture model is used to evaluate their mechanical performance by simulating a uniaxial tensile test. The simulated output properties at a lower scale are passed to the next higher scale to serve as input local properties. A three-level multiscale lattice fracture analysis is demonstrated, including cement paste at the micrometer scale, mortar at the millimeter scale, and concrete at centimeter scale. Cement-based materials, such as cement paste, mortar, and concrete, are multiscale heterogeneous construction materials. Normal concrete is made from coarse aggregates , fine aggregates , cement, and water. The chemical reaction starts immediately when water is mixed with cement, and cement paste is produced. The cement paste keeps aggregates together, and forms a system which is able to carry loads. Mortar consists of cement paste and sands, and concrete is composed of mortar and coarse aggregates.A three-level approach was proposed by Wittmann  for the Cement-based materials have different fracture behaviors at different scales, due to different material structures at the level of interest. The mechanical performance of the material structure is determined by the distribution of the phases, and the local mechanical properties of an individual phase. They can be measured in the laboratory, as well as be simulated by computational models.The concept of lattice was proposed by Hrennikoff in the 1940s to solve elasticity problems using the framework method . In the In the lattice fracture model, the continuum is replaced by a lattice network of beam elements. Subsequently, the microstructure of the material can be mapped onto these beam elements by assigning them different properties, depending on whether the beam element represents a grain or matrix. More details about the modeling procedures can be found in The 3D lattice fracture model, which was implemented in ,16,17, cA parameter-passing multiscale modeling scheme can be defined to link the fracture in cement paste at the microscale to the mechanical performance of concrete at the macroscale. The lattice fracture model is called three times to simulate the global mechanical properties of cement paste at the microscale, mortar at the mesoscale, and concrete at the macroscale, respectively. Each higher scale asks for local mechanical properties from its neighboring lower scale, and the global mechanical properties simulated at a lower scale are passed to the next higher scale to be used as inputs. Applying the parameter-passing scheme towards cement paste, mortar, and concrete yields the following modeling procedures. The mechanical properties of cement paste at the microscale, including its elastic properties and fracture properties, are simulated by the lattice fracture model, and then these properties are used as inputs to predict the mechanical properties of mortar at the mesoscale. After that, the simulated properties of mortar are passed to the macroscale to obtain the global mechanical performance of concrete. A schematic diagram of the parameter-passing multiscale modeling scheme is given in The material structures of cement paste, mortar, and concrete are analyzed by the lattice fracture model at their respective scales, with part of the input parameters coming from lower-scale simulations. The methods to obtain these material structures are discussed in this section.The clinker of Portland cement is mainly composed of calcium, silicon, and oxygen. In cement chemistry, it is usually represented in terms of constituents as tricalcium silicate The microstructure of cement paste can be obtained either experimentally or numerically. Micro X-ray Computed Tomography (micro CT) offers a non-destructive experimental technique to collect microstructure information of cement paste in terms of digitized voxels . ComputeIn the HYMOSTRUC3D model, the cement particles are modeled as spheres and these spherical particles grow during the hydration process. The inputs include the specimen size, the mineralogical composition of the cement, the cement fineness in terms of the Blaine value (Rosin-Rammler particle size distribution is assumed) and the water/cement ratio. The amount of hydration products is dependent on the degree of hydration. A simplification is made in the model that the amount of The cement grain dissolves and the hydration products are generated gradually during the hydration process, which yields expansion and layer thickness change of the cement particle, as shown in The initial microstructure of cement paste can be created by parking multiple spherical particles into an empty container, as shown in Mortar can be made by putting sands into cement paste, and if some additional coarse aggregates are also inserted into the system, then it becomes concrete. From a modeling point of view, the material mesostructures of both mortar and concrete can be represented as particles embedded in a matrix. The particles are interpreted as sands, and the matrix as cement paste in the mortar model, while the particles are coarse aggregates, and the matrix is mortar in the concrete model. Therefore, it is achievable to make a universal material mesostructure model for mortar and concrete. However, the particle shape characterizations can be different for sands and coarse aggregates, furthermore, they can even be different for different classes of sands or coarse aggregates. This requires the universal material model to be able to recognize various particle shape characterizations. It is pointed out by Garboczi  that theIn the Anm material model, the concept of particles embedded in matrix applies. An empty container is created to represent a specimen at the beginning, and then all of the particles are placed one after one into this container, from the larger ones to the smaller ones. It is good to start with the largest particles as it would be more difficult to place them if they were processed at a later stage. All of the particles are separated into several sieve ranges, according to the particle sizes indicated by the particle widths. The largest sieve range is processed first. A width within this sieve range is picked up randomly, and then it is assigned to a particle which is chosen from the appropriate particle shape database. The particle shape database can be created for varying classes of powders and aggregates with the procedures proposed in . An arbiThe mesostructure of mortar is simulated for a cubic specimen of the size 10 mm, and it is represented by sand particles embedded in a cement paste matrix. A periodic material boundary condition is employed, which mirrors the sticking-out particles to the opposite surfaces, as this mortar represents a randomly-chosen material phase inside concrete. The Anm material model parks all of the sand particles into the empty simulation box with periodic material boundaries one after one, ensuring that there is no overlap between any of the two particles. The resulting mesostructure of the 10 mm cubic mortar specimen with irregularly-shaped sand particles is sketched in A concrete specimen of the size 150 mm in cubic shape is simulated, as shown in A smaller piece of concrete 40 mm in size is cut out from the original simulated 150 mm concrete specimen at its center, as shown in The 3D lattice fracture model is employed to evaluate the mechanical performance of cement paste at the microscale, based on the microstructures of cement paste which are provided by the HYMOSTRUC3D model. The microstructures of cement paste, in terms of spherical particles, are converted into voxel-based digital images. After that, a lattice network is constructed on the basis of the digital image, which represents the microstructure of cement paste. The lattice construction procedures are discussed in ,16.2 in this simulation example.The specimen of the size 100 µm is meshed at the resolution 1 µm/voxel, and a 3D hexahedral lattice network is constructed. A cell is created within each voxel sharing the same center, and the length ratio of the cell to the voxel is defined as randomness. The value of randomness is always between 0 and 1. More details about the randomness can be found in . A lattiThe elastic properties of solid phases can be measured or simulated as presented in ,28, the The assignment of local mechanical properties to a lattice element is related to the type of the lattice element in question, which is determined by the locations of its two nodes. If both ends of an element are located in the same phase, then this element is assigned the same mechanical properties as the phase in question, otherwise it is classified as an interface element. The mechanical properties of an interface element are preferred to be measured in laboratory test, but if it lacks experimental data, the following guidelines may be applied. The Young’s modulus of an interface element A conventional uniaxial tensile test is simulated on the lattice system. The external tensile load is imposed on the top and bottom surfaces in the The fracture process is simulated by the removal of lattice elements step by step. The basic idea of lattice fracture analysis is that of imposing a prescribed displacement on the lattice structure, finding the critical element that has the highest stress/strength ratio, and then removing it from the system. At every analysis step, a unit displacement is first imposed, and the reaction force is calculated. Then the displacement and the force are scaled linearly to make the weakest element just broken. The corresponding pair of displacement and force is recorded and becomes a point on the final simulated load-displacement curve for the system. This procedure is repeated until the system