Bioactive MaterialsPub Date : 2024-09-05DOI: 10.1016/j.bioactmat.2024.08.037
{"title":"3D bioprinted breast cancer model reveals stroma-mediated modulation of extracellular matrix and radiosensitivity","authors":"","doi":"10.1016/j.bioactmat.2024.08.037","DOIUrl":"10.1016/j.bioactmat.2024.08.037","url":null,"abstract":"<div><p>Deciphering breast cancer treatment resistance remains hindered by the lack of models that can successfully capture the four-dimensional dynamics of the tumor microenvironment. Here, we show that microextrusion bioprinting can reproducibly generate distinct cancer and stromal compartments integrating cells relevant to human pathology. Our findings unveil the functional maturation of this millimeter-sized model, showcasing the development of a hypoxic cancer core and an increased surface proliferation. Maturation was also driven by the presence of cancer-associated fibroblasts (CAF) that induced elevated microvascular-like structures complexity. Such modulation was concomitant to extracellular matrix remodeling, with high levels of collagen and matricellular proteins deposition by CAF, simultaneously increasing tumor stiffness and recapitulating breast cancer fibrotic development. Importantly, our bioprinted model faithfully reproduced response to treatment, further modulated by CAF. Notably, CAF played a protective role for cancer cells against radiotherapy, facilitating increased paracrine communications. This model holds promise as a platform to decipher interactions within the microenvironment and evaluate stroma-targeted drugs in a context relevant to human pathology.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X2400375X/pdfft?md5=0837622d391b6d86ed51e30b3f071294&pid=1-s2.0-S2452199X2400375X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2024-09-05DOI: 10.1016/j.bioactmat.2024.08.040
{"title":"Harnessing the power of bioprinting for the development of next-generation models of thrombosis","authors":"","doi":"10.1016/j.bioactmat.2024.08.040","DOIUrl":"10.1016/j.bioactmat.2024.08.040","url":null,"abstract":"<div><p>Thrombosis, a leading cause of cardiovascular morbidity and mortality, involves the formation of blood clots within blood vessels. Current animal models and <em>in vitro</em> systems have limitations in recapitulating the complex human vasculature and hemodynamic conditions, limiting the research in understanding the mechanisms of thrombosis. Bioprinting has emerged as a promising approach to construct biomimetic vascular models that closely mimic the structural and mechanical properties of native blood vessels. This review discusses the key considerations for designing bioprinted vascular conduits for thrombosis studies, including the incorporation of key structural, biochemical and mechanical features, the selection of appropriate biomaterials and cell sources, and the challenges and future directions in the field. The advancements in bioprinting techniques, such as multi-material bioprinting and microfluidic integration, have enabled the development of physiologically relevant models of thrombosis. The future of bioprinted models of thrombosis lies in the integration of patient-specific data, real-time monitoring technologies, and advanced microfluidic platforms, paving the way for personalized medicine and targeted interventions. As the field of bioprinting continues to evolve, these advanced vascular models are expected to play an increasingly important role in unraveling the complexities of thrombosis and improving patient outcomes. The continued advancements in bioprinting technologies and the collaboration between researchers from various disciplines hold great promise for revolutionizing the field of thrombosis research.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003785/pdfft?md5=f55b7c8b105c42ea839a161e37fdb32a&pid=1-s2.0-S2452199X24003785-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2024-09-04DOI: 10.1016/j.bioactmat.2024.08.033
{"title":"Peptide nanozymes: An emerging direction for functional enzyme mimics","authors":"","doi":"10.1016/j.bioactmat.2024.08.033","DOIUrl":"10.1016/j.bioactmat.2024.08.033","url":null,"abstract":"<div><p>The abundance of molecules on early Earth likely enabled a wide range of prebiotic chemistry, with peptides playing a key role in the development of early life forms and the evolution of metabolic pathways. Among peptides, those with enzyme-like activities occupy a unique position between peptides and enzymes, combining both structural flexibility and catalytic functionality. However, their full potential remains largely untapped. Further exploration of these enzyme-like peptides at the nanoscale could provide valuable insights into modern nanotechnology, biomedicine, and even the origins of life. Hence, this review introduces the groundbreaking concept of “peptide nanozymes (PepNzymes)”, which includes single peptides exhibiting enzyme-like activities, peptide-based nanostructures with