Yuxiang Zhu, Shenghan Guo, Dharneedar Ravichandran, Arunachalam Ramanathan, M Taylor Sobczak, Alaina F Sacco, Dhanush Patil, Sri Vaishnavi Thummalapalli, Tiffany V Pulido, Jessica N Lancaster, Johnny Yi, Jeffrey L Cornella, David G Lott, Xiangfan Chen, Xuan Mei, Yu Shrike Zhang, Linbing Wang, Xianqiao Wang, Yiping Zhao, Mohammad K Hassan, Lindsay B Chambers, Taylor G Theobald, Sui Yang, Liang Liang, Kenan Song
{"title":"3D-Printed Polymeric Biomaterials for Health Applications.","authors":"Yuxiang Zhu, Shenghan Guo, Dharneedar Ravichandran, Arunachalam Ramanathan, M Taylor Sobczak, Alaina F Sacco, Dhanush Patil, Sri Vaishnavi Thummalapalli, Tiffany V Pulido, Jessica N Lancaster, Johnny Yi, Jeffrey L Cornella, David G Lott, Xiangfan Chen, Xuan Mei, Yu Shrike Zhang, Linbing Wang, Xianqiao Wang, Yiping Zhao, Mohammad K Hassan, Lindsay B Chambers, Taylor G Theobald, Sui Yang, Liang Liang, Kenan Song","doi":"10.1002/adhm.202402571","DOIUrl":"https://doi.org/10.1002/adhm.202402571","url":null,"abstract":"<p><p>3D printing, also known as additive manufacturing, holds immense potential for rapid prototyping and customized production of functional health-related devices. With advancements in polymer chemistry and biomedical engineering, polymeric biomaterials have become integral to 3D-printed biomedical applications. However, there still exists a bottleneck in the compatibility of polymeric biomaterials with different 3D printing methods, as well as intrinsic challenges such as limited printing resolution and rates. Therefore, this review aims to introduce the current state-of-the-art in 3D-printed functional polymeric health-related devices. It begins with an overview of the landscape of 3D printing techniques, followed by an examination of commonly used polymeric biomaterials. Subsequently, examples of 3D-printed biomedical devices are provided and classified into categories such as biosensors, bioactuators, soft robotics, energy storage systems, self-powered devices, and data science in bioplotting. The emphasis is on exploring the current capabilities of 3D printing in manufacturing polymeric biomaterials into desired geometries that facilitate device functionality and studying the reasons for material choice. Finally, an outlook with challenges and possible improvements in the near future is presented, projecting the contribution of general 3D printing and polymeric biomaterials in the field of healthcare.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402571"},"PeriodicalIF":10.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji Ding, Zhaojun Cheng, Yulong Ma, Tongxing Zhang, Lilong Du, Xiaobing Jiang, Meifeng Zhu, Wen Li, Baoshan Xu
{"title":"Engineering Injectable and Highly Interconnected Porous Silk Fibroin Microspheres for Tissue Regeneration.","authors":"Ji Ding, Zhaojun Cheng, Yulong Ma, Tongxing Zhang, Lilong Du, Xiaobing Jiang, Meifeng Zhu, Wen Li, Baoshan Xu","doi":"10.1002/adhm.202402932","DOIUrl":"https://doi.org/10.1002/adhm.202402932","url":null,"abstract":"<p><p>Injectable porous microspheres represent a promising therapeutic platform for cell delivery, drug delivery, and tissue regeneration. Yet, the engineering of silk fibroin microspheres with a highly interconnected porous structure remains an unsolved challenge. In this study, a simple and efficient method is developed that does not require the use of organic solvents to prepare silk fibroin microspheres with a predictable structure. Through extensive screening, the addition of glucose is found to direct the formation of a highly interconnected porous structure from the interior to the surface of silk fibroin microspheres. Compared to silk fibroin microspheres (SF microspheres) produced through a combination of electro-spray, cryopreservation, and freeze drying, silk fibroin-glucose microspheres (SF-Glu microspheres) demonstrates enhanced capabilities in promoting cell adhesion and proliferation in vitro. Both SF-Glu and SF microspheres exhibit the capacity to maintain the sustained release kinetics of the loaded model drug. Furthermore, SF-Glu microspheres facilitate the recruitment of endogenous cells, capillary migration, and macrophage phenotype switch following subcutaneous injection in the rats. This study opens a new avenue for the construction of porous silk fibroin microspheres, which could lead to a broader range of applications in regenerative medicine.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402932"},"PeriodicalIF":10.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wisberty J Gordián-Vélez, Kevin D Browne, Jonathan H Galarraga, Dimple Chouhan, John E Duda, Rodrigo A España, H Isaac Chen, Jason A Burdick, D Kacy Cullen
{"title":"Dopaminergic Axon Tracts Within a Hyaluronic Acid Hydrogel Encasement to Restore the Nigrostriatal Pathway.","authors":"Wisberty J Gordián-Vélez, Kevin D Browne, Jonathan H Galarraga, Dimple Chouhan, John E Duda, Rodrigo A España, H Isaac Chen, Jason A Burdick, D Kacy Cullen","doi":"10.1002/adhm.202402997","DOIUrl":"https://doi.org/10.1002/adhm.202402997","url":null,"abstract":"<p><p>Parkinson's disease is characterized by motor deficits emerging from insufficient dopamine in the striatum after degeneration of dopaminergic neurons and their long-projecting axons comprising the nigrostriatal pathway. To address this, a tissue-engineered nigrostriatal pathway (TE-NSP) featuring a tubular hydrogel with a collagen/laminin core that encases aggregated dopaminergic neurons and their axonal tracts is developed. This engineered microtissue can be implanted to replace neurons and axons with fidelity to the lost pathway and thus may provide dopamine according to feedback from host circuitry. While TE-NSPs have traditionally been fabricated with agarose, here a hyaluronic acid (HA) hydrogel is utilized to have a more bioactive encasement while expanding control over physical and biochemical properties. Using rat ventral midbrain neurons, it is found that TE-NSPs exhibited improved neurite growth with HA relative to agarose, with no differences in electrically-evoked dopamine release. When transplanted, HA hydrogels reduced average host neuron loss and inflammation around the implant compared to agarose, and TE-NSP neurons and axonal tracts survived for at least 2 weeks to structurally emulate the lost pathway. This study represents an innovative use of HA hydrogels for neuroregenerative medicine and enables future studies expanding the control and functionality of TE-NSPs.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402997"},"PeriodicalIF":10.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yasunari Hayashi, Taro Fujii, Seungil Kim, Takahiro Ozeki, Stephen F Badylak, Antonio D'Amore, Masato Mutsuga, William R Wagner
{"title":"Intervening to Preserve Function in Ischemic Cardiomyopathy with a Porous Hydrogel and Extracellular Matrix Composite in a Rat Myocardial Infarction Model.","authors":"Yasunari Hayashi, Taro Fujii, Seungil Kim, Takahiro Ozeki, Stephen F Badylak, Antonio D'Amore, Masato Mutsuga, William R Wagner","doi":"10.1002/adhm.202402757","DOIUrl":"https://doi.org/10.1002/adhm.202402757","url":null,"abstract":"<p><p>Multiple hydrogels are developed for injection therapy after myocardial infarction, with some incorporating substances promoting tissue regeneration and others emphasizing mechanical effects. In this study, porosity and extracellular matrix-derived digest (ECM) are incorporated, into a mechanically optimized, thermoresponsive, degradable hydrogel (poly(N-isopropylacrylamide-co-N-vinylpyrrolidone-co-MAPLA)) and evaluate whether this biomaterial injectate can abrogate adverse remodeling in rat ischemic cardiomyopathy. After myocardial infarction, rats are divided into four groups: NP (non-porous hydrogel) without either ECM or porosity, PM (porous hydrogel) from the same synthetic copolymer with mannitol beads as porogens, and PME with porosity and ECM digest added to the synthetic copolymer. PBS injection alone is a control group. Intramyocardial injections occurred 3 days after myocardial infarction followed by serial echocardiography and histological assessments 8 weeks after infarction. Echocardiographic function and neovascularization improved in the PME group compared to the other hydrogels and PBS injection. The PME group also demonstrated improved LV geometry and macrophage polarization (toward M2) compared to PBS, whereas differences are not observed in the NP or PM groups versus control. These results demonstrate further functional improvement may be achieved in hydrogel injection therapy for ischemic cardiomyopathy by incorporating porosity and ECM digest, representing combined mechanical and biological effects.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402757"},"PeriodicalIF":10.0,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fabrication of MnO<sub>2</sub>-Modified Decellularized Tendon Membrane for Enhancing Tendon Repair.","authors":"Wanqing Lun, Huajun Wang, Mengyuan Li, Jiuzhi Ma, Yilin Ding, Xiaofei Zheng, Xiaodong Cao, Qingtao Li","doi":"10.1002/adhm.202402584","DOIUrl":"https://doi.org/10.1002/adhm.202402584","url":null,"abstract":"<p><p>Repairing tendon/ligament injuries is a major challenge in sports medicine. It has been reported that tendon injury healing is hindered by massive production of reactive oxygen species (ROS). Manganese oxides nanoparticles are generally non-toxic, can scavenge ROS, promote tissue regeneration, and hold promise for sustainable nanotechnologies. However, the effective and safe integration of MnO<sub>2</sub> nanoparticles on decellularized scaffold mediating tissue repair is still a great challenge. To address these issues, an in situ MnO<sub>2</sub>-modified decellularized scaffold is developed to enhance tendon regeneration through improving microenvironment. The decellularized fibrous membrane is designed and prepared using the central tendon of the porcine diaphragm. Then MnO<sub>2</sub> nanozymes are in situ grown on the collagen fibers using tannic acid (TA) as cross-linking agent and reducing agent. The results showed that MnO<sub>2</sub>-modified scaffold eliminates excessive accumulation of ROS in cells, protects mitochondrial, and maintains the phenotype of tendon cells in an oxidative stress environment. Notably, it is found that the MnO<sub>2</sub>-modified scaffold exhibits good biocompatibility and is able to promote the tendon healing in the rat patellar tendon defect model. Altogether, this study confirmed that this nanozyme-functionalized decellularized extracellular matrix effectively enhanced tendon repair by scavenging ROS, which provides new strategies for enhancing tendon regeneration.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402584"},"PeriodicalIF":10.0,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tim Kaden, Raquel Alonso-Román, Johannes Stallhofer, Mark S Gresnigt, Bernhard Hube, Alexander S Mosig
{"title":"Leveraging Organ-on-Chip Models to Investigate Host-Microbiota Dynamics and Targeted Therapies for Inflammatory Bowel Disease.","authors":"Tim Kaden, Raquel Alonso-Román, Johannes Stallhofer, Mark S Gresnigt, Bernhard Hube, Alexander S Mosig","doi":"10.1002/adhm.202402756","DOIUrl":"https://doi.org/10.1002/adhm.202402756","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is an idiopathic gastrointestinal disease with drastically increasing incidence rates. Due to its multifactorial etiology, a precise investigation of the pathogenesis is extremely difficult. Although reductionist cell culture models and more complex disease models in animals have clarified the understanding of individual disease mechanisms and contributing factors of IBD in the past, it remains challenging to bridge research and clinical practice. Conventional 2D cell culture models cannot replicate complex host-microbiota interactions and stable long-term microbial culture. Further, extrapolating data from animal models to patients remains challenging due to genetic and environmental diversity leading to differences in immune responses. Human intestine organ-on-chip (OoC) models have emerged as an alternative in vitro model approach to investigate IBD. OoC models not only recapitulate the human intestinal microenvironment more accurately than 2D cultures yet may also be advantageous for the identification of important disease-driving factors and pharmacological interventions targets due to the possibility of emulating different complexities. The predispositions and biological hallmarks of IBD focusing on host-microbiota interactions at the intestinal mucosal barrier are elucidated here. Additionally, the potential of OoCs to explore microbiota-related therapies and personalized medicine for IBD treatment is discussed.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402756"},"PeriodicalIF":10.0,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yijie Yang, Wen Gu, Xue Jiang, Xiaolei Lv, Jianxu Wei, Xiaomeng Zhang, Kai Zheng, Hongchang Lai
