Pub Date : 2024-06-07DOI: 10.1016/j.biomaterials.2024.122659
Fan Yang , Rui Shu , Wenyu Dai , Bin Li , Chuang Liu , Hang Yang , Hannah M. Johnson , Sheng Yu , Ding Bai , Weizhong Yang , Yi Deng
Pathogenic infection leads to excessive senescent cell accumulation and stagnation of wound healing. To address these issues, we devise and develop a hydrogen selenide (H2Se)-evolving bio-heterojunction (bio-HJ) composed of graphene oxide (GO) and FeSe2 to deracinate bacterial infection, suppress cellular senescence and remedy recalcitrant infected wounds. Excited by near-infrared (NIR) laser, the bio-HJ exerts desired photothermal and photodynamic effects, resulting in rapid disinfection. The crafted bio-HJ could also evolve gaseous H2Se to inhibit cellular senescence and dampen inflammation. Mechanism studies reveal the anti-senescence effects of H2Se-evolving bio-HJ are mediated by selenium pathway and glutathione peroxidase 1 (GPX1). More critically, in vivo experiments authenticate that the H2Se-evolving bio-HJ could inhibit cellular senescence and potentiate wound regeneration in rats. As envisioned, our work not only furnishes the novel gasotransmitter-delivering bio-HJ for chronic infected wounds, but also gets insight into the development of anti-senescence biomaterials.
{"title":"H2Se-evolving bio-heterojunctions promote cutaneous regeneration in infected wounds by inhibiting excessive cellular senescence","authors":"Fan Yang , Rui Shu , Wenyu Dai , Bin Li , Chuang Liu , Hang Yang , Hannah M. Johnson , Sheng Yu , Ding Bai , Weizhong Yang , Yi Deng","doi":"10.1016/j.biomaterials.2024.122659","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.122659","url":null,"abstract":"<div><p>Pathogenic infection leads to excessive senescent cell accumulation and stagnation of wound healing. To address these issues, we devise and develop a hydrogen selenide (H<sub>2</sub>Se)-evolving bio-heterojunction (bio-HJ) composed of graphene oxide (GO) and FeSe<sub>2</sub> to deracinate bacterial infection, suppress cellular senescence and remedy recalcitrant infected wounds. Excited by near-infrared (NIR) laser, the bio-HJ exerts desired photothermal and photodynamic effects, resulting in rapid disinfection. The crafted bio-HJ could also evolve gaseous H<sub>2</sub>Se to inhibit cellular senescence and dampen inflammation. Mechanism studies reveal the anti-senescence effects of H<sub>2</sub>Se-evolving bio-HJ are mediated by selenium pathway and glutathione peroxidase 1 (GPX1). More critically, <em>in vivo</em> experiments authenticate that the H<sub>2</sub>Se-evolving bio-HJ could inhibit cellular senescence and potentiate wound regeneration in rats. As envisioned, our work not only furnishes the novel gasotransmitter-delivering bio-HJ for chronic infected wounds, but also gets insight into the development of anti-senescence biomaterials.</p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141298185","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 : 2024-06-05DOI: 10.1016/j.biomaterials.2024.122647
Hulya Bayraktutan , Peter Symonds , Victoria A. Brentville , Cara Moloney , Charlotte Galley , Clare L. Bennett , Alvaro Mata , Lindy Durrant , Cameron Alexander , Pratik Gurnani
DNA technology has emerged as a promising route to accelerated manufacture of sequence agnostic vaccines. For activity, DNA vaccines must be protected and delivered to the correct antigen presenting cells. However, the physicochemical properties of the vector must be carefully tuned to enhance interaction with immune cells and generate sufficient immune response for disease protection. In this study, we have engineered a range of polymer-based nanocarriers based on the poly(beta-amino ester) (PBAE) polycation platform to investigate the role that surface poly(ethylene glycol) (PEG) density has on pDNA encapsulation, formulation properties and gene transfectability both in vitro and in vivo. We achieved this by synthesising a non-PEGylated and PEGylated PBAE and produced formulations containing these PBAEs, and mixed polyplexes to tune surface PEG density. All polymers and co-formulations produced small polyplex nanoparticles with almost complete encapsulation of the cargo in all cases. Despite high gene transfection in HEK293T cells, only the fully PEGylated and mixed formulations displayed significantly higher expression of the reporter gene than the negative control in dendritic cells. Further in vivo studies with a bivalent SARS-CoV-2 pDNA vaccine revealed that only the mixed formulation led to strong antigen specific T-cell responses, however this did not translate into the presence of serum antibodies indicating the need for further studies into improving immunisation with polymer delivery systems.
