Pub Date : 2024-10-09DOI: 10.1016/j.biomaterials.2024.122883
Zhe Yang , Ying Zhou , Xiaozhen Liu , Liujiao Ren , Xinyang Liu , Rong Yun , Liangliang Jia , Xuechun Ren , Ying Wang , Yan Sun , Jia Li , Di Gao , Zhongmin Tian
Developing endogenous hyperthermia offers a promising strategy to address challenges with current exogenous hyperthermia techniques in clinics. Herein, a CD44-targeted and thermal-responsive nanocarrier was developed for the simultaneous delivery of 2,4-dinitrophenol and syrosingopine. The objective was to induce endogenous hyperthermia and regulate immunometabolism, ultimately augmenting anti-tumour immune responses. Dinitrophenol as mitochondrial uncoupler can convert electrochemical potential energy of inner mitochondrial membrane into heat, facilitating endogenous hyperthermia. Meanwhile, syrosingopine not only inhibits excessive lactate efflux caused by dinitrophenol but also downregulates tumour cell glycolysis, thus alleviating immunosuppression and heat shock protein (HSP)-dependent thermo-resistance through immunometabolism regulation. The synergistic effects of endogenous hyperthermia and immunometabolism regulation by this nanomedicine have potential to enhance tumor immunogenicity, reshape the tumour immune microenvironment, and effectively suppress the growth of subcutaneous tumours and patient-derived organoids in triple-negative breast cancer. Therefore, the endogenous hyperthermia strategy developed in this study would revolutionize hyperthermia for cancer treatment.
{"title":"Mitochondrial-uncoupling nanomedicine for self-heating and immunometabolism regulation in cancer cells","authors":"Zhe Yang , Ying Zhou , Xiaozhen Liu , Liujiao Ren , Xinyang Liu , Rong Yun , Liangliang Jia , Xuechun Ren , Ying Wang , Yan Sun , Jia Li , Di Gao , Zhongmin Tian","doi":"10.1016/j.biomaterials.2024.122883","DOIUrl":"10.1016/j.biomaterials.2024.122883","url":null,"abstract":"<div><div>Developing endogenous hyperthermia offers a promising strategy to address challenges with current exogenous hyperthermia techniques in clinics. Herein, a CD44-targeted and thermal-responsive nanocarrier was developed for the simultaneous delivery of 2,4-dinitrophenol and syrosingopine. The objective was to induce endogenous hyperthermia and regulate immunometabolism, ultimately augmenting anti-tumour immune responses. Dinitrophenol as mitochondrial uncoupler can convert electrochemical potential energy of inner mitochondrial membrane into heat, facilitating endogenous hyperthermia. Meanwhile, syrosingopine not only inhibits excessive lactate efflux caused by dinitrophenol but also downregulates tumour cell glycolysis, thus alleviating immunosuppression and heat shock protein (HSP)-dependent thermo-resistance through immunometabolism regulation. The synergistic effects of endogenous hyperthermia and immunometabolism regulation by this nanomedicine have potential to enhance tumor immunogenicity, reshape the tumour immune microenvironment, and effectively suppress the growth of subcutaneous tumours and patient-derived organoids in triple-negative breast cancer. Therefore, the endogenous hyperthermia strategy developed in this study would revolutionize hyperthermia for cancer treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122883"},"PeriodicalIF":12.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417531","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}
Pub Date : 2024-10-08DOI: 10.1016/j.biomaterials.2024.122876
Yunhao Wang , Lei Ding , Juan Feng , Ziguo Lin , Hanlin Yao , Xinyu You , Xiaolong Zhang , Wen Sun , Yang Liu , Peiyuan Wang
Tumor cells can survive when detached from the extracellular matrix or lose cell-to-cell connections, leading to a phenomenon known as anoikis resistance (AR). AR is closely associated with the metastasis and proliferation of tumor cells, enabling them to disseminate, migrate, and invade after detachment. Here, we have investigated a novel composite nanoenzyme comprising mesoporous silica/nano-cerium oxide (MSN-Ce@SP/PEG). This nanoenzyme exhibited satisfactory catalase (CAT) activity, efficiently converting high levels of H2O2 within tumor cells into O2, effectively alleviating tumor hypoxia. Furthermore, MSN-Ce@SP/PEG nanoenzyme demonstrated high peroxidase (POD) activity, elevating reactive oxygen species (ROS) levels and attenuating AR in hepatocellular carcinoma (HCC) cells. The MSN-Ce@SP/PEG nanoenzyme exhibited satisfactory dual bioactivity in CAT and POD and was significantly enhanced under favorable photothermal conditions. Through the synergistic effects of these capabilities, the nanoenzyme disrupted the epithelial-mesenchymal transition (EMT) process in detached HCC cells, ultimately inhibiting the recurrence and metastasis potential of anoikis-resistant HCC cells. This study represents the first report of a novel nanoenzyme based on mesoporous silica/nano-cerium oxide for treating AR in HCC cells, thereby suppressing HCC recurrence and metastasis. The findings of this work offer a pioneering perspective for the development of innovative strategies to prevent the recurrence and metastasis of HCC.
