Tays Troncoso‐Bravo, Valentina Pavez, Pedro Letelier, Javier Del Río, Cristian Anabalón, Hernán F. Peñaloza, Pablo A. González, Susan M. Bueno, Alexis M. Kalergis
Monoclonal antibodies have revolutionized modern medicine due to their target‐specific properties and effectiveness in treating a wide range of diseases, including cancer, autoimmune disorders, infectious diseases, and neurological conditions. Importantly, their large‐scale production for human use requires strict adherence to good manufacturing practice (GMP) standards to ensure quality, safety, and efficacy. This article reviews key aspects of monoclonal antibody production under GMP standards, from cell‐line selection to culture strategies, antibody purification, formulation, and quality control processes. Additionally, we discuss the significance of validation and traceability in production, as well as the implementation of emerging technologies to enhance manufacturing efficiency and safety. Despite progress in bioprocesses and regulatory frameworks, several challenges, such as batch‐to‐batch variability, high production costs, and the need to continuously adapt processes to new regulations, remain to be solved. The integration of innovative approaches with evolving regulations will enable the optimization of monoclonal antibody production and ensure their global accessibility.
{"title":"Current GMP standards for the large‐scale production of monoclonal antibodies","authors":"Tays Troncoso‐Bravo, Valentina Pavez, Pedro Letelier, Javier Del Río, Cristian Anabalón, Hernán F. Peñaloza, Pablo A. González, Susan M. Bueno, Alexis M. Kalergis","doi":"10.1002/btm2.70121","DOIUrl":"https://doi.org/10.1002/btm2.70121","url":null,"abstract":"Monoclonal antibodies have revolutionized modern medicine due to their target‐specific properties and effectiveness in treating a wide range of diseases, including cancer, autoimmune disorders, infectious diseases, and neurological conditions. Importantly, their large‐scale production for human use requires strict adherence to good manufacturing practice (GMP) standards to ensure quality, safety, and efficacy. This article reviews key aspects of monoclonal antibody production under GMP standards, from cell‐line selection to culture strategies, antibody purification, formulation, and quality control processes. Additionally, we discuss the significance of validation and traceability in production, as well as the implementation of emerging technologies to enhance manufacturing efficiency and safety. Despite progress in bioprocesses and regulatory frameworks, several challenges, such as batch‐to‐batch variability, high production costs, and the need to continuously adapt processes to new regulations, remain to be solved. The integration of innovative approaches with evolving regulations will enable the optimization of monoclonal antibody production and ensure their global accessibility.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"387 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146145936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kun Yu, Liang Ma, Pengkun Han, Yinshen Liu, Longfei Zou, Sen Wang, Jiesi Hu, Kai Zhong, Jiaqiang Liu, Bo Guo, Jie Zou, Houyin Shi, Xing Guo, Meiyun Tan
Osteoarthritis (OA) is a widespread degenerative condition marked by inflammation‐induced damage to chondrocytes and gradual breakdown of the cartilage extracellular matrix. Adipose‐derived mesenchymal stem cells (ADSCs) hold potential for treating OA due to their capacity to differentiate into various cell types and their paracrine signaling functions. However, the inflammatory environment in OA reduces ADSC viability post‐injection, while the absence of a supportive carrier causes significant cell loss, impairing their capacity for cartilage repair. To address these challenges, we improved the stemness and paracrine activity of ADSCs through hypoxia preconditioning and integrated them into an injectable small intestinal submucosa (SIS) tissue repair scaffold. This resulted in an SIS + ADSC composite material, designed for intra‐articular injection to enhance cartilage repair in arthritis. Our findings revealed that exposing ADSCs to 2% oxygen during hypoxia preconditioning and incorporating them into injectable SIS significantly increased the secretion of growth factors (VEGF, bFGF, EGF) and upregulated key hypoxia and stem cell markers (HIF‐1α, NANOG, SOX‐2, Oct‐4). In a rat OA model, hypoxia‐preconditioned SIS + ADSC composites markedly enhanced cartilage repair by stimulating anabolic activity, suppressing catabolic pathways, and reducing inflammation, thereby exhibiting strong protective and reparative effects. In summary, combining hypoxia preconditioning with injectable SIS offers an innovative and effective approach to optimize OA treatment by enhancing paracrine signaling, paving the way for new insights and technologies in cartilage repair within regenerative medicine.
{"title":"Hypoxia‐preconditioned adipose‐derived stem cells with injectable small intestinal submucosa for enhanced cartilage repair in osteoarthritis","authors":"Kun Yu, Liang Ma, Pengkun Han, Yinshen Liu, Longfei Zou, Sen Wang, Jiesi Hu, Kai Zhong, Jiaqiang Liu, Bo Guo, Jie Zou, Houyin Shi, Xing Guo, Meiyun Tan","doi":"10.1002/btm2.70116","DOIUrl":"https://doi.org/10.1002/btm2.70116","url":null,"abstract":"Osteoarthritis (OA) is a widespread degenerative condition marked by inflammation‐induced damage to chondrocytes and gradual breakdown of the cartilage extracellular matrix. Adipose‐derived mesenchymal stem cells (ADSCs) hold potential for treating OA due to their capacity to differentiate into various cell types and their paracrine signaling functions. However, the inflammatory environment in OA reduces ADSC viability post‐injection, while the absence of a supportive carrier causes significant cell loss, impairing their capacity for cartilage repair. To address these challenges, we improved the stemness and paracrine activity of ADSCs through hypoxia preconditioning and integrated them into an injectable small intestinal submucosa (SIS) tissue repair scaffold. This resulted in an SIS + ADSC composite material, designed for intra‐articular injection to enhance cartilage repair in arthritis. Our findings revealed that exposing ADSCs to 2% oxygen during hypoxia preconditioning and incorporating them into injectable SIS significantly increased the secretion of growth factors (VEGF, bFGF, EGF) and upregulated key hypoxia and stem cell markers (HIF‐1α, NANOG, SOX‐2, Oct‐4). In a rat OA model, hypoxia‐preconditioned SIS + ADSC composites markedly enhanced cartilage repair by stimulating anabolic activity, suppressing catabolic pathways, and reducing inflammation, thereby exhibiting strong protective and reparative effects. In summary, combining hypoxia preconditioning with injectable SIS offers an innovative and effective approach to optimize OA treatment by enhancing paracrine signaling, paving the way for new insights and technologies in cartilage repair within regenerative medicine.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"42 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hakan Ceylan, Edoardo Sinibaldi, