Bioactive MaterialsPub Date : 2024-12-07DOI: 10.1016/j.bioactmat.2024.12.007
Xiang Gao , Jirong Yang , Lingna Liu , Zilong Hu , Rui Lin , Lan Tang , Mei Yu , Zhiping Chen , Chongjian Gao , Min Zhang , Li Li , Changshun Ruan , Yanzhi Liu
{"title":"An electrostatic encapsulation strategy to motivate 3D-printed polyelectrolyte scaffolds for repair of osteoporotic bone defects","authors":"Xiang Gao , Jirong Yang , Lingna Liu , Zilong Hu , Rui Lin , Lan Tang , Mei Yu , Zhiping Chen , Chongjian Gao , Min Zhang , Li Li , Changshun Ruan , Yanzhi Liu","doi":"10.1016/j.bioactmat.2024.12.007","DOIUrl":"10.1016/j.bioactmat.2024.12.007","url":null,"abstract":"<div><div>Repair of osteoporotic bone defects (OBD) remains a clinical challenge due to dysregulated bone homeostasis, characterized by impaired osteogenesis and excessive osteoclast activity. While drug-loaded 3D-printed scaffolds hold great potential in the restoration of bone homeostasis for enhanced OBD repair, achieving the controlled release and targeted delivery of drugs in a 3D-printed scaffold is still unmet. Herein, we developed an electrostatic encapsulation strategy to motivate 3D-printed polyelectrolyte scaffolds (APS@P) with bone-targeting liposome formulation of salvianolic acid B (SAB-BTL). Benefiting from this strategy, SAB, an unstable and untargetable plant-derived osteogenic compound, was effectively encapsulated in APS@P, demonstrating stable and precise delivery with improved therapeutic efficacy. Owing to SAB-mediated bone homeostasis, APS@P significantly promoted angiogenesis and new bone formation while suppressing bone resorption, resulting in a significant 146 % increase in bone mass and improved microstructure compared to the OBD group. It was confirmed that the encapsulation of SAB into APS@P could promote the osteogenic differentiation of MSCs by stimulating Tph2/Wnt/β-catenin signaling axis, coupled with the stimulation of type H angiogenesis and the suppression of RANKL-mediate bone resorption, thereby enhance OBD repair. This study provides a universal platform for enhancing the bioactivity of tissue-engineered scaffolds, offering an effective solution for the efficient regeneration of osteoporotic bone.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 1-20"},"PeriodicalIF":18.0,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884842","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 : 2024-12-06DOI: 10.1016/j.bioactmat.2024.11.033
Gianluca Fontana , Brett Nemke , Yan Lu , Connie Chamberlain , Jae-Sung Lee , Joshua A. Choe , Hongli Jiao , Michael Nelson , Margot Amitrano , Wan-Ju Li , Mark Markel , William L. Murphy
{"title":"Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defects","authors":"Gianluca Fontana , Brett Nemke , Yan Lu , Connie Chamberlain , Jae-Sung Lee , Joshua A. Choe , Hongli Jiao , Michael Nelson , Margot Amitrano , Wan-Ju Li , Mark Markel , William L. Murphy","doi":"10.1016/j.bioactmat.2024.11.033","DOIUrl":"10.1016/j.bioactmat.2024.11.033","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a condition that affects the quality of life of millions of patients worldwide. Current clinical treatments, in most cases, lead to cartilage repair with deposition of fibrocartilage tissue, which is mechanically inferior and not as durable as hyaline cartilage tissue. We designed an mRNA delivery strategy to enhance the natural healing potential of autologous bone marrow aspirate concentrate (BMAC) for articular cartilage repair. We used mineral-coated microparticles to deliver TGF-β1 mRNA to autologous BMAC. mRNA-activated BMAC was suspended in peripheral blood to generate therapeutic BMAC clots, which were then implanted in rabbit osteochondral defects. Tracking studies revealed that the clots were reliably maintained in the defects for at least 2 weeks. TGF-β1 mRNA delivery significantly increased TGF-β1 production in BMAC clots and increased early expression of articular chondrocyte markers within osteochondral defects. At 9 weeks post-surgery, the mRNA-treated defects had a superior macroscopic cartilage appearance, decreased type I collagen deposition, increased stain intensity for type II collagen and increased glycosaminoglycan deposition area when compared to the controls. Despite the transient expression of therapeutic mRNA we have detected lasting effects, such as a decrease in fibrocartilage formation demonstrated by the decrease in type I collagen deposition and the improvement in macroscopic appearance in the treatment group.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 509-519"},"PeriodicalIF":18.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881060","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 : 2024-12-05DOI: 10.1016/j.bioactmat.2024.11.023
Haoyu Wang , Sheng'e Su , Xin An , Yuan Xu , Jiacheng Sun , Mingming Zhen , Chunru Wang , Chunli Bai
{"title":"A charge reversal nano-assembly prevents hepatic steatosis by resolving inflammation and improving lipid metabolism","authors":"Haoyu Wang , Sheng'e Su , Xin An , Yuan Xu , Jiacheng Sun , Mingming Zhen , Chunru Wang , Chunli Bai","doi":"10.1016/j.bioactmat.2024.11.023","DOIUrl":"10.1016/j.bioactmat.2024.11.023","url":null,"abstract":"<div><div>Lipid metabolism imbalance combined with over-activated inflammation are two key factors for hepatic stestosis. However, on-demand anchoring inflammation and lipid metabolism disorder for hepatic stestosis treatment has yet to be realized. Here we propose a charge reversal fullerene based nano-assembly to migrate hepatic steatosis via inhibiting macrophage-mediated inflammation and normalizing hepatocellular lipid metabolism in obesity mice. Our nano-assembly (abbreviated as FPPD) is comprised of electropositive polyetherimide (PEI), charge-shielded dimethylmaleic anhydride (DMA), and poly(lactic-co-glycolic acid) (PLGA), which provides hydrophobic chains for self-assembly with anti-oxidative dicarboxy fullerene poly(ethylene glycol) molecule (FP). The obtained FPPD nano-assembly owns a charge reversal ability that switches to a positive charge in an acidic environment that targets the electronegative mitochondria both in pro-inflammatory macrophages and steatosis hepatocytes. We demonstrate that the anti-oxidative and mitochondria-targeting FPPD notably reduces inflammation in macrophages and lipid accumulation in hepatocytes by quenching excessive reactive oxygen species (ROS) and improving mitochondrial function <em>in vitro</em>. Importantly, FPPD nano-assembly reveals a superior anti-hepatic steatosis effect via migrating inflammation and facilitating lipid transport in obesity mice. Overall, the charge reversal nano-assembly reduces over-activated inflammation and promotes lipid metabolism that provides an effectiveness of a multi-target strategy for hepatic steatosis treatment.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 496-508"},"PeriodicalIF":18.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881048","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 : 2024-12-05DOI: 10.1016/j.bioactmat.2024.11.015
Kai Chen , Fang Wang , Xiumei Sun , Wenwei Ge , Mingjun Zhang , Lin Wang , Haoyu Zheng , Shikang Zheng , Haoyu Tang , Zhengjie Zhou , Guomin Wu
{"title":"3D-printed zinc oxide nanoparticles modified barium titanate/hydroxyapatite ultrasound-responsive piezoelectric ceramic composite scaffold for treating infected bone defects","authors":"Kai Chen , Fang Wang , Xiumei Sun , Wenwei Ge , Mingjun Zhang , Lin Wang , Haoyu Zheng , Shikang Zheng , Haoyu Tang , Zhengjie Zhou , Guomin Wu","doi":"10.1016/j.bioactmat.2024.11.015","DOIUrl":"10.1016/j.bioactmat.2024.11.015","url":null,"abstract":"<div><div>Clinically, infectious bone defects represent a significant threat, leading to osteonecrosis, severely compromising patient prognosis, and prolonging hospital stays. Thus, there is an urgent need to develop a bone graft substitute that combines broad-spectrum antibacterial efficacy and bone-inductive properties, providing an effective treatment option for infectious bone defects. In this study, the precision of digital light processing (DLP) 3D printing technology was utilized to construct a scaffold, incorporating zinc oxide nanoparticles (ZnO-NPs) modified barium titanate (BT) with hydroxyapatite (HA), resulting in a piezoelectric ceramic scaffold designed for the repair of infected bone defects. The results indicated that the addition of ZnO-NPs significantly improved the piezoelectric properties of BT, facilitating a higher HA content within the ceramic scaffold system, which is essential for bone regeneration. In vitro antibacterial assessments highlighted the scaffold's potent antibacterial capabilities. Moreover, combining the synergistic effects of low-intensity pulsed ultrasound (LIPUS) and piezoelectricity, results demonstrated that the scaffold promoted notable osteogenic and angiogenic potential, enhancing bone growth and repair. Furthermore, transcriptomics analysis results suggested that the early growth response-1 (EGR1) gene might be crucial in this process. This study introduces a novel method for constructing piezoelectric ceramic scaffolds exhibiting outstanding osteogenic, angiogenic, and antibacterial properties under the combined influence of LIPUS, offering a promising treatment strategy for infectious bone defects.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 479-495"},"PeriodicalIF":18.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881046","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 : 2024-12-04DOI: 10.1016/j.bioactmat.2024.11.031