fails, and these multiple steps produce multiple points. These points are connected to form the load-displacement diagram, which can be converted to a stress-strain diagram, as shown in The stress-strain diagram reveals the tensile behavior of cement paste at the microscale, from which the elastic modulus, tensile strength, strain at peak load, and fracture energy can be obtained. The Young’s modulus is the slope of the curve at the linear stage in the stress-strain diagram in In The material structures of cement paste are simulated by the HYMOSTRUC3D model, and mortar and concrete are simulated by the Anm material model, respectively, in The scale division of cement paste, mortar and concrete is given in The microstructure of cement paste of the size 100 µm is simulated by the HYMOSTRUC3D model, as shown in The mesostructure of mortar of the size 10 mm is simulated by the Anm material model, as shown in Rather than directly evaluating the global mechanical performance of the 10 mm mortar, the lattice system in The simulated Young’s modulus of a 1 mm block is in the range of 17–65 GPa and the average value over these 1000 blocks is 29 GPa. The tensile strength is in the range of 1.1–19.5 MPa and the average value is 5.8 MPa. The stress-strain responses of these blocks are randomly passed onto the concrete mesomechanical modeling and serve as inputs there, as elaborated in The block-by-block technique is employed for the upscaling from mortar to concrete, due to the length scale overlap between them, as indicated in Having obtained the mechanical properties of the 1 mm mortar blocks, the concrete mesomechanical modeling can now proceed. The mesostructure of the concrete is simulated by the Anm material model, as presented in A uniaxial tensile test is simulated on the lattice system meshed from the 40 mm concrete specimen as shown in The pattern of the simulated stress-strain response of the concrete specimen of the size 40 mm is similar to the one observed in laboratory, and the mechanical properties computed from the stress-strain diagram are also located within the reasonable range .Cement-based materials, such as cement paste, mortar, and concrete, are multiscale heterogeneous construction materials. In this paper, the parameter-passing multiscale modeling scheme is established and applied to simulate fracture mechanisms.The starting point of the fracture simulations is the microstructure of hardened cement paste at the microscale. It is assumed that the local mechanical properties are brittle at this scale. This is an arbitrary assumption. The properties at this scale are difficult to measure experimentally, and therefore, there is no proof yet for this assumption of brittle behavior at the microscale. Perhaps it is necessary to go to the nanoscale, or even to the atomic scale, to have real local brittle behavior, but at least it seems reasonable to assume that the behavior becomes more brittle at lower scales.At the microscale, the local mechanical properties can be determined with the help of a nanoindentation test. The test gives local stiffness and hardness, which can be related to the tensile strength of the components. In this paper, the absolute values of the tensile strength are not measured directly by the test, but the tensile strength ratios of the components are used to assume the tensile strength values of the components at the microscale. The real tensile strength values can be corrected after simulations on a level  where mechanical tests can be performed easily. At the microscale, some attempts have been made to conduct direct mechanical tests on the composites, and they seem quite successful .In the multiscale modeling scheme presented in this paper, the block-by-block technique, is employed to solve the length scale overlap between mortar and concrete. The material structures of cement paste are simulated by the HYMOSTRUC3D model, and mortar and concrete are simulated by the Anm material model, respectively. The 3D lattice fracture model is used to evaluate their mechanical performance by simulating a uniaxial tensile test. The simulated output properties at a lower scale are passed to a higher scale to be served as input local properties, thus, a three-level multiscale lattice fracture analysis is demonstrated.Bažant concluded that the only valid approach was a discrete (lattice-particle) simulation of the mesostructure of the entire structural region, in which softening damage could occur . HoweverThe proposed model will be adopted in the future to simulate fracture at multiple scales in different geometries. For example, the sample size, aggregate shapes, and boundary conditions are taken the same as in the laboratory. An experimental campaign has started to perform tests on different levels and different materials. This would be able to validate the modeling procedure further, and to obtain proof for the assumed local material properties.


The construction industry generates a considerable amount of waste. Faced with this undesirable situation, the ready-mix concrete sector, in particular, has invested energy and resources into reusing its own waste in its production process as it works towards the goal of more sustainable construction. This study examines the feasibility of incorporating two types of concrete waste, which currently end up in landfill, into the production process of ready-mix concrete: the waste generated during the initial production stage (ready-mix concrete waste), and waste created when demolition waste is treated to obtain artificial aggregate. The first phase of the study’s methodology corroborates the suitability of the recycled aggregate through characterization tests. After this phase, the impact of incorporating different percentages of recycled coarse aggregate is evaluated by examining the performance of the produced concrete. The replacement rate varied between 15% and 50%. The results indicate that recycled aggregates are, indeed, suitable to be incorporated into ready-mix concrete production. The impact on the final product’s performance is different for the two cases examined herein. Incorporating aggregates from generic concrete blocks led to a 20% decrease in the produced concrete’s strength performance. On the other hand, using recycled aggregates made from the demolition waste led to a smaller decrease in the concrete’s performance: about 8%. The results indicate that with adequate management and prior treatment, the waste from these plants can be re-incorporated into their production processes. If concrete waste is re-used, concrete production, in general, becomes more sustainable for two reasons: less waste ends up as landfill and the consumption of natural aggregates is also reduced. As more buildings are demolished every day, effectively reusing demolition waste is essential to conserving non-renewable natural resources ,2,3,4. TIt is important to remember that the source of waste conditions its subsequent reuse. Nevertheless, there is often a lack of information available regarding the origins of waste. For example, using waste from different sources does not represent a problem in the case of subbases for transportation infrastructure ,9,10,11.RCA was originally used as landfill and mainly for low-value purposes, because of limited recycling facilities and for economic efficiency. Nowadays, this situation has changed after extensive research and because of recent significant advances in modern sustainable concrete technology. The first applications of RCA were implemented in civil engineering . ResearcClearly, concrete made with recycled aggregates is no longer merely a research topic but, rather, it is already a practical reality. For several years, a number of countries have been pioneering research in this area . VariousSeveral different teams of researchers have obtained results ,37,38,39The European Commission emphasizes that converting waste into a resource is key to improving the efficient use of resources and advancing towards a more circular economy. In areas where natural resources are scarce, the feasibility of recycled concrete waste has been confirmed . In areaThe key to taking advantage of and re-using waste is accurately characterizing it, and then determining the amount of recycled aggregate that can be incorporated into an RCA mix. This task should be undertaken by the entity generating said waste, thus avoiding heterogeneous mixes and unnecessary operations.The present study focuses on proving the feasibility of incorporating recycled aggregate, generated during concrete production, into new structural concrete. The strength properties of the concrete obtained dictate its future use or application. By comparing concrete waste, from two sources in the construction sector, the new concrete can be evaluated.In order to reach this goal, homogenous recycled aggregates must be used that are created and managed during the production process at a ready-mix concrete plant. Improvements in production processes ought to aim for the lofty goal of zero waste. The two cases presented herein constitute examples that may serve as an incentive for other ready-mix concrete plants or even precast concrete companies that could recycle their own waste. The party generating the waste should implement guidelines and procedures for reusing waste.The source of the material to be recycled affects the properties of the concrete made with those recycled materials. The concrete sector should re-use waste generated during production and from concrete structure demolition.In this study, two sources were chosen: ready-mix concrete waste from the company Hormigones Ebro and demolition waste from Hormigones