{"title":"Mesoporous cerium oxide nanoenzyme for Efficacious impeding tumor and metastasis via Conferring resistance to anoikis","authors":"Yunhao Wang , Lei Ding , Juan Feng , Ziguo Lin , Hanlin Yao , Xinyu You , Xiaolong Zhang , Wen Sun , Yang Liu , Peiyuan Wang","doi":"10.1016/j.biomaterials.2024.122876","DOIUrl":"10.1016/j.biomaterials.2024.122876","url":null,"abstract":"<div><div>Tumor cells can survive when detached from the extracellular matrix or lose cell-to-cell connections, leading to a phenomenon known as anoikis resistance (AR). AR is closely associated with the metastasis and proliferation of tumor cells, enabling them to disseminate, migrate, and invade after detachment. Here, we have investigated a novel composite nanoenzyme comprising mesoporous silica/nano-cerium oxide (MSN-Ce@SP/PEG). This nanoenzyme exhibited satisfactory catalase (CAT) activity, efficiently converting high levels of H<sub>2</sub>O<sub>2</sub> within tumor cells into O<sub>2</sub>, effectively alleviating tumor hypoxia. Furthermore, MSN-Ce@SP/PEG nanoenzyme demonstrated high peroxidase (POD) activity, elevating reactive oxygen species (ROS) levels and attenuating AR in hepatocellular carcinoma (HCC) cells. The MSN-Ce@SP/PEG nanoenzyme exhibited satisfactory dual bioactivity in CAT and POD and was significantly enhanced under favorable photothermal conditions. Through the synergistic effects of these capabilities, the nanoenzyme disrupted the epithelial-mesenchymal transition (EMT) process in detached HCC cells, ultimately inhibiting the recurrence and metastasis potential of anoikis-resistant HCC cells. This study represents the first report of a novel nanoenzyme based on mesoporous silica/nano-cerium oxide for treating AR in HCC cells, thereby suppressing HCC recurrence and metastasis. The findings of this work offer a pioneering perspective for the development of innovative strategies to prevent the recurrence and metastasis of HCC.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122876"},"PeriodicalIF":12.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386753","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}
Pub Date : 2024-10-05DOI: 10.1016/j.biomaterials.2024.122872
Waishan Lam , Yufei Yao , Chenxi Tang , Yue Wang , Quan Yuan , Lin Peng
Periodontal bone defects represent an irreversible consequence of periodontitis associated with reactive oxygen species (ROS). However, indiscriminate removal of ROS proves to be counterproductive for tissue repair and insufficient for addressing existing bone defects. In the treatment of periodontitis, it is crucial to rationally alleviate local ROS while simultaneously promoting bone regeneration. In this study, Zr-based large-pore hierarchical mesoporous metal-organic framework (MOF) nanoparticles (NPs) HMUiO-66-NH2 were successfully proposed as bifunctional nanomaterials for bone regeneration and ROS scavenging in periodontitis therapy. HMUiO-66-NH2 NPs demonstrated outstanding biocompatibility both in vitro and in vivo. Significantly, these NPs enhanced the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under normal and high ROS conditions, upregulating osteogenic gene expression and mitigating oxidative stress. Furthermore, in vivo imaging revealed a gradual degradation of HMUiO-66-NH2 NPs in periodontal tissues. Local injection of HMUiO-66-NH2 effectively reduced bone defects and ROS levels in periodontitis-induced C57BL/6 mice. RNA sequencing highlighted that differentially expressed genes (DEGs) are predominantly involved in bone tissue development, with notable upregulation in Wnt and TGF-β signaling pathways. In conclusion, HMUiO-66-NH2 exhibits dual functionality in alleviating oxidative stress and promoting bone repair, positioning it as an effective strategy against bone resorption in oxidative stress-related periodontitis.