{"title":"MBG/BSA Bone Grafts Immunomodulate Bone Regeneration by Releasing Bioactive Ions in Inflammatory Bone Defects.","authors":"Yijie Yang, Wen Gu, Xue Jiang, Xiaolei Lv, Jianxu Wei, Xiaomeng Zhang, Kai Zheng, Hongchang Lai","doi":"10.1002/adhm.202402610","DOIUrl":"https://doi.org/10.1002/adhm.202402610","url":null,"abstract":"<p><p>Since the diseases that cause bone defects are mostly inflammatory diseases, the current bone grafts are unable to effectively regulate osteoimmune activity, leading to the impaired osteogenesis and unfavorable bone regeneration. In this study, inspired by bone composition, biomimetic mesoporous bioactive glass nanoparticle (MBG)/bovine serum albumin (BSA) bone grafts are designed for inflammatory bone defects. Systematically, MBG/BSA bone grafts are evaluated for characterization, bioactivity, anti-inflammatory, antioxidant activity, and osteogenic activity. MBG/BSA bone grafts are proved to be biocompatible and can release bioactive ions including calcium and silicon in a sustained manner. Furthermore, MBG/BSA reprograms the macrophage phenotype toward anti-inflammation that is beneficial for bone regeneration. The antioxidative activity is also validated under inflammation and the mechanism may be via the interleukin-4 (IL-4)/Signal transducer and activator of transcription 6 (STAT6) pathway. The osteogenic differentiation and mineralization are also facilitated due to the improved immunoregulation of MBG/BSA. Overall, this work suggests that the MBG/BSA bone grafts with improved immunomodulatory properties are an ideal material for inflammatory bone regeneration application.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402610"},"PeriodicalIF":10.0,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Minimalist Adjuvant-Free Nano-Vaccine Based on Antigen Self-Assembled Amyloid-Like Fibrils to Induce Potent Immune Response.","authors":"Xiang Wang, Haiyang Xia, Tiantian Li, Qinhua Zuo, Zhen Wang, Kangjian Yan, Zejun Xu, Wei Xue, Guodong Sun, Zonghua Liu, Yi Zhang","doi":"10.1002/adhm.202401625","DOIUrl":"https://doi.org/10.1002/adhm.202401625","url":null,"abstract":"<p><p>The development of cancer vaccines is at the forefront of cancer immunotherapy. Most existing strategies to induce an efficient anti-tumor immune response rely on molecular adjuvants and the incorporation of complex synthetic vectors into vaccine formulations. In contrast, this study introduces a one-step engineering technique to assemble the model antigen, Ovalbumin (OVA), into amyloid aggregates, leveraging biomimetic folding and aggregation to create non-fibrillar OVA globular aggregates and OVA amyloid-like fibrils as single-component, adjuvant-free vaccines. Notably, the OVA amyloid-like fibrils induced stronger immune responses compared to the native form, as evidenced by robust humoral immune reactions and the establishment of immune memory. These enhanced responses can be attributed to the self-adjuvant effect of the unique assembled structure, which preserves antigenic epitopes, improves antigen stability, facilitates antigen internalization, prolongs retention at the injection site, enhances antigen trafficking to the lymphoid organs, and promotes increased secretion of antibodies and cytokines. Furthermore, the efficacy of the vaccine was validated in a high OVA-expressing tumor model, demonstrating the potential of OVA amyloid-like fibrils as an effective vaccine for cancer immunoprevention. This minimalist self-adjuvant vaccine strategy holds promising implications for cancer immunotherapy and can inform the design of other protein antigen-based vaccines.