Rioja. These two types of waste were analyzed and compared to characterize the concrete made with the recycled materials. Given the results of this study, the construction sector should consider using recycled materials in a variety of applications.This study analysed the behaviour of different types of concrete made with recycled aggregates in terms of their mechanical properties. The final objective was to evaluate the possibility of re-using waste and thereby contribute to a closed cycle in the construction industry. Coarse aggregate was partially replaced in different percentages and then, the new concrete’s properties were compared with the reference concrete. The driving idea is to promote the utilization of recycled aggregate in the construction industry in order to reduce landfill waste and reign in the unfettered use of natural resources, with the end goal of consolidated sustainable development in the construction sector. Circular economy theory and practice were implemented at two ready-mix concrete plants in Spain applying the corresponding regulations.In this endeavour, the properties of the different concrete compositions were analysed wherein five different percentages of recycled aggregate replaced coarse aggregate: 0%, 15%, 20%, 30%, and 50%. Concrete properties were evaluated in fresh and hardened states.Hormigones Ebro (HE). Aggregate made from the waste of concrete blocks that were not classified beforehand a.Hormigones Rioja (HR). These aggregates come from the rejection stage of the industrial process for recycling demolition materials to obtain artificial aggregate.Natural aggregates (NA), gravel, and sand, produced by crushing and supplied by La Peña quarry, were incorporated into concrete production in three different percentages. These materials are of siliceous origin. The company Hormigones Ebro normally utilizes them to manufacture concrete. The recycled aggregate (RA) came from two different sources:Both images depict aggregates derived from concrete, but there are some differences between the two types. HE recycled aggregate is waste from different types of concrete (primarily concrete used for building construction HA-25-B-20-IIa) that it crushed and sieved once. On the other hand, the HR recycled aggregate derived from demolition concrete is used to obtain artificial aggregate after undergoing treatment. This process involves eliminating large pieces of concrete. This material is then crushed and classified to be used as recycled aggregate. In both plants, CA-12/20-T-R aggregate was obtained after crushing and then sieving. The different physical and chemical properties of these recycled aggregates were assessed by the tests detailed below. The first step is to evaluate the aggregates’ suitability for structural concrete. Then the specific materials and the different percentages of aggregate to be utilized in concrete manufacturing are defined. The methodology employed to manufacture concrete in the laboratory is also presented, as well as the methodology followed in the characterization tests conducted on the different concretes produced.Before utilizing recycled aggregates in structural concrete, their suitability must be confirmed by means of the corresponding tests. A description of the proposed testing methods to characterize recycled coarse aggregate (12/20) is included below, including the limit values stipulated by regulations. These requirements are divided into two sections: physical-mechanical requirements and chemical requirements.In order to guarantee the fulfilment of the physical-mechanical requirements, certain tests must be conducted. The most relevant aspects are included below and the tests carried out as well.The size and shape of the aggregates to be incorporated into structural concrete affect the strength performance. The geometric properties of aggregates were determined by the sieving method indicated in regulation UNE-EN 933-1:2012 . In addiThe presence of clay in the coarse aggregate fraction is also subject to restrictions, especially in the case of those aggregates made from recycled materials. For concrete wherein recycled aggregate constitutes no more than 20% of the total aggregate quantity, the amount of clay lumps must not be greater than 0.6%, and the clay content in the fraction of natural coarse aggregate cannot exceed 0.15%. In the extreme case of using 100% recycled coarse aggregate, the percentage of clay lumps in the aggregate must not exceed 0.25% . When woTo produce quality concrete, the correct amount of water is essential, as indicated by regulations regarding the water to cement ratio. Therefore, it is imperative that one be familiar with the water absorption of the different components of concrete. This value is determined for recycled aggregates according to regulation UNE-EN 1097-6:2014 . To manuResistance to freezing and thawing cycles is related to the strength of aggregate particles and the distribution of pores in the aggregate. Recycled aggregates lose more weight than natural aggregates, because of the mortar adhered to the rock matrix when subjected to 10 frost/thaw cycles in water or five cycles in a magnesium sulphate solution. In order to determine the maximum weight loss experienced by recycled aggregates when subjected to treatment cycles with sulphate magnesium solutions, the sample must undergo prior preparation: consisting of thorough washing and sieving with a 10 mm sieve, to eliminate all the friable particles (which crumble easily) before proceeding with the test outlined in regulation UNE-EN 1367-2:2010 . The EHEThere is a second set of requirements for aggregates involving chemical testing. These tests are necessary to guarantee the quality of the concrete made from the different types of aggregate. Chlorides in concrete must be limited when dealing with reinforced structural concrete. In this type of concrete, chlorides must be within permissible values so as to avoid corrosion of reinforcement. Chloride content present in recycled aggregates is an important factor to consider when aggregates come from construction sites where they may have come into contact with liquid salts, such as in high mountainous areas, or in direct contact with seawater, or if during the manufacture of concrete some accelerating product was employed. Being aware of the source of waste allows for more efficient management. Nevertheless, even if the source is known, in the case of recycled aggregates, it is also advantageous to determine the quantity of soluble chlorides in water and the total amount of chloride contained in the aggregate. This is significant information because of the fact that different combinations of chlorides may exist and can be reactive, such as the case of the chlorine hydrated calcium aluminate, which can release chloride ions in the presence of sulphate ions. EHE-08 limits the maximum content of soluble chlorides in water to 0.05% for coarse and fine aggregate when utilized for reinforced concrete. If aggregates are to be used to manufacture pre-stressed concrete, said limit is reduced to 0.03%. This percentage applies to the mass of dry aggregate  and is addressed in Article 7 of regulation UNE-EN 1744-1:2010 .3 in coarse and fine aggregates, is determined according to Article 12 of regulation UNE-EN 1744-1:2010 [The amount of sulphates must also be controlled in materials to be used in concrete production. The quantity of sulphate contained in recycled aggregate can be a significant factor due to the sum of sulphate corresponding to natural aggregates and that of aggregate’s adhered mortar. In the case of concrete from building demolitions, gypsum is also considered a contaminant. These sulphates can cause problems in concrete since they can combine with hydrated tricalcium aluminate in cement to create ettringita  and provoke detrimental expansions. Another possible transformation is that of free calcium hydroxide, or calcium released during concrete hydration, which also entails an increase in volume that can fracture concrete. The content of soluble sulphates in acid, expressed as SO4-1:2010 , and can4-1:2010 .Recycled aggregates do not present potential chemical reactivity with those alkalines present in concrete. In the case of recycled aggregates from one controlled source, that is concrete with known compositions and characteristics, instruction EHE-08 must be followed. To this end, a petrographic study was completed in order to obtain information on the type of reactivity that could occur. Although there are no limit values, it is essential that the recycled aggregates do not present any potential for reactivity.When working with recycled materials, the presence of impurities and contaminants is commonplace. In recycled aggregates, such contaminants significantly and adversely affect the properties of ready-made concrete. Wood, plastic, gypsum, metal, glass, brick, asphalt, organic material, etc. are all common contaminants. One of the primary problems these contaminants pose for concrete is that they adversely affect its compressive strength. When the contaminating elements are clay or lime residues, compressive strength suffers even more than when recycled aggregate includes asphalt or paint waste. The type of contaminant found in recycled aggregates depends on the aggregate’s source. Recycled aggregate from concrete waste presents considerably fewer impurities than aggregates from demolition waste. EHE-08 establishes the limitations on contaminants and impurities as follows .The tests proposed herein verifies whether or not recycled aggregates comply with the requirements indicated by EHE-08 for their use and incorporation as a component of