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In so doing, Chinese high school students were recruited to complete the online questionnaire of the four variables. The results showed that students had moderate levels of perceived teacher support, enjoyment, and academic engagement and a low level of boredom. Further correlation analyses indicated medium to large correlations between perceived teacher support, enjoyment, boredom, and academic engagement. Enjoyment and boredom collectively mediated the relationship between perceived teacher support and academic engagement. Directions for future research and implications for researchers and educators are presented at the end. Among teacher-related factors, teacher support as a combination of various types of support that teachers offer to their students has the potential to foster a positive relationship between teachers and their students Lei et al. However, the influence of teacher support has only received scant attention in the English as a Foreign Language EFL context Sadoughi and Hejazi, Since the two emotions were introduced into the EFL context, there has been an upsurge of interest in investigating the antecedents and outcomes of the two achievement emotions separately to understand their sources and influence e. However, relatively limited attention has been paid to investigating the antecedents and outcomes of the two achievement emotions within the same study to gain a more comprehensive understanding of these emotions Dewaele and Li, As the outcome of the interaction between both individual factors and the instructional context Baker et al. As above-mentioned, this study differs from previous ones in the following three aspects. First, this study explores an important but largely ignored teacher-related factor, i. Second, the antecedent and outcome of the two emotions are explored together, which offers a more comprehensive understanding when compared with previous studies that only focus on one aspect. Third, engagement is explored as an outcome of enjoyment and boredom, which lacks clarity in previous studies. The introduction of Positive Psychology in SLA makes researchers look beyond cognitive factors and pay close attention to positive psychological factors Shao et al. However, what needs to be warned is that Positive Psychology does not mean that negative emotions can be overlooked and margined Shao et al. Boredom, as the most pervasively experienced emotion that may cause dissatisfaction, amotivation, and attention deficit Pawlak et al. Moreover, along with the recognition of the importance of emotions in language learning, investigation into its influential factors has also received increased attention e. Due to the fact that language learning requires a lot of interaction between teachers and students Ellis, , the influence of teacher-related factors is highly valued e. In the present study, this theoretical framework was used to link enjoyment and boredom to perceived teacher support i. It is an important component of social support in the classroom context Tardy, Supportive teachers value and are interested in establishing personal relationships with their students, and they can provide help, assistance, and advice to their students in need Ryan and Patrick, ; Liu et al. Timely help from the teacher is likely to make students feel safe and motivated Wentzel et al. As a multifaceted construct, teacher support has been defined differently from different theoretical perspectives. According to the self-determination perspective, teacher support incorporates three dimensions, i. From a social support perspective, teacher support can be defined as a teacher providing informational, instrumental, appraisal, and emotional support to their students Malecki and Demary, Informational support refers to providing students with information or advice on a particular subject area; instrumental support is offering time, service, or skills to students; appraisal support is giving students evaluative feedback; emotional support means providing students with love, trust, and empathy Malecki and Elliott, As an important contextual factor, teacher support is a valuable resource for students to increase their academic engagement, improve learning achievement, and cultivate positive emotions toward the learning process e. As the communicative nature of language learning and frequent interactions between teachers and students in language classes have identified the teacher as an important source of encouragement and support for their students Jiang and Dewaele, , teacher support, as a core teacher-related factor, should be further explored Sadoughi and Hejazi, Enjoyment has received increasing scholarly attention along with the development of positive psychology e. Enjoyment is regarded as a component of flow, and it refers to a positive state in which challenges and the skills needed to deal with them are in line with each other Csikszentmihalyi, In other words, students are likely to experience enjoyment when they can deal with the challenges that they meet. Enjoyment is also closely related to pleasure but differs from it in that enjoyment incorporates the notion of successfully dealing with challenges Boudreau et al. They identified two factors, i. Moreover, previous studies Jiang and Dewaele, ; Moskowitz and Dewaele, indicated that enjoyment was more likely to be attributed to teacher-related factors than to learner-related factors. Boredom is a commonly experienced deactivating emotion in academic settings Kruk, It refers to a mild, silent, and unpleasant affective state or psychological experience that makes students show an indifferent attitude toward what goes on around them, and it is a combination of disappointment, dissatisfaction, and amotivation Kruk and Zawodniak, ; Zawodniak et al. Students tend to be bored when they cannot