Accurate imaging of tumor hypoxia in vivo is critical for early cancer diagnosis and clinical outcomes, highlighting the great need for its detection specificity and sensitivity. In this report, we propose a probe (HTRNP) that simultaneously has hypoxia-targeting and hypoxia-responsive capabilities to enhance the tumor hypoxia imaging efficiency. HTRNP was successfully prepared through the encapsulation of Pt(II)-tetrakis(pentafluorophenyl)porphyrin (PtPFPP), which exhibits hypoxia-dependent phosphorescence, within the amphiphilic block copolymer OPDMA-PF, which has hypoxia-targeting tertiary amine N-oxide moieties and hydrophobic perfluorobenzene ring structures, which highly improved the loading content and water solubility of PtPFPP. By combining targeting and response abilities toward hypoxic conditions, the HTRNP micelles efficiently accumulate in the tumor tissues and emit intense phosphorescence, thus enabling ultrasensitive detection of various tumor models, even of hundreds of cancer cells, indicating its promising potential for early cancer detection and phenotypic characterization.
{"title":"A hypoxia-targeting and hypoxia-responsive nano-probe for tumor detection and early diagnosis†","authors":"Yong Chen, Huimin Wang, Xiaodan Xu, Hongxia Xu, Bing Xiao, Pengcheng Yuan, Shiqun Shao, Wenjing Sun, Zhuxian Zhou, Youqing Shen and Jianbin Tang","doi":"10.1039/D4BM01499E","DOIUrl":"10.1039/D4BM01499E","url":null,"abstract":"<p >Accurate imaging of tumor hypoxia <em>in vivo</em> is critical for early cancer diagnosis and clinical outcomes, highlighting the great need for its detection specificity and sensitivity. In this report, we propose a probe (HTRNP) that simultaneously has hypoxia-targeting and hypoxia-responsive capabilities to enhance the tumor hypoxia imaging efficiency. HTRNP was successfully prepared through the encapsulation of Pt(<small>II</small>)-tetrakis(pentafluorophenyl)porphyrin (PtPFPP), which exhibits hypoxia-dependent phosphorescence, within the amphiphilic block copolymer OPDMA-PF, which has hypoxia-targeting tertiary amine <em>N</em>-oxide moieties and hydrophobic perfluorobenzene ring structures, which highly improved the loading content and water solubility of PtPFPP. By combining targeting and response abilities toward hypoxic conditions, the HTRNP micelles efficiently accumulate in the tumor tissues and emit intense phosphorescence, thus enabling ultrasensitive detection of various tumor models, even of hundreds of cancer cells, indicating its promising potential for early cancer detection and phenotypic characterization.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 5","pages":" 1261-1271"},"PeriodicalIF":5.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianan Zhan, Yueying Kong, Xi Zhou, Haihuan Gong, Qiwei Chen, Xianlin Zhang, Jiankai Zhang, Yilin Wang and Wenhua Huang
Myoelectric biofeedback (EMG-BF) is a widely recognized and effective method for treating movement disorders caused by impaired nerve function. However, existing EMG-feedback devices are almost entirely located in large medical centers, which greatly limits patient accessibility. To address this critical limitation, there is an urgent need to develop a portable, cost-effective, and real-time monitoring device that can transcend the existing barriers to the treatment of EMG-BF. Our proposed solution leverages polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) as core materials, ingeniously incorporating wood pulp nano celluloses (CNF-P)-Na+ to enhance the structural integrity. Additionally, the inclusion of nano-silica particles further augments the sensor's capabilities, enabling the creation of a stress-sensitive mineral ionization hydrogel sensor. This innovative approach not only capitalizes on the superior rheological properties of the materials but also, through advanced 3D printing technology, facilitates the production of a micro-scale structural hydrogel sensor with unparalleled sensitivity, stability, and durability. The potential of this sensor in the realm of human motion detection is nothing short of extraordinary. This development can potentially improve the treatment landscape for EMG-BF offering patients more convenient and efficient therapeutic options.