{"title":"Sparsely PEGylated poly(beta-amino ester) polyplexes enhance antigen specific T-cell response of a bivalent SARS-CoV-2 DNA vaccine","authors":"Hulya Bayraktutan , Peter Symonds , Victoria A. Brentville , Cara Moloney , Charlotte Galley , Clare L. Bennett , Alvaro Mata , Lindy Durrant , Cameron Alexander , Pratik Gurnani","doi":"10.1016/j.biomaterials.2024.122647","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.122647","url":null,"abstract":"<div><p>DNA technology has emerged as a promising route to accelerated manufacture of sequence agnostic vaccines. For activity, DNA vaccines must be protected and delivered to the correct antigen presenting cells. However, the physicochemical properties of the vector must be carefully tuned to enhance interaction with immune cells and generate sufficient immune response for disease protection. In this study, we have engineered a range of polymer-based nanocarriers based on the poly(beta-amino ester) (PBAE) polycation platform to investigate the role that surface poly(ethylene glycol) (PEG) density has on pDNA encapsulation, formulation properties and gene transfectability both in vitro and in vivo. We achieved this by synthesising a non-PEGylated and PEGylated PBAE and produced formulations containing these PBAEs, and mixed polyplexes to tune surface PEG density. All polymers and co-formulations produced small polyplex nanoparticles with almost complete encapsulation of the cargo in all cases. Despite high gene transfection in HEK293T cells, only the fully PEGylated and mixed formulations displayed significantly higher expression of the reporter gene than the negative control in dendritic cells. Further in vivo studies with a bivalent SARS-CoV-2 pDNA vaccine revealed that only the mixed formulation led to strong antigen specific T-cell responses, however this did not translate into the presence of serum antibodies indicating the need for further studies into improving immunisation with polymer delivery systems.</p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0142961224001819/pdfft?md5=eef5d088f0b9570b7a2a9cabbf019f66&pid=1-s2.0-S0142961224001819-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141325154","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 : 2024-06-05DOI: 10.1016/j.biomaterials.2024.122649
Kun Xu , Yanan Zou , Chuanchuan Lin , Liangshuai Zhang , Meijun Tan , Meng Li , Jing Wu , Xuan Li , Ye He , Peng Liu , Ke Li , Kaiyong Cai
Innovative solutions are required for the intervention of implant associated infections (IAIs), especially for bone defect patients with chronic inflammatory diseases like diabetes mellitus (DM). The complex immune microenvironment of infections renders implants with direct antibacterial ability inadequate for the prolonged against of bacterial infections. Herein, a synergistic treatment strategy was presented that combined sonodynamic therapy (SDT) with adaptive immune modulation to treat IAIs in diabetes patients. A multifunctional coating was created on the surface of titanium (Ti) implants, consisting of manganese dioxide nanoflakes (MnO2 NFs) with cascade catalytic enzyme activity and a responsive degradable hydrogel containing a sonosensitizer. The reactive oxygen species (ROS) generated by glucose-hydrogen peroxide (H2O2) cascade catalysis and ultrasound (US) activation sonosensitizer helped kill bacteria and release bacterial antigens. Meanwhile, Mn2+ facilitated dendritic cells (DCs) maturation, enhancing antigen presentation to activate both cellular and humoral adaptive immunity against bacterial infections. This approach effectively eliminated bacteria in established diabetic IAIs model and activated systemic antibacterial immunity, providing long-term antibacterial protection. This study presents a non-antibiotic immunotherapeutic strategy for fighting IAIs in chronic diseases.
