Biomaterials最新文献

英文中文

Two-dimensionally cultured functional hepatocytes generated from human induced pluripotent stem cell-derived hepatic organoids for pharmaceutical research

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-01-28 DOI: 10.1016/j.biomaterials.2025.123148

Jumpei Inui , Yukiko Ueyama-Toba , Chiharu Imamura , Wakana Nagai , Rei Asano , Hiroyuki Mizuguchi

Human induced pluripotent stem (iPS) cell-derived hepatocyte-like cells (HLCs) are expected to replace primary human hepatocytes (PHHs) as a new stable source of hepatocytes for pharmaceutical research. However, HLCs have lower hepatic functions than PHHs, require a long time for differentiation and cannot be prepared in large quantities because they do not proliferate after their terminal differentiation. To overcome these problems, we here established hepatic organoids (iHOs) from HLCs. We then showed that the iHOs could proliferate approximately 10⁵-fold by more than 3 passages and expressed most hepatic genes more highly than HLCs. In addition, to enable their widespread use for in vitro drug discovery research, we developed a two-dimensional culture protocol for iHOs. Two-dimensionally cultured iHOs (iHO-Heps) expressed most of the major hepatocyte marker genes at much higher levels than HLCs, iHOs, and even PHHs. The iHO-Heps exhibited glycogen storage capacity, the capacity to uptake and release indocyanine green (ICG), albumin and urea secretion, and the capacity for bile canaliculi formation. Importantly, the iHO-Heps had the activity of major drug-metabolizing enzymes and responded to hepatotoxic drugs, much like PHHs. Thus, iHO-Heps overcome the limitations of the current models and promise to provide robust and reproducible pharmaceutical assays.

{"title":"Two-dimensionally cultured functional hepatocytes generated from human induced pluripotent stem cell-derived hepatic organoids for pharmaceutical research","authors":"Jumpei Inui , Yukiko Ueyama-Toba , Chiharu Imamura , Wakana Nagai , Rei Asano , Hiroyuki Mizuguchi","doi":"10.1016/j.biomaterials.2025.123148","DOIUrl":"10.1016/j.biomaterials.2025.123148","url":null,"abstract":"<div><div>Human induced pluripotent stem (iPS) cell-derived hepatocyte-like cells (HLCs) are expected to replace primary human hepatocytes (PHHs) as a new stable source of hepatocytes for pharmaceutical research. However, HLCs have lower hepatic functions than PHHs, require a long time for differentiation and cannot be prepared in large quantities because they do not proliferate after their terminal differentiation. To overcome these problems, we here established hepatic organoids (iHOs) from HLCs. We then showed that the iHOs could proliferate approximately 10<sup>5</sup>-fold by more than 3 passages and expressed most hepatic genes more highly than HLCs. In addition, to enable their widespread use for in vitro drug discovery research, we developed a two-dimensional culture protocol for iHOs. Two-dimensionally cultured iHOs (iHO-Heps) expressed most of the major hepatocyte marker genes at much higher levels than HLCs, iHOs, and even PHHs. The iHO-Heps exhibited glycogen storage capacity, the capacity to uptake and release indocyanine green (ICG), albumin and urea secretion, and the capacity for bile canaliculi formation. Importantly, the iHO-Heps had the activity of major drug-metabolizing enzymes and responded to hepatotoxic drugs, much like PHHs. Thus, iHO-Heps overcome the limitations of the current models and promise to provide robust and reproducible pharmaceutical assays.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123148"},"PeriodicalIF":12.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143129146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multifunctional nanozymes for sonodynamic-enhanced immune checkpoint blockade therapy by inactivating PI3K/AKT signal pathway

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-01-27 DOI: 10.1016/j.biomaterials.2025.123125

Mei Wen , Pu Qiu , Jialan Meng , Wenjing Zhao , Xiao Wang , Shining Niu , Cheng Tao , Nuo Yu , Zhigang Chen , Dong Xie

Insufficient activation efficacy and tumor immunosuppressive microenvironments hinder the infiltration of cytotoxic T lymphocytes (CTLs) for effective immunotherapy. Herein, the pH-selective multienzyme-mimetic nanozymes have been developed based on Pd-hemoporfin (Pd⁰/Pd²⁺‒H) nanoagents for tumor sono-immunotherapy via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway inactivation. The Pd⁰/Pd²⁺‒H is capable of catalase-mimetic, peroxidase-mimetic, and sonodynamic effects, creating an O₂-rich environment and elevating the reactive oxygen species (ROS) levels. The elevated ROS levels down-regulate the expression of PI3K and p-AKT on both gene and protein levels, leading to PI3K/AKT pathway inactivation. Subsequently, the augmented immunogenic cell death effectively recruits dendritic cells, presents tumor-associated antigens, and activates antitumor T-cell immunity. As a result, the combination of Pd⁰/Pd²⁺‒H and anti-programmed cell death protein ligand 1 results in growth restraints of primary and precaution of tumor metastases. This work offers insights into developing multienzyme-mimetic nanozymes in signaling pathway regulation and antitumor strategy.