{"title":"Bifunctional mesoporous HMUiO-66-NH2 nanoparticles for bone remodeling and ROS scavenging in periodontitis therapy","authors":"Waishan Lam , Yufei Yao , Chenxi Tang , Yue Wang , Quan Yuan , Lin Peng","doi":"10.1016/j.biomaterials.2024.122872","DOIUrl":"10.1016/j.biomaterials.2024.122872","url":null,"abstract":"<div><div>Periodontal bone defects represent an irreversible consequence of periodontitis associated with reactive oxygen species (ROS). However, indiscriminate removal of ROS proves to be counterproductive for tissue repair and insufficient for addressing existing bone defects. In the treatment of periodontitis, it is crucial to rationally alleviate local ROS while simultaneously promoting bone regeneration. In this study, Zr-based large-pore hierarchical mesoporous metal-organic framework (MOF) nanoparticles (NPs) HMUiO-66-NH<sub>2</sub> were successfully proposed as bifunctional nanomaterials for bone regeneration and ROS scavenging in periodontitis therapy. HMUiO-66-NH<sub>2</sub> NPs demonstrated outstanding biocompatibility both <em>in vitro</em> and <em>in vivo.</em> Significantly, these NPs enhanced the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under normal and high ROS conditions, upregulating osteogenic gene expression and mitigating oxidative stress. Furthermore, <em>in vivo</em> imaging revealed a gradual degradation of HMUiO-66-NH<sub>2</sub> NPs in periodontal tissues. Local injection of HMUiO-66-NH<sub>2</sub> effectively reduced bone defects and ROS levels in periodontitis-induced C57BL/6 mice. RNA sequencing highlighted that differentially expressed genes (DEGs) are predominantly involved in bone tissue development, with notable upregulation in Wnt and TGF-β signaling pathways. In conclusion, HMUiO-66-NH<sub>2</sub> exhibits dual functionality in alleviating oxidative stress and promoting bone repair, positioning it as an effective strategy against bone resorption in oxidative stress-related periodontitis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122872"},"PeriodicalIF":12.8,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386750","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}
Pub Date : 2024-10-05DOI: 10.1016/j.biomaterials.2024.122879
Nila C. Wu , Rene Quevedo , Michelle Nurse , Kebria Hezaveh , Haijiao Liu , Fumao Sun , Julien Muffat , Yu Sun , Craig A. Simmons , Tracy L. McGaha , Panagiotis Prinos , Cheryl H. Arrowsmith , Laurie Ailles , Elisa D'Arcangelo , Alison P. McGuigan
Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression, including mediating tumour cell invasion via their pro-invasive secretory profile and ability to remodel the extracellular matrix (ECM). Given that reduced CAF abundance in tumours correlates with improved outcomes in various cancers, we set out to identify epigenetic targets involved in CAF activation in regions of tumour-stromal mixing with the goal of reducing tumour aggressiveness. Using the GLAnCE (Gels for Live Analysis of Compartmentalized Environments) platform, we performed an image-based, phenotypic screen that enabled us to identify modulators of CAF abundance and the capacity of CAFs to induce tumour cell invasion. We identified EHMT2 (also known as G9a), an enzyme that targets the methylation of histone 3 lysine 9 (H3K9), as a potent modulator of CAF abundance and CAF-mediated tumour cell invasion. Transcriptomic and functional analysis of EHMT2-inhibited CAFs revealed EHMT2 participated in driving CAFs towards a pro-invasive phenotype and mediated CAF hyperproliferation, a feature typically associated with activated fibroblasts in tumours. Our study suggests that EHMT2 regulates CAF state within the tumour microenvironment by impacting CAF activation, as well as by magnifying the pro-invasive effects of these activated CAFs on tumour cell invasion through promoting CAF hyperproliferation.