{"title":"Cascade catalysis nanozyme for interfacial functionalization in combating implant infections associated with diabetes via sonodynamic therapy and adaptive immune activation","authors":"Kun Xu , Yanan Zou , Chuanchuan Lin , Liangshuai Zhang , Meijun Tan , Meng Li , Jing Wu , Xuan Li , Ye He , Peng Liu , Ke Li , Kaiyong Cai","doi":"10.1016/j.biomaterials.2024.122649","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.122649","url":null,"abstract":"<div><p>Innovative solutions are required for the intervention of implant associated infections (IAIs), especially for bone defect patients with chronic inflammatory diseases like diabetes mellitus (DM). The complex immune microenvironment of infections renders implants with direct antibacterial ability inadequate for the prolonged against of bacterial infections. Herein, a synergistic treatment strategy was presented that combined sonodynamic therapy (SDT) with adaptive immune modulation to treat IAIs in diabetes patients. A multifunctional coating was created on the surface of titanium (Ti) implants, consisting of manganese dioxide nanoflakes (MnO<sub>2</sub> NFs) with cascade catalytic enzyme activity and a responsive degradable hydrogel containing a sonosensitizer. The reactive oxygen species (ROS) generated by glucose-hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) cascade catalysis and ultrasound (US) activation sonosensitizer helped kill bacteria and release bacterial antigens. Meanwhile, Mn<sup>2+</sup> facilitated dendritic cells (DCs) maturation, enhancing antigen presentation to activate both cellular and humoral adaptive immunity against bacterial infections. This approach effectively eliminated bacteria in established diabetic IAIs model and activated systemic antibacterial immunity, providing long-term antibacterial protection. This study presents a non-antibiotic immunotherapeutic strategy for fighting IAIs in chronic diseases.</p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141286004","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 : 2024-06-03DOI: 10.1016/j.biomaterials.2024.122650
Wenyi Zheng , Li Ma , Xueshi Luo , Renhao Xu , Zhiying Cao , Yanni He , Yanzhou Chang , Yuanyuan You , Tianfeng Chen , Hongmei Liu
The dysfunction of bone mesenchymal stem cells (BMSCs), caused by the physical and chemical properties of the inflammatory and repair phases of bone regeneration, contributes to the failure of bone regeneration. To meet the spatiotemporal needs of BMSCs in different phases, designing biocompatible materials that respond to external stimuli, improve migration in the inflammatory phase, reduce apoptosis in the proliferative phase, and clear the hurdle in the differentiation phase of BMSCs is an effective strategy for multistage repair of bone defects. In this study, we designed a cascade-response functional composite hydrogel (Gel@Eb/HA) to regulate BMSCs dysfunction in vitro and in vivo. Gel@Eb/HA improved the migration of BMSCs by upregulating the expression of chemokine (C–C motif) ligand 5 (CCL5) during the inflammatory phase. Ultrasound (US) triggered the rapid release of Ebselen (Eb), eliminating the accumulation of reactive oxygen species (ROS) in BMSCs, and reversing apoptosis under oxidative stress. Continued US treatment accelerated the degradation of the materials, thereby providing Ca2+ for the osteogenic differentiation of BMSCs. Altogether, our study highlights the prospects of US-controlled intelligent system, that provides a novel strategy for addressing the complexities of multistage bone repair.