{"title":"Multifunctional nanozymes for sonodynamic-enhanced immune checkpoint blockade therapy by inactivating PI3K/AKT signal pathway","authors":"Mei Wen , Pu Qiu , Jialan Meng , Wenjing Zhao , Xiao Wang , Shining Niu , Cheng Tao , Nuo Yu , Zhigang Chen , Dong Xie","doi":"10.1016/j.biomaterials.2025.123125","DOIUrl":"10.1016/j.biomaterials.2025.123125","url":null,"abstract":"<div><div>Insufficient activation efficacy and tumor immunosuppressive microenvironments hinder the infiltration of cytotoxic T lymphocytes (CTLs) for effective immunotherapy. Herein, the pH-selective multienzyme-mimetic nanozymes have been developed based on Pd-hemoporfin (Pd<sup>0</sup>/Pd<sup>2+</sup>‒H) nanoagents for tumor sono-immunotherapy via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway inactivation. The Pd<sup>0</sup>/Pd<sup>2+</sup>‒H is capable of catalase-mimetic, peroxidase-mimetic, and sonodynamic effects, creating an O<sub>2</sub>-rich environment and elevating the reactive oxygen species (ROS) levels. The elevated ROS levels down-regulate the expression of PI3K and <em>p</em>-AKT on both gene and protein levels, leading to PI3K/AKT pathway inactivation. Subsequently, the augmented immunogenic cell death effectively recruits dendritic cells, presents tumor-associated antigens, and activates antitumor T-cell immunity. As a result, the combination of Pd<sup>0</sup>/Pd<sup>2+</sup>‒H and anti-programmed cell death protein ligand 1 results in growth restraints of primary and precaution of tumor metastases. This work offers insights into developing multienzyme-mimetic nanozymes in signaling pathway regulation and antitumor strategy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123125"},"PeriodicalIF":12.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging prodrug and nano-drug delivery strategies for the detection and elimination of senescent tumor cells

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-01-27 DOI: 10.1016/j.biomaterials.2025.123129

Tao Wang , Xianbao Shi , Xiaolan Xu , Jiaming Zhang , Zhengdi Ma , Chen Meng , Dian Jiao , Yubo Wang , Yanfei Chen , Zhonggui He , Ying Zhu , He-nan Liu , Tianhong Zhang , Qikun Jiang

Tumor cellular senescence, characterized by reversible cell cycle arrest following anti-cancer therapies, presents a complex paradigm in oncology. Given that senescent tumor cells may promote angiogenesis, tumorigenesis, and metastasis, selective killing senescent cells (SCs)-a strategy termed senotherapy-has emerged as a promising approach to improve cancer treatment. However, the clinical implementation of senotherapy faces significant hurdles, including lack of precise methods for SCs identification and the potential for adverse effects associated with highly cytotoxic senolytic agents. In this account, we elucidate recent advancement in developing novel approaches for the detection and selective elimination of SCs, encompassing prodrugs, nanoparticles, and other cutting-edge drug delivery systems such as PROTAC technology and CAR T cell therapy. Furthermore, we explore the paradoxical nature of SCs, which can induce growth arrest in adjacent neoplastic cells and recruit immunomodulatory cells that contribute to tumor suppression. Therefore, we utilize SCs membrane as vehicles to elicit antitumor immunity and potentially augment existing anti-cancer therapies. Finally, the opportunities and challenges are put forward to facilitate the development and clinical transformation of SCs detection, elimination or utilization.