{"title":"3D printing of wearable sensors with strong stretchability for myoelectric rehabilitation†","authors":"Jianan Zhan, Yueying Kong, Xi Zhou, Haihuan Gong, Qiwei Chen, Xianlin Zhang, Jiankai Zhang, Yilin Wang and Wenhua Huang","doi":"10.1039/D4BM01434K","DOIUrl":"10.1039/D4BM01434K","url":null,"abstract":"<p >Myoelectric biofeedback (EMG-BF) is a widely recognized and effective method for treating movement disorders caused by impaired nerve function. However, existing EMG-feedback devices are almost entirely located in large medical centers, which greatly limits patient accessibility. To address this critical limitation, there is an urgent need to develop a portable, cost-effective, and real-time monitoring device that can transcend the existing barriers to the treatment of EMG-BF. Our proposed solution leverages polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) as core materials, ingeniously incorporating wood pulp nano celluloses (CNF-P)-Na<small><sup>+</sup></small> to enhance the structural integrity. Additionally, the inclusion of nano-silica particles further augments the sensor's capabilities, enabling the creation of a stress-sensitive mineral ionization hydrogel sensor. This innovative approach not only capitalizes on the superior rheological properties of the materials but also, through advanced 3D printing technology, facilitates the production of a micro-scale structural hydrogel sensor with unparalleled sensitivity, stability, and durability. The potential of this sensor in the realm of human motion detection is nothing short of extraordinary. This development can potentially improve the treatment landscape for EMG-BF offering patients more convenient and efficient therapeutic options.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 4","pages":" 1021-1032"},"PeriodicalIF":5.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yingao Ma, Jingyu Xiao, Gina Jinna Chen, Hong Dang, Yaran Zhang, Xiaoqin He, Perry Ping Shum and Qiongyu Guo
Photothermal treatment has attracted immense interest as a promising approach for biomedical applications such as cancer ablation, yet its effectiveness is often limited by insufficient laser penetration and challenges in achieving efficient targeting of photothermal agents. Here we developed a transvascular interventional photothermal therapy (Ti-PTT), which employed a small-sized microcatheter (outer diameter: 0.60 mm, 1.8 Fr) equipped with an ultrafine optical fiber (diameter: 100 μm) capable of simultaneously delivering photothermal agents while performing 808 nm laser irradiation via an endovascular route. Specifically, we employed two types of indocyanine green (ICG)-based photothermal agents, i.e. ICG solution serving as a purely photothermal agent and ICG-ethiodized oil (ICG–EO) emulsion acting as a radiopaque photothermal embolic agent. Using the customized microcatheter with the ICG solution, both proximal and distal embolization were able to be performed in a rat liver model. Compared to the ICG solution, the ICG–EO emulsion dramatically enhanced the ICG retention time, enabling a photothermally triggered precision vascular blockade to induce local embolization of large tissue volumes in a rat kidney model with an unfavorable ICG leakage rate. The Ti-PTT paves the way to broadening the potential applications of photothermal therapy through combination with clinical intervention-based approaches.
光热治疗作为一种有前途的生物医学应用方法,如癌症消融,引起了人们的极大兴趣,但其有效性往往受到激光穿透不足和实现光热剂有效靶向的挑战的限制。在这里,我们开发了一种经血管介入光热疗法(Ti-PTT),它采用了一个小尺寸的微导管(外径:0.60 mm, 1.8 Fr),配备了超细光纤(直径:100 μm),能够在通过血管内途径进行808 nm激光照射的同时输送光热剂。具体来说,我们采用了两种基于吲哚菁绿(ICG)的光热剂,即ICG溶液作为纯粹的光热剂,ICG-乙硫化油(ICG- eo)乳剂作为不透射线的光热栓塞剂。使用定制的微导管与ICG溶液,可以在大鼠肝脏模型中进行近端和远端栓塞。与ICG溶液相比,ICG- eo乳状液显著提高了ICG保留时间,使光热触发的精确血管阻断能够在具有不利ICG泄漏率的大鼠肾脏模型中诱导大组织体积的局部栓塞。Ti-PTT通过结合临床干预方法,为扩大光热疗法的潜在应用铺平了道路。
{"title":"Ultrafine fiber-mediated transvascular interventional photothermal therapy using indocyanine green for precision embolization treatment†","authors":"Yingao Ma, Jingyu Xiao, Gina Jinna Chen, Hong Dang, Yaran Zhang, Xiaoqin He, Perry Ping Shum and Qiongyu Guo","doi":"10.1039/D4BM01592D","DOIUrl":"10.1039/D4BM01592D","url":null,"abstract":"<p >Photothermal treatment has attracted immense interest as a promising approach for biomedical applications such as cancer ablation, yet its effectiveness is often limited by insufficient laser penetration and challenges in achieving efficient targeting of photothermal agents. Here we developed a transvascular interventional photothermal therapy (Ti-PTT), which employed a small-sized microcatheter (outer diameter: 0.60 mm, 1.8 Fr) equipped with an ultrafine optical fiber (diameter: 100 μm) capable of simultaneously delivering photothermal agents while performing 808 nm laser irradiation <em>via</em> an endovascular route. Specifically, we employed two types of indocyanine green (ICG)-based photothermal agents, <em>i.e.</em> ICG solution serving as a purely photothermal agent and ICG-ethiodized oil (ICG–EO) emulsion acting as a radiopaque photothermal embolic agent. Using the customized microcatheter with the ICG solution, both proximal and distal embolization were able to be performed in a rat liver model. Compared to the ICG solution, the ICG–EO emulsion dramatically enhanced the ICG retention time, enabling a photothermally triggered precision vascular blockade to induce local embolization of large tissue volumes in a rat kidney model with an unfavorable ICG leakage rate. The Ti-PTT paves the way to broadening the potential applications of photothermal therapy through combination with clinical intervention-based approaches.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 4","pages":" 1091-1100"},"PeriodicalIF":5.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Myagmartsend Enkhbat, Jodhbir S. Mehta, Gary S. L. Peh and Evelyn K. F. Yim