perceive meaning and pleasure from the ongoing activity Eastwood et al. Different researchers have classified boredom into different types to shed light on the complexities of this construct Pawlak et al. In accordance with its stability, boredom can be divided into trait boredom and state boredom. Trait boredom refers to a general tendency to perceive surrounding environments as uninteresting Bench and Lench, , while state boredom is a context-dependent, transient, and reversible negative feeling Pawlak et al. According to the control-value theory of achievement emotions, boredom can be divided along a three-dimensional taxonomy, i. In line with this division, boredom refers to a negative deactivating emotion that pertains to ongoing achievement-related activities. Although boredom is a frequently experienced emotion in educational settings, because of its silent and elusive characteristic, it has been undervalued for years in the language learning context Kruk, However, up to now, there is a paucity of empirical research using large-scale quantitative designs to investigate the relationship between boredom and other individual and contextual variables Li, Some existing studies e. Among these teacher-related factors, teacher support has rarely been studied in quantitative studies in the EFL context. Although it is closely intertwined with motivation, the biggest difference between the two concepts is that motivation is intention-oriented, while engagement is action-based Reschly and Christenson, ; Mercer, The most commonly recognized model conceptualizes engagement as encompassing three aspects, that is, behavioral, cognitive, and emotional engagement Fredricks, The proposed four-dimension model is empirically validated in the EFL context e. To date, scant attention has been paid to the predictors of engagement in L2 learning Khajavy, , especially the influence of learner-external factors Oga-Baldwin, Moreover, although previous studies e. Correspondingly, a mediating model is proposed, in which boredom and enjoyment collaboratively mediate the effect of perceived teacher support on academic engagement. Specifically, the present study intended to answer the following three research questions:. RQ 2: What are the relationships between foreign language learning enjoyment, boredom, perceived teacher support, and academic engagement? A convenience sampling strategy was adopted in the present study. A total of first-year high school students in 21 classes from three different high schools participated in the present study. However, the data of 87 students was deleted due to short answer time and failure in the lie detector, thus the final sample was consisting of Among them, The same curriculum regulated by the Ministry of Education of China was followed, and it is aimed to prepare students for the College Entrance Examination held at the end of the third academic year. All the participants were native Chinese speakers and did not have overseas experiences. At the time of data collection, they had eight English classes every week, and each of them lasted for 45 min. Before the data collection, students were informed of the purposes of this study and could choose to participate or not according to their own will. Meanwhile, they were assured that their responses would remain strictly confidential and only be used for research purposes. In order to eliminate the influence of order effect, survey items were administered in a random manner Sudina, These scales were translated into Chinese by the first author, then in order to assure that the translated questionnaire was comprehensible, two Ph. They were first informed of the research objective and design and then asked to score the acceptability of each item on a point scale. Detailed information on the four scales is presented as follows:. Perceived teacher support was measured through the item teacher subscale of the Child and Adolescent Social Support Scale developed by Malecki and Demary The teacher subscale divides support from the teacher into four perspectives, i. The teacher subscale is a five-point Likert scale, ranging from strongly disagree 1 to strongly agree 5 , and it has demonstrated sound psychometric properties in previous studies e. With a five-point Likert scale ranging from strongly disagree 1 to strongly agree 5 , this questionnaire contains 11 items and three dimensions, i. Responses were rated on a five-point Likert scale ranging from strongly disagree 1 to strongly agree 5. This scale was chosen for its comprehensiveness, good construct validity, and high internal consistency. The data collection began in early April and ended in late April First, we contacted five teachers in five different schools and asked them to help with the data collection. Three of them agreed to help and assisted us in getting consent from their school directors and contacting other teachers in their schools. Finally, a total of 11 teachers agreed to be volunteer helpers, and they helped us explain the objective of the present study to their students and sent them the link to the online questionnaire. Students who agreed to participate in the study scanned the quick response code and finished the questionnaire in their spare time. In order to show our thankfulness to these participants, a link to some prestored useful learning materials was presented at the end of the questionnaire. If participants need these learning materials, they can download them for free. After data were collected, they were input into SPSS 24 for processing. Data screening was conducted at first. Since the computer system required students to choose from 1 to 5 for each item, the process of analyzing and missing data was left out. During the data cleansing procedure, we mainly checked and deleted cases that failed in the lie detector i. The total number of delated cases was 