Acta biomaterialia最新文献

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Autologous platelet-rich plasma dual-network hydrogel promotes human endometrial regeneration. 自体富血小板血浆双网水凝胶促进人子宫内膜再生。
IF 9.6
Acta biomaterialia Pub Date : 2025-08-23 DOI: 10.1016/j.actbio.2025.08.038
Xiao Chen, Chengcheng Zhu, Lu Wang, Jialing Deng, Zhuomin Wang, Xiaolin Wu, Haimin Tan, Yiyuan Qu, Bingbing Wu, Yu Li, Keren Cheng, Jian Xu
{"title":"Autologous platelet-rich plasma dual-network hydrogel promotes human endometrial regeneration.","authors":"Xiao Chen, Chengcheng Zhu, Lu Wang, Jialing Deng, Zhuomin Wang, Xiaolin Wu, Haimin Tan, Yiyuan Qu, Bingbing Wu, Yu Li, Keren Cheng, Jian Xu","doi":"10.1016/j.actbio.2025.08.038","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.08.038","url":null,"abstract":"<p><p>Intrauterine perfusion of platelet-rich plasma (PRP) is often used for the treatment of intrauterine adhesions (IUA). However, the further application of PRP is limited by its difficulty in attaching to the endometrial surface and its inability to release growth factors persistently. Therefore, in this study, a dual-network (DN) hydrogel was prepared by using hyaluronate gel as the matrix and cross-linked PRP, which was applied to the clinical treatment of IUA. The DN hydrogel showed non-swelling in PBS, and 28 % of DN hydrogel remained after 96 h in vivo, in which PDGF-BB and VEGF showed sustained linear releasement. Also, DN hydrogel could promote the proliferation of endometrial epithelial cells in human endometrial epithelial organoids, suggesting that PRP releasing PDGF-BB and VEGF in DN hydrogel played a role. After treatment of DN hydrogel in patients with moderate to severe IUA, the menstrual volume and subendometrial blood flow were significantly increased, the IUA score was significantly decreased, the number of endometrial epithelial glands was increased, and the expression levels of ERα, MKI67 and CD31 were increased after treatment. Further single-cell sequencing analysis of the endometrium before and after DN hydrogel treatment revealed that WNT signaling pathway was significantly enriched after treatment. Immunohistochemical results confirmed that the increased expression of SOX9 and LGR5 in human endometrial glands after treatment, and also DN hyrdrogel promoted SOX9 and LGR5 expression in organoids. In conclusion, this DN hydrogel can improve the therapeutic effect of PRP and promote endometrial repair and regeneration in patients. STATEMENT OF SIGNIFICANCE: Dual-network hydrogels combined with Platelet-rich plasma (PRP) were successfully applied to human intrauterine adhesions and achieved the desired therapeutic effect. The PRP dual-network hydrogel enhanced the mechanical properties of PRP and promoted endometrial repair and regeneration in clinical patients probably by activating the WNT signaling pathway. This study proposes a clinically practical therapeutic strategy and provides a foundation for the utilization of PRP in the field of endometrial regeneration.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Injectable protein hydrogel microspheres with reactive oxygen species-responsive nitric oxide release for cardiac protection against ischemia/reperfusion injury. 具有活性氧响应型一氧化氮释放的可注射蛋白水凝胶微球对心脏缺血/再灌注损伤的保护作用。
IF 9.6
Acta biomaterialia Pub Date : 2025-08-22 DOI: 10.1016/j.actbio.2025.08.040
Houwei Zheng, Fan Jia, Ying Gao, Kaicheng Deng, Liyin Shen, Chao Zheng, Xin Xie, Changyou Gao, Tanchen Ren, Yang Zhu
{"title":"Injectable protein hydrogel microspheres with reactive oxygen species-responsive nitric oxide release for cardiac protection against ischemia/reperfusion injury.","authors":"Houwei Zheng, Fan Jia, Ying Gao, Kaicheng Deng, Liyin Shen, Chao Zheng, Xin Xie, Changyou Gao, Tanchen Ren, Yang Zhu","doi":"10.1016/j.actbio.2025.08.040","DOIUrl":"10.1016/j.actbio.2025.08.040","url":null,"abstract":"<p><p>Nitric oxide (NO) can alleviate cardiac ischemia/reperfusion injury with its anti-inflammatory, antioxidant, and angiogenic effects. However, local NO availability is limited due to its short half-life, reduced production, and consumption by excess reactive oxygen species (ROS) generated in injured myocardium. Here, we designed an injectable hydrogel microsphere system (WPI-H-N) based on acrylated whey protein (WPI), onto which phenylborate ester group was attached and served as a ROS-cleavable