The treatment of corneal blindness due to corneal diseases and injuries often requires the transplantation of healthy cadaveric corneal endothelial graft tissue to restore corneal clarity and visual function. However, the limited availability of donor corneas poses a significant challenge in meeting the demand for corneal transplantation. As a result, there is a growing interest in developing strategies alleviate this unmet need, and one of the postulated approaches is to isolate and expand primary human corneal endothelial cells (HCECs) in vitro for use in cell therapy. This review summarizes the recent advancements in the expansion of HCECs using biomaterials. Two principal biomaterial-based approaches, including extracellular matrix (ECM) coating and functionalized synthetic polymers, have been investigated to create an optimal microenvironment for the expansion and maintenance of corneal endothelial cells (CECs). This review highlights the challenges and opportunities in expanding primary HCECs using biomaterials. It emphasizes the importance of optimizing biomaterial properties, cell culture conditions, and the roles of biophysical cues to achieve efficient expansion and functional maintenance of CECs. Biomaterial-based strategies hold significant promise for expanding primary HCECs and improving the outcomes of CEC transplantation. The integration of biomaterials as cell culture substrates and transplantable carriers offers a comprehensive approach to address the limitations associated with current corneal tissue engineering techniques.
{"title":"Biomaterial-based strategies for primary human corneal endothelial cells for therapeutic applications: from cell expansion to transplantable carrier","authors":"Myagmartsend Enkhbat, Jodhbir S. Mehta, Gary S. L. Peh and Evelyn K. F. Yim","doi":"10.1039/D4BM00941J","DOIUrl":"10.1039/D4BM00941J","url":null,"abstract":"<p >The treatment of corneal blindness due to corneal diseases and injuries often requires the transplantation of healthy cadaveric corneal endothelial graft tissue to restore corneal clarity and visual function. However, the limited availability of donor corneas poses a significant challenge in meeting the demand for corneal transplantation. As a result, there is a growing interest in developing strategies alleviate this unmet need, and one of the postulated approaches is to isolate and expand primary human corneal endothelial cells (HCECs) <em>in vitro</em> for use in cell therapy. This review summarizes the recent advancements in the expansion of HCECs using biomaterials. Two principal biomaterial-based approaches, including extracellular matrix (ECM) coating and functionalized synthetic polymers, have been investigated to create an optimal microenvironment for the expansion and maintenance of corneal endothelial cells (CECs). This review highlights the challenges and opportunities in expanding primary HCECs using biomaterials. It emphasizes the importance of optimizing biomaterial properties, cell culture conditions, and the roles of biophysical cues to achieve efficient expansion and functional maintenance of CECs. Biomaterial-based strategies hold significant promise for expanding primary HCECs and improving the outcomes of CEC transplantation. The integration of biomaterials as cell culture substrates and transplantable carriers offers a comprehensive approach to address the limitations associated with current corneal tissue engineering techniques.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 5","pages":" 1114-1130"},"PeriodicalIF":5.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/bm/d4bm00941j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sidra Kanwal, Umer Bin Abdul Aziz, Elisa Quaas, Katharina Achazi and Daniel Klinger