87, taking up 7. After data screening, descriptive analyses and normal distribution tests were conducted. Then, correlational and regression analyses were done using SPSS It makes the mediation analysis simplified, and we can have most of the statistics for interpretation via this macro easily Igartua and Hayes, A summary of the mean, range, standard deviations, median, and mode for each variable is presented in Table 2. Based on previous research Shao et al. Based on this standard, varying from 12 to 60, the total score of perceived teacher support below 36 represented a low level, between 36 and 48 was regarded as a moderate level, while 48 and above was a high level. Further frequency analysis found that 25 2. This indicated that most of the students perceived a moderate level of teacher support in their English classes. Concerning boredom, the mean, median, and mode were 7. Additional frequency analysis on boredom found that All the three parameters fell into the range of 33— Frequency analysis signified that In terms of academic engagement, its mean, median, and mode were A further frequency analysis showed that around Concerning the second research question, Pearson correlation analyses were conducted to explore the relationships among the four variables. The results showed that the four variables under investigation significantly correlated with each other see Table 3. The interpretation of effect size for correlations followed the criteria proposed by Plonsky and Oswald Specifically, 0. Table 3. Perceived teacher support was found to be significantly correlated with enjoyment, boredom, and academic engagement. The findings indicated that students who perceived higher levels of teacher support tended to enjoy language learning, get bored less often, and engage in language learning. This showed that students who felt less bored were likely to enjoy language learning, show a positive attitude toward the learning process, and be more engaged. To answer the third research question, a multiple regression analysis was conducted. Before running the regression test, a multicollinearity test was performed at first. As shown in Table 4 , all the tolerance values were above 0. According to the criteria put forward by Tabachnick and Fidell , there was no multicollinearity problem between these variables. The results of multiple regressions are presented in Table 4. The total indirect effect size was 0. The indirect effect through boredom was 0. CI referred to the difference between the two mediating effect paths, i. It was —0. More specifically, as shown in Table 5 , the mediating effect of enjoyment accounted for This indicated that enjoyment was a stronger mediator than boredom. These results supported the proposed parallel mediation model Figure 1. Figure 1. Mediating effect of enjoyment and boredom between teacher support and engagement. The present study aimed to explore the relationship between perceived teacher support, enjoyment, boredom, and academic engagement. With respect to the first research question, descriptive analyses indicated a general tendency that most of the students perceived a moderate level of teacher support, enjoyment, and engagement and a low level of boredom. The overall level of perceived teacher support was close to that reported by junior high school students Liu et al. This indicated that younger students were likely to perceive higher levels of teacher support. The following two reasons may help to explain the higher levels of perceived teacher support reported by younger students. On the one hand, compared with university students, pre-university students tend to spend more time with their English language teachers in school, thus they are more likely to build a close relationship with their teachers and receive more support from them. On the other hand, as teenagers are still in the period of psychological weaning Lu, , teachers are likely to give them more help and assistance during the learning process. Previous studies indicated that Chinese students were likely to show a lower level of enjoyment than international students MacIntyre et al. These evidences imply that further exploration is needed before making conclusive inferences on the higher level of enjoyment in international students. This suggests that university students in the skill-oriented instructional context were more likely to feel enjoyable than high school students in the examination-oriented context Jiang and Dewaele, As pointed out by Dewaele and MacIntyre , younger learners tended to have lower levels of enjoyment than their older counterparts. Due to the fact that English is not as important a major in university as it is in high school and the requirements for high school students are lower than that for college students, high school students are likely to perceive higher value and control appraisal in English language learning. Shao et al. Thus, with a perception of higher levels of control and value, high school students tend to have lower levels of boredom when compared to university students. What needs to be noticed is that although most of the students had lower levels of boredom, there was still around one-third of the students who showed a moderate level of boredom. The mean scores of it were higher than that reported in Konold et al. This supports the findings of previous studies e. High school students in China spend 3 years preparing for the College Entrance Examination Wang and Chen, , and when entering college, most of them experience a period of over-relaxation and temporary loss of goals Zhang et al. Thus, it is reasonable for high school students to have a higher level of academic engagement in English language learning. However, more than one-fifth of the students reported that they were less engaged in their English language learning. Concerning the second research