{"title":"Emerging prodrug and nano-drug delivery strategies for the detection and elimination of senescent tumor cells","authors":"Tao Wang , Xianbao Shi , Xiaolan Xu , Jiaming Zhang , Zhengdi Ma , Chen Meng , Dian Jiao , Yubo Wang , Yanfei Chen , Zhonggui He , Ying Zhu , He-nan Liu , Tianhong Zhang , Qikun Jiang","doi":"10.1016/j.biomaterials.2025.123129","DOIUrl":"10.1016/j.biomaterials.2025.123129","url":null,"abstract":"<div><div>Tumor cellular senescence, characterized by reversible cell cycle arrest following anti-cancer therapies, presents a complex paradigm in oncology. Given that senescent tumor cells may promote angiogenesis, tumorigenesis, and metastasis, selective killing senescent cells (SCs)-a strategy termed senotherapy-has emerged as a promising approach to improve cancer treatment. However, the clinical implementation of senotherapy faces significant hurdles, including lack of precise methods for SCs identification and the potential for adverse effects associated with highly cytotoxic senolytic agents. In this account, we elucidate recent advancement in developing novel approaches for the detection and selective elimination of SCs, encompassing prodrugs, nanoparticles, and other cutting-edge drug delivery systems such as PROTAC technology and CAR T cell therapy. Furthermore, we explore the paradoxical nature of SCs, which can induce growth arrest in adjacent neoplastic cells and recruit immunomodulatory cells that contribute to tumor suppression. Therefore, we utilize SCs membrane as vehicles to elicit antitumor immunity and potentially augment existing anti-cancer therapies. Finally, the opportunities and challenges are put forward to facilitate the development and clinical transformation of SCs detection, elimination or utilization.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123129"},"PeriodicalIF":12.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nanomedicine-enabled concurrent regulations of ROS generation and copper metabolism for sonodynamic-amplified tumor therapy

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-01-27 DOI: 10.1016/j.biomaterials.2025.123137

Jinhong Bing , Bangguo Zhou , Minqi Chen , Yucui Shen , Min Zhou , Han Lin , Wencheng Wu , Jianlin Shi

Sonodynamic therapy (SDT) shows substantial potentials in cancer treatment thanks to the deep tissue penetration of ultrasound. However, its clinical translation suffers from the potential damages to healthy tissues and the resistance of tumors, particularly from cancer stem-like cells (CSCs), to the ultrasound. To address these challenges, we designed a novel glutathione (GSH)-activated nanomedicine to simultaneously enhance the safety and efficacy of SDT by in situ regulating the generation of reactive oxygen species (ROS) and copper metabolism. This nanomedicine, Es@CuTCPP, was created by loading elesclomol (Es) onto CuTCPP nanosheets. By accumulating this nanomedicine in tumors, the Cu(II)-TCPP is reduced to the highly sonosensitive Cu(I)-TCPP by the intra-tumoral-overexpressed GSH, leading to the production of abundant ROS upon ultrasound exposure, which effectively kills large amounts of tumor cells. Concurrently, the released copper ions react with co-released Es to form a CuEs complex, which induces cuproptosis of CSCs surviving the ROS attack by disrupting cellular copper metabolism, evidently amplifying the effectiveness of SDT. This work presents the first paradigm of a GSH-activated and cuproptosis-enhanced SDT approach, offering a promising novel strategy for cancer therapy.

{"title":"Nanomedicine-enabled concurrent regulations of ROS generation and copper metabolism for sonodynamic-amplified tumor therapy","authors":"Jinhong Bing , Bangguo Zhou , Minqi Chen , Yucui Shen , Min Zhou , Han Lin , Wencheng Wu , Jianlin Shi","doi":"10.1016/j.biomaterials.2025.123137","DOIUrl":"10.1016/j.biomaterials.2025.123137","url":null,"abstract":"<div><div>Sonodynamic therapy (SDT) shows substantial potentials in cancer treatment thanks to the deep tissue penetration of ultrasound. However, its clinical translation suffers from the potential damages to healthy tissues and the resistance of tumors, particularly from cancer stem-like cells (CSCs), to the ultrasound. To address these challenges, we designed a novel glutathione (GSH)-activated nanomedicine to simultaneously enhance the safety and efficacy of SDT by in situ regulating the generation of reactive oxygen species (ROS) and copper metabolism. This nanomedicine, Es@CuTCPP, was created by loading elesclomol (Es) onto CuTCPP nanosheets. By accumulating this nanomedicine in tumors, the Cu(II)-TCPP is reduced to the highly sonosensitive Cu(I)-TCPP by the intra-tumoral-overexpressed GSH, leading to the production of abundant ROS upon ultrasound exposure, which effectively kills large amounts of tumor cells. Concurrently, the released copper ions react with co-released Es to form a CuEs complex, which induces cuproptosis of CSCs surviving the ROS attack by disrupting cellular copper metabolism, evidently amplifying the effectiveness of SDT. This work presents the first paradigm of a GSH-activated and cuproptosis-enhanced SDT approach, offering a promising novel strategy for cancer therapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123137"},"PeriodicalIF":12.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent advances in smart hydrogels derived from polysaccharides and their applications for wound dressing and healing