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2401625"},"PeriodicalIF":10.0,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Incorporating Hydrogel (with Low Polymeric Content) into 3D-Printed PLGA Scaffolds for Local and Sustained Release of BMP2 in Repairing Large Segmental Bone Defects.","authors":"Rongpeng Dong, Mingyang Kang, Yang Qu, Tingting Hou, Jianwu Zhao, Xueliang Cheng","doi":"10.1002/adhm.202403613","DOIUrl":"https://doi.org/10.1002/adhm.202403613","url":null,"abstract":"<p><p>Treating large bone defects remains a considerable challenge for clinicians: bone repair requires scaffolds with mechanical properties and bioactivities. Herein, based on crosslinking o-phthalaldehyde (OPA) with amine groups, 4-arm polyethylene glycol (4armPEG)-OPA/Gelatin hydrogel loaded with bone morphogenetic protein 2 (BMP2) is prepared and a three dimensional (3D)-printed poly (lactic-co-glycolic acid) (PLGA) porous scaffold is filled with the hydrogel solution. The composite scaffold, with a compression modulus of 0.68 ± 0.097 GPa similar to the cancellous bone, has a porosity of 56.67 ± 4.72% and a pore size of about 380 µm, promoting bone growth. The hydrogel forms a porous network at low concentrations, aiding protein release and cell migration. The hydrogel degrades in approximately three weeks, and the scaffold takes five months, matching bone repair timelines. BMP2 release experiment shows a sustained BMP2 release with a 72.4 ± 0.53% release ratio. The ALP activity test and alizarin red staining shows effective osteogenic promotion, while RT-PCR confirms BMP2@Gel enhanced COL-1 and OPN expression. Animal experiments further validate the composite scaffold's bone repair efficacy. This study demonstrates the effectiveness of the hydrogel in releasing BMP2 and the mechanical support of the 3D-printed PLGA porous scaffold, providing a new treatment for bone defects.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403613"},"PeriodicalIF":10.0,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi Sun, Xin Peng, Yudong Guan, Tong Su, Zezun Xie, Ziying Wu, Yongxuan Long, Huihui Zhu, Jie Shao, Xiaoli Mai, Xuzhi Shi, Tingting Wu, Zhaogang Teng, Bing Zhang, Kun Chen, Xiaoyan Xin
{"title":"K<sub>2</sub>FeO<sub>4</sub>-Enhanced Photodynamic Therapy of Breast Cancer via In Situ Synthesis of Fe<sub>2</sub>O<sub>3</sub> and O<sub>2</sub>.","authors":"Yi Sun, Xin Peng, Yudong Guan, Tong Su, Zezun Xie, Ziying Wu, Yongxuan Long, Huihui Zhu, Jie Shao, Xiaoli Mai, Xuzhi Shi, Tingting Wu, Zhaogang Teng, Bing Zhang, Kun Chen, Xiaoyan Xin","doi":"10.1002/adhm.202402827","DOIUrl":"https://doi.org/10.1002/adhm.202402827","url":null,"abstract":"<p><p>Photodynamic Therapy (PDT) offers a promising minimally invasive treatment for breast cancer, but its efficacy is limited by the hostile tumor microenvironment (TME), including hypoxia and high glutathione (GSH) levels. Although various strategies to improve oxygen concentration or reduce reactive oxygen species (ROS) resistance for enhanced PDT have been explored, they typically require intricate design and complex synthesis of multifunctional nanocarriers. Thus, this study introduces a facile K<sub>2</sub>FeO<sub>4</sub>-induced strategy to enhance PDT efficiency in breast cancer through the tumor in situ synthesis of Fe<sub>2</sub>O<sub>3</sub> and O<sub>2</sub>. Inspired by the successful application of K<sub>2</sub>FeO<sub>4</sub> in ecological remediation and hemostasis, K<sub>2</sub>FeO<sub>4</sub> reacts with GSH, biological system, H<sub>2</sub>O<sub>2</sub>, and water, to generate Fe<sub>2</sub>O<sub>3</sub> and O<sub>2</sub>. Intratumoral injection of K<sub>2</sub>FeO<sub>4</sub> improves the TME, followed by Ce6 administration to enhance PDT through synergistic ferroptosis. This approach boosts PDT efficacy significantly by increasing ROS generation, lipid peroxidation, and inhibiting GSH and GPX4. Proteomic analysis revealed alterations in key pathways, including endocytosis and energy metabolism. This K<sub>2</sub>FeO<sub>4</sub>-PDT strategy creates a positive feedback loop by enhancing oxidative stress, providing an interesting and promising approach to PDT.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402827"},"PeriodicalIF":10.0,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}