question, correlational analyses found that significant relationships existed among the four variables. Perceived teacher support was positively related to enjoyment and academic engagement and negatively related to boredom. These results indicated that students who could get sufficient and timely help from their English teachers were likely to experience more enjoyment and less boredom, and they tended to invest more time and energy in English language learning. This echoes the findings of previous studies e. As stated by Li et al. In addition, a prominent finding of the present study was that teacher support could help students relieve their English language learning boredom. Theoretically, the results also provide further support for the control-value theory concerning the correlational relationship between achievement emotions and their antecedents in the foreign language learning context Shao et al. In the future, it would be interesting to examine whether teacher support is related to and can relieve other negative emotions. Moreover, enjoyment was significantly correlated with academic engagement, indicating that when students are in control of their language learning and feel enjoyable, they are more likely to participate in classroom activities. Positive emotions can provide students with energy for language learning Zhang L. Boredom showed a negative correlation with enjoyment and academic engagement with medium effect sizes. The medium effect size between boredom and engagement in the present study may be influenced by the similarities and differences between the two achievement emotions. Specifically, boredom and enjoyment share the common activity-oriented feature and show a clear difference in value and activation, i. As boredom was also closely related to teacher support, boredom-deducing teaching strategies should be introduced to language classrooms to help students relieve the deleterious emotion Li, Similar findings also appeared in Liu et al. These findings help broaden the applicability of control-value theory to include new antecedents and be generalized to the domain of foreign language learning Shao et al. Moreover, students who are bored may hide this emotion to avoid potential criticism or negative evaluations from their teachers Kruk and Zawodniak, The finding is consistent with Liu et al. Previous studies e. The present study also has some limitations. Taking engagement as an example, future studies can adopt other measures to capture engagement in real-time and conduct data triangulation. For example, Lambert et al. Third, boredom was only measured by three items. Fourthly, as the questionnaires were distributed to 21 classes, the multi-level structure of the data was ignored. Future studies can adopt doubly latent multilevel analysis to explore these relationships both at the individual and class levels Shao and Parkinson, Finally, no covariates were controlled in the present study. The present study explored the relationship between perceived teacher support, boredom, enjoyment, and academic engagement and testified the mediating role of boredom and enjoyment in the relationship between perceived teacher support and academic engagement. The results showed that Chinese high school students perceived moderate levels of perceived teacher support, enjoyment, and academic engagement. Additionally, boredom and enjoyment played mediating roles in the relationship between perceived teacher support and academic engagement. This study has important theoretical as well as practical implications. Theoretically, the high correlation between enjoyment and engagement offers further supporting evidence for the assumption that enjoyment is an important indicator of engagement, especially its emotional dimension. Meanwhile, the positive relationship between enjoyment and engagement, and the negative relationship between boredom and engagement also provide empirical evidence for the broaden-and-build theory of achievement emotions in the foreign language learning context. Practically, the findings of the present study provide supporting evidence for the effects of teacher support in helping students generate language learning enjoyment, reduce language learning boredom and become more engaged in language learning. Teachers can take some efforts to make students feel support from them. For example, they can emotionally connect with their students, encourage them to ask questions, and treat them equally Tennant et al. This result also provides valuable implications for the design of teacher development programs. These programs should include sections to help teachers learn how to provide effective support for their students from emotional, instrumental, appraisal, and informational aspects. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. YZ: conceptualization, validation, formal analysis, methodology, investigation, and writing-original draft. LY: writing-review and editing, resources, project administration, and funding acquisition. Both authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Baker, J. The differential influence of instructional context on the academic engagement of students with behavior problems. Bear, G. Differences in school climate and student engagement in China and the United States. Bench, S. On the function of boredom. Botes, E. Taking stock: An overview of the literature and a preliminary meta-analysis of Foreign Language Enjoyment and other individual difference variables. Google Scholar. Boudreau, C. Enjoyment and anxiety in second language communication: An idiodynamic approach. Second Lang. Bronfenbrenner, U. The ecology of human development: Experiments by nature and design. Wozniak and K. Conner, J. Not just robo-students: Why full engagement matters and how schools can promote it. Youth Adolesc. Csikszentmihalyi, M. Flow: The psychology of optimal experience. De Ruiter, N. 