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-01-26 DOI: 10.1016/j.biomaterials.2025.123134

Xuehao Tian , Yuting Wen , Zhongxing Zhang , Jingling Zhu , Xia Song , Toan Thang Phan , Jun Li

Owing to their inherent biocompatibility and biodegradability, hydrogels derived from polysaccharides have emerged as promising candidates for wound management. However, the complex nature of wound healing often requires the development of smart hydrogels---intelligent materials capable of responding dynamically to specific physical or chemical stimuli. Over the past decade, an increasing number of stimuli-responsive polysaccharide-based hydrogels have been developed to treat various types of wounds. While a range of hydrogel types and their versatile functions for wound management have been discussed in the literature, there is still a need for a review of the crosslinking strategies used to create smart hydrogels from polysaccharides. This review provides a comprehensive overview of how stimuli-responsive hydrogels can be designed and made using five key polysaccharides: chitosan, hyaluronic acid, alginate, dextran, and cellulose. Various methods, such as chemical crosslinking, dynamic crosslinking, and physical crosslinking, which are used to form networks within these hydrogels, ultimately determine their ability to respond to stimuli, have been explored. This article further looks at different polysaccharide-based hydrogel wound dressings that can respond to factors such as reactive oxygen species, temperature, pH, glucose, light, and ultrasound in the wound environment and discusses how these responses can enhance wound healing. Finally, this review provides insights into how stimuli-responsive polysaccharide-based hydrogels can be developed further as advanced wound dressings in the future.

{"title":"Recent advances in smart hydrogels derived from polysaccharides and their applications for wound dressing and healing","authors":"Xuehao Tian , Yuting Wen , Zhongxing Zhang , Jingling Zhu , Xia Song , Toan Thang Phan , Jun Li","doi":"10.1016/j.biomaterials.2025.123134","DOIUrl":"10.1016/j.biomaterials.2025.123134","url":null,"abstract":"<div><div>Owing to their inherent biocompatibility and biodegradability, hydrogels derived from polysaccharides have emerged as promising candidates for wound management. However, the complex nature of wound healing often requires the development of smart hydrogels---intelligent materials capable of responding dynamically to specific physical or chemical stimuli. Over the past decade, an increasing number of stimuli-responsive polysaccharide-based hydrogels have been developed to treat various types of wounds. While a range of hydrogel types and their versatile functions for wound management have been discussed in the literature, there is still a need for a review of the crosslinking strategies used to create smart hydrogels from polysaccharides. This review provides a comprehensive overview of how stimuli-responsive hydrogels can be designed and made using five key polysaccharides: chitosan, hyaluronic acid, alginate, dextran, and cellulose. Various methods, such as chemical crosslinking, dynamic crosslinking, and physical crosslinking, which are used to form networks within these hydrogels, ultimately determine their ability to respond to stimuli, have been explored. This article further looks at different polysaccharide-based hydrogel wound dressings that can respond to factors such as reactive oxygen species, temperature, pH, glucose, light, and ultrasound in the wound environment and discusses how these responses can enhance wound healing. Finally, this review provides insights into how stimuli-responsive polysaccharide-based hydrogels can be developed further as advanced wound dressings in the future.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123134"},"PeriodicalIF":12.8,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143093285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Photochemical bomb: Precision nuclear targeting to activate cGAS-STING pathway for enhanced bladder cancer immunotherapy

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-01-25 DOI: 10.1016/j.biomaterials.2025.123126

Dexiang Feng , Xiaoying Kang , He Wang , Zhangxin He , Haodong Xu , Yue Li , Aohua Fan , Hongbo Xu , Yuan Zhang , Jianwen Song , Jianquan Hou , Ji Qi , Weijie Zhang