We are facing a shortage of new antibiotics to fight against increasingly resistant bacteria. As an alternative to conventional small molecule antibiotics, antimicrobial polymers (AMPs) have great potential. These polymers contain cationic and hydrophobic groups and disrupt bacterial cell membranes through a combination of electrostatic and hydrophobic interactions. While most examples focus on ammonium-based cations, sulfonium groups are recently emerging to broaden the scope of polymeric therapeutics. Here, main-chain sulfonium polymers exhibit good antimicrobial activity. In contrast, the potential of side-chain sulfonium polymers remains less explored with structure–activity relationships still being limited. To address this limitation, we thoroughly investigated key factors influencing antimicrobial activity in side-chain sulfonium-based AMPs. For this, we combined sulfonium cations with different hydrophobic (aliphatic/aromatic) and hydrophilic polyethylene glycol (PEG) groups to create a library of polymers with comparable chain lengths. For all compositions, we additionally examined the position of cationic and hydrophobic groups on the polymer backbone, i.e., we systematically compared same center and different center structures. Bactericidal tests against Gram-positive and Gram-negative bacteria suggest that same center polymers are more active than different center polymers of similar clog P. Ultimately, sulfonium-based AMPs show superior bactericidal activity and selectivity when compared to their quaternary ammonium cationic analogues.
{"title":"Sulfonium-based polymethacrylamides for antimicrobial use: influence of the structure and composition†","authors":"Sidra Kanwal, Umer Bin Abdul Aziz, Elisa Quaas, Katharina Achazi and Daniel Klinger","doi":"10.1039/D4BM01247J","DOIUrl":"10.1039/D4BM01247J","url":null,"abstract":"<p >We are facing a shortage of new antibiotics to fight against increasingly resistant bacteria. As an alternative to conventional small molecule antibiotics, antimicrobial polymers (AMPs) have great potential. These polymers contain cationic and hydrophobic groups and disrupt bacterial cell membranes through a combination of electrostatic and hydrophobic interactions. While most examples focus on ammonium-based cations, sulfonium groups are recently emerging to broaden the scope of polymeric therapeutics. Here, main-chain sulfonium polymers exhibit good antimicrobial activity. In contrast, the potential of side-chain sulfonium polymers remains less explored with structure–activity relationships still being limited. To address this limitation, we thoroughly investigated key factors influencing antimicrobial activity in side-chain sulfonium-based AMPs. For this, we combined sulfonium cations with different hydrophobic (aliphatic/aromatic) and hydrophilic polyethylene glycol (PEG) groups to create a library of polymers with comparable chain lengths. For all compositions, we additionally examined the position of cationic and hydrophobic groups on the polymer backbone, <em>i.e.</em>, we systematically compared same center and different center structures. Bactericidal tests against Gram-positive and Gram-negative bacteria suggest that same center polymers are more active than different center polymers of similar clog <em>P</em>. Ultimately, sulfonium-based AMPs show superior bactericidal activity and selectivity when compared to their quaternary ammonium cationic analogues.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 4","pages":" 993-1009"},"PeriodicalIF":5.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/bm/d4bm01247j?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
San Seint Seint Aye, Zhongqi Fang, Mike C. L. Wu, Khoon S. Lim and Lining Arnold Ju
Thrombosis, a major cause of morbidity and mortality worldwide, presents a complex challenge in cardiovascular medicine due to the intricacy of clotting mechanisms in living organisms. Traditional research approaches, including clinical studies and animal models, often yield conflicting results due to the inability to control variables in these complex systems, highlighting the need for more precise investigative tools. This review explores the evolution of in vitro thrombosis models, from conventional polydimethylsiloxane (PDMS)-based microfluidic devices to advanced hydrogel-based systems and cutting-edge 3D bioprinted vascular constructs. We discuss how these emerging technologies, particularly vessel-on-a-chip platforms, are enabling researchers to control previously unmanageable factors, thereby offering unprecedented opportunities to pinpoint specific clotting mechanisms. While PDMS-based devices offer optical transparency and fabrication ease, their inherent limitations, including non-physiological rigidity and surface properties, have driven the development of hydrogel-based systems that better mimic the extracellular matrix of blood vessels. The integration of microfluidics with biomimetic materials and tissue engineering approaches has led to the development of sophisticated models capable of simulating patient-specific vascular geometries, flow dynamics, and cellular interactions under highly controlled conditions. The advent of 3D bioprinting further enables the creation of complex, multi-layered vascular structures with precise spatial control over geometry and cellular composition. Despite significant progress, challenges remain in achieving long-term stability, incorporating immune components, and translating these models to clinical applications. By providing a comprehensive overview of current advancements and future prospects, this review aims to stimulate further innovation in thrombosis research and accelerate the development of more effective, personalized approaches to thrombosis prevention and treatment.