{"title":"The use of a multi-metric readout screen to identify EHMT2/G9a-inhibition as a modulator of cancer-associated fibroblast activation state","authors":"Nila C. Wu , Rene Quevedo , Michelle Nurse , Kebria Hezaveh , Haijiao Liu , Fumao Sun , Julien Muffat , Yu Sun , Craig A. Simmons , Tracy L. McGaha , Panagiotis Prinos , Cheryl H. Arrowsmith , Laurie Ailles , Elisa D'Arcangelo , Alison P. McGuigan","doi":"10.1016/j.biomaterials.2024.122879","DOIUrl":"10.1016/j.biomaterials.2024.122879","url":null,"abstract":"<div><div>Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression, including mediating tumour cell invasion via their pro-invasive secretory profile and ability to remodel the extracellular matrix (ECM). Given that reduced CAF abundance in tumours correlates with improved outcomes in various cancers, we set out to identify epigenetic targets involved in CAF activation in regions of tumour-stromal mixing with the goal of reducing tumour aggressiveness. Using the GLAnCE (Gels for Live Analysis of Compartmentalized Environments) platform, we performed an image-based, phenotypic screen that enabled us to identify modulators of CAF abundance and the capacity of CAFs to induce tumour cell invasion. We identified EHMT2 (also known as G9a), an enzyme that targets the methylation of histone 3 lysine 9 (H3K9), as a potent modulator of CAF abundance and CAF-mediated tumour cell invasion. Transcriptomic and functional analysis of EHMT2-inhibited CAFs revealed EHMT2 participated in driving CAFs towards a pro-invasive phenotype and mediated CAF hyperproliferation, a feature typically associated with activated fibroblasts in tumours. Our study suggests that EHMT2 regulates CAF state within the tumour microenvironment by impacting CAF activation, as well as by magnifying the pro-invasive effects of these activated CAFs on tumour cell invasion through promoting CAF hyperproliferation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122879"},"PeriodicalIF":12.8,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417470","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}
Pub Date : 2024-10-05DOI: 10.1016/j.biomaterials.2024.122878
Laura Li-En Foo , Muthualagu Natarajan Logeshwari , Bertrand Czarny , Kee Woei Ng
Interfacial Polyelectrolyte Complexation (IPC) is a convenient way to produce composite, micro-scale fibers. In this paper, we report the successful development of novel keratin-based IPC fibers and also demonstrate the feasibility of using these fibers as sutures through a proof-of-concept in vivo study. Two composite fibers were produced: chitosan-keratin (CK) and keratin-keratin (KK). These fibers were evaluated for their physico-chemical, mechanical and biochemical properties. In the dry state, the CK fiber had a greater Young's modulus of about 2 GPa while the KK fiber registered a longer strain-at-break of about 100 % due to the strain-stiffening effect. Notably, the keratins were found to assemble into amyloids within the composite fibers based on Congo red staining and Wide-Angle X-Ray Scattering. Functionally, both fibers were malleable could be weaved, braided and knotted. When used as sutures to close incisional wounds in mice over 21 days, these fibers were found to elicit minimal host tissue response and were partially degraded over the duration. Interestingly, the KK fiber evoked a lower extent of immune cell response and fibrous capsule encapsulation that was comparable to commercial, non-absorbable Dafilon® sutures. This work demonstrated the possibility of producing keratin-based IPC fibers which may find practicality as medical sutures.
界面聚电解质复合（IPC）是一种生产复合微尺度纤维的便捷方法。在本文中，我们报告了基于角蛋白的新型 IPC 纤维的成功开发，并通过一项体内概念验证研究证明了将这些纤维用作缝合线的可行性。我们生产了两种复合纤维：壳聚糖-角蛋白（CK）和角蛋白-角蛋白（KK）。对这些纤维的物理化学、机械和生物化学特性进行了评估。在干燥状态下，CK 纤维的杨氏模量更大，约为 2 GPa，而 KK 纤维由于应变加固效应，断裂应变更长，约为 100%。值得注意的是，根据刚果红染色和广角 X 射线散射法，发现角蛋白在复合纤维内组装成淀粉样。在功能上，这两种纤维都具有延展性，可以编织、编结和打结。当用作缝合线缝合小鼠的切口超过 21 天时，发现这些纤维引起的宿主组织反应极小，并在持续时间内部分降解。有趣的是，KK 纤维引起的免疫细胞反应和纤维囊包裹程度较低，与商用非吸收性 Dafilon® 缝合线相当。这项工作证明了生产基于角蛋白的 IPC 纤维的可能性，这种纤维可作为医用缝合线使用。
{"title":"Development of keratin-based fibers fabricated by interfacial polyelectrolyte complexation for suture applications","authors":"Laura Li-En Foo , Muthualagu Natarajan Logeshwari , Bertrand Czarny , Kee Woei Ng","doi":"10.1016/j.biomaterials.2024.122878","DOIUrl":"10.1016/j.biomaterials.2024.122878","url":null,"abstract":"<div><div>Interfacial Polyelectrolyte Complexation (IPC) is a convenient way to produce composite, micro-scale fibers. In this paper, we report the successful development of novel keratin-based IPC fibers and also demonstrate the feasibility of using these fibers as sutures through a proof-of-concept <em>in vivo</em> study. Two composite fibers were produced: chitosan-keratin (CK) and keratin-keratin (KK). These fibers were evaluated for their physico-chemical, mechanical and biochemical properties. In the dry state, the CK fiber had a greater Young's modulus of about 2 GPa while the KK fiber registered a longer strain-at-break of about 100 % due to the strain-stiffening effect. Notably, the keratins were found to assemble into amyloids within the composite fibers based on Congo red staining and Wide-Angle X-Ray Scattering. Functionally, both fibers were malleable could be weaved, braided and knotted. When used as sutures to close incisional wounds in mice over 21 days, these fibers were found to elicit minimal host tissue response and were partially degraded over the duration. Interestingly, the KK fiber evoked a lower extent of immune cell response and fibrous capsule encapsulation that was comparable to commercial, non-absorbable Dafilon® sutures. This work demonstrated the possibility of producing keratin-based IPC fibers which may find practicality as medical sutures.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122878"},"PeriodicalIF":12.8,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405771","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}