Activating the cGAS-STING pathway presents a promising strategy to enhance the innate immunity and combat the immunosuppressive tumor microenvironment. One key mechanism for triggering this pathway involves the release of damaged DNA fragments caused by nuclear DNA damage. However, conventional cGAS-STING agonists often suffer from limited nucleus-targeting efficiency and potential biotoxicity. In this study, we develop a novel nucleus-targeting theranostic nanoplatform designed to synergistically activate the cGAS-STING pathway through the combination of photodynamic therapy (PDT) and cisplatin chemotherapy for orthotopic bladder cancer treatment. The nanoplatform integrates a new high-performance type-I photosensitizer with near-infrared-II emission, a TAT^SA peptide for enhanced nuclear targeting, and a biosafe platinum (IV) cisplatin prodrug. Upon NIR laser irradiation, the nanoagent delivers synergistic nucleus-targeted PDT and chemotherapy, causing substantial DNA damage and the release of double-stranded DNA, which subsequently activates the cGAS-STING pathway and triggers potent immunomodulation. This activation promotes dendritic cells maturation, enhances cytotoxic T infiltration, and facilitates the formation of memory T cells, leading to immune microenvironment remodeling, and long-lasting immune memory, thus effectively inhibiting orthotopic bladder tumors and reducing the risk of metastasis. These findings highlight the substantial potential of this strategy to overcome the limitations of current immunotherapies by leveraging nucleus-targeted PDT to activate the cGAS-STING pathway for cancer treatment.

{"title":"Photochemical bomb: Precision nuclear targeting to activate cGAS-STING pathway for enhanced bladder cancer immunotherapy","authors":"Dexiang Feng , Xiaoying Kang , He Wang , Zhangxin He , Haodong Xu , Yue Li , Aohua Fan , Hongbo Xu , Yuan Zhang , Jianwen Song , Jianquan Hou , Ji Qi , Weijie Zhang","doi":"10.1016/j.biomaterials.2025.123126","DOIUrl":"10.1016/j.biomaterials.2025.123126","url":null,"abstract":"<div><div>Activating the cGAS-STING pathway presents a promising strategy to enhance the innate immunity and combat the immunosuppressive tumor microenvironment. One key mechanism for triggering this pathway involves the release of damaged DNA fragments caused by nuclear DNA damage. However, conventional cGAS-STING agonists often suffer from limited nucleus-targeting efficiency and potential biotoxicity. In this study, we develop a novel nucleus-targeting theranostic nanoplatform designed to synergistically activate the cGAS-STING pathway through the combination of photodynamic therapy (PDT) and cisplatin chemotherapy for orthotopic bladder cancer treatment. The nanoplatform integrates a new high-performance type-I photosensitizer with near-infrared-II emission, a TAT<sup>SA</sup> peptide for enhanced nuclear targeting, and a biosafe platinum (IV) cisplatin prodrug. Upon NIR laser irradiation, the nanoagent delivers synergistic nucleus-targeted PDT and chemotherapy, causing substantial DNA damage and the release of double-stranded DNA, which subsequently activates the cGAS-STING pathway and triggers potent immunomodulation. This activation promotes dendritic cells maturation, enhances cytotoxic T infiltration, and facilitates the formation of memory T cells, leading to immune microenvironment remodeling, and long-lasting immune memory, thus effectively inhibiting orthotopic bladder tumors and reducing the risk of metastasis. These findings highlight the substantial potential of this strategy to overcome the limitations of current immunotherapies by leveraging nucleus-targeted PDT to activate the cGAS-STING pathway for cancer treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123126"},"PeriodicalIF":12.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Self-healing and cell-free vascular grafts

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-01-25 DOI: 10.1016/j.biomaterials.2025.123121

Yulun Wu , Mohamed Alaa Mohamed , Tai Yi , Arundhati Das , Clayton L. Rumsey , Martin Trebbin , Christopher K. Breuer , Stelios T. Andreadis

We developed an innovative self-healing tissue engineering vessel (SH-TEV) that heals fast after repeated needle punctures, while maintaining artery like mechanical strength and toughness even under wet conditions. The SH-TEV is designed as a bilayer tube engineered by electrospinning an autonomous self-healing polyurethane, PU-DAA, around a tube of a native biomaterial, small intestinal submucosa (SIS), that can be functionalized with biomolecules to recruit host cells and promote endothelialization. The self-healing PU-DAA was designed to incorporate multi-strength H-bonds and reversible hydrazone bonds and exhibited high strength (3.95 ± 0.16 MPa), toughness (23.01 ± 2.37 MJ/m³), and fast autonomous self-healing (86.44 ± 6.65 % after 12 h) under physiological conditions. The self-healing layer supported attachment, spreading and proliferation of fibroblasts, indicating biocompatibility. When SH-TEVs were implanted as interpositional grafts into the rat aorta for 4 weeks, they remained patent without any thrombosis (100 % animal survival and 100 % graft patency), were endothelialized and developed a smooth muscle cell containing vascular wall. In addition, they showed excellent self-healing ability following needle puncture (hemostatic time <40 s) immediately after implantation and four weeks later. Collectively, these results demonstrate the potential of SH-TEVs as vascular access conduits for hemodialysis applications.

