BioprintingPub Date : 2025-10-01Epub Date: 2025-06-27DOI: 10.1016/j.bprint.2025.e00423
Laura Chastagnier , Lucie Essayan , Celine Thomann , Julia Niemann , Elisabeth Errazuriz-Cerda , Manon Laithier , Anne Baudouin , Christophe Marquette , Emma Petiot
{"title":"3D bioprinting of bioproduction cell lines","authors":"Laura Chastagnier , Lucie Essayan , Celine Thomann , Julia Niemann , Elisabeth Errazuriz-Cerda , Manon Laithier , Anne Baudouin , Christophe Marquette , Emma Petiot","doi":"10.1016/j.bprint.2025.e00423","DOIUrl":"10.1016/j.bprint.2025.e00423","url":null,"abstract":"<div><div>Three-dimensional (3D) bioprinting presents a transformative approach to replicating vivo-like environments for mammalian cell cultures, offering potential advances in bioproduction and tissue engineering. In this study, we investigated the growth, metabolic activity, and structural organization of four mammalian cell lines (HEK, MDCK, CHO, and Vero) in 3D bioprinted constructs. Our results demonstrate that even highly selected, immortalized cell lines can regain physiological traits closer to their native tissue when cultured in 3D environments. We observed significant shifts in proliferation kinetics, including reduced growth rates and reduced fermentative activity. A Design of Experiment (DOE) approach identified critical biofabrication parameters—such as hydrogel microporosity and cross-linking conditions—that modulate cell behavior and proliferation in 3D matrices. These findings highlight the potential of 3D bioprinting not only for medical applications, such as regenerative medicine and drug testing, but also for enhancing bioproduction processes by supporting higher cell densities and metabolic efficiency. Our work underscores the importance of optimizing 3D culture conditions to mimic vivo-like behaviors and improve productivity, offering new insights into the scalability of bioprinted constructs for industrial applications.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"50 ","pages":"Article e00423"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioprintingPub Date : 2025-10-01Epub Date: 2025-07-30DOI: 10.1016/j.bprint.2025.e00429
Kentaro Umemori, Dianne Little
{"title":"Impact of Polymer Degradation on Cellular Behavior in Tissue Engineering.","authors":"Kentaro Umemori, Dianne Little","doi":"10.1016/j.bprint.2025.e00429","DOIUrl":"10.1016/j.bprint.2025.e00429","url":null,"abstract":"<p><p>Tissue engineering frequently employs biomimetic scaffolds to direct cell responses and facilitate the differentiation of cells into specific lineages. Biodegradable scaffolds mitigate immune responses, stress shielding concerns in load bearing tissues, and the need for secondary or revision surgical procedures for retrieval. However, during the degradation process, scaffold properties such as fiber diameter, fiber porosity, fiber alignment, surface properties and mechanical properties undergo changes that significantly alter the initial properties. This review aims to comprehensively assess the impact of degradation on scaffold properties from the perspective of their effects on cellular behavior by addressing four key aspects of polymer degradation: First, we review the variables that influence scaffold degradation. Second, we examine how degradation impacts scaffold properties. Third, we explore the effects of scaffold degradation products. Finally, we investigate measures to increase tunability of degradation rate. Harnessing and incorporating these degradation mechanisms into scaffold design holds great promise for advancing the development of tissue-engineered scaffolds, ultimately improving their efficacy and clinical utility.</p>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"50 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioprintingPub Date : 2025-10-01Epub Date: 2025-07-02DOI: 10.1016/j.bprint.2025.e00424
Hui Ling Ma, Raiane de Oliveira Ferreira, Danyllo Felipe de Oliveira, Alice Kei Endo, Oswaldo Keith Okamoto, Mayana Zatz
{"title":"3D bioprinted neural progenitor cell constructs for enhancing ex vivo brain integration and neuron-astrocyte differentiation","authors":"Hui Ling Ma, Raiane de Oliveira Ferreira, Danyllo Felipe de Oliveira, Alice Kei Endo, Oswaldo Keith Okamoto, Mayana Zatz","doi":"10.1016/j.bprint.2025.e00424","DOIUrl":"10.1016/j.bprint.2025.e00424","url":null,"abstract":"<div><div>Neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (hiPSCs) hold great promise for neural tissue engineering, disease modeling, and regenerative therapies due to their self-renewal and differentiation potential. In this study, we utilized 3D extrusion bioprinting to encapsulate hiPSC-NPCs within a composite bioink composed of Gelatin methacryloyl (GelMA) and Pluronic F127 (P-127). This composite was engineered to enhance matrix remodeling, mechanical tunability, and cell-specific differentiation. Incorporating P-127 improved gelation, printability, swelling