linker for 5-isosorbide mononitrate (ISMN), a NO donor. This injectable hydrogel microsphere system was designed to scavenge excess ROS, and release NO in response to oxidative stress in the niche in order to achieve on-demand NO release, reduce NO depletion by ROS, and prolong NO retention in the infarcted myocardium. In a rat I/R model, WPI-H-N protected cardiomyocytes from apoptosis, attenuated cardiac oxidative injury and improved angiogenesis in the infarcted myocardium. These results demonstrate that the combination of ROS scavenging and responsive NO release can simultaneously overcome the two major limitations of NO therapy, supporting the development of more efficient NO delivery strategies. STATEMENT OF SIGNIFICANCE: This study presents an injectable hydrogel microsphere system that synergistically scavenges reactive oxygen species (ROS) and enables on-demand nitric oxide (NO) release for cardiac protection against ischemia/reperfusion injury. Unlike existing NO delivery platforms, the ROS-responsive phenylborate ester linkage ensures spatiotemporally controlled NO release, minimizing premature consumption by ROS and secondary nitrosative stress. The microspheres' dual functionality-simultaneously neutralizing oxidative stress and promoting angiogenesis-addresses critical limitations of conventional NO therapies. In vivo results demonstrate significant reductions in cardiomyocyte apoptosis, oxidative damage, and infarct size, alongside improved cardiac function and vascularization. This strategy offers a potentially translatable approach for local and controlled NO release to achieve cardiac repair. The work holds broad implications for ROS-related pathologies and precision therapeutic delivery in regenerative medicine.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in biomimetic nano delivery systems for pulmonary hypertension therapy. 用于肺动脉高压治疗的仿生纳米输送系统研究进展。
IF 9.6
Acta biomaterialia Pub Date : 2025-08-22 DOI: 10.1016/j.actbio.2025.08.034
Pengtao Zhao, Min Wang, Ziwen Liu, Miaotiao Zhang, Zhigui Cai, Bo Zhang, Zhaoling Shi, Manling Liu, Ying Cheng
{"title":"Advances in biomimetic nano delivery systems for pulmonary hypertension therapy.","authors":"Pengtao Zhao, Min Wang, Ziwen Liu, Miaotiao Zhang, Zhigui Cai, Bo Zhang, Zhaoling Shi, Manling Liu, Ying Cheng","doi":"10.1016/j.actbio.2025.08.034","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.08.034","url":null,"abstract":"<p><p>Pulmonary hypertension (PH), a condition triggered by various pathogenic factors, is characterized by a progressive increase in intra-pulmonary artery pressure and pulmonary resistance and progressive right ventricular hypertrophy, eventually culminating in right heart failure. Despite the fact that the conventional treatments can alleviate symptoms, they are limited by sub-optimal drug accumulation in the pulmonary vasculature and low bioavailability. Currently, as an emerging technology, the Nano Drug Delivery System (NDDS) has played a decisive role in enhancing drug targeting and precision and concomitantly minimizing side effects. This paper aims to summarize the pathophysiological mechanisms underlying PH and the knowledge related to the preparation and modification of cell-derived Biomimetic Nano Delivery Systems (BNDS), and to review the latest advancements in the application of BNDS for PH treatment, thereby laying a theoretical reference and offering novel insights for developing effective therapeutic strategies for PH. STATEMENT OF SIGNIFICANCE: Pulmonary hypertension (PH) remains a life-threatening cardiopulmonary disorder with limited therapeutic efficacy. While nanotechnology-based drug delivery systems hold promise for addressing these challenges, the emerging field of cell-derived biomimetic nanodelivery systems (BNDS) represents a groundbreaking shift toward intelligent, targeted, and biocompatible therapeutic strategies. This review not only synthesizes the pathophysiological underpinnings of PH and the design principles of BNDS but also critically evaluates their transformative potential in overcoming pulmonary vascular targeting barriers and improving therapeutic precision. By bridging cutting-edge advancements in biomimetic nanotechnology with PH pathophysiology, this work provides a comprehensive theoretical framework and innovative perspectives to inspire the development of next-generation therapies, ultimately paving the way for improved clinical outcomes and reduced mortality in PH patients.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structuring of gellan hydrogel enables the production of inherently antifibrotic, lubricating eye drops. 结冷胶水凝胶的结构使生产固有的抗纤维化,润滑滴眼液。