{"title":"Self-healing and cell-free vascular grafts","authors":"Yulun Wu , Mohamed Alaa Mohamed , Tai Yi , Arundhati Das , Clayton L. Rumsey , Martin Trebbin , Christopher K. Breuer , Stelios T. Andreadis","doi":"10.1016/j.biomaterials.2025.123121","DOIUrl":"10.1016/j.biomaterials.2025.123121","url":null,"abstract":"<div><div>We developed an innovative self-healing tissue engineering vessel (SH-TEV) that heals fast after repeated needle punctures, while maintaining artery like mechanical strength and toughness even under wet conditions. The SH-TEV is designed as a bilayer tube engineered by electrospinning an autonomous self-healing polyurethane, PU-DAA, around a tube of a native biomaterial, small intestinal submucosa (SIS), that can be functionalized with biomolecules to recruit host cells and promote endothelialization. The self-healing PU-DAA was designed to incorporate multi-strength H-bonds and reversible hydrazone bonds and exhibited high strength (3.95 ± 0.16 MPa), toughness (23.01 ± 2.37 MJ/m<sup>3</sup>), and fast autonomous self-healing (86.44 ± 6.65 % after 12 h) under physiological conditions. The self-healing layer supported attachment, spreading and proliferation of fibroblasts, indicating biocompatibility. When SH-TEVs were implanted as interpositional grafts into the rat aorta for 4 weeks, they remained patent without any thrombosis (100 % animal survival and 100 % graft patency), were endothelialized and developed a smooth muscle cell containing vascular wall. In addition, they showed excellent self-healing ability following needle puncture (hemostatic time <40 s) immediately after implantation and four weeks later. Collectively, these results demonstrate the potential of SH-TEVs as vascular access conduits for hemodialysis applications.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123121"},"PeriodicalIF":12.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ultrasonic disruption of circulating amyloid β aggregates via phase-change peptide nanoemulsions

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-01-25 DOI: 10.1016/j.biomaterials.2025.123146

Inhye Kim , Scott H. Medina

Amyloid β (Aβ) assemblies exist not only in the central nervous system, but can circulate within the bloodstream to trigger and exacerbate peripheral, cerebrovascular, and neurodegenerative disorders. Eliminating excess peripheral Aβ fibrils, therefore, holds promise to improve the management of amyloid-related diseases. Here, we present nanoemulsion-mediated ultrasonic ablation of circulating Aβ fibrils to both destroy established plaques and prevent the re-growth of ablated fragments back into toxic species. This approach is made possible using a de novo designed peptide emulsifier that contains the self-associating sequence from the amyloid precursor protein. Emulsification of the peptide surfactant with fluorous nanodroplets produces contrast agents that rapidly adsorb Aβ assemblies and allows their ultrasound-controlled destruction via acoustic cavitation. Vessel-mimetic flow experiments demonstrate that nanoemulsion-assisted Aβ disruption can be achieved in circulation using clinical diagnostic ultrasound transducers. Additional cell-based assays confirm the ablated fragments are less toxic to neuronal and glial cells compared to mature fibrils, and can be rapidly phagocytosed by both peripheral and brain macrophages. These results highlight the potential of nanoemulsion contrast agents to deliver new imaging enabled strategies for non-invasive management of Aβ-related diseases using traditional diagnostic ultrasound modalities.