Pub Date : 2024-10-05DOI: 10.1016/j.biomaterials.2024.122880
Junjie Tang, Penglei Zhang, Yadong Liu, Dingyu Hou, You Chen, Lili Cheng, Yifang Xue, Jie Liu
Pressure ulcers are a common issue in elderly and medically compromised individuals, posing significant challenges in healthcare. Human umbilical cord mesenchymal stem cells (HUMSCs) offer therapeutic benefits like inflammation modulation and tissue regeneration, yet challenges in cell survival, retention, and implantation rates limit their clinical application. Hydrogels in three-dimensional (3D) stem cell culture mimic the microenvironment, improving cell survival and therapeutic efficacy. A thermosensitive injectable hydrogel (adEHG) combining gallic acid-modified hydroxybutyl chitosan (HBC-GA) with soluble extracellular matrix (adECM) has been developed to address these challenges. The hybrid hydrogel, with favorable physical and chemical properties, shields stem cells from oxidative stress and boosts their therapeutic potential by clearing ROS. The adEHG hydrogel promotes angiogenesis, cell proliferation, and collagen deposition, further enhancing inflammation modulation and wound healing through the sustained release of therapeutic factors and cells. Additionally, the adEHG@HUMSC composite induces macrophage polarization towards an M2 phenotype, which is crucial for wound inflammation inhibition and successful healing. Our research significantly propels the field of stem cell-based therapies for pressure ulcer treatment and underscores the potential of the adEHG hydrogel as a valuable tool in advancing regenerative medicine.
{"title":"Revolutionizing pressure ulcer regeneration: Unleashing the potential of extracellular matrix-derived temperature-sensitive injectable antioxidant hydrogel for superior stem cell therapy","authors":"Junjie Tang, Penglei Zhang, Yadong Liu, Dingyu Hou, You Chen, Lili Cheng, Yifang Xue, Jie Liu","doi":"10.1016/j.biomaterials.2024.122880","DOIUrl":"10.1016/j.biomaterials.2024.122880","url":null,"abstract":"<div><div>Pressure ulcers are a common issue in elderly and medically compromised individuals, posing significant challenges in healthcare. Human umbilical cord mesenchymal stem cells (HUMSCs) offer therapeutic benefits like inflammation modulation and tissue regeneration, yet challenges in cell survival, retention, and implantation rates limit their clinical application. Hydrogels in three-dimensional (3D) stem cell culture mimic the microenvironment, improving cell survival and therapeutic efficacy. A thermosensitive injectable hydrogel (adEHG) combining gallic acid-modified hydroxybutyl chitosan (HBC-GA) with soluble extracellular matrix (adECM) has been developed to address these challenges. The hybrid hydrogel, with favorable physical and chemical properties, shields stem cells from oxidative stress and boosts their therapeutic potential by clearing ROS. The adEHG hydrogel promotes angiogenesis, cell proliferation, and collagen deposition, further enhancing inflammation modulation and wound healing through the sustained release of therapeutic factors and cells. Additionally, the adEHG@HUMSC composite induces macrophage polarization towards an M2 phenotype, which is crucial for wound inflammation inhibition and successful healing. Our research significantly propels the field of stem cell-based therapies for pressure ulcer treatment and underscores the potential of the adEHG hydrogel as a valuable tool in advancing regenerative medicine.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122880"},"PeriodicalIF":12.8,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386754","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}
Pub Date : 2024-10-05DOI: 10.1016/j.biomaterials.2024.122877
Xinbo Wei , Li Wang , Zheng Xing , Peng Chen , Xi He , Xiaoye Tuo , Haoran Su , Gang Zhou , Haifeng Liu , Yubo Fan
Endothelial cell (EC) dysfunction within the aorta has long been recognized as a prominent contributor to the progression of atherosclerosis and the subsequent failure of vascular graft transplantation. However, the direct relationship between EC dysfunction and vascular remodeling remains to be investigated. In this study, we sought to address this knowledge gap by employing a strategy involving the release of glutamine synthetase (GS), which effectively activated endothelial metabolism and mitigates EC dysfunction. To achieve this, we developed GS-loaded small-diameter vascular grafts (GSVG) through the electrospinning technique, utilizing dual-component solutions consisting of photo-crosslinkable hyaluronic acid and polycaprolactone. Through an in vitro model of oxidized low-density lipoprotein-induced injury in human umbilical vein endothelial cells (HUVECs), we provided compelling evidence that the GSVG promoted the restoration of motility, angiogenic sprouting, and proliferation in dysfunctional HUVECs by enhancing cellular metabolism. Furthermore, the sequencing results indicated that these effects were mediated by miR-122-5p-related signaling pathways. Remarkably, the GSVG also exhibited regulatory capabilities in shifting vascular smooth muscle cells towards a contractile phenotype, mitigating inflammatory responses and thereby preventing vascular calcification. Finally, our data demonstrated that GS incorporation significantly enhanced re-endothelialization of vascular grafts in a ferric chloride-injured rat model. Collectively, our results offer insights into the promotion of re-endothelialization in vascular grafts by restoring dysfunctional ECs through the augmentation of cellular metabolism.