IF 9.6
Acta biomaterialia Pub Date : 2025-08-22 DOI: 10.1016/j.actbio.2025.08.039
Samuel R Moxon, Rachel C Vincent, A Taylor, B Cassidy, Richard J A Moakes, Gibran F Butt, Graham R Wallace, Anthony D Metcalfe, Richard L Williams, Nicholas M Barnes, Ann Logan, Saaeha Rauz, Liam M Grover
{"title":"Structuring of gellan hydrogel enables the production of inherently antifibrotic, lubricating eye drops.","authors":"Samuel R Moxon, Rachel C Vincent, A Taylor, B Cassidy, Richard J A Moakes, Gibran F Butt, Graham R Wallace, Anthony D Metcalfe, Richard L Williams, Nicholas M Barnes, Ann Logan, Saaeha Rauz, Liam M Grover","doi":"10.1016/j.actbio.2025.08.039","DOIUrl":"10.1016/j.actbio.2025.08.039","url":null,"abstract":"<p><p>Gellan is an anionic polysaccharide that forms optically clear hydrogels, making it suitable for use in ocular applications. Previous research has demonstrated that gellan fluid gels, when used alongside standard treatments (antibiotics and corticosteroid eye drops), reduce corneal scarring in models of microbial keratitis. This study investigated the potential mechanisms behind the enhanced corneal healing observed with drug-free gellan fluid gels. The impact of varying formulation parameters, such as polymer concentration and applied shear rate, on the physical properties of the fluid gels, including viscosity, stiffness, and lubricity, was examined to optimise gellan fluid gels for use as therapeutic eye drops. Biological analyses were undertaken that highlighted the capacity of gellan fluid gels to provide corneal cells with effective lubrication preventing cell removal on the application of shear. Additionally, gellan fluid gels were shown to sequester TGFβ1, a pro-fibrotic cytokine. Sequestration of the TGFβ1 resulted from electrostatic interactions between the negatively charged gellan and positively charged TGFβ1. As a consequence of this, gellan fluid gels inhibit TGFβ1-induced pro-fibrotic gene expression in corneal fibroblasts, contributing to reduced scarring and improved wound healing. The results suggest that gellan fluid gels, through modulation of physical properties and biological interactions, offer a mechanism for promoting ocular healing and mitigating inflammation-induced scarring, even in the absence of pharmaceutical actives. STATEMENT OF SIGNIFICANCE: This study presents the development of gellan fluid gel eye drops designed to prevent ocular fibrosis after damage. The formulation achieved lubricity comparable to commercial eye drops but with significantly enhanced viscosity and superior capacity to shield cells from damaging shear forces. By optimising gellan concentration and fabrication parameters, the eye drops exhibited reduced ocular friction and improved therapeutic efficacy. Additionally, the fluid gels sequestered TGFβ1, a key fibrosis molecule, with higher gellan concentrations showing enhanced absorption. Importantly, the formulations maintained ease of application through droppers, making them practical for daily use. This work highlights a cost-effective and patient-friendly solution, advancing biomaterial-based therapies for ocular therapies.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A hydrogel tissue adhesive incorporating basic fibroblast growth factor-loaded liposomes accelerates cutaneous wound healing by enhancing cell proliferation, collagen synthesis and angiogenesis. 一种水凝胶组织胶粘剂,含有装载基本成纤维细胞生长因子的脂质体,通过促进细胞增殖、胶原合成和血管生成来加速皮肤伤口愈合。
IF 9.6
Acta biomaterialia Pub Date : 2025-08-21 DOI: 10.1016/j.actbio.2025.08.035
Yujia Geng, Yang Gao, Desheng Qi, Zhen Wang, Zheng Zou, Zhiyun Zhang, Jiaqi Lian, Zhen Zhang, Chaoliang He, Ying Shao
