Bio-Design and Manufacturing最新文献

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Bone marrow mesenchymal stem cell-loaded HAMA hydrogel within highly bionic nerve guidance conduits for peripheral nerve regeneration 骨髓间充质干细胞负载的HAMA水凝胶用于周围神经再生的高度仿生神经引导导管
1区 医学
Bio-Design and Manufacturing Pub Date : 2025-11-01 DOI: 10.1631/bdm.2500026
Chao Li, Lifang Zhu, Ming‐Wei Chang, Hao Li, Shiheng Liu, Baolin Wang
{"title":"Bone marrow mesenchymal stem cell-loaded HAMA hydrogel within highly bionic nerve guidance conduits for peripheral nerve regeneration","authors":"Chao Li, Lifang Zhu, Ming‐Wei Chang, Hao Li, Shiheng Liu, Baolin Wang","doi":"10.1631/bdm.2500026","DOIUrl":"https://doi.org/10.1631/bdm.2500026","url":null,"abstract":"Abstract Nerve guidance conduits (NGCs) effectively support and guide the regeneration of injured nerves. However, traditional NGCs often lack essential growth factors and fail to create a biomimetic microenvironment conducive to nerve regrowth. This study develops a highly bionic nerve guidance conduit (HB-NGC) using hybrid high-voltage electrotechnologies that integrate electrospinning with electrohydrodynamic (EHD) printing. The outer layer consists of electrospun polycaprolactone fibers loaded with carboxyl-multi-walled carbon nanotubes, while the inner layer is composed of highly aligned polycaprolactone fibers created by EHD printing. The tubular core of the HB-NGC is filled with hyaluronic acid methacryloyl (HAMA) hydrogel encapsulating bone marrow mesenchymal stem cells (BMSCs). This highly biomimetic NGC is conductive, capable of guiding axon growth, and sustainably releases growth factors, effectively mimicking the structure, function, and characteristics of natural peripheral nerves. Its distinctive architectural layers provide an exceptional bionic microenvironment by restoring physical pathways, facilitating electrical signal conduction, and supplying an extracellular matrix (ECM) environment enriched with essential growth factors. Additionally, the HB-NGC’s morphology, along with its physicochemical and mechanical properties, effectively bridges the gap between severed nerve ends. In vivo animal studies validate the HB-NGC’s effectiveness, highlighting its significant potential to enhance peripheral nerve regeneration.","PeriodicalId":48627,"journal":{"name":"Bio-Design and Manufacturing","volume":"8 6","pages":"976-993"},"PeriodicalIF":0.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1631/bdm.2500026.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147909103","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}
引用次数: 0
Targeting cyclooxygenase-2 using photothermal-anti-inflammatory nanoparticles to inhibit tumor growth and metastasis 利用光热抗炎纳米颗粒靶向环氧化酶-2抑制肿瘤生长和转移
1区 医学
Bio-Design and Manufacturing Pub Date : 2025-09-01 DOI: 10.1631/bdm.2400470
Jiahui Cai, Zutong Cui, Wenming Liang, Jianming Sun, Zihan Zhang, Shasha Zhao, Zhiwei Liu, Xiaoling Li, Jian Li
{"title":"Targeting cyclooxygenase-2 using photothermal-anti-inflammatory nanoparticles to inhibit tumor growth and metastasis","authors":"Jiahui Cai, Zutong Cui, Wenming Liang, Jianming Sun, Zihan Zhang, Shasha Zhao, Zhiwei Liu, Xiaoling Li, Jian Li","doi":"10.1631/bdm.2400470","DOIUrl":"https://doi.org/10.1631/bdm.2400470","url":null,"abstract":"","PeriodicalId":48627,"journal":{"name":"Bio-Design and Manufacturing","volume":"8 5","pages":"759-775"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147919249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Silk fibroin bandage for preventing tendon adhesions 防止肌腱粘连的丝素绷带
1区 医学
Bio-Design and Manufacturing Pub Date : 2025-09-01 DOI: 10.1631/bdm.2400495
Pengcheng Xia, Guofeng Liu, Tianhong Qiao, Ke Yao, Chaofan He, Yong He, Jianchao Gui, Yuan Sun
{"title":"Silk fibroin bandage for preventing tendon adhesions","authors":"Pengcheng Xia, Guofeng Liu, Tianhong Qiao, Ke Yao, Chaofan He, Yong He, Jianchao Gui, Yuan Sun","doi":"10.1631/bdm.2400495","DOIUrl":"https://doi.org/10.1631/bdm.2400495","url":null,"abstract":"","PeriodicalId":48627,"journal":{"name":"Bio-Design and Manufacturing","volume":"8 5","pages":"800-818"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147916945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Machine learning-assisted stiffness prediction in high-cell-density bioprinting. 高细胞密度生物打印中机器学习辅助刚度预测。