{"title":"Glutamine synthetase accelerates re-endothelialization of vascular grafts by mitigating endothelial cell dysfunction in a rat model","authors":"Xinbo Wei , Li Wang , Zheng Xing , Peng Chen , Xi He , Xiaoye Tuo , Haoran Su , Gang Zhou , Haifeng Liu , Yubo Fan","doi":"10.1016/j.biomaterials.2024.122877","DOIUrl":"10.1016/j.biomaterials.2024.122877","url":null,"abstract":"<div><div>Endothelial cell (EC) dysfunction within the aorta has long been recognized as a prominent contributor to the progression of atherosclerosis and the subsequent failure of vascular graft transplantation. However, the direct relationship between EC dysfunction and vascular remodeling remains to be investigated. In this study, we sought to address this knowledge gap by employing a strategy involving the release of glutamine synthetase (GS), which effectively activated endothelial metabolism and mitigates EC dysfunction. To achieve this, we developed GS-loaded small-diameter vascular grafts (GSVG) through the electrospinning technique, utilizing dual-component solutions consisting of photo-crosslinkable hyaluronic acid and polycaprolactone. Through an in vitro model of oxidized low-density lipoprotein-induced injury in human umbilical vein endothelial cells (HUVECs), we provided compelling evidence that the GSVG promoted the restoration of motility, angiogenic sprouting, and proliferation in dysfunctional HUVECs by enhancing cellular metabolism. Furthermore, the sequencing results indicated that these effects were mediated by miR-122-5p-related signaling pathways. Remarkably, the GSVG also exhibited regulatory capabilities in shifting vascular smooth muscle cells towards a contractile phenotype, mitigating inflammatory responses and thereby preventing vascular calcification. Finally, our data demonstrated that GS incorporation significantly enhanced re-endothelialization of vascular grafts in a ferric chloride-injured rat model. Collectively, our results offer insights into the promotion of re-endothelialization in vascular grafts by restoring dysfunctional ECs through the augmentation of cellular metabolism.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122877"},"PeriodicalIF":12.8,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386751","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}
Cationic oncolytic polypeptides have gained increasing attention owing to their ability to directly lyse cancer cells and activate potent antitumor immunity. However, the low tumor cell selectivity and inherent toxicity induced by positive charges of oncolytic polypeptides hinder their systemic application. Herein, a tumor microenvironment-responsive nanoparticle (DNP) is developed by the self-assembly of a cationic oncolytic polypeptide (PLP) with a pH-sensitive anionic polypeptide via electrostatic interactions. After the formation of DNP, the positive charges of PLP are shielded. DNPs can keep stable in physiological conditions (pH 7.4) but respond to acidic tumor microenvironment (pH 6.8) to release oncolytic PLP. As a result, DNPs evoke potent immunogenic cell death by disrupting cell membranes, damaging mitochondria and increasing intracellular levels of reactive oxygen species. In vivo results indicate that DNPs significantly improve the biocompatibility of PLP, and inhibit tumor growth, recurrence and metastasis by direct oncolysis and activation of antitumor immune responses. In summary, these results indicate that pH-sensitive DNPs represent a prospective strategy to improve the tumor selectivity and biosafety of cationic polymers for oncolytic immunotherapy.