Tianhui Chen , Zhongxing Chen , Juan Du , Min Zhang , Zexu Chen , Qingyi Gao , Aodong Chen , Qinghao Meng , Yang Sun , Yan liu , Linghao Song , Xinyue Wang , Pranav Prakash Edavi , Chen Xu , Hongmei Zhang , Jinhai Huang , Yongxiang Jiang
{"title":"Reprogramming of iPSCs to NPCEC-like cells by biomimetic scaffolds for zonular fiber reconstruction","authors":"Tianhui Chen , Zhongxing Chen , Juan Du , Min Zhang , Zexu Chen , Qingyi Gao , Aodong Chen , Qinghao Meng , Yang Sun , Yan liu , Linghao Song , Xinyue Wang , Pranav Prakash Edavi , Chen Xu , Hongmei Zhang , Jinhai Huang , Yongxiang Jiang","doi":"10.1016/j.bioactmat.2024.11.031","DOIUrl":"10.1016/j.bioactmat.2024.11.031","url":null,"abstract":"<div><div>Ectopia lentis (EL), characterised by impaired zonular fibers originating from non-pigmented ciliary epithelial cells (NPCEC), presents formidable surgical complexities and potential risks of visual impairment. Cataract surgery is the only treatment method for EL, but it leads to the loss of accommodative power of the lens post-operatively. Furthermore, the challenge of repairing zonular ligaments <em>in situ</em> remains a significant global issue. Ocular tissue and aqueous humour samples from patients with EL were subjected to RNA sequencing and Olink high-throughput proteomic analysis, revealing the downregulation of pathogenic genes (<em>FBN1</em>, <em>MFAP2</em>) and upregulation of secretory proteins (IL-12, MMP-1). The high expression of <em>FBN1</em> and <em>MFAP2</em> in NPCECs suggests their potential as candidates for zonular fiber construction; however, the limited availability of donor sources restricts the feasibility of NPCEC transplantation therapy. The reprogramming and directional differentiation of induced pluripotent stem cells (iPSC) to NPCEC was successfully achieved using the developed biomimetic scaffolds that mimic the microstructures of natural radial zonular fibers. Excitingly, the single injection of induced NPCEC-like cells significantly contributed to restoring and enhancing mechanical properties in zonular fiber structures in a rabbit model with EL. This proposed <em>in situ</em> iPSC-based regeneration technique might serve as an innovative therapeutic strategy for clinical EL patients, reduce the cataract surgery rate, and retain the adjustment capacity of inherent lentis.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 446-458"},"PeriodicalIF":18.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852261","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 : 2024-12-04DOI: 10.1016/j.bioactmat.2024.11.034
Chen-Yu Zou , Chen Han , Fei Xing , Yan-Lin Jiang , Ming Xiong , Jesse Li-Ling , Hui-Qi Xie
{"title":"Smart design in biopolymer-based hemostatic sponges: From hemostasis to multiple functions","authors":"Chen-Yu Zou , Chen Han , Fei Xing , Yan-Lin Jiang , Ming Xiong , Jesse Li-Ling , Hui-Qi Xie","doi":"10.1016/j.bioactmat.2024.11.034","DOIUrl":"10.1016/j.bioactmat.2024.11.034","url":null,"abstract":"<div><div>Uncontrolled hemorrhage remains the leading cause of death in clinical and emergency care, posing a major threat to human life. To achieve effective bleeding control, many hemostatic materials have emerged. Among them, nature-derived biopolymers occupy an important position due to the excellent inherent biocompatibility, biodegradability and bioactivity. Additionally, sponges have been widely used in clinical and daily life because of their rapid blood absorption. Therefore, we provide the overview focusing on the latest advances and smart designs of biopolymer-based hemostatic sponge. Starting from the component, the applications of polysaccharide and polypeptide in hemostasis are systematically introduced, and the unique bioactivities such as antibacterial, antioxidant and immunomodulation are also concerned. From the perspective of sponge structure, different preparation processes can obtain unique physical properties and structures, which will affect the material properties such as hemostasis, antibacterial and tissue repair. Notably, as development frontier, the multi-functions of hemostatic materials is summarized, mainly including enhanced coagulation, antibacterial, avoiding tumor recurrence, promoting tissue repair, and hemorrhage monitoring. Finally, the challenges facing the development of biopolymer-based hemostatic sponges are emphasized, and future directions for <em>in vivo</em> biosafety, emerging materials, multiple application scenarios and translational research are proposed.