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School context, achievement motivation, and academic engagement: A longitudinal study of school engagement using a multidimensional perspective. Wang, Q. Ruan and C. Leung Cham: Springer , 85— Wang, Y. Wentzel, K. Peer and teacher supports in relation to motivation and effort: A multi-level study. Yasemin, T. The role of motivation between perceived teacher support and student engagement in science class. Zawodniak, J. Boredom as an aversive emotion experienced by English majors. RELC J. Zhang, C. Zhang, L. Zhang, Z. Undergraduate student engagement at a Chinese university: A case study. Zhou, S. Mercer Bristol: Multilingual Matters , 75— Keywords : perceived teacher support, enjoyment, boredom, academic engagement, second language learning. The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Top bar navigation. About us About us. Sections Sections. About journal About journal. Article types Author guidelines Editor guidelines Publishing fees Submission checklist Contact editorial office. Literature review Emotion research in SLA The introduction of Positive Psychology in SLA makes researchers look beyond cognitive factors and pay close attention to positive psychological factors Shao et al. Enjoyment Enjoyment has received increasing scholarly attention along with the development of positive psychology e. Boredom Boredom is a commonly experienced deactivating emotion in academic settings Kruk, Methods Participants A convenience sampling strategy was adopted in the present study. Table 1. Table 2. Table 4. Table 5. Analysis of the parallel mediation model.

Advanced Drug Delivery Micro- and Nanosystems for Cardiovascular Diseases

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Official websites use. Share sensitive information only on official, secure websites. Correspondence: siavashira gmail. Designing novel micro- and nanosystems with suitable targeting properties and smart release behaviors can help circumvent crucial challenges of the tolerability, low stability, high toxicity, and possible side- and off-target effects of conventional drug delivery routes. To overcome different challenging issues, namely physiological barriers, low efficiency of drugs, and possible adverse side effects, various biomaterials-mediated drug delivery systems have been formulated with reduced toxicity, improved pharmacokinetics, high bioavailability, sustained release behavior, and enhanced therapeutic efficacy for targeted therapy of cardiovascular diseases. Despite the existing drug delivery systems encompassing a variety of biomaterials for treating cardiovascular diseases, the number of formulations currently approved for clinical use is limited due to the regulatory and experimental obstacles. Herein, the most recent advancements in drug delivery micro- and nanosystems designed from different biomaterials for the treatment of cardiovascular diseases are deliberated, with a focus on the important challenges and future perspectives. Keywords: cardiovascular diseases, drug delivery nanosystems, biocompatibility, targeted drug delivery, advanced delivery systems. Generally, conventional synthetic drugs and natural products e. To improve the bioavailability, solubility, and drug loading capacity, micro- and nanoscale DDSs have been designed with sustained and controlled release behavior for poorly soluble pharmaceuticals \[ 17 , 18 \]. For instance, to improve the pharmacological properties of carvedilol e. This nanosystem exhibited rapid and pH-responsive drug release behavior under acidic conditions in vitro , representing non-toxic DDS for oral drug delivery in CVDs \[ 17 \]. Additionally, novel systems were developed using poly lactide polycarboxybetaine, cardiac homing peptide, and gold Au nanoparticles NPs to improve myocardial hypertrophy and fibrosis \[ 19 \]. Overall, targeted micro- or nano-delivery of therapeutic agents represents a novel tactic in the treatment of CVDs to efficiently reduce the burden of atherosclerosis, recover the outcomes in patients with ischemic stroke, and improve the ventricular function in patients with MI and heart failure Table 1 \[ 20 \]. Micro- and nanostructures with their unique physiochemical properties and architectures can be loaded with various therapeutic agents to show improved pharmacokinetics, pharmacodynamics, solubility, efficacy, and selectivity properties suitable for smart targeted drug delivery in treating CVDs \[ 29 , 30 \]; the tolerability, stability, and safety of drugs can be enhanced while their toxicity and off-target properties are reduced by applying DDSs \[ 31 \]. Notably, innovatively designed systems inspired from natural biological systems can help address some important clinical barriers, including cytotoxicity, valve thrombus, endothelialization complexity, rapid clearance, and immune responses \[ 33 \]. For instance, heart valves cross-networked with erythrocyte membrane drug- filled NPs have been designed from poly lactic-co-glycolic acid NPs for anti-calcification, endothelialization, anticoagulation, and anti-inflammation activities. This manuscript highlighted most recent advancements in drug delivery micro- and nanosystems designed from various biomaterials for the treatment of cardiovascular diseases, focusing on important challenges and future perspectives. Various natural polysaccharide- and protein-based nano structures have been utilized in developing smart DDSs for CVDs therapy purposes. Among them, chitosan-based biomaterials with biocompatibility, biodegradability, and versatility advantages have been explored for designing DDSs in cardiac therapies \[ 34 , 35 , 36 , 37 , 38 \]. Assorted forms of chitosan-based materials have been prepared, including nano-coatings, microcapsules, three-dimensional-printed materials, and nanofibrous patches