骨间充质干细胞(BMSCs)在骨再生的炎症期和修复期的物理和化学特性导致其功能失调,是骨再生失败的原因之一。为了满足 BMSCs 在不同阶段的时空需求,设计能对外界刺激做出反应的生物相容性材料,改善 BMSCs 在炎症阶段的迁移、减少增殖阶段的凋亡以及扫清分化阶段的障碍,是多阶段修复骨缺损的有效策略。在这项研究中,我们设计了一种级联反应功能复合水凝胶(Gel@Eb/HA)来调节 BMSCs 在体外和体内的功能障碍。在炎症阶段,Gel@Eb/HA通过上调趋化因子(C-C基序)配体5(CCL5)的表达改善了BMSCs的迁移。超声波(US)可引发依布硒的快速释放,从而消除活性氧(ROS)在BMSCs中的积累,并逆转氧化应激下的细胞凋亡。持续的 US 处理加速了材料的降解,从而为 BMSCs 的成骨分化提供了 Ca2+。总之,我们的研究凸显了由 US 控制的智能系统的前景,它为解决多阶段骨修复的复杂性提供了一种新策略。
{"title":"Ultrasound-triggered functional hydrogel promotes multistage bone regeneration","authors":"Wenyi Zheng , Li Ma , Xueshi Luo , Renhao Xu , Zhiying Cao , Yanni He , Yanzhou Chang , Yuanyuan You , Tianfeng Chen , Hongmei Liu","doi":"10.1016/j.biomaterials.2024.122650","DOIUrl":"10.1016/j.biomaterials.2024.122650","url":null,"abstract":"<div><p>The dysfunction of bone mesenchymal stem cells (BMSCs), caused by the physical and chemical properties of the inflammatory and repair phases of bone regeneration, contributes to the failure of bone regeneration. To meet the spatiotemporal needs of BMSCs in different phases, designing biocompatible materials that respond to external stimuli, improve migration in the inflammatory phase, reduce apoptosis in the proliferative phase, and clear the hurdle in the differentiation phase of BMSCs is an effective strategy for multistage repair of bone defects. In this study, we designed a cascade-response functional composite hydrogel (Gel@Eb/HA) to regulate BMSCs dysfunction <em>in vitro</em> and <em>in vivo</em>. Gel@Eb/HA improved the migration of BMSCs by upregulating the expression of chemokine (C–C motif) ligand 5 (CCL5) during the inflammatory phase. Ultrasound (US) triggered the rapid release of Ebselen (Eb), eliminating the accumulation of reactive oxygen species (ROS) in BMSCs, and reversing apoptosis under oxidative stress. Continued US treatment accelerated the degradation of the materials, thereby providing Ca<sup>2+</sup> for the osteogenic differentiation of BMSCs. Altogether, our study highlights the prospects of US-controlled intelligent system, that provides a novel strategy for addressing the complexities of multistage bone repair.</p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141281565","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 : 2024-06-02DOI: 10.1016/j.biomaterials.2024.122646
Jinbin Pan , Jiaojiao Wang , Yujie Zhao , Bing Han , Gang Shu , Min Ma , Xu Wang , Xi Wei , Wenjing Hou , Shao-Kai Sun
Anastomotic leaks are among the most dreaded complications following gastrointestinal (GI) surgery, and contrast-enhanced X-ray gastroenterography is considered the preferred initial diagnostic method for GI leaks. However, from fundamental research to clinical practice, the only oral iodinated contrast agents currently available for GI leaks detection are facing several challenges, including low sensitivity, iodine allergy, and contraindications in patients with thyroid diseases. Herein, we propose a cinematic contrast-enhanced X-ray gastroenterography for the real-time detection of GI leaks with an iodine-free bismuth chelate (Bi-DTPA) for the first time. The Bi-DTPA, synthesized through a straightforward one-pot method, offers distinct advantages such as no need for purification, a nearly 100 % yield, large-scale production capability, and good biocompatibility. The remarkable X-ray attenuation properties of Bi-DTPA enable real-time dynamic visualization of whole GI tract under both X-ray gastroenterography and computed tomography (CT) imaging. More importantly, the leaky site and severity can be both clearly displayed during Bi-DTPA-enhanced gastroenterography in a rat model with esophageal leakage. The proposed movie-like Bi-DTPA-enhanced X-ray imaging approach presents a promising alternative to traditional GI radiography based on iodinated molecules. It demonstrates significant potential in addressing concerns related to iodine-associated adverse effects and offers an alternative method for visually detecting gastrointestinal leaks.