recycled structural concrete.In the present study, coarse aggregate was incorporated as a replacement for natural aggregate without any additional modification in the concrete mix design, and maintaining the same quantity of cement and the same water-cement ratio. Recycled concrete was mixed using the same methods employed for traditional concrete.A reference mix was prepared with natural aggregates. As noted above, the traditional aggregates for the concrete mix design came from the quarry La Peña, which is owned by the company Hormigones Ebro. In this case , three t3. Since mixing is done in a laboratory with a smaller-sized mixer, the values presented are for 60 L of sample concrete, henceforth referred to as H0.Our present study focuses on concrete’s compressive strength as the primary data, based on the concrete mix design previously validated through characterization testing conducted at the ready-mix concrete plant. Based on the real mixes used in pre-mixed concrete plants, and establishing the amount of cement, a percentage of the natural coarse aggregate was replaced by recycled coarse aggregate. The goal was to create economically and environmentally viable mixes ,48. ThusTo manufacture each different mix, the different fractions of aggregate utilized were weighed separately See . A calibCA-12/20-T-S-L, mixer rotated for 3 s to evenly distribute material. In the substitution mixes, the corresponding fraction of CA-12/20-T-R was added at the same time.CA-6/12-T-S-L, mixer rotated for 3 s to evenly distribute material.FA-0/6-T-S-L, mixer rotated for 3 s to completely mix materials.Cement was added and evenly distributed manually; the mixer was then switched on and rotated for 2 s.Half the total water quantity was added and mixing resumed.The remaining quantity of water was added with the mixer in motion during a period of time no greater than 30 s. This first mixing stage lasted 3 min and 30 s.Let mix stand for 3 min with the mixer cover open.After two minutes the mixing process was finished. Then ambient temperature and humidity were recorded, as well as the temperature of the cement mix.To create the mix, a laboratory mixer was used with a capacity of 60 L . Before introducing the materials in the mixer, the inside of the drum was moistened with water. The raw materials were placed in the cement mixer in the following order:Then, testing of the fresh concrete began and cylindrical specimens were prepared to test the hardened concrete. This mixing process was repeated three times for each different mix of concrete, so as to obtain average values for the results.Various tests were performed on the concrete produced in each mix cycle (60 L): two consistency measurements with an Abrams cone in accordance with regulation UNE-EN 12350-2:2009 , occludeThe cylindrical specimens were faced with a polishing machine to reduce the dispersion in the results.The cylindrical specimens were broken, by tensile force and compression, with an authorized and calibrated press . For the hardened concrete produced in this study, the following data was obtained for each mix: three measurements of compressive strength, aged seven days; nine measurements of compressive strength, aged 28 days; 12 measurements of density; nine measurements of absorption; nine measurements of indirect tensile strength; and nine measurements of water penetration.Conducting the tests identified in This study analyzes the feasibility of obtaining structural concrete when recycled aggregates are utilized. The results are presented according to the characterization of recycled aggregates from structural concrete waste. This waste came from two different plants: Hormigones Ebro (HE), and Hormigones Rioja (HR). Natural aggregate is also characterized, which was replaced by recycled aggregate in different percentages. The results displayed in Once the suitability of recycled aggregates as a substitute for natural aggregates in the manufacture of recycled reinforced concrete was verified, different mixes were made varying the percentage of coarse aggregate (CA) substituted and utilizing the mix proportions indicated in the methodology. The total number of mix designs is 10: that is, a total of five for each of the two different recycled aggregates from two different sources: a standard sample mix and four substitutions of coarse aggregate . The analysis of each mix was completed with three mixes used to test fresh and hardened concrete.For fresh concrete, there is a generalized decrease in consistency (increased slump in an Abrams cone) when recycled aggregates are incorporated. However, the quantity of aggregate incorporated does not appear to influence the extent of said decrease. The data obtained is depicted graphically in For the hardened concrete produced in this study, the following data was obtained for each mix. The results in ck) is one of the variables used to calculate structural concrete. In this case, using the data recorded, a normal distribution was carried out for each batch of concrete made. To facilitate the reader’s interpretation of the results, two graphs are included according to the source of the recycled aggregate. Compressive strength and indirect tensile strength have remarkable values for the performance of structural concrete. The tests realized after seven days aimed to follow-up and confirm that the cylindrical specimens were made correctly. The representative value for compressive strength at an age of 28 days  or Hormigones Rioja (demolition waste) only slightly affected the indirect tensile strength, and the extent of this effect was not influenced by the amount of recycled aggregate used as a substitute.Using recycled aggregates generated greater dispersion in the results. It was expected that increasing the amount of natural aggregate to be substituted would diminish the concrete’s strength properties. However, this phenomenon is not observed in the compressive strength of any of the cases examined herein. The dispersion present in the results is derived from the heterogeneous composition of the recycled aggregates. The source HE includes waste from pre-mixed concrete created in the plant: blinding concrete, non-structural concrete, and structural concrete. The HR source, on the other hand, consists exclusively of structural concrete from demolition waste. Thus, dispersion can be avoided by adequately managing and classifying said materials. The selection and classification of waste prior to producing recycled aggregate should be promoted and improved. Conducting this type of work beforehand improves the quality of the recycled aggregate produced. The use of recycled aggregate ought to be stimulated, given that its role will certainly take on increasing importance in the future. As the European Commission’s proposals recommend, it is important to plan for, and promote, the re-use of waste in the area where it is generated.Spanish regulations recommend limiting recycled coarse aggregate to 20% of the total weight of materials used. This study demonstrates that a greater percentage of recycled aggregate can be incorporated if the materials to be recycled are characterized and treated before being processed. Economic and environmental limitations must be taken into consideration to recycle responsibly and sustainably. The results indicate that to produce non-structural concrete, the percentage of recycled aggregate used in the concrete mix can be increased.This study demonstrates that the treatment of concrete through crushing and screening yields recycled aggregate that is suitable for producing structural concrete. In the case examined herein, the concrete manufacturing plants create the waste that is reincorporated into their product: this serves as a clear, practical, and effective example of a circular economy. Two sources of waste were analyzed.The two treatments realized on the demolition waste entail significant costs. However, these treatments have been proven to contribute added value to the recycled aggregate obtained.The concrete produced with recycled aggregate at the HR plant obtained results similar to those of the control concrete.This study demonstrates that recycled aggregates that are made from concrete and undergo prior treatment can replace natural aggregate by up to 50% without provoking significant modifications in the produced concrete’s strength performance.In the case of recycled aggregates from Hormigones Rioja (demolition waste):There is a greater negative impact on the compressive strength of the concrete produced.The presence of low strength concrete in the HE source presents an obstacle for recycling with the aim of producing structural concrete.2 at age 28 days. This type of waste, which undergoes a simple prior treatment of crushing and sieving, presents a significant quantity of adhered mortar.The concrete block aggregate was derived from concrete with a strength less than 25 N/mmThis undesirable effect can be remedied by introducing an initial classification step to categorize waste according to its strength. Thus, one could select only those recycled materials of equal or greater strength than the strength of the concrete to be made.In the case of recycled aggregates from Hormigones Ebro (ready-mix concrete waste):In the future, we should be able to avoid wasting materials when concrete is supplied to construction sites by efficiently commercializing the unused or leftover materials. Future lines of research should focus on concrete production processes with a reduced dispersion. Cataloging and classifying the materials to be used in concrete mixes must be an initial step to incorporating recycled materials into concrete production.