{"title":"Tumor microenvironment-activated polypeptide nanoparticles for oncolytic immunotherapy","authors":"Zhihui Guo , Tianze Huang , Xueli Lv , Renyong Yin , Pengqi Wan , Gao Li , Peng Zhang , Chunsheng Xiao , Xuesi Chen","doi":"10.1016/j.biomaterials.2024.122870","DOIUrl":"10.1016/j.biomaterials.2024.122870","url":null,"abstract":"<div><div>Cationic oncolytic polypeptides have gained increasing attention owing to their ability to directly lyse cancer cells and activate potent antitumor immunity. However, the low tumor cell selectivity and inherent toxicity induced by positive charges of oncolytic polypeptides hinder their systemic application. Herein, a tumor microenvironment-responsive nanoparticle (DNP) is developed by the self-assembly of a cationic oncolytic polypeptide (PLP) with a pH-sensitive anionic polypeptide via electrostatic interactions. After the formation of DNP, the positive charges of PLP are shielded. DNPs can keep stable in physiological conditions (pH 7.4) but respond to acidic tumor microenvironment (pH 6.8) to release oncolytic PLP. As a result, DNPs evoke potent immunogenic cell death by disrupting cell membranes, damaging mitochondria and increasing intracellular levels of reactive oxygen species. <em>In vivo</em> results indicate that DNPs significantly improve the biocompatibility of PLP, and inhibit tumor growth, recurrence and metastasis by direct oncolysis and activation of antitumor immune responses. In summary, these results indicate that pH-sensitive DNPs represent a prospective strategy to improve the tumor selectivity and biosafety of cationic polymers for oncolytic immunotherapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122870"},"PeriodicalIF":12.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379688","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}
Pub Date : 2024-10-03DOI: 10.1016/j.biomaterials.2024.122861
Yanfei Zhao , Seungbeom Lee , Tingyu Long , Hea-Lim Park , Tae-Woo Lee
Neuromorphic electronics use neural models in hardware to emulate brain-like behavior, and provide power-efficient, extremely compact, and massively-parallel processing, so they are ideal candidates for next-generation information-processing units. However, traditional rigid neuromorphic devices are limited by their unavoidable mechanical and geometrical mismatch with human tissues or organs. At the same time, the rapid development of these electronic devices has generated a large amount of electronic waste, thereby causing severe ecological problems. Natural biomaterials have mechanical properties compatible with biological tissues, and are environmentally benign, ultra-thin, and lightweight, so use of these materials can address these limitations and be used to create next-generation sustainable flexible neuromorphic electronics. Here, we explore the advantages of natural biomaterials in simulating synaptic behavior of sustainable neuromorphic devices. We present the flexibility, biocompatibility, and biodegradability of these neuromorphic devices, and consider the potential applicability of these properties in wearable and implantable bioelectronics. Finally, we consider the challenges of device fabrication and neuromorphic system integration by natural biomaterials, then suggest future research directions.
{"title":"Natural biomaterials for sustainable flexible neuromorphic devices","authors":"Yanfei Zhao , Seungbeom Lee , Tingyu Long , Hea-Lim Park , Tae-Woo Lee","doi":"10.1016/j.biomaterials.2024.122861","DOIUrl":"10.1016/j.biomaterials.2024.122861","url":null,"abstract":"<div><div>Neuromorphic electronics use neural models in hardware to emulate brain-like behavior, and provide power-efficient, extremely compact, and massively-parallel processing, so they are ideal candidates for next-generation information-processing units. However, traditional rigid neuromorphic devices are limited by their unavoidable mechanical and geometrical mismatch with human tissues or organs. At the same time, the rapid development of these electronic devices has generated a large amount of electronic waste, thereby causing severe ecological problems. Natural biomaterials have mechanical properties compatible with biological tissues, and are environmentally benign, ultra-thin, and lightweight, so use of these materials can address these limitations and be used to create next-generation sustainable flexible neuromorphic electronics. Here, we explore the advantages of natural biomaterials in simulating synaptic behavior of sustainable neuromorphic devices. We present the flexibility, biocompatibility, and biodegradability of these neuromorphic devices, and consider the potential applicability of these properties in wearable and implantable bioelectronics. Finally, we consider the challenges of device fabrication and neuromorphic system integration by natural biomaterials, then suggest future research directions.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122861"},"PeriodicalIF":12.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432211","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}