吻合口漏是胃肠道(GI)手术后最可怕的并发症之一,造影剂增强 X 射线胃肠造影术被认为是胃肠道漏的首选初步诊断方法。然而,从基础研究到临床实践,目前唯一可用于胃肠道渗漏检测的口服碘造影剂都面临着一些挑战,包括灵敏度低、碘过敏以及甲状腺疾病患者的禁忌症。在此,我们首次提出使用无碘铋螯合物(Bi-DTPA)进行电影对比增强 X 射线胃肠造影术,以实时检测消化道漏液。Bi-DTPA 通过简单的一锅法合成,具有无需纯化、收率接近 100%、可大规模生产、生物相容性好等显著优势。Bi-DTPA 具有出色的 X 射线衰减特性,可在 X 射线胃肠造影和计算机断层扫描(CT)成像下实时动态地观察整个消化道。更重要的是,在食管渗漏的大鼠模型中,Bi-DTPA 增强胃肠造影可清晰显示渗漏部位和严重程度。所提出的类似电影的 Bi-DTPA 增强 X 射线成像方法是基于碘化分子的传统胃肠道放射成像的一种有前途的替代方法。它在解决与碘相关的不良反应方面显示出巨大的潜力,并为目测胃肠道渗漏提供了另一种方法。
{"title":"Real-time detection of gastrointestinal leaks via bismuth chelate-enhanced X-ray gastroenterography","authors":"Jinbin Pan , Jiaojiao Wang , Yujie Zhao , Bing Han , Gang Shu , Min Ma , Xu Wang , Xi Wei , Wenjing Hou , Shao-Kai Sun","doi":"10.1016/j.biomaterials.2024.122646","DOIUrl":"10.1016/j.biomaterials.2024.122646","url":null,"abstract":"<div><p>Anastomotic leaks are among the most dreaded complications following gastrointestinal (GI) surgery, and contrast-enhanced X-ray gastroenterography is considered the preferred initial diagnostic method for GI leaks. However, from fundamental research to clinical practice, the only oral iodinated contrast agents currently available for GI leaks detection are facing several challenges, including low sensitivity, iodine allergy, and contraindications in patients with thyroid diseases. Herein, we propose a cinematic contrast-enhanced X-ray gastroenterography for the real-time detection of GI leaks with an iodine-free bismuth chelate (Bi-DTPA) for the first time. The Bi-DTPA, synthesized through a straightforward one-pot method, offers distinct advantages such as no need for purification, a nearly 100 % yield, large-scale production capability, and good biocompatibility. The remarkable X-ray attenuation properties of Bi-DTPA enable real-time dynamic visualization of whole GI tract under both X-ray gastroenterography and computed tomography (CT) imaging. More importantly, the leaky site and severity can be both clearly displayed during Bi-DTPA-enhanced gastroenterography in a rat model with esophageal leakage. The proposed movie-like Bi-DTPA-enhanced X-ray imaging approach presents a promising alternative to traditional GI radiography based on iodinated molecules. It demonstrates significant potential in addressing concerns related to iodine-associated adverse effects and offers an alternative method for visually detecting gastrointestinal leaks.</p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141277304","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 : 2024-05-31DOI: 10.1016/j.biomaterials.2024.122648
Yuanyuan Hu , Zuoxu Hou , Zhengqi Liu , Xiao Wang , Jintao Zhong , Jinjin Li , Xiaoming Guo , Changshun Ruan , Hongxun Sang , Beiwei Zhu
Osteoporosis is a major public health problem with an urgent need for safe and effective therapeutic interventions. The process of shell formation in oysters is similar to that of bone formation in mammals, and oyster extracts have been proven to exert osteoprotective effects. Oyster mantle is the most crucial organ regulating shell formation, in which exosomes play an important role. However, the effects of oyster mantle-derived exosomes (OMEs) on mammalian osteoporosis and the underlying mechanisms remain unknown. The OMEs investigated herein was found to carry abundant osteogenic cargos. They could also survive hostile gastrointestinal conditions and accumulate in the bones following oral administration. Moreover, they promoted osteoblastic differentiation and inhibited osteoclastic differentiation simultaneously. Further mechanistic examination revealed that OMEs likely promoted osteogenic activity by activating PI3K/Akt/β-catenin pathway in osteoblasts and blunted osteoclastic activity by inhibiting NF-κB pathway in osteoclasts. These favorable pro-osteogenic effects of OMEs were also corroborated in a rat femur defect model. Importantly, oral administration of OMEs effectively attenuated bone loss and improved the bone microstructure in ovariectomy-induced osteoporotic mice, and demonstrating excellent biosafety. The mechanistic insights from our data support that OMEs possess promising therapeutic potential against osteoporosis.