In our previous strategy some key features of CSi ceramic have been significantly improved by dilute magnesium doping for regulating mechanical properties and biodegradation. Here we demonstrate that 6 ~ 14% of Ca substituted by Mg in CSi  can enhance the mechanical strength (>40 MPa) but not compromise biological performances of the 3D printed porous scaffolds with open porosity of 60‒63%. The in vitro cell culture tests in vitro indicated that the dilute Mg doping into CSi was beneficial for ALP activity and high expression of osteogenic marker genes of MC3T3-E1 cells in the scaffolds. A good bone tissue regeneration response and elastoplastic response in mechanical strength in vivo were determined after implantation in rabbit calvarial defects for 6‒12 weeks. Particularly, the CSi-Mg10 and CSi-Mg14 scaffolds could enhance new bone regeneration with a significant increase of newly formed bone tissue (18 ~ 22%) compared to the pure CSi (~14%) at 12 weeks post-implantation. It is reasonable to consider that, therefore, such CSi-Mgx scaffolds possessing excellent strength and reasonable degradability are promising for bone reconstruction in thin-wall bone defects.Wollastonite  ceramic is a promising bioactive material for bone defect repair due to slightly fast degradation of its porous constructs  The large demand for bone grafts is increasing with the number of bone defect caused by trauma, inflammation and tumor resection, especially in orthopedic and maxillofacial surgery1472+, has shown its superiority in pre-osseous and osseous tissue repair in vitro and vivo12131415163; CSi), which exhibited faster degradation rate and higher osteogenesis, has received a great deal of attention. This ceramics is superior to traditional calcium phosphates in cell attachment, proliferation and differentiationin vitro12Artificially synthesized calcium phosphates (CaPs) such as hydroxyapatite (HA), β-tricalcium phosphate (β-TCP) and their biphasic calcium phosphate (BCP), due to their compositional similarity to natural bone mineral, have been applied in clinic. However, poor biodegradability and lack of osteoinductivity are their major drawbacks1011x, x = 0–17). Such CSi-Mgx ceramic exhibited significantly improved densification, excellent fracture toughness (>3.2 MPa m1/2), and good bioactivity in SBF (simulated body fluid) in vitrox bioceramics to reconstruct certain challengeable thin-wall bone defects.Magnesium (Mg), another important biologically essential mineral microelement in bone remodeling, was found to have the ability to enhance bone regeneration of the bone substitute22x  both in vitro and in vivo.On the other hand, the formation of a fully interconnected macroporous 3D structure is the primary objective in bone scaffold fabrication. Nowadays various techniques have been employed to fabricate isotropic, anisotropic, and periodic pore structure scaffolds, including polymer foam replication2728x  powders with diluted Mg doping were synthesized through a conventional chemical precipitation method previously describedθ and a dwell time of 1.5 s to identify any crystallization of the powders. The Mg contents in the synthetic powders were measured by inductively coupled plasma atomic emission spectrometer . Prior to measure, the powders were dissolved in the mixture solutions containing 10% HCl and 10 HNO3, respectively.The CSi-Mgx scaffolds (Ø8 × 3 mm), the ink was prepared by mixing 5.0 g of CSi-Mgx powders with 4.5 g of 6% polyvinyl alcohol (PVA) solution. The porous scaffolds were prepared by using 3D ceramic ink writing equipment. The CSi-Mgx ink was added to a 5 ml syringe and extruded through a conical nozzle by the movement of a piston rod. A cylindrical porous CSi-Mgx scaffold model with 3D rectangular periodic porous architecture was designed using software. The CSi scaffolds were also fabricated simultaneously. The scaffolds using initial distance between green filaments were ~450 μm. The moving speed of the dispensing unit was set to 6 mm/s, and the nozzle diameter was 450 μm. The obtained scaffolds were dried for 24 h in ambient atmosphere, and another 24 h at 90 °C, and then underwent a one-step sintering in a micro-controller controlled temperature furnace , with temperature increased at the heating rate of 2 °C/min to the target temperature of 1150 °C, held for 3 h and then under natural cooling.For layer-by-layer (LbL) ceramic ink writing of the CSi-Mg1). Then the scaffolds were immersed in a beaker of water and held under vacuum to make the liquid into the pores until no bubbles emerged from the scaffolds. Subsequently, the samples were re-weighed under water to produce the suspension weight (W2). Afterwards, the scaffolds were carefully taken from the beaker with dabbing off surface saturated water, and they were quickly re-weighed in air to produce the saturated wet weight (W3). The porosity of the scaffolds (n = 5) was calculated via the following equation: porosity (%) = (W3 − W1)/(W3 − W2) × 100%.The strut microstructures and the average strut and pore size of the scaffolds were measured through scanning electron microscopy . The porosity (macro pores) was measured by Archimedes method in deionized water at room temperature. The ceramic scaffolds were weighed as dry weight  were test for each group.Uniaxial compression tests of the ceramic scaffolds were evaluated by a universal testing machine  with a 10 KN load cell and a crosshead-loading rate of 1.0 mm·min2. Then the cells were detached with 0.25% trypsin, 0.03% ethylene diamine tetraacetic acid (EDTA) and the cell density counted. After counting, the cell suspension was diluted to the desired density in later experiments.MC3T3, an osteoblast precursor cell line derived from mouse  was used to evaluate influence of different materials on proliferation and differentiation. MC3T3 were cultured in Dulbecco’s Modified eagle Medium  at 37 °C in a humidified atmosphere of 5% CO5 MC3T3 cells and incubated at 37 °C in a humidified atmosphere of 5% CO2.After sterilized by ethylene oxide, four groups of scaffolds were placed into 24-well plate and immersed in DMEM with 10% FBS for 2 h. Then each scaffold was seeded with 1 × 10After 48-hour incubation, samples were washed with phosphate buffer solution (PBS) twicex ceramic scaffolds. Briefly, MG3T3 cells were seeded onto the different CSi-Mgx ceramic scaffolds in the 24-well plates and incubated for 1, 4, and 7 d, or cultured in the scaffold-free condition which was served as control, each group containing six samples. All wells were added with 0.5 mL DMEM containing 10% CCK-8 and having incubated for 120 min. The culture media (100 μL) were transferred from the wells to a 96-well plate. The absorbance of the culture media was measured at 570 nm using an MRX Revelation 96-well multiscanner .Cell viability was tested by Cell Counting Kit-8  to evaluate the cytocompatibility of the CSi-Mgx ceramic scaffolds in the 24-well plates and incubated for 14 d, with those cultured in the scaffold-free condition as control. After the culture medium was aspirated, each well was added into with 200 μL of 1% Nonidet P-40 (NP-40) solution and incubated at room temperature for 1 h. The cell lysate was centrifuged and 50 μL of supernatant was transferred to 96-well plates. Fifty milliliters of p-nitrophenylphosphate  substrate solution (2 mg/mL) composed of 0.1 mol l−1 glycine, 1 mmol l−1 MgCl. 6H2O was added to the 96-well plates and incubated for 30 min at 37 °C. The reaction was quenched by adding 100 mL of 0.1 N NaOH. The absorbance of ALP was quantified at a wavelength of 405 nm using a microplate reader . The total protein content in the cell lysate was determined using the bicinchoninic acid method in aliquots of the same samples with the Pierce protein assay kit , read at 562 nm and calculated according to a series of albumin  standards. The ALP levels were normalized to the total protein content, and all the experiments were performed in quadruple.For cell differentiation assay, MG3T3 cells were seeded onto the different CSi-Mg2O with Bio-Rad real-time PCR system  by using glyceraldehydes-3-phosphatedehydrogenase (GADPH) as the internal control gene for normalization. The forward and reverse primer sequences utilized were listed in −ΔCT = CT(target) − CT(control). Then the relative mRNA expression quantification was analyzed with 2−ΔΔCT methods, taking the CSi group as the control.Real-time PCR was used to detect the expression of several osteogenic differentiation-related maker genes (Collagen I (Col I), osteocalcin (OCN), Osterix and runt-related transcription factor 2 (Runx2)) at day 7. Total RNA was extracted using Trizol reagent (Invitrogen) according to the manufacturer’s instructions. The concentration of total RNA was determined using NanoDrop 2000c (Thermo Fisher Scientific