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 459-478"},"PeriodicalIF":18.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852277","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}
{"title":"In situ magnetic-field-assisted bioprinting process using magnetorheological bioink to obtain engineered muscle constructs","authors":"Hanjun Hwangbo , SooJung Chae , Dongryeol Ryu , GeunHyung Kim","doi":"10.1016/j.bioactmat.2024.11.035","DOIUrl":"10.1016/j.bioactmat.2024.11.035","url":null,"abstract":"<div><div>Tissue-engineered anisotropic cell constructs are promising candidates for treating volumetric muscle loss (VML). However, achieving successful cell alignment within macroscale 3D cell constructs for skeletal muscle tissue regeneration remains challenging, owing to difficulties in controlling cell arrangement within a low-viscosity hydrogel. Herein, we propose the concept of a magnetorheological bioink to manipulate the cellular arrangement within a low-viscosity hydrogel. This bioink consisted of gelatin methacrylate (GelMA), iron oxide nanoparticles, and human adipose stem cells (hASCs). The cell arrangement is regulated by the responsiveness of iron oxide nanoparticles to external magnetic fields. A bioprinting process using ring magnets was developed for <em>in situ</em> bioprinting, resulting in well-aligned 3D cell structures and enhanced mechanotransduction effects on hASCs. <em>In vitro</em> analyses revealed upregulation of cellular activities, including myogenic-related gene expression, in hASCs. When implanted into a VML mouse model, the bioconstructs improved muscle functionality and regeneration, validating the effectiveness of the proposed approach.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 417-433"},"PeriodicalIF":18.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852246","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 : 2024-12-03DOI: 10.1016/j.bioactmat.2024.11.016
Hongxia Zhou , Wenbo Huang , Jieting Li , Peier Chen , Lihan Shen , Wenjing Huang , Kailin Mai , Heyan Zou , Xueqin Shi , Yunceng Weng , Yuhua Liu , Zifeng Yang , Caiwen Ou
{"title":"Oral probiotic extracellular vesicle therapy mitigates Influenza A Virus infection via blunting IL-17 signaling","authors":"Hongxia Zhou , Wenbo Huang , Jieting Li , Peier Chen , Lihan Shen , Wenjing Huang , Kailin Mai , Heyan Zou , Xueqin Shi , Yunceng Weng , Yuhua Liu , Zifeng Yang , Caiwen Ou","doi":"10.1016/j.bioactmat.2024.11.016","DOIUrl":"10.1016/j.bioactmat.2024.11.016","url":null,"abstract":"<div><div>The influenza A virus (IAV) damages intestinal mucosal tissues beyond the respiratory tract. Probiotics play a crucial role in maintaining the balance and stability of the intestinal microecosystem. Extracellular vesicles (EVs) derived from probiotics have emerged as potential mediators of host immune response and anti-inflammatory effect. However, the specific anti-inflammatory effects and underlying mechanisms of probiotics-derived EVs on IAV remain unclear. In the present study, we investigated the therapeutic efficacy of <em>Lactobacillus reuteri</em> EHA2-derived EVs (LrEVs) in a mouse model of IAV infection. Oral LrEVs were distributed in the liver, lungs, and gastrointestinal tract. In mice infected with IAV, oral LrEVs administration alleviated IAV-induced damages in the lungs and intestines, modified the microbiota compositions, and increased the levels of short-chain fatty acids in those organs. Mechanistically, LrEVs exerted their protective effects against IAV infection by blunting the pro-inflammatory IL-17 signaling. Furthermore, FISH analysis detected miR-4239, one of the most abundant miRNAs in LrEVs, in both lung and intestinal tissues. We confirmed that miR-4239 directly targets <em>IL-17a</em>. Our findings paved the ground for future application of LrEVs in influenza treatment and offered new mechanistic insights regarding the anti-inflammatory role of miR-4239.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 401-416"},"PeriodicalIF":18.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852257","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 : 2024-12-03DOI: 10.1016/j.bioactmat.2024.11.009