{"title":"Oyster mantle-derived exosomes alleviate osteoporosis by regulating bone homeostasis","authors":"Yuanyuan Hu , Zuoxu Hou , Zhengqi Liu , Xiao Wang , Jintao Zhong , Jinjin Li , Xiaoming Guo , Changshun Ruan , Hongxun Sang , Beiwei Zhu","doi":"10.1016/j.biomaterials.2024.122648","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.122648","url":null,"abstract":"<div><p>Osteoporosis is a major public health problem with an urgent need for safe and effective therapeutic interventions. The process of shell formation in oysters is similar to that of bone formation in mammals, and oyster extracts have been proven to exert osteoprotective effects. Oyster mantle is the most crucial organ regulating shell formation, in which exosomes play an important role. However, the effects of oyster mantle-derived exosomes (OMEs) on mammalian osteoporosis and the underlying mechanisms remain unknown. The OMEs investigated herein was found to carry abundant osteogenic cargos. They could also survive hostile gastrointestinal conditions and accumulate in the bones following oral administration. Moreover, they promoted osteoblastic differentiation and inhibited osteoclastic differentiation simultaneously. Further mechanistic examination revealed that OMEs likely promoted osteogenic activity by activating PI3K/Akt/β-catenin pathway in osteoblasts and blunted osteoclastic activity by inhibiting NF-κB pathway in osteoclasts. These favorable pro-osteogenic effects of OMEs were also corroborated in a rat femur defect model. Importantly, oral administration of OMEs effectively attenuated bone loss and improved the bone microstructure in ovariectomy-induced osteoporotic mice, and demonstrating excellent biosafety. The mechanistic insights from our data support that OMEs possess promising therapeutic potential against osteoporosis.</p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141241799","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 : 2024-05-28DOI: 10.1016/j.biomaterials.2024.122628
Qiannan Cao , Huapan Fang , Huayu Tian
Messenger RNA (mRNA) therapeutics have been widely employed as strategies for the treatment and prevention of diseases. Amid the global outbreak of COVID-19, mRNA vaccines have witnessed rapid development. Generally, in the case of mRNA vaccines, the initiation of the innate immune system serves as a prerequisite for triggering subsequent adaptive immune responses. Critical cells, cytokines, and chemokines within the innate immune system play crucial and beneficial roles in coordinating tailored immune reactions towards mRNA vaccines. Furthermore, immunostimulators and delivery systems play a significant role in augmenting the immune potency of mRNA vaccines. In this comprehensive review, we systematically delineate the latest advancements in mRNA vaccine research, present an in-depth exploration of strategies aimed at amplifying the immune effectiveness of mRNA vaccines, and offer some perspectives and recommendations regarding the future advancements in mRNA vaccine development.
{"title":"mRNA vaccines contribute to innate and adaptive immunity to enhance immune response in vivo","authors":"Qiannan Cao , Huapan Fang , Huayu Tian","doi":"10.1016/j.biomaterials.2024.122628","DOIUrl":"10.1016/j.biomaterials.2024.122628","url":null,"abstract":"<div><p>Messenger RNA (mRNA) therapeutics have been widely employed as strategies for the treatment and prevention of diseases. Amid the global outbreak of COVID-19, mRNA vaccines have witnessed rapid development. Generally, in the case of mRNA vaccines, the initiation of the innate immune system serves as a prerequisite for triggering subsequent adaptive immune responses. Critical cells, cytokines, and chemokines within the innate immune system play crucial and beneficial roles in coordinating tailored immune reactions towards mRNA vaccines. Furthermore, immunostimulators and delivery systems play a significant role in augmenting the immune potency of mRNA vaccines. In this comprehensive review, we systematically delineate the latest advancements in mRNA vaccine research, present an in-depth exploration of strategies aimed at amplifying the immune effectiveness of mRNA vaccines, and offer some perspectives and recommendations regarding the future advancements in mRNA vaccine development.</p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183137","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 : 2024-05-28DOI: 10.1016/j.biomaterials.2024.122632
Hin Kiu Lee , Ye Ji Yang , Gyan Raj Koirala , Suyoun Oh , Tae-il Kim
Functional hydrogels have emerged as foundational materials in diagnostics, therapy, and wearable devices, owing to their high stretchability, flexibility, sensing, and outstanding biocompatibility. Their significance stems from their resemblance to biological tissue and their exceptional versatility in electrical, mechanical, and biofunctional engineering, positioning themselves as a bridge between living organisms and electronic systems, paving the way for the development of highly compatible, efficient, and stable interfaces. These multifaceted capability revolutionizes the essence of hydrogel-based wearable devices, distinguishing them from conventional biomedical devices in real-world practical applications. In this comprehensive review, we first discuss the fundamental chemistry of hydrogels, elucidating their distinct properties and functionalities. Subsequently, we examine the applications of these bioelectronics within the human body, unveiling their transformative potential in diagnostics, therapy, and human-machine interfaces (HMI) in real wearable bioelectronics. This exploration serves as a scientific compass for researchers navigating the interdisciplinary landscape of chemistry, materials science, and bioelectronics.