enzyme-like activities, and peptide-based nanozymes, thus enabling the investigation of biological phenomena at nanoscale dimensions. Through the rational design of enzyme-like peptides or their assembly with nanostructures and nanozymes, researchers have found or created PepNzymes capable of catalyzing a wide range of reactions. By scrutinizing the interactions between the structures and enzyme-like activities of PepNzymes, we have gained valuable insights into the underlying mechanisms governing enzyme-like activities. Generally, PepNzymes play a crucial role in biological processes by facilitating small-scale enzyme-like reactions, speeding up molecular oxidation-reduction, cleavage, and synthesis reactions, leveraging the functional properties of peptides, and creating a stable microenvironment, among other functions. These discoveries make PepNzymes useful for diagnostics, cellular imaging, antimicrobial therapy, tissue engineering, anti-tumor treatments, and more while pointing out opportunities. Overall, this research provides a significant journey of PepNzymes’ potential in various biomedical applications, pushing them towards new advancements.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003712/pdfft?md5=ef76c780f9507e22103c9092f1216943&pid=1-s2.0-S2452199X24003712-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2024-09-04DOI: 10.1016/j.bioactmat.2024.08.036
{"title":"3-D bioprinted human-derived skin organoids accelerate full-thickness skin defects repair","authors":"","doi":"10.1016/j.bioactmat.2024.08.036","DOIUrl":"10.1016/j.bioactmat.2024.08.036","url":null,"abstract":"<div><p>The healing of large skin defects remains a significant challenge in clinical settings. The lack of epidermal sources, such as autologous skin grafting, limits full-thickness skin defect repair and leads to excessive scar formation. Skin organoids have the potential to generate a complete skin layer, supporting in-situ skin regeneration in the defect area. In this study, skin organoid spheres, created with human keratinocytes, fibroblasts, and endothelial cells, showed a specific structure with a stromal core surrounded by surface keratinocytes. We selected an appropriate bioink and innovatively combined an extrusion-based bioprinting technique with dual-photo source cross-linking technology to ensure the overall mechanical properties of the 3D bioprinted skin organoid. Moreover, the 3D bioprinted skin organoid was customized to match the size and shape of the wound site, facilitating convenient implantation. When applied to full-thickness skin defects in immunodeficient mice, the 3D bioprinted human-derived skin organoid significantly accelerated wound healing through in-situ regeneration, epithelialization, vascularization, and inhibition of excessive inflammation. The combination of skin organoid and 3D bioprinting technology can overcome the limitations of current skin substitutes, offering a novel treatment strategy to address large-area skin defects.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003748/pdfft?md5=73f50c5e3f0a77ce6726d02e5f28b4ee&pid=1-s2.0-S2452199X24003748-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2024-09-04DOI: 10.1016/j.bioactmat.2024.08.045
{"title":"Low-molecular-weight estrogenic phytoprotein suppresses osteoporosis development through positive modulation of skeletal estrogen receptors","authors":"","doi":"10.1016/j.bioactmat.2024.08.045","DOIUrl":"10.1016/j.bioactmat.2024.08.045","url":null,"abstract":"<div><p>Age-related osteoporosis is a metabolic skeletal disorder caused by estrogen deficiency in postmenopausal women. Prolonged use of anti-osteoporotic drugs such as bisphosphonates and FDA-approved anti-resorptive selective estrogen receptor modulators (SERMs) has been associated with various clinical drawbacks. We recently discovered a low-molecular-weight biocompatible and osteoanabolic phytoprotein, called HKUOT-S2 protein (32 kDa), from <em>Dioscorea opposita</em> Thunb that can accelerate bone defect healing. Here, we demonstrated that the HKUOT-S2 protein treatment can enhance osteoblasts-induced ossification and suppress osteoporosis development by upregulating skeletal estrogen receptors (ERs) ERα, ERβ, and GPR30 expressions <em>in vivo</em>. Also, HKUOT-S2 protein estrogenic activities promoted hMSCs-osteoblasts differentiation and functions by increasing osteogenic markers, ALP, and RUNX2 expressions, ALP activity, and osteoblast biomineralization <em>in vitro</em>. Fulvestrant treatment impaired the HKUOT-S2 protein-induced ERs expressions, osteoblasts differentiation, and functions. Finally, we demonstrated that the HKUOT-S2 protein could bind to ERs to exert osteogenic and osteoanabolic properties. Our results showed that the biocompatible HKUOT-S2 protein can exert estrogenic and osteoanabolic properties by positively modulating skeletal estrogen receptor signaling to promote ossification and suppress osteoporosis. Currently, there is no or limited data if any, on osteoanabolic SERMs. The HKUOT-S2 protein can be applied as a new osteoanabolic SERM for osteoporosis treatment.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003827/pdfft?md5=ec5126ce9c8d5a3e6d8e00a489474d04&pid=1-s2.0-S2452199X24003827-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2024-09-04DOI: 10.1016/j.bioactmat.2024.08.002