Inc. USA). First-stranded complementary DNAs (cDNAs), synthesized from 0.5 μg of the isolated RNA by oligo (deoxythymidine) (oligo (dT)) using DyNamoTM cDNA Sythesis Kit (Fermentas), were applied as templates for real-time PCR. The PCR was performed on a final volume of 25 μL consisting of 1 μL cDNA, 0.5 μL of each primer (forward and reverse), 12.5 μL Power SYBR® Master Mix (2×)  and 10.5 μL dd Hin vivo study was performed in accordance with the standard animal study guideline of Zhejiang University, and all experimental protocols were approved by the Zhejiang University Ethics Committee (ZJU2014-1-05-093). This study applied 16 New Zealand white rabbits of 2.8 ± 0.2 kg in weight . The procedure was similar to our previous studyThe n = 3) were dehydrated in graded series of alcohol (80–100%) and embedded in polymethyl methacrylate (PMMA) without decalcification. Three longitudinal sections of approximately 200-μm thickness were cut from each sample using a microtome . Using a special grinding machine , the sections were ground to a thickness of about 40‒50 μm and polished. The sections were stained with Van Gieson’s (V-G) picrofuchsin and examined under light microscopy . The area of newly formed bone was measured by Image Pro 5.0  and reported as the percentage of the whole bone defect area, respectively. The Newly formed bone (NB) (%) was calculated as follows:After the non-invasive MicroCT scanning, the harvested samples (n = 6) were cut down from the skull and fixed, MicroCT measurement was performed using a microCT system  in the parallel to the circular defect. The dataset was processed with Mic View software. The 8 mm-in-diameter circular region of interest (ROI) was traced manually and virtually reconstructed. The area of newly formed bone of ROI was measured. The volume of newly formed bone in the calvarial defects was calculated as BV/TV ratio.After the samples (n = 5) was examined using the above-mentioned method  at 6 and 12 weeks after implantation, respectively.The samples (~8 mm in diameter and ~3 mm in height) were harvested using a trephine drill and dental burr. After the non-invasive MicroCT scanning, the compressive strength of the samples . Statistical analysis was performed with one-way analysis of variance (ANOVA), using the SPSS 16.0 for Windows statistics software package. Differences were considered significant at x ceramic powders were shown in x ceramic scaffolds  was 1.28%, 2.09%, and 2.99%, respectively. Thus, these magnesium values in the new synthetic products are close to the theoretical data in the crystalline products of CSi-Mg6 , CSi-Mg10 , and CSi-Mg14  according to the stoichiometric compounds.The XRD patterns of the CSi-Mgcaffolds , it dispp < 0.05). Meanwhile, the CSi-Mg6 and CSi-Mg14 scaffolds also showed a significant higher initial strength (over 40 MPa) than the pure CSi scaffolds (p < 0.05). The compressive strength of all groups of scaffolds showed a remarked reduction from 0 to 6 weeks and then an increase at 12 weeks. It is notable that the CSi-Mg10 group still possessed the highest average strength (20.6~27.4 MPa) among the four groups at 6 and 12 weeks and it was significantly higher than that of the CSi group (p < 0.05) at 6 weeks.p > 0.05).x groups showed higher ALP activity than the control. However, no significant difference was found among three groups (p > 0.05). x scaffolds for 7 d. The CSi-Mg14 group showed significantly higher relative expression of Col I, Osterix, and Runx2 than the other three groups (p  < 0.05) and higher relative expression of OCN than CSi-Mg6 group (p < 0.05). The CSi-Mg10 group showed a significantly higher Col I expression than the CSi group (p < 0.05). The CSi group showed a significantly higher OCN expression than the CSi-Mg6 group (p < 0.05).As was shown in x  groups than the pure CSi group. In addition, Haversian canals-like structure was also observed. Blood vessels were found in the newly formed bone. More new bone and osteoid formed with time. It is worth mentioning that more bone and osteoid were observed in the skull defects that were repaired with the scaffolds of higher Mg doping.p < 0.05) at both week 6 and week 12, higher than the CSi-Mg6 group (p > 0.05) and the CSi-Mg10 group (p > 0.05) at week 6. The highest BV/TV ratio was found in the CSi-Mg14 group at week 12 (p < 0.05). At week 12, the BV/TV ratio in the groups of CSi-Mg6 and CSi-Mg10 were significantly higher than the CSi group (p < 0.05). It is worthy of mention that the BV/TV ratio of the CSi-Mg14 group was the highest in both week 6 and week 12. These results were consistent with the histomorphometric analysis.Osteoconduction, osseointegration and osteoinduction play an important role in successful bone regeneration of bioactive porous scaffold biomaterial. The biocompatibility and bioactivity of the biomaterials both contribute to this procedure, as well as the morphology of the materials3O9)6−. There are a number of monoclinic and triclinic polytypes of wollastonite, which are as follows: wollastonite-1A, wollastonite-2M, wollastonite-3A, wollastonite-4A, wollastonite-5A, and wollastonite-7A. In compared with the wollastonite-2M (parawollastonite) and wollastonite-7A (pseudwollastonite), wollastonite-1A (wollastonite) is more widely obtained in the polytypes of wollastonite families, and furthermore wollastonite-1A and wollastonite-7A are thought to be the low and high-temperature phase, respectively. In general, the pseudwollastonite belong to high-temperature phase, and the wollastonite-1A and wollastonite-2M are low temperature phase. In particular, the foreign ion doping could helpful for the production of wollastonite-2M phase. In our studies, the magnesium doping readily produced wollastonite-1A, and the amount of wollastonite-2M increase with increasing Mg content.The XRD show that the crystallization decreased with addition of magnesium (the XRD line intensity are decreased). Structurally, wollastonite is composed of the repeating unit As mentioned above, the CSi-Mgin vivo, the scaffolds showed a markedly different mechanical response compared with our previous studies in vitro24in vivox groups showed an high-low-high change. The compressive strength of the samples of the CSi-Mgx groups at week 6 was much lower than that of the initial scaffolds (week 0). Such decrease in compressive strength obviously resulted from material degradation. However, the CSi group only showed two regions at 6 weeks. It might be because the compressive strength of CSi scaffold was similar to the newly formed bone. The compressive strength of the samples of all groups at week 12 was higher than that of samples at week 6. This may be attributed to the new bone in-growth.After implantation x scaffolds performed its high compressive strength (~65 MPa) originally to support the segmental bone defect at early stagex scaffolds in vivo match the biological procedure of bone regeneration.All these changes in compressive strength are preferable for the biological procedure of the bone regeneration, especially in segmental bone defect. In general, the bone implants with good compressive strength, for instance, polymethyl methacrylate and titanium, can afford stable support to the defect in the early stagex scaffolds showed good cell viability and ALP expression activity, and the CSi-Mgx groups showed higher expression of important osteogenic differentiation markers . Meanwhime point  and 8. Ax ceramic and the slower is the dissolution rate in vitroIn addition, it seems that the osteogenic capacity of CSi-based bioceramic scaffolds is correlated to Mg doping ratio. It has been demonstrated in our previous studies that the higher is the Mg doping ratio, the higher is the densification of the CSi-MgIn summary, this research presents for the first time that 3D printed diluted magnesium doping wollastonite porous scaffolds have the superiority of both bone regeneration potential and mechanical evolution in repairing the thin-wall bone defects. The dilute Mg doped CSi scaffolds are superior to the pure CSi scaffolds in viability, ALP activity and expression of osteogenesis-related genes of the osteogenic cells on their surface. The Mg icons in the mechanically strong bioceramics also enhance bone regeneration in the model of rabbit calvarial critical-size bone defect reparation. In this regard, the mechanically strong CSi-Mg scaffolds with appropriate dilute Mg doping is promising for certain scenarios of bone defect reparation, especially the reparation of the thin-wall cranio-maxillofacial bone defects.How to cite this article: Sun, M. et al. Systematical Evaluation of Mechanically Strong 3D Printed Diluted magnesium Doping Wollastonite Scaffolds on Osteogenic Capacity in Rabbit Calvarial Defects. Sci. Rep.6, 34029; doi: 10.1038/srep34029 (2016).