behavior, degradation kinetics, and microstructural features, collectively supporting enhanced NPC proliferation. Mechanical characterization revealed adjustable stiffness (Young's modulus: 1–8 kPa), with GelMA/P-127 blends exhibiting greater strength than GelMA alone. Immunostaining showed elevated GFAP and reduced Neurofilament M (NeuF-M) expression, indicating a shift toward astrocytic differentiation influenced by matrix mechanics. Calcium imaging and transient signal analysis confirmed the functional activity of the differentiated neurons. Gene expression profiling supported these findings, showing upregulation of GFAP, TUBB3, and MAP2 and downregulation of SOX2, marking the transition from progenitor to mature neural phenotypes. Furthermore, bioprinted constructs integrated with ex vivo brain slices and expressed TUBB3 and NeuF-M, confirming neuronal differentiation capacity. These results underscore the potential of GelMA/P-127 composite bioinks as biomimetic, tunable platforms for engineering 3D neural tissue constructs, offering a versatile tool for studying neurodevelopment and advancing translational regenerative strategies.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"50 ","pages":"Article e00424"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144570996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioprintingPub Date : 2025-09-01Epub Date: 2025-04-14DOI: 10.1016/j.bprint.2025.e00413
Joyce R. de Souza , Maedeh Rahimnejad , Igor P. Mendes Soares , Caroline Anselmi , Pedro H.C. de Oliveira , Alexandre H. dos Reis-Prado , Victoria Maglaras , Renan Dal-Fabbro , Eliandra S. Trichês , Marco C. Bottino
{"title":"3D Printing β-TCP-laden GelMA/Alginate interpenetrating-polymer-network biomaterial inks for bone tissue engineering","authors":"Joyce R. de Souza , Maedeh Rahimnejad , Igor P. Mendes Soares , Caroline Anselmi , Pedro H.C. de Oliveira , Alexandre H. dos Reis-Prado , Victoria Maglaras , Renan Dal-Fabbro , Eliandra S. Trichês , Marco C. Bottino","doi":"10.1016/j.bprint.2025.e00413","DOIUrl":"10.1016/j.bprint.2025.e00413","url":null,"abstract":"<div><div>Bone's capacity for self-repair is limited when large defects arise from trauma or infection. Traditional grafting methods like autografts and allografts often face challenges like immune rejection and limited availability. Traditional scaffold manufacturing techniques for bone tissue engineering frequently lack precise control over the constructs' material composition and pore architecture. Recently, 3D printing technology, particularly with interpenetrating polymer networks (IPNs), has successfully addressed these limitations, improving biocompatibility, strength, and degradation. Our study investigated gelatin methacryloyl (GelMA)/Alginate IPNs laden with beta tri-calcium phosphate (β-TCP) particles in a 3D-printed format to optimize cell proliferation and tissue regeneration conditions. Rheology studies showed shear-thinning viscosity and fast recovery (∼90 %) to primary viscosity after stress removal, confirming the inks' suitability for extrusion-based printing. Both inks demonstrated high resolution and acceptable printability (0.9–1). Incorporating β-TCP increased the compressive modulus (0.09 ± 0.01 MPa for the control group vs. 0.15 ± 0.01 MPa for 15 % (w/v) β-TCP, ∗∗∗p < 0.001) and swelling ratio, decreasing biodegradation over 35 days. Cell assays showed enhanced cell proliferation over 7 days, with no significant differences between groups. Compared to basal and osteogenic media controls, higher mineralization and osteogenic gene expression were observed in 15 % β-TCP-laden 3D-printed constructs on days 14 and 21. Histological analysis <em>in vivo</em> showed no signs of inflammation after three weeks, suggesting favorable tissue compatibility. Furthermore, calcium carbonate deposits were identified, evidencing the successful differentiation of mesenchymal stem cells into cells capable of producing a mineralized matrix. This study demonstrated that the (GelMA)/Alginate IPN containing β-TCP could be a successful biomaterial ink with promising bioactive properties for bone tissue engineering.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"49 ","pages":"Article e00413"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioprintingPub Date : 2025-09-01Epub Date: 2025-05-31DOI: 10.1016/j.bprint.2025.e00420
Musa Yilmaz , Derya Kapusuz Yavuz