{"title":"Ultrasonic disruption of circulating amyloid β aggregates via phase-change peptide nanoemulsions","authors":"Inhye Kim , Scott H. Medina","doi":"10.1016/j.biomaterials.2025.123146","DOIUrl":"10.1016/j.biomaterials.2025.123146","url":null,"abstract":"<div><div>Amyloid <em>β</em> (A<em>β</em>) assemblies exist not only in the central nervous system, but can circulate within the bloodstream to trigger and exacerbate peripheral, cerebrovascular, and neurodegenerative disorders. Eliminating excess peripheral A<em>β</em> fibrils, therefore, holds promise to improve the management of amyloid-related diseases. Here, we present nanoemulsion-mediated ultrasonic ablation of circulating A<em>β</em> fibrils to both destroy established plaques and prevent the re-growth of ablated fragments back into toxic species. This approach is made possible using a <em>de novo</em> designed peptide emulsifier that contains the self-associating sequence from the amyloid precursor protein. Emulsification of the peptide surfactant with fluorous nanodroplets produces contrast agents that rapidly adsorb A<em>β</em> assemblies and allows their ultrasound-controlled destruction via acoustic cavitation. Vessel-mimetic flow experiments demonstrate that nanoemulsion-assisted A<em>β</em> disruption can be achieved in circulation using clinical diagnostic ultrasound transducers. Additional cell-based assays confirm the ablated fragments are less toxic to neuronal and glial cells compared to mature fibrils, and can be rapidly phagocytosed by both peripheral and brain macrophages. These results highlight the potential of nanoemulsion contrast agents to deliver new imaging enabled strategies for non-invasive management of A<em>β</em>-related diseases using traditional diagnostic ultrasound modalities.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123146"},"PeriodicalIF":12.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tailoring extracellular matrix niches: Impact of glycosaminoglycan content on multiple differentiation of human mesenchymal stem cells

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-01-25 DOI: 10.1016/j.biomaterials.2025.123130

Xingxing Yang , Maitraee Mistry , Abigail Dee Chen , Barbara Pui Chan

Glycosaminoglycan (GAG) represents an important extracellular matrix (ECM), particularly in GAG-rich tissues such as nucleus pulposus and cartilage. The ratio of GAGs/hydroxyproline (HYP) is an indicator of the relative abundance of the space-filling GAG matrix to the fibrous collagen matrix in a particular tissue. Here, we hypothesize that ECM niche with different GAG/HYP ratios will affect the outcomes of multiple differentiation of human mesenchymal stem cells (hMSCs). Specifically, we fabricated collagen-based biomaterials with different GAG/HYP ratios, and differentiate hMSCs in these materials towards osteogenic, chondrogenic and discogenic lineages. In osteogenic differentiation, Collagen without GAG (GAG/HYP ratio 0) showed higher calcium (Ca) and phosphorus (P) deposition and Ca/P ratio, more biomimetic ultrastructure, and better osteogenic phenotypic expression. For chondrogenic differentiation, aminated collagen (aCol-GAG) with intermediate GAG content (GAG/HYP ratio 5.0:1) showed higher GAG deposition, more biomimetic ultrastructure, and better chondrogenic phenotype. In discogenic differentiation, aminated collagen-aminated hyaluronic acid (aHA)-GAG (aCol-aHA-GAG) with the highest GAG content (GAG/HYP ratio 19.8:1), showed intensive GAG deposition, biomimetic ultrastructure, and higher phenotypic marker expression. This study contributes to developing collagen-based biomimetic materials with different GAG/HYP ratios and suggests the use of tissue-specific GAG/HYP ratio as a scaffold design parameter for hMSCs-based musculoskeletal tissue engineering. (198 words).

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引用次数: 0

Flexible, surface-lighting MicroLED skin patch for multiple human skincare

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-01-25 DOI: 10.1016/j.biomaterials.2025.123139

Jae Hee Lee , Min Seo Kim , Seung Hyung Lee , Sang Hyun Park , Ki Yun Nam , Jaehun An , Myoung Song , Ki Soo Kim , Sang Ho Oh , Taek-Soo Kim , Keon Jae Lee

As the global population ages, concerns regarding aesthetic appearance have increased. Wearable light-emitting diode (LED) devices have received significant attention in the cosmetic fields due to their non-invasive, non-thermal, home-use characteristics. However, conventional bulk LED chips have limitations in flexibility and uniform irradiation, hindering efficient light penetration into the skin. Here, we introduce a flexible, surface-lighting microLED (FSLED) patch with uniform light-emission for various skincare applications. The FSLED was fabricated using a pick-and-place transfer technique, which allows for high-density irradiation over the large area, while maintaining outstanding mechanical flexibility. In addition, the FSLED was designed to deliver light efficiently and emit light evenly by conforming to the skin. Finally, we prove the effect of the FSLED for pore tightening and skin rejuvenation through clinical trials.

引用次数: 0

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