{"title":"Integrating microfluidics, hydrogels, and 3D bioprinting for personalized vessel-on-a-chip platforms","authors":"San Seint Seint Aye, Zhongqi Fang, Mike C. L. Wu, Khoon S. Lim and Lining Arnold Ju","doi":"10.1039/D4BM01354A","DOIUrl":"10.1039/D4BM01354A","url":null,"abstract":"<p >Thrombosis, a major cause of morbidity and mortality worldwide, presents a complex challenge in cardiovascular medicine due to the intricacy of clotting mechanisms in living organisms. Traditional research approaches, including clinical studies and animal models, often yield conflicting results due to the inability to control variables in these complex systems, highlighting the need for more precise investigative tools. This review explores the evolution of <em>in vitro</em> thrombosis models, from conventional polydimethylsiloxane (PDMS)-based microfluidic devices to advanced hydrogel-based systems and cutting-edge 3D bioprinted vascular constructs. We discuss how these emerging technologies, particularly vessel-on-a-chip platforms, are enabling researchers to control previously unmanageable factors, thereby offering unprecedented opportunities to pinpoint specific clotting mechanisms. While PDMS-based devices offer optical transparency and fabrication ease, their inherent limitations, including non-physiological rigidity and surface properties, have driven the development of hydrogel-based systems that better mimic the extracellular matrix of blood vessels. The integration of microfluidics with biomimetic materials and tissue engineering approaches has led to the development of sophisticated models capable of simulating patient-specific vascular geometries, flow dynamics, and cellular interactions under highly controlled conditions. The advent of 3D bioprinting further enables the creation of complex, multi-layered vascular structures with precise spatial control over geometry and cellular composition. Despite significant progress, challenges remain in achieving long-term stability, incorporating immune components, and translating these models to clinical applications. By providing a comprehensive overview of current advancements and future prospects, this review aims to stimulate further innovation in thrombosis research and accelerate the development of more effective, personalized approaches to thrombosis prevention and treatment.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 5","pages":" 1131-1160"},"PeriodicalIF":5.8,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ellen W. van Wijngaarden, Sandra L. Arias, Matthew Rhee, Meredith N. Silberstein and Ilana L. Brito
An increase in plastic waste and its release into the environment has led to health concerns over microplastics (MPs) in the environment. The intestinal mucosal layer is a key defense mechanism against ingested MPs, preventing the migration of particles to other parts of the body. MP migration through intestinal mucus is challenging to study due to difficulties in obtaining intact mucus layers for testing and numerous formulations, shapes, and sizes of microplastics. Previous studies have primarily used mucus from animals, hydrogel models, and mucus samples from other parts of the body as substitutes. This study examines how different MP compositions, sizes (40–500 nm), and surface functionalizations alter MP migration through human intestinal mucus; how the mucus layer protects cells from MP uptake, toxicity, and inflammation; and how the intestinal mucus prevents the migration of other environmental toxins via MP particles. The presence of a mucus layer also provides critical protection against cytotoxicity, reactive oxygen species production, and uptake for all particles tested, although certain functionalizations, such as streptavidin, are particularly harmful to cells with high toxicity and inflammation. Understanding the properties that assist of impede the diffusion of MPs through mucus is relevant to the overall bioaccumulation and health effects of MPs as well as drug delivery purposes.