{"title":"High throughput and rapid isolation of extracellular vesicles and exosomes with purity using size exclusion liquid chromatography","authors":"","doi":"10.1016/j.bioactmat.2024.08.002","DOIUrl":"10.1016/j.bioactmat.2024.08.002","url":null,"abstract":"<div><p>Extracellular vesicles (EVs) have emerged as potential biomarkers for diagnosing a range of diseases without invasive procedures. Extracellular vesicles also offer advantages compared to synthetic vesicles for delivery of various drugs; however, limitations in segregating EVs from other particles and soluble proteins have led to inconsistent EV retrieval rates with low levels of purity. Here, we report a new high-yield (88.47 %) and rapid (<20 min) EV isolation method termed size exclusion – fast protein liquid chromatography (SE-FPLC). We show SE-FPLC can effectively isolate EVs from multiple sources including EVs derived from human and mouse cells and serum samples. The results indicate that SE-FPLC can successfully remove highly abundant protein contaminants such as albumin and lipoprotein complexes, which can represent a major hurdle in large scale isolation of EVs. The high-yield nature of SE-FPLC allows for easy industrial scaling up of EV production for various clinical utilities. SE-FPLC also enables analysis of small volumes of blood for use in point-of-care diagnostics in the clinic. Collectively, SE-FPLC offers many advantages over current EV isolation methods and offers rapid clinical translation.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003219/pdfft?md5=f0c2e6b68f9caae3a20e48d22bc9a2a1&pid=1-s2.0-S2452199X24003219-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2024-09-04DOI: 10.1016/j.bioactmat.2024.08.035
{"title":"ECM-mimicking composite hydrogel for accelerated vascularized bone regeneration","authors":"","doi":"10.1016/j.bioactmat.2024.08.035","DOIUrl":"10.1016/j.bioactmat.2024.08.035","url":null,"abstract":"<div><p>Bioactive hydrogel materials have great potential for applications in bone tissue engineering. However, fabrication of functional hydrogels that mimic the natural bone extracellular matrix (ECM) remains a challenge, because they need to provide mechanical support and embody physiological cues for angiogenesis and osteogenesis. Inspired by the features of ECM, we constructed a dual-component composite hydrogel comprising interpenetrating polymer networks of gelatin methacryloyl (GelMA) and deoxyribonucleic acid (DNA). Within the composite hydrogel, the GelMA network serves as the backbone for mechanical and biological stability, whereas the DNA network realizes dynamic capabilities (e.g., stress relaxation), thereby promoting cell proliferation and osteogenic differentiation. Furthermore, functional aptamers (Apt19S and AptV) are readily attached to the DNA network to recruit bone marrow mesenchymal stem cells (BMSCs) and achieve sustained release of loaded vascular endothelial growth factor towards angiogenesis. Our results showed that the composite hydrogel could facilitate the adhesion of BMSCs, promote osteogenic differentiation by activating focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/β-Catenin signaling pathway, and eventually enhance vascularized bone regeneration. This study shows that the multifunctional composite hydrogel of GelMA and DNA can successfully simulate the biological functions of natural bone ECM and has great potential for repairing bone defects.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003736/pdfft?md5=03df51dc27e5c4d30415b98c3d959b66&pid=1-s2.0-S2452199X24003736-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2024-09-04DOI: 10.1016/j.bioactmat.2024.08.038
{"title":"Monascus pigment-protected bone marrow-derived stem cells for heart failure treatment","authors":"","doi":"10.1016/j.bioactmat.2024.08.038","DOIUrl":"10.1016/j.bioactmat.2024.08.038","url":null,"abstract":"<div><p>Mesenchymal stem cells (MSCs) have demonstrated significant therapeutic potential in heart failure (HF) treatment. However, their clinical application is impeded by low retention rate and low cellular activity of MSCs caused by high inflammatory and reactive oxygen species (ROS) microenvironment. In this study, monascus pigment (MP) nanoparticle (PPM) was proposed for improving adverse microenvironment and assisting in transplantation of bone marrow-derived MSCs (BMSCs). Meanwhile, in order to load PPM and reduce the mechanical damage of BMSCs, injectable hydrogels based on Schiff base cross-linking were prepared. The PPM displays ROS-scavenging and macrophage phenotype-regulating capabilities, significantly enhancing BMSCs survival and activity in HF microenvironment. This hydrogel demonstrates superior biocompatibility, injectability, and tissue adhesion. With the synergistic effects of injectable, adhesive hydrogel and the microenvironment-modulating properties of MP, cardiac function was effectively improved in the pericardial sac of rats. Our results offer insights into advancing BMSCs-based HF therapies and their clinical applications.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003773/pdfft?md5=f5daa6d183562f5d711df703a9887d4a&pid=1-s2.0-S2452199X24003773-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2024-09-03DOI: 10.1016/j.bioactmat.2024.07.019