IF 7.9 1区 医学
Bio-Design and Manufacturing Pub Date : 2025-07-01 Epub Date: 2025-04-24 DOI: 10.1631/bdm.2400454
Jiaao Guan, Yazhi Sun, Emmie J Yao, Yi Xiang, Mary K Melarkey, Grace Y Lu, Amelia H Burns, Nancy Zhang, Shaochen Chen
{"title":"Machine learning-assisted stiffness prediction in high-cell-density bioprinting.","authors":"Jiaao Guan, Yazhi Sun, Emmie J Yao, Yi Xiang, Mary K Melarkey, Grace Y Lu, Amelia H Burns, Nancy Zhang, Shaochen Chen","doi":"10.1631/bdm.2400454","DOIUrl":"10.1631/bdm.2400454","url":null,"abstract":"<p><p>Bioprinting of cell-laden hydrogels is a rapidly growing field in tissue engineering. The advent of digital light processing (DLP) three-dimensional (3D) bioprinting technique has revolutionized the fabrication of complex 3D structures. By adjusting light exposure, it becomes possible to control the mechanical properties of the structure, a critical factor in modulating cell activities. To better mimic cell densities in real tissues, recent progress has been made in achieving high-cell-density (HCD) printing with high resolution. However, regulating the stiffness in HCD constructs remains challenging. The large volume of cells greatly affects the light-based DLP bioprinting by causing light absorption, reflection, and scattering. Here, we introduce a neural network-based machine learning technique to predict the stiffness of cell-laden hydrogel scaffolds. Using comprehensive mechanical testing data from 3D bioprinted samples, the model was trained to deliver accurate predictions. To address the demand of working with precious and costly cell types, we employed various methods to ensure the generalizability of the model, even with limited datasets. We demonstrated a transfer learning method to achieve good performance for a precious cell type with a reduced amount of data. The chosen method outperformed many other machine learning techniques, offering a reliable and efficient solution for stiffness prediction in cell-laden scaffolds. This breakthrough paves the way for the next generation of precision bioprinting and more customized tissue engineering.</p>","PeriodicalId":48627,"journal":{"name":"Bio-Design and Manufacturing","volume":"8 4","pages":"543-557"},"PeriodicalIF":7.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12948305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327852","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}
引用次数: 0
Homologous cancer cell membrane-camouflaged natural pH-sensitive chalk for enhanced drug targeting delivery in hepatocellular carcinoma 同源癌细胞膜伪装的天然ph敏感粉笔增强肝细胞癌药物靶向递送
1区 医学
Bio-Design and Manufacturing Pub Date : 2025-07-01 DOI: 10.1631/bdm.2400341
Yang-Bo Zhu, Peng‐Fei Cui, Lijuan Zhao, Qi Ling, Jiayi Qin
{"title":"Homologous cancer cell membrane-camouflaged natural pH-sensitive chalk for enhanced drug targeting delivery in hepatocellular carcinoma","authors":"Yang-Bo Zhu, Peng‐Fei Cui, Lijuan Zhao, Qi Ling, Jiayi Qin","doi":"10.1631/bdm.2400341","DOIUrl":"https://doi.org/10.1631/bdm.2400341","url":null,"abstract":"The therapeutic efficacy of hepatocellular carcinoma (HCC) medication is severely compromised by inadequate drug delivery to tumor sites. Herein, we fabricated a biomimetic nanoplatform for improved drug targeting ability by wrapping H22 tumor cell membranes around natural chalk to encapsulate the model drug doxorubicin (C-DOX@H22 CM). When camouflaged with H22 tumor cell membranes, C-DOX@H22 CM achieved primary targeting to the tumor tissues due to the immune escape ability and secondary deep targeting to HCC cells owing to the homologous targeting properties. The cellular uptake of C-DOX@H22 CM by H22 cells was via clathrin-mediated endocytosis. Meanwhile, C-DOX@H22 CM exhibited the property of deep penetration into dense tumor tissues. Moreover, the pH-responsive characteristics of the natural chalk enabled C-DOX@H22 CM to achieve endosomal escape and drug release, thereby expanding its antitumor effects without compromising biocompatibility. Importantly, the in vivo experiments also confirmed that C-DOX@H22 CM had favorable antitumor efficacy and biosafety in the H22 tumor-bearing mouse model. Overall, the novel C-DOX@H22 CM nanoplatform provides a safe and effective treatment option for HCC and has the potential to achieve clinical translation for the targeted delivery of other drugs for the treatment of various tumors.","PeriodicalId":48627,"journal":{"name":"Bio-Design and Manufacturing","volume":"8 4","pages":"609-624"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1631/bdm.2400341.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147890587","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}