{"title":"The role of human intestinal mucus in the prevention of microplastic uptake and cell damage†","authors":"Ellen W. van Wijngaarden, Sandra L. Arias, Matthew Rhee, Meredith N. Silberstein and Ilana L. Brito","doi":"10.1039/D4BM01574F","DOIUrl":"10.1039/D4BM01574F","url":null,"abstract":"<p >An increase in plastic waste and its release into the environment has led to health concerns over microplastics (MPs) in the environment. The intestinal mucosal layer is a key defense mechanism against ingested MPs, preventing the migration of particles to other parts of the body. MP migration through intestinal mucus is challenging to study due to difficulties in obtaining intact mucus layers for testing and numerous formulations, shapes, and sizes of microplastics. Previous studies have primarily used mucus from animals, hydrogel models, and mucus samples from other parts of the body as substitutes. This study examines how different MP compositions, sizes (40–500 nm), and surface functionalizations alter MP migration through human intestinal mucus; how the mucus layer protects cells from MP uptake, toxicity, and inflammation; and how the intestinal mucus prevents the migration of other environmental toxins <em>via</em> MP particles. The presence of a mucus layer also provides critical protection against cytotoxicity, reactive oxygen species production, and uptake for all particles tested, although certain functionalizations, such as streptavidin, are particularly harmful to cells with high toxicity and inflammation. Understanding the properties that assist of impede the diffusion of MPs through mucus is relevant to the overall bioaccumulation and health effects of MPs as well as drug delivery purposes.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 4","pages":" 1010-1020"},"PeriodicalIF":5.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/bm/d4bm01574f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taha Cagri Senocak, Pavan Kumar Reddy Gudeti, Joanna Żur-Pińska and Małgorzata Katarzyna Włodarczyk-Biegun
Metallic biomaterials are extensively used in orthopedics and dentistry, either as implants or coatings. In both cases, metal ions come into contact with surrounding tissues causing a particular cell response. Here, we present a biofabricated in vitro tissue model, consisting of a hydrogel reinforced with a melt electrowritten mesh, to study the effects of bound and released metal ions on surrounding cells embedded in a hydrogel matrix. We evaluate the biocompatibility, bioactivity, and antibacterial properties of these metal coatings. Our approach involves integrating physical vapour deposition coating technology with 3D bioprinting methods. To produce tissue models, melt electrowritten (MEW) meshes composed of polycaprolactone (PCL) were printed and integrated into cell-laden methacrylated galatin (GelMa). The mouse embryonic fibroblast cell line (NIH3T3) was used. GelMa concentration and printing parameters for MEW were adjusted and mechanical analysis of the models was performed to find the optimal material composition. Optimized models were placed on the glass slide surfaces coated with typically non-toxic metals, i.e. titanium (Ti), tantalum (Ta), zirconium (Zr), silver (Ag), tungsten (W), and niobium (Nb). Except for W, all other coatings were stable in a physiological wet environment, as studied by SEM. The viability of the cells at different distances from the coated surface was analyzed. Antibacterial tests against pathogens Staphylococcus aureus and Escherichia coli were used to assess the models’ resistance, important for infection control. While Ag coatings showed toxicity, Nb, Ta, Ti, and Zr coatings promoted fibroblast growth, with the highest cell viability after 14 days of culture revealed for Ta and Nb. The strongest antimicrobial effect against E. coli and S. aureus was observed for Ag and W, while Ta exhibited antibacterial activity only against S. aureus. From a broader perspective, our work offers an effective 3D in vitro model for an in-depth characterization of the biocompatibility of metals and metal coatings.