or scaffolds, etc. The short processing time to prepare these biomaterials, with alluring capabilities, on industrial scales makes them promising candidates for drug delivery in CVDs \[ 42 \]. However, there are some persistent challenges, especially pertaining to the environmentally unfriendly techniques applied for the chemical production of these materials; large amounts of alkaline wastes; or organic materials typically ensue \[ 47 \]. In order to reduce the severe side effects of milrinone and improve its circulation time, an albumin protein-based nanoformulation conjugated with angiotensin II peptide the targeting ligand was designed for heart-targeted transferring of milrinone to improve the myocardial contractility and heart function in vivo \[ 48 \]. Compared to the control non-targeted drug, milrinone lactate—the nanosystem exhibited—improved pharmacokinetics with efficient function for elevating the cardiac output factors. These nanosystems could also highly improve the fractional shortening factors and ejection fraction, thereby enhancing the cardiac function \[ 48 \]. No noticeable induction of matrix metallopeptidase 9 MMP-9 expression could be detected, offering nanosystems with high therapeutic efficacy in CVDs \[ 49 \]. Synthetic biodegradable polymeric nano materials have been broadly explored for constructing smart micro- and nanosystems for drug delivery in treating CVDs, with biodegradability and biocompatibility advantages \[ 50 \]. Hardy et al. In addition, pitavastatin could be transferred by a DDS composed of poly lactic-co-glycolic acid NPs to inhibit the destabilization and rupture of atherosclerotic plaque in mice via the regulation of the enrollment of inflammatory monocytes, thus providing enormous opportunities for the prevention of acute MI \[ 52 \]. Thus, these nanosystems could be further designed with cytocompatibility advantage for antithrombotic and anti-atherosclerosis appliances \[ 53 \]. Therapeutic angiogenesis can play important roles in atherosclerosis and cardiac ischemic disease by creating new blood vessels, offering the auto-rhythmicity and contractility of remaining cardiomyocytes, constraining cardiac remodeling, and stimulating infarction remedial. In this context, nanomaterials can be applied for the regulation of endothelial behavior to promote angiogenesis \[ 54 \]. In one study, a DDS with no noticeable toxicity was designed from poly lactic-co-glycolic acid NPs comprising adrenomedullin-2 for therapeutic angiogenesis. In addition, to solve the restricted targeting properties and rapid clearance of routinely applied drugs for atherosclerosis, core-shell nanosystems with improved targeting property and multifunctionality have been formulated using ginsenoside- and catalase-co-loaded porous poly lactic-co-glycolic acid NPs, after the additional surface functionalization with U cell membranes \[ 56 \]. These nanosystems could escape from phagocytosis of macrophages and specifically target atherosclerotic plaques; suitable antioxidant activities and H 2 O 2 -responsive drug release, as well as reactive oxygen scavenging properties and down-regulation of some factors e. Biodegradable porous silicon NPs were functionalized with atrial natriuretic peptide A for directed drug transport into the endocardial layer of the left ventricle with the purpose of cardiac therapy. The prepared system exhibited improved cellular exchanges with cardiomyocytes and non-myocytes in addition to the enhanced colloidal stability with no noticeable toxicity, showing cardio-protective potentials particularly ischemic heart disease \[ 57 \]. Additionally, the amelioration of angiogenesis and cardiac operation in infarcted heart tissue was reported via local transport of exosomes using antibody-conjugated magnetic NPs comprising Fe 3 O 4 core and silica shell NPs adorned with poly ethylene glycol. These nanosystems could successfully target CD63 antigens on the surfaces of extracellular vesicles or myosin-light-chain surface markers on damaged cardiomyocytes \[ 58 \]; exosomes are associated with cardiac myocytes, as well as stem, progenitor, endothelial, and vascular cells, paying crucial therapeutic and diagnostic roles in CVDs especially cardiac regeneration \[ 59 \]. Various types of functional hydrogels with attributes of biocompatibility, controllable swelling behavior, and biodegradability have been widely formulated using biomaterials e. Based on their functions and properties, these hydrogels have been categorized as matrix metalloproteinase MMP -responsive, immunomodulatory, conductive, proangiogenic, three-dimensional printed hydrogels, among others \[ 60 , 63 , 64 \]. The injectable and cleavable hydrogel was prepared in situ through a Schiff base reaction between oxidized sodium hyaluronic acid and hydrazided hyaluronic acid. The adhesive conductive hydrogel patch together with an injectable hydrogel could achieve improvement of the cardiac function, providing efficient hydrogel-based systems for treating MI Figure 2 \[ 62 \]. However, they may suffer from the possible immune reactions repeated sensitization , restricted degrees of functionalization, and enough flexibility in structural design. The design of an injectable hydrogel and adhesive hydrogel patch, as well as the combined internal—external treatment strategy for MI. Adapted from Ref. Copyright American Chemical Society. As an example, vascularized cardiac patches containing biomimetic microvessels encapsulated in a fibrin gel spiked with human CSCs were constructed for promoting the proliferation of cardiomyocytes and neovascularization after acute MI, providing vast opportunities for treating ischemic heart injuries \[ 67 \]. In one study, Hua et al. The designed nanosystem exhibited significant stability with unique physicochemical properties suitable for cardiac regeneration appliances. After