{"title":"Bioactivity, mineralization, and mechanical properties of 3D-printed nano TiO2-reinforced polymer composite immersed in SBF","authors":"Musa Yilmaz , Derya Kapusuz Yavuz","doi":"10.1016/j.bprint.2025.e00420","DOIUrl":"10.1016/j.bprint.2025.e00420","url":null,"abstract":"<div><div>In this work, 3D-printed polylactic acid (PLA) composites reinforced with 2 wt% nanosized titanium dioxide (TiO<sub>2</sub>) were fabricated via fused filament fabrication (FFF) to enhance surface bioactivity and overall material performance. The incorporation of TiO<sub>2</sub> markedly improved the apatite-forming ability of the composite surfaces, as evidenced by increased calcium and phosphorus deposition up to 0.032 and 0.046 %, respectively. Surface roughness measurements revealed that TiO<sub>2</sub> addition led to smoother and more uniform 3D-printed surfaces. Mechanical testing showed ∼24 % reduction in tensile strength and ∼17 % reduction in bending force compared to unreinforced PLA-polymer, predominantly attributed to nanoparticle-induced microvoid formation; despite that, the mechanical properties remained within acceptable ranges for biomedical applications. These findings suggest that the enhanced mineralization behavior, improved surface characteristics, and satisfactory mechanical integrity of TiO<sub>2</sub>–PLA composites render them promising candidates for load-bearing biomedical applications, such as bone fixation devices and regenerative bone scaffolds.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"49 ","pages":"Article e00420"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioprintingPub Date : 2025-09-01Epub Date: 2025-05-20DOI: 10.1016/j.bprint.2025.e00419
Narges Johari , Zary Adabavazeh , Francesco Baino
{"title":"PVA-based bioinks for 3D bioprinting: A comprehensive review of their applications in tissue engineering","authors":"Narges Johari , Zary Adabavazeh , Francesco Baino","doi":"10.1016/j.bprint.2025.e00419","DOIUrl":"10.1016/j.bprint.2025.e00419","url":null,"abstract":"<div><div>3D bioprinting is an innovative approach that overcomes the limitations of traditional methods for creating cell-laden biomaterials and constructs. It allows for the fabrication of complex and biologically active tissue structures. This review aims to provide a comprehensive evaluation of polyvinyl alcohol (PVA)-based bioinks within a 3D bioprinting framework. PVA-based bioinks exhibit remarkable properties, such as biocompatibility, biodegradability, and the ability to enhance cell growth and differentiation. These properties make them appropriate for many tissue engineering applications. The study evaluates the physicochemical and biological properties of PVA bioinks, including how they combine with other materials such as gelatin, chitin, chitosan, alginate, agarose, cellulose, κ-carrageenan, methacrylate, nanoparticles, mineral additives, carbon nanotubes, graphene oxide, and extracellular matrix components. Furthermore, this review evaluates the benefits of market availability and enhanced printing resolution, in addition to the challenges posed by complexity, dependency on support baths, and the risk of contamination. The objective of this review is to draw attention to the capabilities of PVA-based bioinks and provide guidelines for future research to improve the effectiveness of these materials in tissue engineering and regenerative medicine.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"49 ","pages":"Article e00419"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioprintingPub Date : 2025-09-01Epub Date: 2025-05-01DOI: 10.1016/j.bprint.2025.e00418
Sally AbdulHussain Kadhum, Nassier A. Nassir
{"title":"Mechanical, in vitro and in vivo characterization of 3D-printed photo crosslinking acrylic/nano ZnO biocomposites for bone tissue engineering","authors":"Sally AbdulHussain Kadhum, Nassier A. Nassir","doi":"10.1016/j.bprint.2025.e00418","DOIUrl":"10.1016/j.bprint.2025.e00418","url":null,"abstract":"<div><div>Bone is a highly vascularized tissue and self-repairing organ. However, the bone tissue may not be able to heal itself, especially when the injury size is higher than the critical size of the bone defect. Bone tissue engineering (BTE) is a well-recognized and successful approach to enhancing the remodeling process of diseased bone tissue. In this study, initial attention is focused on investigating the mechanical response of nanocomposites-based scaffolds. Photo crosslinking acrylic (PCA) resin and different weight percentages of nanoparticles of zinc oxide (nZnO) were used to make the nanocomposites using stereolithography (SLA) as a 3D printing technology. Here, the influence of nZnO on the mechanical response of the specimens was investigated under tension, compression and bending conditions. The results of these tests suggest that samples containing 1 wt% of nZnO exhibit the highest strength values under the various loading conditions used. Porous scaffolds, with a honeycomb pore shape, were then manufactured using 1 wt% of nZnO. In vitro bioactivity, in vivo biocompatibility, FTIR analysis, scanning electron microscope (SEM) morphological, X-ray radiological, and histopathological analysis were performed. Finally, it is suggested that the high osteogenesis of the 3D-printed porous scaffolds investigated makes it a promising and effective candidate for bone infection treatment.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"49 ","pages":"Article e00418"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioprintingPub Date : 2025-09-01Epub Date: 2025-04-25DOI: 10.1016/j.bprint.2025.e00417