引用次数: 0
Magnetic nanoparticles for single-neuron manipulation to design a customized neural circuit 磁性纳米颗粒单神经元操纵设计定制的神经回路
1区 医学
Bio-Design and Manufacturing Pub Date : 2025-05-22 DOI: 10.1631/bdm.2400372
Hongyong Zhang, Lingrui Zhao, Nan Huang, Xiaobo Zhang, Xu Tian, Sumin Bian, Mohamad Sawan
{"title":"Magnetic nanoparticles for single-neuron manipulation to design a customized neural circuit","authors":"Hongyong Zhang, Lingrui Zhao, Nan Huang, Xiaobo Zhang, Xu Tian, Sumin Bian, Mohamad Sawan","doi":"10.1631/bdm.2400372","DOIUrl":"https://doi.org/10.1631/bdm.2400372","url":null,"abstract":"Abstract The complexity and intricacy of the brain, which is composed of billions of neurons, pose significant challenges to its study. Understanding neural connections and communication at the single-cell level is crucial for unraveling the brain’s functions. This study presents a novel strategy that utilizes magnetic nanoparticles (MNPs) and magnetic fields to manipulate neurons, thereby creating customized small-scale neural circuits for studying neural connections. To establish the feasibility of this approach, the effects of MNPs on neurons were initially investigated, demonstrating their low toxicity. Subsequently, a micromagnet array (MMA) chip was employed to manipulate the neurons, facilitating their precise arrangement on the electrodes. Over several days, the neurons extended their axons and established connections with neighboring cells, forming small-scale circular neural circuits. These artificially engineered circuits offer a simplified and controlled environment for studying neural networks in contrast to naturally occurring biological networks. Furthermore, electrophysiological recordings were conducted to investigate the connections between the manipulated neurons. This study introduces a customized small-scale neural circuit platform with electrode-specific recording and stimulating capabilities, enabling the study of neuron-to-neuron interactions at the single-cell level. By leveraging MNPs and an MMA chip, this research offers a powerful tool for studying neural connections and advancing our understanding of the brain’s intricate workings.","PeriodicalId":48627,"journal":{"name":"Bio-Design and Manufacturing","volume":"8 4","pages":"511-523"},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147879391","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}
引用次数: 2
A redox-responsive nanovaccine for cytosolic delivery of antigen and adjuvant to enhance cancer immunotherapy 一种氧化还原反应性纳米疫苗,用于细胞内递送抗原和佐剂,以增强癌症免疫治疗
1区 医学
Bio-Design and Manufacturing Pub Date : 2025-05-22 DOI: 10.1631/bdm.2400339
Taisheng Liu, Biao He, Jiaqing Tao, Shaoying He, Nanqing Fu, Kewei Wang, Hui Fan
{"title":"A redox-responsive nanovaccine for cytosolic delivery of antigen and adjuvant to enhance cancer immunotherapy","authors":"Taisheng Liu, Biao He, Jiaqing Tao, Shaoying He, Nanqing Fu, Kewei Wang, Hui Fan","doi":"10.1631/bdm.2400339","DOIUrl":"https://doi.org/10.1631/bdm.2400339","url":null,"abstract":"Cancer vaccines have garnered significant attention in cancer immunotherapy because they trigger tumor-specific immune responses. However, their effectiveness is hindered by inefficient antigen and adjuvant delivery at the subcellular level, which is essential to stimulate a robust CD8+ T cell response. This study presents PAR/OVA, a cancer nanovaccine developed by combining imiquimod (R837)-modified polyamidoamine dendrimers with the model protein antigen ovalbumin (OVA). Within the nanovaccine, R837 is an adjuvant for the Toll-like receptor 7 (TLR7) pathway and a structural