in vitro evaluations, it was established that the cell survival rate was improved and the expression of pro-inflammatory factors was increased. The analysis of pro-angiogenic factors illustrated promising outcomes regarding the fibrosis area, vessel density with reduced size of infractions, and ejection fraction, providing superb opportunities for healing cardiac function after MIs \[ 68 \]. Notably, cell-degradable and mechanical features of these hydrogels could be enhanced to adjust the secretory phenotype of mesenchymal stromal cells, especially for accelerating the secretion of cytokines and stimulating growth factors for additional vascularization \[ 69 \]. Various target-specific liposomes have been developed for the delivery of small molecule drugs in CVDs, especially after reperfused MI. For instance, specific peptides with high affinity to the cells existed in the post-infarct myocardium e. Furthermore, microRNA with responsibility to the pathophysiological effects of acute MI by affecting downstream vital regulators was encapsulated into liposome functionalized with the cardiac troponin T antibody for specific transfer to the ischemic myocardium, thus resolving the inadequate cellular uptake and poor stability challenges \[ 72 \]. The nanosystem exhibited improved targeting features to hypoxia primary cardiomyocytes in vitro and enhanced accumulations in the ischemic heart of rats with acute MI after injecting in the tail vein because of specific targeting to the overexpressed troponin, consequently improving the cardiac function and decreasing the infarct size, together with the viability maintenance in cardiomyocytes \[ 72 \]. Santos et al. After assessment of these nanosystems in MI induced by isoproterenol in mice, it was revealed that the cytotoxic and inflammatory effects of them were size dependent Figure 3 \[ 75 \]. Liposome-based systems for targeted delivery of biopharmaceuticals in heart diseases, with related inflammation on heart tissue. Copyright Elsevier. For instance, dendrimer NPs loaded with simvastatin acid were designed with adsorption ability to the surface of red blood cells, providing reactive oxygen stress ROS and shear stress dual-sensitive bionic systems for treating atherosclerosis. Consequently, the prepared systems with sustained release behavior exhibited better therapeutic effects toward atherosclerosis and high in vivo safety \[ 78 \]. Dendrimer- N -acetylcysteine conjugate nanosystems were developed for targeting activated microglial cells subsequent to cardiac arrest to provide improvements in survival rate, neurological recovery, and short-term motor shortfalls. These nanosystems offer as promising strategies for the treatment of post-cardiac arrest syndrome \[ 79 \]. Niosomes have shown some salient advantages, compared to liposomes, including the suitable physicochemical stability, cost-effectiveness, simple formulation processes, and up-scalable potentials. They have been utilized for constructing a variety of formulations in treating CVDs. In one study, to solve the broad pre-systemic disposition and low rate of dissolution, chitosan-encapsulated niosomes were formulated to improve the oral delivery of atorvastatin, providing enhanced anti-hyperlipidemic effects \[ 80 \]. Additionally, to improve the poor oral bioavailability of rosuvastatin, the niosome-based systems were developed via the film hydration technique and sonication utilizing Span 40 and cholesterol. Simvastatin-loaded nano-niosomes were designed to improve water solubility, half-life, and bioavailability of this drug against myocardial ischemia and reperfusion injury. These nanosystems could efficiently improve cardiac function and inhibit the necroptosis trail \[ 35 \]. For instance, daidzein-loaded solid lipid NPs with sustained release behavior, improved the pharmacokinetics, and significant increase in circulation time can be employed for treating cardio-cerebrovascular diseases \[ 83 \]. In addition, solid lipid nanosystems were designed for the delivery of phytostanols for the management of hypercholesterolemia, signifying the potentials of these NPs in treating CVDs \[ 84 \]. However, limited studies have been focused on this field of science, and more elaborative works ought to be planned for constructing novel solid lipid NPs for CVDs therapy. Chaves et al. These nanosystems exhibited controlled drug release behavior with mucoadhesive features and enhanced retention time, offering suitable sublingual dosage forms in treating CVDs \[ 86 \]. Further, shear-sensitive nanocapsules have been developed for the site-specific drug release with inhibitory effects against occlusive thrombus generation. Consequently, thrombus generation was selectively inhibited in vitro under stenotic and excessive shear flow circumstances. Future explorations need to focus on in vivo and clinical applicability of these nanosystems \[ 87 \]. In addition, these platforms can be employed for evaluating the progression of CVDs e. Notably, the cardiotoxicity induced by drugs is one of the important concerns in drug development pipelines \[ 91 , 92 \]. Microfluidic heart-on-chip devices can recapitulate the functionality levels of cardiac tissue and the communication between cells and extracellular matrices, thus providing suitable platforms for measurement of cellular dynamics along with the computational modeling for clinical purposes \[ 91 , 93 \]. The electrophysiology and mechanobiology of the evaluations can be used for better mimicking the in vivo conditions using these platforms with unique electrical and mechanical properties \[ 93 , 94 \]. In one study, a cardiac chip was designed for recording cardiac tissue adhesion, electrophysiology, and contractility \[ 95 \]. This platform applied the transplantation of cardiomyocytes derived from human-induced pluripotent stem cells to evaluate the