{"title":"Biofabricated tissue model for determining biocompatibility of metallic coatings†","authors":"Taha Cagri Senocak, Pavan Kumar Reddy Gudeti, Joanna Żur-Pińska and Małgorzata Katarzyna Włodarczyk-Biegun","doi":"10.1039/D4BM01335B","DOIUrl":"10.1039/D4BM01335B","url":null,"abstract":"<p >Metallic biomaterials are extensively used in orthopedics and dentistry, either as implants or coatings. In both cases, metal ions come into contact with surrounding tissues causing a particular cell response. Here, we present a biofabricated <em>in vitro</em> tissue model, consisting of a hydrogel reinforced with a melt electrowritten mesh, to study the effects of bound and released metal ions on surrounding cells embedded in a hydrogel matrix. We evaluate the biocompatibility, bioactivity, and antibacterial properties of these metal coatings. Our approach involves integrating physical vapour deposition coating technology with 3D bioprinting methods. To produce tissue models, melt electrowritten (MEW) meshes composed of polycaprolactone (PCL) were printed and integrated into cell-laden methacrylated galatin (GelMa). The mouse embryonic fibroblast cell line (NIH3T3) was used. GelMa concentration and printing parameters for MEW were adjusted and mechanical analysis of the models was performed to find the optimal material composition. Optimized models were placed on the glass slide surfaces coated with typically non-toxic metals, <em>i.e.</em> titanium (<strong>Ti</strong>), tantalum (<strong>Ta</strong>), zirconium (<strong>Zr</strong>), silver (<strong>Ag</strong>), tungsten (<strong>W</strong>), and niobium (<strong>Nb</strong>). Except for <strong>W</strong>, all other coatings were stable in a physiological wet environment, as studied by SEM. The viability of the cells at different distances from the coated surface was analyzed. Antibacterial tests against pathogens <em>Staphylococcus aureus</em> and <em>Escherichia coli</em> were used to assess the models’ resistance, important for infection control. While <strong>Ag</strong> coatings showed toxicity, <strong>Nb</strong>, <strong>Ta</strong>, <strong>Ti</strong>, and <strong>Zr</strong> coatings promoted fibroblast growth, with the highest cell viability after 14 days of culture revealed for <strong>Ta</strong> and <strong>Nb</strong>. The strongest antimicrobial effect against <em>E. coli</em> and <em>S. aureus</em> was observed for <strong>Ag</strong> and <strong>W</strong>, while <strong>Ta</strong> exhibited antibacterial activity only against <em>S. aureus</em>. From a broader perspective, our work offers an effective 3D <em>in vitro</em> model for an in-depth characterization of the biocompatibility of metals and metal coatings.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 4","pages":" 1075-1090"},"PeriodicalIF":5.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/bm/d4bm01335b?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Herllan V. de Almeida, Mateus P. Bomediano, Daniele M. Catori, Elizaura H. C. Silva and Marcelo G. de Oliveira
The pivotal roles played by nitric oxide (NO) in tissue repair, inflammation, and immune response have spurred the development of a wide range of NO-releasing biomaterials. More recently, 3D printing techniques have significantly broadened the potential applications of polymeric biomaterials in biomedicine. In this context, the development of NO-releasing biomaterials that can be fabricated through 3D printing techniques has emerged as a promising strategy for harnessing the benefits of localized NO release from implantable devices, tissue regeneration scaffolds, or bandages for topical applications. Although 3D printing techniques allow for the creation of polymeric constructs with versatile designs and high geometric precision, integrating NO-releasing functional groups or molecules into these constructs poses several challenges. NO donors, such as S-nitrosothiols (RSNOs) or diazeniumdiolates (NONOates), may release NO thermally, complicating their incorporation into resins that require heating for extrusion-based 3D printing. Conversely, NO released photochemically from RSNOs effectively inhibits radical propagation, thus hindering photoinduced 3D printing processes. This review outlines the primary strategies employed to overcome these challenges in developing NO-releasing biomaterials via 3D printing, and explores future prospects in this rapidly evolving field.