{"title":"From lab to wearables: Innovations in multifunctional hydrogel chemistry for next-generation bioelectronic devices","authors":"Hin Kiu Lee , Ye Ji Yang , Gyan Raj Koirala , Suyoun Oh , Tae-il Kim","doi":"10.1016/j.biomaterials.2024.122632","DOIUrl":"10.1016/j.biomaterials.2024.122632","url":null,"abstract":"<div><p>Functional hydrogels have emerged as foundational materials in diagnostics, therapy, and wearable devices, owing to their high stretchability, flexibility, sensing, and outstanding biocompatibility. Their significance stems from their resemblance to biological tissue and their exceptional versatility in electrical, mechanical, and biofunctional engineering, positioning themselves as a bridge between living organisms and electronic systems, paving the way for the development of highly compatible, efficient, and stable interfaces. These multifaceted capability revolutionizes the essence of hydrogel-based wearable devices, distinguishing them from conventional biomedical devices in real-world practical applications. In this comprehensive review, we first discuss the fundamental chemistry of hydrogels, elucidating their distinct properties and functionalities. Subsequently, we examine the applications of these bioelectronics within the human body, unveiling their transformative potential in diagnostics, therapy, and human-machine interfaces (HMI) in real wearable bioelectronics. This exploration serves as a scientific compass for researchers navigating the interdisciplinary landscape of chemistry, materials science, and bioelectronics.</p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141194236","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 : 2024-05-28DOI: 10.1016/j.biomaterials.2024.122645
Haixia Wang , Zheng Liu , Youqiang Fang , Xing Luo , Chunxiong Zheng , Yanteng Xu , Xiangfu Zhou , Qing Yuan , Shixian Lv , Limin Ma , Yeh-Hsing Lao , Yu Tao , Mingqiang Li
Immunotherapy through the activation of the stimulator of interferon genes (STING) signaling pathway is increasingly recognized for its robust anti-tumor efficacy. However, the effectiveness of STING activation is often compromised by inadequate anti-tumor immunity and a scarcity of primed immune cells in the tumor microenvironment. Herein, we design and fabricate a co-axial 3D-printed scaffold integrating a non-nucleotide STING agonist, SR-717, and an AKT inhibitor, MK-2206, in its respective shell and core layers, to synergistically enhance STING activation, thereby suppressing tumor recurrence and growth. SR-717 initiates the STING activation to enhance the phosphorylation of the factors along the STING pathway, while MK-2206 concurrently inhibits the AKT phosphorylation to facilitate the TBK1 phosphorylation of the STING pathway. The sequential and sustained release of SR-717 and MK-2206 from the scaffold results in a synergistic STING activation, demonstrating substantial anti-tumor efficacy across multiple tumor models. Furthermore, the scaffold promotes the recruitment and enrichment of activated dendritic cells and M1 macrophages, subsequently stimulating anti-tumor T cell activity, thereby amplifying the immunotherapeutic effect. This precise and synergistic activation of STING by the scaffold offers promising potential in tumor immunotherapy.
