Tarek Saleh, Lorenzo Caciolli, Giovanni Giuseppe Giobbe, Paolo De Coppi
{"title":"Ex vivo organ engineering using decellularized tissue scaffolds","authors":"Tarek Saleh, Lorenzo Caciolli, Giovanni Giuseppe Giobbe, Paolo De Coppi","doi":"10.1038/s44222-025-00322-5","DOIUrl":"10.1038/s44222-025-00322-5","url":null,"abstract":"End-stage organ failure requires the transplantation of a new organ. However, the number of patients awaiting donor organs exceeds the number of available organs. To address this organ shortage, solid organs, such as the kidneys, liver, heart and lungs, can be engineered based on decellularized human and non-human tissues. These decellularized scaffolds can then be recellularized with autologous or allogeneic cells and modified to ensure engraftment and function following transplantation. In this Review, we discuss the creation of decellularized neo-solid organs, including animal donor considerations, pre-decellularization processes, decellularization protocols, post-decellularization characterization, sterilization and storage conditions. We highlight various cell seeding and modification strategies and examine bioreactor culture conditions to grow functional solid organs. Finally, we outline mechanisms of transplant-recipient crosstalk and discuss challenges and opportunities for the clinical translation of engineered solid organs. New organs can be engineered based on decellularized human and animal tissues to address the global shortage of donor organs. This Review discusses design principles for the engineering of new organs using decellularized animal-derived tissues, including decellularization, functionalization and characterization protocols.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 9","pages":"761-774"},"PeriodicalIF":37.6,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145122914","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}
Yunching Chen (, ), Yu-Cheng Su (, ), Steve R. Roffler
{"title":"Polyethylene glycol immunogenicity in nanomedicine","authors":"Yunching Chen \u0000 (, ), Yu-Cheng Su \u0000 (, ), Steve R. Roffler","doi":"10.1038/s44222-025-00321-6","DOIUrl":"10.1038/s44222-025-00321-6","url":null,"abstract":"Polyethylene glycol (PEG) endows nanomedicines with stealth properties, reducing interactions with immune cells, prolonging blood circulation and stabilizing lipid-based formulations. However, anti-PEG antibodies, either pre-existing or induced by PEGylated medicines and vaccines, might adversely affect the safety and efficacy of nanomedicines by altering nanocarrier biodistribution, inducing unwanted inflammatory responses, destabilizing lipid formulations and causing hypersensitivity reactions. Therefore, the effect of PEG immunogenicity on nanomedicines should be critically assessed, and alternative approaches explored. In this Review, we first discuss PEG immunogenicity and the sources, detection and effects of anti-PEG antibodies. We then highlight strategies to address PEG immunogenicity, including the adjustment of dosing, routes and timing of nanomedicine administration, competition with high-molecular-mass PEG, engineering strategies to improve stealth effects of PEG and the design of complement inhibitors to reduce opsonization. In addition, we examine approaches for the design of PEG-free stealth nanomedicines, such as the use of alternative polymers, protein nanocages and biomimetic particles cloaked with cell membranes, serum components or bioactive molecules to prevent immune system recognition. Finally, we explore the application of anti-PEG antibodies in the creation of artificial cell receptors, reloadable hydrogels and bispecific antibodies for targeted delivery of PEGylated therapeutics. Polyethylene glycol (PEG) is used in many nanomedicines but might cause the production of anti-PEG antibodies. This Review critically assesses mechanisms and effects of PEG immunogenicity and explores strategies to address PEG immunogenicity in the context of nanomedicine.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 9","pages":"742-760"},"PeriodicalIF":37.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145122918","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}
{"title":"Improving transfusion medicine in resource-limited settings by point-of-care diagnostics","authors":"Rijo Rajeev, Paresh Mohanty, Suvro Sankha Datta, Parikshit Moitra","doi":"10.1038/s44222-025-00331-4","DOIUrl":"10.1038/s44222-025-00331-4","url":null,"abstract":"To ensure comprehensive understanding of blood group antigens — including minor antigens — blood transfusions require extended erythrocyte phenotyping or genotyping. However, such advanced testing is frequently unavailable in resource-limited settings. Implementing point-of-care testing on extended blood group antigens can enhance patient care in transfusion medicine by improving the accessibility, safety and efficiency of blood transfusions.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 9","pages":"718-720"},"PeriodicalIF":37.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145122917","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}
{"title":"Engineering cell-based ovarian hormone therapy","authors":"Maria João Sousa, Christiani A. Amorim","doi":"10.1038/s44222-025-00325-2","DOIUrl":"10.1038/s44222-025-00325-2","url":null,"abstract":"Biomimetic endocrine implants bridge tissue engineering and reproductive medicine to offer adaptive and long-lasting hormone therapies for the treatment of ovarian premature insufficiency and menopause. Their clinical translation requires aligned regulatory, ethical and manufacturing pathways.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 8","pages":"620-622"},"PeriodicalIF":37.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145122731","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}