{"title":"A hydrogel tissue adhesive incorporating basic fibroblast growth factor-loaded liposomes accelerates cutaneous wound healing by enhancing cell proliferation, collagen synthesis and angiogenesis.","authors":"Yujia Geng, Yang Gao, Desheng Qi, Zhen Wang, Zheng Zou, Zhiyun Zhang, Jiaqi Lian, Zhen Zhang, Chaoliang He, Ying Shao","doi":"10.1016/j.actbio.2025.08.035","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.08.035","url":null,"abstract":"<p><p>Tissue adhesives have become substitutes or adjuvants for surgical sutures owing to their minimal tissue damage and ease of application. However, limitations remain for existing tissue adhesives, such as weak adhesion strength, potential toxicity, and lack of bioactivities to promote wound healing. Here, we developed an injectable and biocompatible hydrogel tissue adhesive incorporating basic fibroblast growth factor (bFGF)-loaded liposomes for sutureless wound closure and promoting wound healing. The hydrogel, formed by 10 %(w/v) human serum albumin (HSA) and o-phthalaldehyde (OPA)-functionalized four-arm poly(ethylene glycol) (4aPEG-OPA) through irreversible OPA/amine condensation reaction, demonstrated strong tissue adhesion properties, biodegradability (complete degradation in PBS containing 1 U/mL elastase within 10 days), and biocompatibility. The hydrogel incorporating bFGF-loaded liposomes achieved sustained release of bFGF (cumulative release ratio of 65.4 % over 8 days), and promoted cell proliferation, migration, collagen production, and angiogenesis. In rat and porcine full-thickness skin incision models, the hydrogel effectively closed the wounds and facilitated wound healing within 14 days, outperforming commercially available fibrin glue and cyanoacrylate adhesives. RNA sequencing and western blotting analysis demonstrated that the hydrogel stimulated cell proliferation, collagen production, and angiogenesis. Overall, this hydrogel tissue adhesive shows great potential for encouraging wound closure without suture and promoting wound healing. STATEMENT OF SIGNIFICANCE: This study introduces a multifunctional tissue-adhesive hydrogel formed by covalent cross-linking of human serum albumin with o-phthalaldehyde (OPA)-terminated four-arm poly(ethylene glycol), and incorporated with bFGF-loaded liposomes. The catalyst-free OPA/amine reaction used in its synthesis ensures a mild and controllable gelation process, which is beneficial for maintaining the bioactivity of encapsulated growth factors. This composite system exhibited sustained growth factor release profile and remarkable bioactivity in regulating skin cell behaviors, which facilitates easier clinical translation compared to existing approaches. In rat and porcine models, it achieved sutureless wound healing and outperformed commercial adhesives in promoting re-epithelialization and angiogenesis, offering a promising alternative to traditional sutures and commercial adhesives.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of the intracellular mechanical microenvironment of breast cancer and normal mammary epithelial cells on magnetic hyperthermia of Fe3O4 nanoparticles. 乳腺癌和正常乳腺上皮细胞胞内机械微环境对Fe3O4纳米粒子磁热疗的影响
IF 9.6
Acta biomaterialia Pub Date : 2025-08-20 DOI: 10.1016/j.actbio.2025.08.031
Man Wang, Huajian Chen, Rui Sun, Tianjiao Zeng, Chengyu Lu, Toru Yoshitomi, Hiroaki Mamiya, Masaki Takeguchi, Naoki Kawazoe, Yingnan Yang, Guoping Chen
{"title":"Impact of the intracellular mechanical microenvironment of breast cancer and normal mammary epithelial cells on magnetic hyperthermia of Fe<sub>3</sub>O<sub>4</sub> nanoparticles.","authors":"Man Wang, Huajian Chen, Rui Sun, Tianjiao Zeng, Chengyu Lu, Toru Yoshitomi, Hiroaki Mamiya, Masaki Takeguchi, Naoki Kawazoe, Yingnan Yang, Guoping Chen","doi":"10.1016/j.actbio.2025.08.031","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.08.031","url":null,"abstract":"<p><p>Magnetic hyperthermia has been widely investigated as a promising cancer treatment modality. Efficient heat generation by magnetic nanoparticles under an alternating magnetic field (AMF) is critical for therapeutic efficacy. While extracellular conditions in the tumor microenvironment are considered key determinants of heat generation, the impact of the intracellular microenvironment has received less attention. This study aimed to elucidate how cytoskeletal architecture and intracellular mechanical properties-key components of the intracellular microenvironment-affect the heat generation and hyperthermia efficiency of magnetic Fe<sub>3</sub>O<sub>4</sub> nanoparticles (Fe<sub>3</sub>O<sub>4</sub> NPs) in human breast carcinomas and normal human mammary epithelial cells. Under AMF exposure, identical amounts of internalized Fe<sub>3</sub>O<sub>4</sub> NPs produced different heating effects in the two cell