Limited information exists between the associations of diabetes mellitus (DM) and solar lentigo (SL); a benign, common skin lesion characterized by hyperpigmented macules.This study was conducted on 90 patients diagnosed with DM and their age and sex matched controls who were referred to the Departments of Endocrinology at Babol University of Medical Science in Northern of Iran from January 2013 to December 2015. All demographic data including age, gender, occupation, family history of DM, estimated average sun exposure and presence of skin lesions were collected and analyzed. Presence of SL was significantly higher among patients with DM compared to controls . After adjusting for age, sex and sun exposure rate, results indicated that DM was independently associated with the presence of SL (p=0.002). Stratifying patients based on gender, indicated that DM was significantly associated with SL in females (p=0.03), but not in male patients (p=0.06). The findings of the present study indicate that DM is an independent risk factor for the occurrence of SL lesions. These findings could represent a novel association between DM as a chronic oxidation state and SL as an early sign of aging. Diabetes mellitus (DM) is a multisystem disease and a major endocrine cause of morbidity and mortality around the world , medium  and large . The total number of lesions were also classified into two groups: few (number of macules less than 3) and high (number of macules 4 or more). This study was approved by the Ethics Committee of Babol University of Medical Sciences. All statistical analysis was performed using the SPSS software Version 17. A p-value of less than 0.05 was considered significant.A total of 182 patients  from 2 medical centers were enrolled in the study between January 2013 and December 2015. Among these patients, 90 were diagnosed with DM as the case group and 92 subjects in the healthy control group matched by age and sex were evaluated. The most common age group in this study was between 45 to 50 years (52.7%). A positive family history of diabetes mellitus was more common in cases versus controls . Presence of solar lentigo was significantly higher among the patients diagnosed with DM, compared to controls (p<0.001) . Among the diabetic subjects, the female gender was associated with the higher rate of SL . Data suggested that the frequency of exposure rate to sun was significantly higher in males than females (p<0.001). Regardless of the presence of diabetes, the existence of SL was significantly higher in diabetic female subjects compared to diabetic male subjects (p<0.0001). While the presence of SL was more prevalent in diabetic male subjects (64.7%) compared to non-diabetic males (35.2%), it was not statistically significant which could be partly due to the fewer number of subjects included in the study (p=0.21). After adjustment for age, sex and sun exposure rate, the presence of SL among subjects was analyzed. The results indicated that DM was independently associated with the presence of SL (p=0.002). Stratifying patients based on their gender indicated that DM was significantly associated with SL in female (p=0.03) but not in male patients (p=0.06).The results of the present study indicate that the presence of SL was significantly higher among patients diagnosed with DM, compared to controls. After multivariable analysis, our results demonstrated that DM was independently associated with SL. While previous studies have shown that the incidence of cutaneous manifestation are higher among DM patients compared to general population -7, the aSL also known as senile lentigo or liver spots, are hyperpigmentary disorders more commonly seen in older persons. It is considered to be a hallmark of photodamage and aging process. It is well-known that these spots occur mainly because of chronic ultraviolet (UV) exposure. Exposure to UV radiation results in increased melanin production and may lead to the development of these hyperpigmented lesions. This increase in melanin production is regulated by interactions between melanocytes and neighboring cells, such as keratinocytes or fibroblasts -16. In aBesides the UV induced microvascular pathology, hyperglycemia has also shown to target vascular endothelial cells, playing a major role in the pathogenesis of diabetic macroangiopathy -21 NeuroThe mechanisms of development of SL among patients with DM is unknown. Aging is shown to be independently associated with the development of SL. It has been shown that the cumulative amount of ultraviolet (UV) exposure, plays a role in the progression of SL , 25. TheThe major limitation of the present study is the relatively low number of subjects which prevented any subgroup analysis to determine the influence of variables such baseline demographics including age or the duration and stage of SL. Therefore, the findings of the present study should be interpreted in the context of its limitations. Further studies are required to elucidate the possible mechanisms of this association.In conclusion, the findings in the present study have shown a novel relation between DM as a chronic oxidation state and SL as an early sign of aging.


Polymeric capsules can have an advantage over glass capsules used up to now as proof-of-concept carriers in self-healing concrete. They allow easier processing and afford the possibility to fine tune their mechanical properties. Out of the multiple requirements for capsules used in this context, the capability of rupturing when crossed by a crack in concrete of a typical size is one of the most relevant, as without it no healing agent is released into the crack. This study assessed the fitness of five types of polymeric capsules to fulfill this requirement by using a numerical model to screen the best performing ones and verifying their fitness with experimental methods. Capsules made of a specific type of poly(methyl methacrylate) (PMMA) were considered fit for the intended application, rupturing at average crack sizes of 69 and 128 μm, respectively for a wall thickness of ~0.3 and ~0.7 mm. Thicker walls were considered unfit, as they ruptured for crack sizes much higher than 100 μm. Other types of PMMA used and polylactic acid were equally unfit for the same reason. There was overall good fitting between model output and experimental results and an elongation at break of 1.5% is recommended regarding polymers for this application. An increasing amount of research on encapsulation of healing agents for self-healing concrete has been published during the last decade. The existing research is focusing mainly on the micro-encapsulation of liquid healing agents in spherical capsules with typical sizes in the range of a few micrometers up to a few millimeters, a technique borrowed from self-healing polymeric materials , but alsEncapsulation protects the healing agents from undesired or premature reactions and degradation, to guarantee their availability at the onset of damage in the host concrete matrix. The liquid agents are then released from the capsules typically due to mechanical triggers—i.e., once a certain damage level in concrete is achieved, after which a crack crosses the capsule and eventually causes its rupture. More complex chemical triggers can also be used, by taking advantage of the ingress of chloride ions in maritime environment  or the dOther than being able to effectively release the healing agent after the onset of damage, capsules need to meet other more basic, but challenging requirements. They have to resist the mechanical stresses experienced during placing of concrete, in case of pre-placement of the capsules in the formwork, or during the mixing process, if added to fresh concrete during mixing. The material used for the capsules also has to be compatible with both the healing agent on the inside and the aggressive, high pH environment of the concrete matrix on the outside. Furthermore, the capsule’s wall has to have adequate barrier properties, with low permeability and diffusivity, to be able to retain its content but also to avoid any undesired chemical interaction between the healing agent and the concrete matrix. Finally, capsules have to rupture for very low imposed deformations, so that they release their content when crossed by a crack in concrete. Cracks are typically limited by reinforced concrete design codes to be no more than 300 µm wide, depending on the exposure conditions .It is the latter requirement, the need for capsules to rupture under small crack openings in a concrete matrix, that this study wishes to address. Tubular capsules extruded from different polymers are experimentally tested in order to assess their fitness for this application, with computer simulations aiding the initial screening of polymers.Although tubular glass capsules have been used mostly as a proof-of-concept, they are ideal in terms of barrier properties and rupture for very small deformations. While filling and sealing of glass capsules is definitely possible at a large scale, as they are already used in the pharmaceutical and adhesive industries, polymeric capsules are potentially easier to manufacture, due to their lower processing temperatures and the possibility for integrated extrusion, filling, and sealing steps. Despite this, the development of tubular, polymeric capsules for self-healing concrete has been seldom studied ,8.Moreover, the development and design of capsules for self-healing concrete can greatly benefit from numerical simulations. Numerical simulations are, in general, less costly than laboratory tests and can help in reducing the number of expensive experiments. So far, however, self-healing concrete has mostly been developed using trial-and-error procedures, with little optimization. There is thus a great need for robust numerical models. In Schlangen and Joseph , a revieModels used to design engineered self-healing concrete are less common. For example, Joseph  developeIn this study, numerical modelling is used to simulate breakage of tubular capsules made of different polymers and with various wall thicknesses. This makes it possible to reduce the number of experiments and quickly reject materials that are not suitable, regarding their capability to rupture when crossed by cracks in concrete.n = 195,000 g/mol), polylactic acid (PLA) was obtained from NatureWorks . Two types of poly(methyl methacrylate) were used. PMMA_1 