{"title":"Spatiotemporal release of non-nucleotide STING agonist and AKT inhibitor from implantable 3D-printed scaffold for amplified cancer immunotherapy","authors":"Haixia Wang , Zheng Liu , Youqiang Fang , Xing Luo , Chunxiong Zheng , Yanteng Xu , Xiangfu Zhou , Qing Yuan , Shixian Lv , Limin Ma , Yeh-Hsing Lao , Yu Tao , Mingqiang Li","doi":"10.1016/j.biomaterials.2024.122645","DOIUrl":"https://doi.org/10.1016/j.biomaterials.2024.122645","url":null,"abstract":"<div><p>Immunotherapy through the activation of the stimulator of interferon genes (STING) signaling pathway is increasingly recognized for its robust anti-tumor efficacy. However, the effectiveness of STING activation is often compromised by inadequate anti-tumor immunity and a scarcity of primed immune cells in the tumor microenvironment. Herein, we design and fabricate a co-axial 3D-printed scaffold integrating a non-nucleotide STING agonist, SR-717, and an AKT inhibitor, MK-2206, in its respective shell and core layers, to synergistically enhance STING activation, thereby suppressing tumor recurrence and growth. SR-717 initiates the STING activation to enhance the phosphorylation of the factors along the STING pathway, while MK-2206 concurrently inhibits the AKT phosphorylation to facilitate the TBK1 phosphorylation of the STING pathway. The sequential and sustained release of SR-717 and MK-2206 from the scaffold results in a synergistic STING activation, demonstrating substantial anti-tumor efficacy across multiple tumor models. Furthermore, the scaffold promotes the recruitment and enrichment of activated dendritic cells and M1 macrophages, subsequently stimulating anti-tumor T cell activity, thereby amplifying the immunotherapeutic effect. This precise and synergistic activation of STING by the scaffold offers promising potential in tumor immunotherapy.</p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141290157","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 : 2024-05-27DOI: 10.1016/j.biomaterials.2024.122635
Kai Wang , Xu-Yang Chen , Ren-Wei-Yang Zhang , Ying Yue , Xiao-Lin Wen , Yu-Shun Yang , Chen-Yang Han , Yuan Ma , Hong-Ji Liu , Hai-Liang Zhu
Hepatocellular carcinoma (HCC) seriously threatens the human health. Previous investigations revealed that γ-glutamyltranspeptidase (GGT) was tightly associated with the chronic injury, hepatic fibrosis, and the development of HCC, therefore might act as a potential indicator for monitoring the HCC-related processes. Herein, with the contribution of a structurally optimized probe ETYZE-GGT, the bimodal imaging in both far red fluorescence (FL) and photoacoustic (PA) modes has been achieved in multiple HCC-related models. To our knowledge, this work covered the most comprehensive models including the fibrosis and developed HCC processes as well as the premonitory induction stages (autoimmune hepatitis, drug-induced liver injury, non-alcoholic fatty liver disease). ETYZE-GGT exhibited steady and practical monitoring performances on reporting the HCC stages via visualizing the GGT dynamics. The two modes exhibited working consistency and complementarity with high spatial resolution, precise apparatus and desirable biocompatibility. In cooperation with the existing techniques including testing serum indexes and conducting pathological staining, ETYZE-GGT basically realized the universal application for the accurate pre-clinical diagnosis of as many HCC stages as possible. By deeply exploring the mechanically correlation between GGT and the HCC process, especially during the premonitory induction stages, we may further raise the efficacy for the early diagnosis and treatment of HCC.
{"title":"Multifunctional fluorescence/photoacoustic bimodal imaging of γ-glutamyltranspeptidase in liver disorders under different triggering conditions","authors":"Kai Wang , Xu-Yang Chen , Ren-Wei-Yang Zhang , Ying Yue , Xiao-Lin Wen , Yu-Shun Yang , Chen-Yang Han , Yuan Ma , Hong-Ji Liu , Hai-Liang Zhu","doi":"10.1016/j.biomaterials.2024.122635","DOIUrl":"10.1016/j.biomaterials.2024.122635","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) seriously threatens the human health. Previous investigations revealed that <em>γ</em>-glutamyltranspeptidase (GGT) was tightly associated with the chronic injury, hepatic fibrosis, and the development of HCC, therefore might act as a potential indicator for monitoring the HCC-related processes. Herein, with the contribution of a structurally optimized probe <strong>ETYZE-GGT</strong>, the bimodal imaging in both far red fluorescence (FL) and photoacoustic (PA) modes has been achieved in multiple HCC-related models. To our knowledge, this work covered the most comprehensive models including the fibrosis and developed HCC processes as well as the premonitory induction stages (autoimmune hepatitis, drug-induced liver injury, non-alcoholic fatty liver disease). <strong>ETYZE-GGT</strong> exhibited steady and practical monitoring performances on reporting the HCC stages via visualizing the GGT dynamics. The two modes exhibited working consistency and complementarity with high spatial resolution, precise apparatus and desirable biocompatibility. In cooperation with the existing techniques including testing serum indexes and conducting pathological staining, <strong>ETYZE-GGT</strong> basically realized the universal application for the accurate pre-clinical diagnosis of as many HCC stages as possible. By deeply exploring the mechanically correlation between GGT and the HCC process, especially during the premonitory induction stages, we may further raise the efficacy for the early diagnosis and treatment of HCC.</p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":null,"pages":null},"PeriodicalIF":14.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174181","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}