electrophysiology and contractility of myocardial cells under physiological conditions and drug stimulation, respectively. In addition, it was deployed for testing the effects of norepinephrine clinically deployed for the treatment of hypotension and heart failure. The electrical stimulation using micro-fabricated electrodes could highly improve the structure and arrangement of cardiac cells \[ 95 \]. However, several challenges regarding the vascularization of tissues, controlling the cell density, reproducibility, cell viability assessments, cell—cell interactions monitoring, suitable organ scaling, sterility maintenance, incorporation of cultured organoids, and sensing modules, among others. Generally, several materials have been explored for manufacturing different organ-on-chip platforms, such as poly dimethylsiloxane and poly methyl methacrylate \[ 98 , 99 \]. Some other materials, such as poly acrylic acid , have been deployed for promoting the adhesion between the two parts; polycarbonate, poly ethylene terephthalate , and polystyrene were also utilized for improving the connection between the poly methyl methacrylate substrates \[ \]. Overall, poly dimethylsiloxane exhibited some advantages, such as low cost, easy-to-manufacture, optical transparency, biocompatibility, non-toxicity, permeability to gases, chemical inertness, thermal stability, ultraviolet resistance, and no treatment required for long-term storage. However, it may suffer from some limitations, including non-specific absorption of molecules or incompatibility with specific reagents. Notably, an ultrathin layer of polycaprolactone was electrospun on the poly methyl methacrylate substrate. The endothelial cells were seeded to recreate the blood vessel in one side of the membrane and also a collagen gel layer integrated with macrophages was located on the other side, thus offering a promising model for observing leucocyte infiltration and interaction with perivascular macrophages \[ \]. In addition, Annabi et al. There are some patents describing the therapeutic cardiac patches, such as the ultraviolet-crosslinkable gelatin methacrylate-based cardiac patch with high surface area and electrical conductivity, which was filled with gold nanorods US A1. Moreover, solid lipid NPs with clinical potentials could be applied for treating coronary heart disease CNB. To overcome several challenges, such as physiological barriers, off-target effects, low efficiency of drugs, and possible adverse side effects, various biomaterials-mediated DDSs have been formulated with reduced toxicity, improved pharmacokinetics, high bioavailability, sustained release behavior, and increased therapeutic efficacy for targeted therapy of CVDs. Despite the pervasiveness of numerous micro- and nano-DDSs comprising various biomaterials introduced for treating CVDs, the number of formulations currently approved for clinical use is rather limited due to the regulatory and experimental obstacles. Indeterminate toxicity study on mechanisms of toxicity and the lack of systematical analysis of these materials restrict their further applications. Comprehensive toxicological evaluations and cost benefits of designed DDSs are essential for their future clinical applicability. In this context, smart stimuli-responsive biomaterials-mediated DDSs should be further designed that can respond to the modified environmental signals with alterations in their morphologies and physicochemical characteristics, thus offering targeted therapy opportunities. One of the most important challenges is to simultaneously improve the multifunctionality, biocompatibility, and targeting properties of micro- and nano-DDSs, which need to be explored in future. For clinical applications of nanomedicine in treating CVDs, there are still limited studies performed. All authors have read and agreed to the published version of the manuscript. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Find articles by Siavash Iravani. Find articles by Rajender S Varma. Open in a new tab. Liposomes containing vascular endothelial growth factor VEGF To treat MI and improve cardiac function High enhancement in fractional shortening and improvement in systolic function; excellent improvements in cardiac function and vascular structure \[ 21 \] Polylactic co-glycolic acid NPs containing VEGF To repair the heart after MI Enhancement in the angiogenic and therapeutic potency of VEGF for treating ischemic heart disease. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Liposomes containing vascular endothelial growth factor VEGF. To treat MI and improve cardiac function. High enhancement in fractional shortening and improvement in systolic function; excellent improvements in cardiac function and vascular structure. To repair the heart after MI. Enhancement in the angiogenic and therapeutic potency of VEGF for treating ischemic heart disease. Polymeric NPs. For the targeted delivery of nitric oxide NO ; treatment of portal hypertension. Non-toxicity; these NPs could alleviate the hemodynamic disorders in bile duct-ligated-induced portal hypertension, evidenced by reducing portal pressure and unchanging mean arterial pressure. For the delivery of lacidipine; the management of hypertension. Nano-vesicular lipid carriers. For the delivery of angiotensin II receptor blocker valsartan. Improved anti-hypertensive effects; no skin toxicity. Dendrimeric NPs. For selective delivery of liver-x-receptor ligands to atherosclerotic plaque-associated macrophages while limiting hepatic uptake; modulation of atherosclerosis. High reduction in atherosclerotic plaque progression, plaque necrosis, and plaque inflammation; macrophage-specific delivery platforms for targeted transferring anti-atherosclerotic agents to the plaque-associated macrophages to reduce plaque burden.

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