types, resulting in differential magnetic hyperthermia efficiency. Fe<sub>3</sub>O<sub>4</sub> NPs internalized by breast carcinomas produced greater temperature increase and induced apoptosis more effectively than those in normal mammary epithelial cells. Moreover, alternating current susceptibility analysis revealed that the softer intracellular cytoskeletal mechanics of breast carcinomas enhanced magnetothermal conversion compared with that of normal mammary epithelial cells. These findings highlight the critical role of intracellular cytoskeletal mechanics in regulating the magnetothermal behavior of Fe<sub>3</sub>O<sub>4</sub> NPs during magnetic hyperthermia. STATEMENT OF SIGNIFICANCE: This study reveals the critical role of the intracellular mechanical microenvironment of breast cancer cells in magnetothermal conversion of magnetic nanoparticles. Breast cancer cells have less organized cytoskeletal structure and softer intracellular microenvironment that are inherently more conducive to the magnetothermal conversion and heating performance of Fe<sub>3</sub>O<sub>4</sub> NPs than normal cells. Fe<sub>3</sub>O<sub>4</sub> NPs internalized by breast cancer cells generate higher local temperatures and induce significantly greater apoptotic effects. These findings highlight the breast cancer cell intracellular microenvironment as a key determinant in the effectiveness of magnetic hyperthermia, offering new insights into the design and optimization of nanoparticle-based cancer therapies.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sulfonium lipid nanoparticles for intranasal mRNA delivery to lung epithelial and immune cells. 用于肺上皮细胞和免疫细胞的鼻内mRNA递送的硫脂纳米颗粒。
IF 9.6
Acta biomaterialia Pub Date : 2025-08-20 DOI: 10.1016/j.actbio.2025.08.032
Yuqin Men, David O Popoola, Zhi Cao, Yiran Li, Stephan Wilkens, Yong Teng, Qinghe Meng, Marc Hershenson, Yamin Li
{"title":"Sulfonium lipid nanoparticles for intranasal mRNA delivery to lung epithelial and immune cells.","authors":"Yuqin Men, David O Popoola, Zhi Cao, Yiran Li, Stephan Wilkens, Yong Teng, Qinghe Meng, Marc Hershenson, Yamin Li","doi":"10.1016/j.actbio.2025.08.032","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.08.032","url":null,"abstract":"<p><p>Lung epithelial and immune cells play an important role in respiratory health, serving as the first line of defense. Targeting these cells presents significant therapeutic opportunities, particularly for mRNA-based medicine. However, efficient mRNA delivery to lung cells remains challenging due to mucosal barriers, enzymatic degradation, and complex tissue architecture. In this study, we developed sulfonium lipid nanoparticles (sLNPs) featuring a sulfonium head group and branched tail structure. These sLNPs efficiently delivered mRNA to lung epithelial and immune cells via intranasal instillation in mice, transfecting club cells, ciliated cells, and macrophages, which are key players in lung structure and function. Additionally, sLNPs successfully delivered CRISPR-Cas9 mRNA and sgRNA for genome editing, as well as cytokine mRNA for immune modulation in the lungs. The sLNP platform demonstrated safety in adult mice, with no significant local or systemic tissue damage observed. These findings highlight the sLNP platform's effectiveness and versatility in delivering diverse mRNA molecules, demonstrating its potential for applications ranging from gene editing to immunomodulation therapies. With further optimization, the sLNP system could pave the way for advanced mRNA-based treatments for lung diseases. STATEMENT OF SIGNIFICANCE: Almost all of the previously developed lipids for pulmonary mRNA delivery are amine-based. We designed and synthesized a group of lipids featuring the sulfonium charge-carrying group for mRNA delivery. This is the first demonstration of employing sulfonium lipid nanoparticles (sLNPs) for mRNA delivery to lung epithelial and immune cells in vivo. These sLNPs enabled efficient pulmonary delivery of diverse mRNA cargos, supporting applications such as bioluminescence imaging, gene editing, and immunomodulation. Club and ciliated cells as well as macrophages in the bronchoalveolar fluid, were successfully transfected. No sustained inflammation or toxicity was induced, highlighting the safety of these sulfonium lipid materials.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A viral infection-biomimetic strategy for antibody-guided targeted protein degradation. 抗体引导的靶向蛋白降解的病毒感染仿生策略。