was kindly supplied by Evonik Performance Materials  and PMMA_2 was also obtained from Evonik Performance Materials . PMMA_1-PEG was obtained by melt-blending PMMA_1 with 20 wt % of polyethyleneglycol monomethylether (PEG), which was purchased from Fluka .In this study, five polymers have been selected as encapsulation materials. Polystyrene (PS) was supplied by BASF AG  mixer at 210 °C and a speed of 30 rpm for 3 min. PEG was added after PMMA was completely molten and the compounding process proceeded at 70 rpm for 7 min.PEG was added as a plasticizer for PMMA_1 to assess the feasibility of this option as a way to improve the chances of the capsules surviving the mixing process of concrete. The addition of PEG would increase the ductility of the capsules, making them less prone to be damaged by the stresses seen during concrete mixing. The PEG would then be partially and progressively leached out into the moist concrete, further lowering the ductility of the capsules so that they would rupture when crossed by small cracks in concrete. Resistance to mixing in concrete will be addressed in a separate publication on a realistic implementation of self-healing concrete based on tubular capsules added to concrete during mixing. The strategy of using plasticizer migration to achieve evolving brittleness had already been tried by Gruyaert et al.  on capsuThe mechanical properties of the polymers were then determined by tensile tests performed on dog bone-shaped samples  on a Zwick  universal tensile testing machine with a load cell of 1000 N. A preload of 0.5 N was used, the extension monitored was given by the separation between the grips and the stress–strain curves were obtained at a speed of 1 mm/min at room temperature. The results of the tensile tests are listed in This study also considered glass as an encapsulation material for comparison purposes. The mechanical properties of glass are listed in −1, while the conveyor speed was adjusted to get approximately the desired external diameter and wall-thickness, which were 6 mm and 0.30 mm respectively. For PMMA_1, tubes with thicker walls were also tested. The average dimensions of the tubular sections from which the capsules were cut are listed in To extrude the hollow tubes from which capsules were cut, pellets of polymer were dried in a hot air oven at 60 °C for one day before extrusion. The extrusion was performed on a Brabender  extruder equipped with a single screw and a tubular die with outer and inner diameters of 10 mm and 8 mm, respectively. The processing temperature was 225–235 °C with a screw speed of 10 minTo create the capsules to be tested, sections 5 cm long were cut from the polymeric tubes. The ends of the capsules were heated and shaped to create hooks for improved mechanical locking once embedded in a mortar matrix. To additionally improve adhesion to the cementitious matrix, the capsules were sanded in a direction perpendicular to their length, as highlighted in The capsules were then embedded in reinforced mortar prisms with dimensions 4 cm × 4 cm × 16 cm by placing one capsule inside each mold, 1.3 cm from the bottom and centered relative to the sides, before pouring the mortar. The mortar mix consisted of CEM I 52.5 N, and had a sand-to-cement ratio of 3:1 and a water-to-cement ratio of 0.5. Mixing and molding were performed according to the EN 196-1 standard. The specimens contained also two reinforcing Ø2 mm smooth metal bars, placed 10 mm away from the sides and the bottom of the specimen, to avoid complete splitting during the cracking process. To create and progressively widen cracks that crossed the embedded capsules, the mortar prisms were loaded in a three-point bending test controlled by an external linear variable differential transformer (LVDT)  with a 1 mm range. The LVDT was attached at one of the sides of the specimen, parallel to the embedded capsule and at the same height as its bottom fiber , so thatIn this work, the Delft lattice model is used to simulate rupture of tubular capsules subjected to mechanical loading. Lattice type models have been first used by theoretical physicists to model fracture mechanisms in heterogeneous materials . This tyIn these models, material is discretized as a set of small truss or beam elements that can transfer forces . In the N) and bending moments  are both taken into account by the following general relation:A is the beam cross-sectional area, W the cross-sectional moment of resistance, In the present work, a fracture criterion based on the tensile stress in beams is adopted. Normal force  shows higher tensile strength and ductility than PMMA_1 . As both types of PMMA have a similar Young’s modulus, the higher tensile strength (twice as high) and ductility of PMMA_2 result in larger elongation at break, which explains its much larger crack size at rupture. It can also be said that the inadequate performance of PLA capsules, which break only for crack sizes of ~0.2 mm or higher, is not necessarily intrinsic to the material type, depending also on the molecular weight of the PLA used.As a rule, the mechanical properties of polymers—such as tensile strength, stiffness, and ductility—rise with increasing molecular weight. This can be clearly observed in Overall, different combinations of tensile strength, stiffness, and ductility of the different polymer types and molecular weights result in different values of elongation at break, which is the commanding factor for guaranteeing rupturing of capsules when crossed by small cracks in concrete. Given the good predicted performance of PMMA_1 and PS capsules shown in The mechanical response of the capsules was then experimentally determined by embedding them in mortar specimens cracked under bending, where the capsules rupture under tensile stress once the crack crossing them reaches a critical size. Rupturing of the capsules induces a sharp load drop in the stress-displacement curves and a small reduction in the load capacity after that. These features were then used to experimentally determine the crack size at rupture of the capsules. Representative curves are shown in The experimental data regarding the crack width at rupture for the different capsule types is plotted in For the remaining polymers, the crack width at rupture was much higher than the targeted limit of 100 µm, as expected from the model output and confirming that these polymers are not good candidates for the intended application. For PMMA_2, the model output was very similar to the average crack size at rupture determined experimentally, with a deviation of ~10%. Regarding PLA capsules, it was not possible to assess how accurate the model was, given that their crack size at rupture is larger than the range of the experimental test and estimated by the numerical model to be 0.547 mm.For the best performing PMMA_1 polymer, capsules with thicker walls were then extruded and experimentally tested and the results were compared to the model output based on the exact same dimensions. The results are plotted in Finally, to assess how the results were affected by the treatment of the capsules, which included sanding of the outer surface and molding hooks at the ends , tests wThis proves also that it is unlikely that the poor performance of the PS capsules was related to a lack of adhesion, since the good adhesion between the best performing PMMA_1 capsules and the cement paste matrix was essentially mechanical in nature and achieved due to the roughness of the capsule’s surface introduced by sanding it, i.e., not due to a particularly good compatibility between PMMA and the cement paste.The numerical model identified a wide range of performances for the polymeric capsules and was confirmed to be a useful tool for preliminary screening of materials to be used for encapsulation. The model’s output showed only two types of capsules  potentially rupturing for crack sizes below 100 µm, i.e., the maximum limit after which they should rupture and release the contents in the context of self-healing concrete. The low elongation at break of these polymers was a critical factor in achieving good performance and thus it was suggested that an elongation of less than 1.5% is recommended for this application.For the PMMA_1 capsules, the experimental results agreed well with the model’s output, which showed a maximum deviation of 16%. Capsules with ~0.3 mm thick walls were considered fit for application in self-healing concrete, as they ruptured when crossed by an average crack size of 69 µm, while capsules with ~0.7 mm walls ruptured slightly above the targeted limit, for an average crack size of 128 µm. The latter size can potentially still be used for the considered application, but PMMA_1 capsules with ~1.2 mm were considered unfit. Regarding the PS capsules, the experimental results showed them to rupture only for very large crack sizes, unlike the result foreseen by the numerical model. The reason for this was not clear, although a lack of adhesion was improbable, as proper adhesion was proven to depend mainly on the abrasive treatment applied to the surface of all capsule types. Changes to this material during extrusion were thought to be the reason for the unexpected poor performance of PS capsules.The experimental results confirmed that the remaining types of capsules  rupture for crack sizes much higher than the targeted limit and thus are unfit. The model output showed a high maximum deviation of 33% relative to average experimental results in the case of PMMA_1-PEG, most probably due to the fact that this material is a blend and thus less homogeneous than the other polymers, which resulted in higher scattering of results. Additionally, PEG was expected to leach out from the PMMA_1-PEG matrix towards the moist cementitious matrix, thus reducing the ductility of the capsules, but this was not confirmed. In the case of PMMA_2, its molecular weight was too high, making this material too ductile and strong compared to PMMA_1, but the model accurately predicted its performance, with a maximum deviation of 10%.The presented modelling approach proved to be a valuable tool for designing capsules to be used as carriers of healing agents in self-healing concrete. The use of this and similar approaches in the future can provide guidance for experimental design and reduce the number of tests needed to design a robust self-healing system for use in concrete.