{"title":"Point-of-care tuberculosis testing","authors":"Caroline Beyer","doi":"10.1038/s44222-025-00327-0","DOIUrl":"10.1038/s44222-025-00327-0","url":null,"abstract":"An article in Science Translational Medicine describes a lab-in-tube device for rapid and low-cost detection of tuberculosis from sputum, saliva and serum samples.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 6","pages":"444-444"},"PeriodicalIF":37.6,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145122754","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}
Jessica L. Stelzel, Jonathan P. Schneck, Hai-Quan Mao, Joshua C. Doloff
{"title":"Oversimplified immunology is holding biomaterials back","authors":"Jessica L. Stelzel, Jonathan P. Schneck, Hai-Quan Mao, Joshua C. Doloff","doi":"10.1038/s44222-025-00320-7","DOIUrl":"10.1038/s44222-025-00320-7","url":null,"abstract":"Immune responses are complex, often defying rigid classifications. Instead of interpreting results according to reductionist categories, researchers should rely on comprehensive single-cell data to guide analysis and should remain open to unexpected immunological complexity.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 7","pages":"523-525"},"PeriodicalIF":37.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145122772","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}
{"title":"Protein design and optimization for synthetic cells","authors":"Béla P. Frohn, Shunshi Kohyama, Petra Schwille","doi":"10.1038/s44222-025-00318-1","DOIUrl":"10.1038/s44222-025-00318-1","url":null,"abstract":"Proteins are essential components in synthetic biology, providing multiple functions at the nanoscale. Newly developed protein optimization and design tools allow the generation of proteins with desired properties, offering new opportunities for the engineering of protein-based biological systems. In this Review, we explore how bottom-up synthetic biology, with its aim to construct synthetic cells, can use these tools to devise complex biological functions and functional systems from scratch. We provide an overview of current capabilities in protein optimization, de novo protein design and iterative system optimization, and discuss their potential in synthetic cell science with regard to standardization, the generation of missing functionality and integration. We conclude with the outline of an integrated pipeline that combines protein engineering, automated synthetic cell generation and active learning, which might allow the design of entirely new biological systems that do not rely on naturally evolved protein components. Bottom-up synthetic biology might greatly benefit from custom-made proteins as components of new biological systems. This Review discusses various protein optimization and design approaches, and explores how these can contribute to the generation of controllable synthetic cells.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 8","pages":"645-659"},"PeriodicalIF":37.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145122732","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}
{"title":"Bioengineering needs diversity","authors":"","doi":"10.1038/s44222-025-00317-2","DOIUrl":"10.1038/s44222-025-00317-2","url":null,"abstract":"Policies that limit diversity and inclusion undermine evidence-based science by creating gaps in the data, potentially distorting findings and skewing results. When diversity and inclusion are sidelined, scientific progress is hindered.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 5","pages":"349-350"},"PeriodicalIF":37.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44222-025-00317-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145122667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fabienne Benz, Beatriz Beamud, Raphael Laurenceau, Amandine Maire, Xavier Duportet, Antoine Decrulle, David Bikard
{"title":"CRISPR–Cas therapies targeting bacteria","authors":"Fabienne Benz, Beatriz Beamud, Raphael Laurenceau, Amandine Maire, Xavier Duportet, Antoine Decrulle, David Bikard","doi":"10.1038/s44222-025-00311-8","DOIUrl":"10.1038/s44222-025-00311-8","url":null,"abstract":"Technologies derived from the CRISPR (clustered regularly interspaced short palindromic repeats)–Cas immune system of prokaryotes have revolutionized our ability to cleave and modify target nucleic acid sequences. In addition to the use of CRISPR–Cas tools for the editing of human genes, they can also be designed to target pathogenic and commensal bacteria that colonize the body, offering new pathways for the treatment of infections and microbiome modulation. In this Review, we explore how the CRISPR–Cas toolbox can be engineered to kill or modify specific bacteria. We discuss DNA-targeting and RNA-targeting strategies, outlining how these can be applied to disarm bacteria by removing, modifying or silencing specific genes. Furthermore, we examine the delivery of CRISPR–Cas tools by bacteriophages and through conjugation and explore intracellular barriers to CRISPR–Cas tool maintenance and expression. Finally, we highlight therapeutic opportunities in the treatment of infectious diseases and for the modification of the microbiome, outlining progress and challenges in translating these approaches into clinical applications. CRISPR–Cas tools can be designed to kill or modify specific bacteria. This Review explores the engineering of CRISPR–Cas tools and corresponding delivery strategies for the treatment of bacterial infections and modification of the microbiome.","PeriodicalId":74248,"journal":{"name":"Nature reviews bioengineering","volume":"3 8","pages":"627-644"},"PeriodicalIF":37.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145122934","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}
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