IF 9.6
Acta biomaterialia Pub Date : 2025-08-20 DOI: 10.1016/j.actbio.2025.08.030
Yuanyuan Yang, Chuanda Zhu, Xiaojun Wang, Lidong Gong, Qiang Ma, Yujie Luo, Hongjun Wang, Dan Lu, Ridong Li, Qiang Zhang, Fen Gu, Zhiqiang Lin
{"title":"A viral infection-biomimetic strategy for antibody-guided targeted protein degradation.","authors":"Yuanyuan Yang, Chuanda Zhu, Xiaojun Wang, Lidong Gong, Qiang Ma, Yujie Luo, Hongjun Wang, Dan Lu, Ridong Li, Qiang Zhang, Fen Gu, Zhiqiang Lin","doi":"10.1016/j.actbio.2025.08.030","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.08.030","url":null,"abstract":"<p><p>Targeted protein degradation (TPD) is a valuable strategy for investigating protein functionality in cell biology and drug discovery. Among the various emerging TPD technologies, antibody-guided TPD offers key advantages over other protein degradation methods in terms of compatibility with different proteins of interest (POIs) and cell types. However, increasing the efficiency of cellular antibody internalisation and protein degradation remains challenges. Inspired by viral infection, which often efficiently activates protein degradation pathways in host cells, we developed a strategy called virus infection-mimicking targeted protein degradation (ViTPD) as a universal platform for degrading intracellular proteins. By mimicking three features of viral infection, we produced ViTPD nanoparticles by biomineralising antibodies enveloped by viral membranes or mixed with IFN-α. The biomineralised shell enhanced the cellular uptake of ViTPD nanoparticles via clathrin-mediated endocytosis. Similar to viral neutralising antibodies entering cells, the Fab region of the antibody released from ViTPD nanoparticles binds the POI, while the Fc region can recruit TRIM21, a key enzyme that continuously consumes during protein degradation. Interestingly, viral membrane components or IFN-α in the ViTPD led to increased TRIM21 expression, which enhanced the efficiency of proteolysis. ViTPD can effectively degrade several POIs, including GFP, FAK, COPZ1 and TREX1. Collectively, our results demonstrate that ViTPD provides a novel design strategy and an efficient nanoplatform for targeting intracellular protein degradation. STATEMENT OF SIGNIFICANCE: Antibody-guided targeted protein degradation (TPD) exhibits superior versatility compared to conventional degradation methods, demonstrating broad compatibility with diverse proteins of interest (POIs) across various cell types. Despite these advantages, significant challenges persist in optimizing cellular antibody internalization efficiency and degradation kinetics. In this study, we developed ViTPD, a biomimetic TPD platform that mimicking three viral infection features: (1) virus-like cellular internalization pathways, (2) virus-neutralizing antibody behavior, and (3) host-mediated protein degradation responses during viral infection. The development of ViTPD provides not only a robust platform for degrading diverse intracellular POIs but also establishes new design principles for next-generation protein degradation systems. This platform establishes new design principles for next-generation TPD systems while expanding therapeutic potential for precision medicine.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Artificial uterus with fluidics-driven system using material-switching digital light processing 3D bioprinting. 采用材料切换数字光处理生物3D打印的流体驱动系统人工子宫。
IF 9.6
Acta biomaterialia Pub Date : 2025-08-13 DOI: 10.1016/j.actbio.2025.08.026
Soon Hee Kim, Ji Won Heo, Sudarshini Nath, Moon Sik Oh, Sol Kim, Ji Seung Lee, Kyunghee Kim, Ok Joo Lee, Suk Woo Lee, In-Sun Hong, Chan Hum Park