component that facilitates OVA loading. In dendritic cells (DCs), the high cytoplasmic glutathione levels triggered the breakdown of PAR/OVA, releasing OVA and R837, which induced DC activation and antigen cross-presentation. Furthermore, PAR/OVA vaccination showed a protective effect and effectively inhibited B16-OVA tumor progression, indicating its potential in cancer immunotherapy. Combining this vaccine with an immune checkpoint blockade enhanced antitumor efficacy by improving the ability of cytotoxic T lymphocytes to target cancer cells within the tumor microenvironment. These findings underscore the potential of this adjuvant/antigen-delivering nanovaccine in cancer immunotherapy.","PeriodicalId":48627,"journal":{"name":"Bio-Design and Manufacturing","volume":"8 4","pages":"625-638"},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147880307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Force-controlled 3D mechanical stretching to enhance the exosome secretion of bone mesenchymal stem cells for bone repair 力控三维机械拉伸增强骨间充质干细胞外泌体分泌用于骨修复
1区 医学
Bio-Design and Manufacturing Pub Date : 2025-05-01 DOI: 10.1631/bdm.2400231
Jie Wu, Hao Wang, Tao Sun, Qing Shi, Chen Xie, Yuanbo Qi, Sheng Tao, Jiahua Zhao, Daohong Liu
{"title":"Force-controlled 3D mechanical stretching to enhance the exosome secretion of bone mesenchymal stem cells for bone repair","authors":"Jie Wu, Hao Wang, Tao Sun, Qing Shi, Chen Xie, Yuanbo Qi, Sheng Tao, Jiahua Zhao, Daohong Liu","doi":"10.1631/bdm.2400231","DOIUrl":"https://doi.org/10.1631/bdm.2400231","url":null,"abstract":"Exosomes derived from bone mesenchymal stem cells (BMSCs) show promising potential for treating bone defects. However, their clinical application is hindered by low yield and insufficient repair ability. Three-dimensional (3D) mechanical stimulation has been a well-known method for enhancing exosome secretion; however, the traditional stimulation process is always achieved by controlling the displacement of manipulators, which may induce uneven loading distribution and degradation of stimulation strength. Here, we propose a micro-stretching manipulator that automatically controls the stretching force applied to gelatin methacryloyl (GelMA)/hyaluronic acid methacryloyl (HAMA) hybrid hydrogel sheets containing BMSCs within an incubator. To ensure the structural stability of the sheets after long-term stretching, the mixing ratio between GelMA and HAMA was optimized according to the mechanical property response of the sheets to cyclical loading. Subsequently, force-controlled mechanical loading was applied to the BMSC-laden sheets to produce exosomes. Compared with displacement control, force-controlled loading provides a more stable force stimulation, thereby enhancing exosome secretion. Furthermore, continuously stimulated exosomes exhibited a stronger capacity for promoting osteogenic differentiation of BMSCs and facilitating the repair of bone defects in a rat model. These findings suggest that force-controlled loading of cell-laden hydrogels offers a novel approach for the production of BMSC-derived exosomes and their application in bone repair.","PeriodicalId":48627,"journal":{"name":"Bio-Design and Manufacturing","volume":"8 3","pages":"442-460"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1631/bdm.2400231.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147896902","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}
引用次数: 5
Composite poly(lactic-co-glycolic acid) and a decellularized extracellular matrix conduit with Schwann cells for enhanced nerve regeneration 复合聚乳酸-羟基乙酸和雪旺细胞脱细胞细胞外基质导管增强神经再生
1区 医学
Bio-Design and Manufacturing Pub Date : 2025-05-01 DOI: 10.1631/bdm.2400334
Zhifa Xue, Yuye Huang, D. Bi, Kai Ye, Hangyu Zhou, Lizhe He, Peng Wei, Yangjian Wang