Cui Ren , Zhiyong Shi , Xiaowen Zhang , Xueer Yu , Yang Gao , Zhi Qi , Yu Chen , Yong Wang
{"title":"DNA-mediated self-assembly oxidative damage amplifier combined with copper and MTH1 inhibitor for cancer therapy","authors":"Cui Ren , Zhiyong Shi , Xiaowen Zhang , Xueer Yu , Yang Gao , Zhi Qi , Yu Chen , Yong Wang","doi":"10.1016/j.bioactmat.2024.11.009","DOIUrl":"10.1016/j.bioactmat.2024.11.009","url":null,"abstract":"<div><div>Chemo-dynamic therapy (CDT) has a great potential in tumor extirpation. It entails producing hypertoxic reactive oxygen species (ROS) that damage the DNA of tumor cells and other biomacromolecules. However, the efficiency of CDT is severely hampered by the massive presence of glutathione (GSH) in tumor cells and the interference of ROS defense systems, such as Mutt homolog 1 (MTH1) protein sanitizes ROS-oxidized nucleotide pools. In this research, DNA-mediated self-assembly nanoparticles (HTCG@TA NPs) were engineered with high-performance amplified oxidative damage and gene therapy effect for synergistic anti-tumor treatment. Cu<sup>2+</sup> was converted into Cu <sup>+</sup> by redox reactions to deplete GSH while H<sub>2</sub>O<sub>2</sub> was catalyzed to generate hydroxyl radicals (·OH). As a result, the ROS level was evidently improved. Moreover, controllable-released TH588 prevented MTH1-mediated DNA repairing, thus aggravated oxidative damage to tumor cells. Meanwhile, the released functional nucleic acid G3139 downregulated the expression of Bcl-2, and accelerated the apoptosis of tumor cells. In conclusion, the HTCG@TA demonstrated significant effect in oxidative damage amplification and tumor inhibition both <em>in vitro</em> and <em>in vivo</em>, which has provided a new outlook for the clinical application of chemo-dynamic tumor treatment and synergistic gene therapy with self-delivery nanoplatforms.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 434-445"},"PeriodicalIF":18.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852188","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 : 2024-12-01DOI: 10.1016/j.bioactmat.2024.11.017
Jian Wang , Dongyang Zhou , Ruiyang Li , Shihao Sheng , Guangfeng Li , Yue Sun , Peng Wang , Yulin Mo , Han Liu , Xiao Chen , Zhen Geng , Qin Zhang , Yingying Jing , Long Bai , Ke Xu , Jiacan Su
{"title":"Protocol for engineering bone organoids from mesenchymal stem cells","authors":"Jian Wang , Dongyang Zhou , Ruiyang Li , Shihao Sheng , Guangfeng Li , Yue Sun , Peng Wang , Yulin Mo , Han Liu , Xiao Chen , Zhen Geng , Qin Zhang , Yingying Jing , Long Bai , Ke Xu , Jiacan Su","doi":"10.1016/j.bioactmat.2024.11.017","DOIUrl":"10.1016/j.bioactmat.2024.11.017","url":null,"abstract":"<div><div>Bone organoids are emerging as powerful tools for studying bone development and related diseases. However, the simplified design of current methods somewhat limits their application potential, as these methods produce single-tissue organoids that fail to replicate the bone microarchitecture or achieve effective mineralization. To address this issue, we propose a three-dimensional (3D) construction strategy for generating mineralized bone structures using bone marrow-derived mesenchymal stem cells (BMSCs). By mixing BMSCs with hydrogel to create a bone matrix-mimicking bioink and employing projection-based light-curing 3D printing technology, we constructed 3D-printed structures, which were then implanted subcutaneously into nude mice, away from the native bone microenvironment. Even without external stimulation, these implants spontaneously formed mineralized bone domains. With long-term culture, these structures gradually matured into fully differentiated bone tissue, completing both mineralization and vascularization. This <em>in vivo</em> bone organoid model offers a novel platform for studying bone development, exploring congenital diseases, testing drugs, and developing therapeutic applications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 388-400"},"PeriodicalIF":18.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757627","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}