Pub Date : 2024-10-02DOI: 10.1016/j.biomaterials.2024.122874
Divya Bhansali , Nguyen H. Tu , Kenji Inoue , Shavonne Teng , Tianyu Li , Hung D. Tran , Dong H. Kim , Jessy Dong , Chloe J. Peach , Badr Sokrat , Dane D. Jensen , John C. Dolan , Seiichi Yamano , Valeria Mezzano Robinson , Nigel W. Bunnett , Donna G. Albertson , Kam W. Leong , Brian L. Schmidt
Oral cancer is notoriously painful. Activation of protease-activated receptor 2 (PAR2, encoded by F2RL1) by proteases in the cancer microenvironment is implicated in oral cancer pain. PAR2 is a G protein-coupled receptor (GPCR) expressed on neurons and cells in the cancer microenvironment. Sustained signaling of PAR2 from endosomes of neurons mediates sensitization and nociception. We focused on the differential contribution of PAR2 on oral cancer cells and neurons to oral cancer pain and whether encapsulation of a PAR2 inhibitor, AZ3451 in nanoparticles (NP) more effectively reverses PAR2 activation. We report that F2RL1 was overexpressed in human oral cancers and cancer cell lines. Deletion of F2RL1 on cancer cells reduced cancer-associated mechanical allodynia. A third-generation polyamidoamine dendrimer, functionalized with cholesterol was self-assembled into NPs encapsulating AZ3451. NP encapsulated AZ3451 (PAMAM-Chol-AZ NPs) more effectively reversed activation of PAR2 at the plasma membrane and early endosomes than free drug. The PAMAM-Chol-AZ NPs showed greater efficacy in reversing nociception than free drug, with respect to both level and duration, in three preclinical mouse models of oral cancer pain. The antinociceptive efficacy was confirmed with an operant orofacial assay. Genetic deletion of F2RL1 on cancer cells or F2rl1 on neurons each partially reversed mechanical cancer allodynia. The remaining nociception could be effectively reversed by PAMAM-Chol-AZ NPs. These findings suggest that PAR2 on oral cancer cells and neurons contribute to oral cancer nociception and NPs loaded with a PAR2 antagonist provide increased antinociception and improved oral function compared to free drug.
{"title":"PAR2 on oral cancer cells and nociceptors contributes to oral cancer pain that can be relieved by nanoparticle-encapsulated AZ3451","authors":"Divya Bhansali , Nguyen H. Tu , Kenji Inoue , Shavonne Teng , Tianyu Li , Hung D. Tran , Dong H. Kim , Jessy Dong , Chloe J. Peach , Badr Sokrat , Dane D. Jensen , John C. Dolan , Seiichi Yamano , Valeria Mezzano Robinson , Nigel W. Bunnett , Donna G. Albertson , Kam W. Leong , Brian L. Schmidt","doi":"10.1016/j.biomaterials.2024.122874","DOIUrl":"10.1016/j.biomaterials.2024.122874","url":null,"abstract":"<div><div>Oral cancer is notoriously painful. Activation of protease-activated receptor 2 (PAR<sub>2</sub>, encoded by <em>F2RL1</em>) by proteases in the cancer microenvironment is implicated in oral cancer pain. PAR<sub>2</sub> is a G protein-coupled receptor (GPCR) expressed on neurons and cells in the cancer microenvironment. Sustained signaling of PAR<sub>2</sub> from endosomes of neurons mediates sensitization and nociception. We focused on the differential contribution of PAR<sub>2</sub> on oral cancer cells and neurons to oral cancer pain and whether encapsulation of a PAR<sub>2</sub> inhibitor, AZ3451 in nanoparticles (NP) more effectively reverses PAR<sub>2</sub> activation. We report that <em>F2RL1</em> was overexpressed in human oral cancers and cancer cell lines. Deletion of <em>F2RL1</em> on cancer cells reduced cancer-associated mechanical allodynia. A third-generation polyamidoamine dendrimer, functionalized with cholesterol was self-assembled into NPs encapsulating AZ3451. NP encapsulated AZ3451 (PAMAM-Chol-AZ NPs) more effectively reversed activation of PAR<sub>2</sub> at the plasma membrane and early endosomes than free drug. The PAMAM-Chol-AZ NPs showed greater efficacy in reversing nociception than free drug, with respect to both level and duration, in three preclinical mouse models of oral cancer pain. The antinociceptive efficacy was confirmed with an operant orofacial assay. Genetic deletion of <em>F2RL1</em> on cancer cells or <em>F2rl1</em> on neurons each partially reversed mechanical cancer allodynia. The remaining nociception could be effectively reversed by PAMAM-Chol-AZ NPs. These findings suggest that PAR<sub>2</sub> on oral cancer cells and neurons contribute to oral cancer nociception and NPs loaded with a PAR<sub>2</sub> antagonist provide increased antinociception and improved oral function compared to free drug.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122874"},"PeriodicalIF":12.8,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441916","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}
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