{"title":"Artificial uterus with fluidics-driven system using material-switching digital light processing 3D bioprinting.","authors":"Soon Hee Kim, Ji Won Heo, Sudarshini Nath, Moon Sik Oh, Sol Kim, Ji Seung Lee, Kyunghee Kim, Ok Joo Lee, Suk Woo Lee, In-Sun Hong, Chan Hum Park","doi":"10.1016/j.actbio.2025.08.026","DOIUrl":"10.1016/j.actbio.2025.08.026","url":null,"abstract":"<p><p>Despite various attempts to replicate complex organ structures using 3D bioprinting technologies, the fabrication of a tissue-engineered endometrium with integrated vasculature remains a significant challenge in the field. In this study, we developed three bioinks by combining glycidyl methacrylate-modified GelMA (GelMAGMA) hydrogel precursor with endometrial stem cells, stromal cells, and endothelial cells to create a vascularized endometrial construct. Utilizing a one-step material-switching DLP 3D bioprinter capable of multi-material printing, we successfully fabricated an engineered endometrial construct with a vascular channel extending through both the functional and basal layers. The use of a perfusion culture system to circulate medium through the vascular network promoted cell activation, and estrogen treatment further validated the functionality of the construct. Additionally, in vivo subcutaneous implantation demonstrated the biocompatibility of the engineered tissue. This platform offers significant potential for tissue-engineered endometrial implants as well as research into various vascularized implantable tissues. STATEMENT OF SIGNIFICANCE: This study aims to develop a vascularized tissue-engineered endometrium for use in disease research and tissue implantation. Key findings include the development of GelMAGMA-based bioinks, fabrication of a vascularized endometrial construct, validation of its functionality, and proof of biocompatibility. The results advance tissue engineering and personalized medicine, with significant implications for endometrial disease studies and vascularized tissue model development.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulated cell death-targeted ocular nanomedicine. 调控细胞死亡靶向眼纳米药物。
IF 9.6
Acta biomaterialia Pub Date : 2025-08-09 DOI: 10.1016/j.actbio.2025.08.018
Sok I Ho, Lin Li, Sipeng Zuo, Jieling Tang, Fuxiang Ye, Ping Gu, Zhimin Tang, Linna Lu
{"title":"Regulated cell death-targeted ocular nanomedicine.","authors":"Sok I Ho, Lin Li, Sipeng Zuo, Jieling Tang, Fuxiang Ye, Ping Gu, Zhimin Tang, Linna Lu","doi":"10.1016/j.actbio.2025.08.018","DOIUrl":"10.1016/j.actbio.2025.08.018","url":null,"abstract":"<p><p>The pathological mechanism of ocular disorders is closely related to dysregulated proliferation or death of ocular cells. Regulated cell death (RCD) is a form of cell death controlled by specific signaling pathways. Diverse types of RCD, such as apoptosis, ferroptosis, autophagy, pyroptosis, and necroptosis, are prevalent in many eye diseases, while the modulation of RCD can alter ocular cell fate and improve disease progression. The pharmacological inducers and inhibitors of RCD have been developed as an emerging approach for ocular therapy. However, the complex ocular anatomy and barriers hinder the efficient use of RCD modulating drugs. Nanomedicine has emerged as a versatile tool in ophthalmic applications for its advanced properties in penetrating ocular barriers, preventing burst effects and rapid inactivation, enabling targeted and controlled release, and facilitating co-delivery of therapeutic agents. Similarly, nanomedicine has been widely explored for its potential in modulating RCD to treat ocular disorders. This review provides a comprehensive overview of the mechanistic roles of five major forms of RCD in eye diseases, summarizes the application of ocular nanomedicine that targets the RCD pathways, and discusses the future prospects of RCD-targeted ocular nanomedicine. It is expected that the elaborately designed RCD-targeted nanomedicine for ocular therapy will play an indispensable role for the establishment of next-generation ocular theranostic nanoplatforms. STATEMENT OF SIGNIFICANCE: Regulated cell death (RCD) significantly manipulates ocular cell fate and is a key driver in the progression of several vision-threatening diseases. However, the complex ocular structures limit the effective use of RCD-regulating therapies. Nanomedicine has emerged as a promising tool to overcome the limitations of the ocular anatomy and precisely modulate RCD, offering new avenues for therapeutic intervention in ocular diseases. In this review, we summarize the mechanistic role of RCD in the pathogenesis of ocular disorders, review current ocular nanomedicines that target the RCD pathway, and discuss the future prospects of RCD-targeted ocular nanomedicine. We aim to provide insights into the potential of targeted nanomedicine in advancing the therapeutics of ocular disorders.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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