Satyam Rajput , Kaivalya A. Deo , Tanmay Mathur , Giriraj Lokhande , Kanwar Abhay Singh , Yuxiang Sun , Daniel L. Alge , Abhishek Jain , Tapasree Roy Sarkar , Akhilesh K. Gaharwar
{"title":"Corrigendum to “2D Nanosilicate for additive manufacturing: Rheological modifier, sacrificial ink and support bath Bioprinting” [Bioprinting 25 (2022) e00187]","authors":"Satyam Rajput , Kaivalya A. Deo , Tanmay Mathur , Giriraj Lokhande , Kanwar Abhay Singh , Yuxiang Sun , Daniel L. Alge , Abhishek Jain , Tapasree Roy Sarkar , Akhilesh K. Gaharwar","doi":"10.1016/j.bprint.2025.e00417","DOIUrl":"10.1016/j.bprint.2025.e00417","url":null,"abstract":"","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"49 ","pages":"Article e00417"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BioprintingPub Date : 2025-09-01Epub Date: 2025-04-19DOI: 10.1016/j.bprint.2025.e00416
A. Minin , T. Semerikova , A.V. Belousova , O. Karavashkova , V. Pozdina , M. Tomilina , I. Zubarev
{"title":"MSLASpheroidStamp: 3d cell spheroids for everyone","authors":"A. Minin , T. Semerikova , A.V. Belousova , O. Karavashkova , V. Pozdina , M. Tomilina , I. Zubarev","doi":"10.1016/j.bprint.2025.e00416","DOIUrl":"10.1016/j.bprint.2025.e00416","url":null,"abstract":"<div><div>3D cell cultures, such as cell spheroids, are actively used in biology for modeling biological processes, studying intercellular interactions, and screening pharmacological compounds and are becoming indispensable objects in cell culture laboratories. There are many methods for producing spheroids, which vary in cost and convenience. One of the most convenient and affordable methods is the use of agarose microwells. We developed approaches to fabricate agarose microwells in standard culture plastic with the assistance of a hobby-grade MSLA 3D printer. The use of 3D printing allows the customization of microwells in a wide range of shapes and sizes and scales the production process from a few spheroids to tens of thousands. We have shown that it is possible to create gel microwells in a dish with a glass bottom, which allows us to easily realize time-lapse confocal microscopy of spheroids as well as in situ optical clearing in the same dishes to study the spheroid structure. We demonstrated the ability to study the cytotoxicity of various substances and nanoparticles in commonly used 96-well plates.</div><div>Finally, in this article, we describe the difficulties and limitations of our approach and suggest ways to solve them, allowing the reader not only to reproduce it, but also to adapt it to the specific needs of a certain laboratory, using the provided 3D models and instructions.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"49 ","pages":"Article e00416"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stimuli-responsive smart materials: Bridging the gap between biotechnology and regenerative medicine","authors":"Karthik K. Karunakar , Binoy Varghese Cheriyan , Ragavendran Anandakumar , Akshaya Murugathirumal , Abinaya Senthilkumar , J. Nandhini , Kunal Kataria , Lincy Yabase","doi":"10.1016/j.bprint.2025.e00415","DOIUrl":"10.1016/j.bprint.2025.e00415","url":null,"abstract":"<div><div>Stimuli-responsive smart materials have emerged as transformative tools at the interface of biotechnology and regenerative medicine. These materials, capable of responding dynamically to diverse physical, chemical, and biological stimuli, present innovative solutions to longstanding challenges in tissue engineering, drug delivery, and wound healing. This review covers the main principles of stimuli-responsive materials, their classifications, and underlying mechanisms of response. The emphasis lies on the central role that smart materials play in the advancement of biomedical applications. The versatility and functional adaptability of key categories of smart materials, such as polymers, hydrogels, and nanostructures, are reviewed for their utility in therapeutic applications. With an eye on smart scaffolds, controlled drug delivery systems, and new wound healing techniques, we also go over their uses in tissue engineering. Emerging technologies such as 3D/4D bioprinting, microfluidic fabrication, and the incorporation of biosensors, artificial intelligence (AI), and the Internet of Things (IoT) into the design and development of smart materials are also covered. The review will clearly establish that stimuli-responsive smart materials have boundless potential for transformative usefulness in regenerative medicine and health futures by highlighting key concerns, particularly those related to scalability and the regulatory landscape.</div></div>","PeriodicalId":37770,"journal":{"name":"Bioprinting","volume":"48 ","pages":"Article e00415"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}