{"title":"Integrating 3D printing of biomaterials with nitric oxide release†","authors":"Herllan V. de Almeida, Mateus P. Bomediano, Daniele M. Catori, Elizaura H. C. Silva and Marcelo G. de Oliveira","doi":"10.1039/D4BM01304B","DOIUrl":"10.1039/D4BM01304B","url":null,"abstract":"<p >The pivotal roles played by nitric oxide (NO) in tissue repair, inflammation, and immune response have spurred the development of a wide range of NO-releasing biomaterials. More recently, 3D printing techniques have significantly broadened the potential applications of polymeric biomaterials in biomedicine. In this context, the development of NO-releasing biomaterials that can be fabricated through 3D printing techniques has emerged as a promising strategy for harnessing the benefits of localized NO release from implantable devices, tissue regeneration scaffolds, or bandages for topical applications. Although 3D printing techniques allow for the creation of polymeric constructs with versatile designs and high geometric precision, integrating NO-releasing functional groups or molecules into these constructs poses several challenges. NO donors, such as <em>S</em>-nitrosothiols (RSNOs) or diazeniumdiolates (NONOates), may release NO thermally, complicating their incorporation into resins that require heating for extrusion-based 3D printing. Conversely, NO released photochemically from RSNOs effectively inhibits radical propagation, thus hindering photoinduced 3D printing processes. This review outlines the primary strategies employed to overcome these challenges in developing NO-releasing biomaterials <em>via</em> 3D printing, and explores future prospects in this rapidly evolving field.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 4","pages":" 858-874"},"PeriodicalIF":5.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yafi S. Permana, Mincheol Jang, Kyunghwan Yeom, Erinn Fagan, Yong Jae Kim, Joon Hyeok Choi and Ji-Ho Park
Incorporation of polyethylene glycol (PEG) is widely used in lipid nanoparticle (LNP) formulation in order to achieve adequate stability due to its stealth properties. However, studies have detected the presence of anti-PEG neutralizing antibodies after PEGylated LNP treatment, which are associated with anaphylaxis, accelerated LNP clearance and premature release of cargo. Here, we report the development of LNPs incorporating ganglioside, a naturally occurring stealth lipid, as a PEG-free alternative. Physicochemical characterization showed that ganglioside-LNPs exhibited superior stability throughout prolonged cold storage compared to stealth-free LNPs, preventing particle aggregation. Additionally, there was no significant change in particle size after serum incubation, indicating the ability of ganglioside to prevent unwanted serum protein adsorption. These results exemplify the effective stealth properties of ganglioside. Furthermore, ganglioside-LNPs exhibited significantly higher mRNA transfection in vivo after intravenous administration compared to stealth-free LNPs. The ability of ganglioside to confer excellent stealth properties to LNPs while still enabling in vivo mRNA expression makes it a promising candidate as a natural substitute for immunogenic PEG in mRNA-LNP delivery platforms, contributing to the future advancement of gene therapy.
{"title":"Ganglioside-incorporating lipid nanoparticles as a polyethylene glycol-free mRNA delivery platform†","authors":"Yafi S. Permana, Mincheol Jang, Kyunghwan Yeom, Erinn Fagan, Yong Jae Kim, Joon Hyeok Choi and Ji-Ho Park","doi":"10.1039/D4BM01360C","DOIUrl":"10.1039/D4BM01360C","url":null,"abstract":"<p >Incorporation of polyethylene glycol (PEG) is widely used in lipid nanoparticle (LNP) formulation in order to achieve adequate stability due to its stealth properties. However, studies have detected the presence of anti-PEG neutralizing antibodies after PEGylated LNP treatment, which are associated with anaphylaxis, accelerated LNP clearance and premature release of cargo. Here, we report the development of LNPs incorporating ganglioside, a naturally occurring stealth lipid, as a PEG-free alternative. Physicochemical characterization showed that ganglioside-LNPs exhibited superior stability throughout prolonged cold storage compared to stealth-free LNPs, preventing particle aggregation. Additionally, there was no significant change in particle size after serum incubation, indicating the ability of ganglioside to prevent unwanted serum protein adsorption. These results exemplify the effective stealth properties of ganglioside. Furthermore, ganglioside-LNPs exhibited significantly higher mRNA transfection <em>in vivo</em> after intravenous administration compared to stealth-free LNPs. The ability of ganglioside to confer excellent stealth properties to LNPs while still enabling <em>in vivo</em> mRNA expression makes it a promising candidate as a natural substitute for immunogenic PEG in mRNA-LNP delivery platforms, contributing to the future advancement of gene therapy.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 5","pages":" 1222-1232"},"PeriodicalIF":5.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/bm/d4bm01360c?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}