{"title":"Composite poly(lactic-co-glycolic acid) and a decellularized extracellular matrix conduit with Schwann cells for enhanced nerve regeneration","authors":"Zhifa Xue, Yuye Huang, D. Bi, Kai Ye, Hangyu Zhou, Lizhe He, Peng Wei, Yangjian Wang","doi":"10.1631/bdm.2400334","DOIUrl":"https://doi.org/10.1631/bdm.2400334","url":null,"abstract":"Peripheral nerve injuries (PNIs) affect approximately one million people globally every year. While autologous nerve transplantation remains the gold standard for healing PNIs with large gaps, limitations such as donor site morbidity and limited nerve availability present challenges in clinical application, highlighting the need for innovative solutions based on synthetic biomaterials. In this study, we explored a composite nerve conduit that combines a poly(lactic-co-glycolic acid) (PLGA) shell and a decellularized extracellular matrix (dECM) seeded with Schwann cells (SCs). In particular, the dECM, derived from rat sciatic nerves, retains the native tissue structure and bioactive components. In vitro studies showed that SC-seeded dECM promotes cell viability, proliferation, and alignment. In vivo testing using a rat sciatic nerve defect model demonstrated that the PLGA/dECM-SC conduit significantly improved nerve regeneration compared with conduits without SCs, showing enhanced axonal growth, myelination, and motor function restoration comparable to autografts. This approach offers a promising alternative to autologous nerve grafts in the clinical treatment of PNIs.","PeriodicalId":48627,"journal":{"name":"Bio-Design and Manufacturing","volume":"8 3","pages":"359-374"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1631/bdm.2400334.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147908897","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}
引用次数: 2
Bioprinted integrated gradient biomechanical signal-tailored osteosarcoma model: advancing insights into tumor development and drug screening 生物打印集成梯度生物力学信号定制骨肉瘤模型:推进肿瘤发展和药物筛选的见解
1区 医学
Bio-Design and Manufacturing Pub Date : 2025-05-01 DOI: 10.1631/bdm.2400108
Xuelian Mi, Ren Ya, Hanbo Wang, Lei Qiang, Weiqing Kong, Hui Wang, Xue Yang, Yihao Liu, Han Yang, Di Xiao, Zhenjiang Ma, Guoxing Xu, Changru Zhang, Jinwu Wang
{"title":"Bioprinted integrated gradient biomechanical signal-tailored osteosarcoma model: advancing insights into tumor development and drug screening","authors":"Xuelian Mi, Ren Ya, Hanbo Wang, Lei Qiang, Weiqing Kong, Hui Wang, Xue Yang, Yihao Liu, Han Yang, Di Xiao, Zhenjiang Ma, Guoxing Xu, Changru Zhang, Jinwu Wang","doi":"10.1631/bdm.2400108","DOIUrl":"https://doi.org/10.1631/bdm.2400108","url":null,"abstract":"In the current settings of osteosarcoma research and drug screening, in vitro three-dimensional (3D) models, which overcome the limitations of traditional models, are favored. In in vitro 3D models, tumor microenvironment simulation, particularly of the mechanical microenvironment, is crucial for estimating the biological effects of a tumor. However, current in vitro osteosarcoma model construction is often limited to a single mechanical signal, which fails to simulate the diversity of osteosarcoma mechanical stimuli. In this study, we utilized embedded bioprinting technology and the multiple response properties of calcium ions in soft and hard stiffness systems with osteosarcoma cell biological functions to construct an integrated gradient biomechanical signal-tailored osteosarcoma model (IGBSTOM). We achieved this by printing a fibrinogen bioink containing calcium ions and osteosarcoma tumor spheroids within an extracellular matrix composed of methacryloylated alginate, methacryloylated gelatin, thrombin, and transglutaminase, which is rich in polysaccharides and proteins and exhibits self-healing properties. Our in vitro and in vivo studies showed that the IGBSTOM enhanced tumor stemness, proliferation, and migration, and successfully reproduced the nest-like structure of tumors, providing an in vitro research platform that is more similar to the natural tumor than the existing models. This study proposes a novel IGBSTOM construction and provides a new strategy for the clinical understanding of tumor development, drug screening, and exploration of drug resistance and metastasis mechanisms.","PeriodicalId":48627,"journal":{"name":"Bio-Design and Manufacturing","volume":"8 3","pages":"423-441"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1631/bdm.2400108.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147911399","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}
引用次数: 1
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