{"title":"Multi-modal investigation of the bone micro- and ultrastructure, and elemental distribution in the presence of Mg-xGd screws at mid-term healing stages","authors":"","doi":"10.1016/j.bioactmat.2024.07.019","DOIUrl":"10.1016/j.bioactmat.2024.07.019","url":null,"abstract":"<div><p>Magnesium (Mg) – based alloys are becoming attractive materials for medical applications as temporary bone implants for support of fracture healing, e.g. as a suture anchor. Due to their mechanical properties and biocompatibility, they may replace titanium or stainless-steel implants, commonly used in orthopedic field. Nevertheless, patient safety has to be assured by finding a long-term balance between metal degradation, osseointegration, bone ultrastructure adaptation and element distribution in organs. In order to determine the implant behavior and its influence on bone and tissues, we investigated two Mg alloys with gadolinium contents of 5 and 10 wt percent in comparison to permanent materials titanium and polyether ether ketone. The implants were present in rat tibia for 10, 20 and 32 weeks before sacrifice of the animal. Synchrotron radiation-based micro computed tomography enables the distinction of features like residual metal, degradation layer and bone structure. Additionally, X-ray diffraction and X-ray fluorescence yield information on parameters describing the bone ultrastructure and elemental composition at the bone-to-implant interface. Finally, with element specific mass spectrometry, the elements and their accumulation in the main organs and tissues are traced. The results show that Mg-xGd implants degrade <em>in vivo</em> under the formation of a stable degradation layer with bone remodeling similar to that of Ti after 10 weeks. No accumulation of Mg and Gd was observed in selected organs, except for the interfacial bone after 8 months of healing. Thus, we confirm that Mg-5Gd and Mg-10Gd are suitable material choices for bone implants.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24002901/pdfft?md5=0cd08e0eaeaefb409cbcb445d843b2a7&pid=1-s2.0-S2452199X24002901-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive MaterialsPub Date : 2024-09-03DOI: 10.1016/j.bioactmat.2024.08.032
{"title":"Amphiphilic cytokine traps remodel marrow adipose tissue for hematopoietic microenvironment amelioration","authors":"","doi":"10.1016/j.bioactmat.2024.08.032","DOIUrl":"10.1016/j.bioactmat.2024.08.032","url":null,"abstract":"<div><p>Hematopoietic stem cell transplantation (HSCT) is extensively employed in the treatment of hematological malignancies but is markedly constrained by the paucity of hematopoietic stem/progenitor cells (HSPCs). Recent studies have found that marrow adipose tissue (MAT) acts on hematopoiesis through complicated mechanisms. Therefore, the osteo-organoids fabricated <em>in vivo</em> using biomaterials loaded with recombinant human bone morphogenetic protein 2 (rhBMP-2) have been used as models of MAT for our research. To obtain sufficient amounts of therapeutic HSPCs and healthy MAT, we have developed amphiphilic chitosan (AC)-gelatin as carriers of rhBMP-2 to the regulate type conversion of adipose tissue and trap hematopoietic growth factors. Unlike medicine interventions or cell therapies, the traps based on AC not only attenuate the occupancy of adipocytes within the hematopoietic microenvironment while preserving stem cell factor concentrations, but also improve marrow metabolism by promoting MAT browning. In conclusion, this approach increases the proportion of HSPCs in osteo-organoids, and optimizes the composition and metabolic status of MAT. These findings furnish an experimental basis for regulating hematopoiesis <em>in vivo</em> through materials that promote the development of autologous HSPCs. Additionally, this approach presents a theoretical model of rapid adipogenesis for the study of adipose-related pathologies and potential pharmacological targets.</p></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":null,"pages":null},"PeriodicalIF":18.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452199X24003700/pdfft?md5=41cbe6e7aa53038f40de74c5830f0314&pid=1-s2.0-S2452199X24003700-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142128908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}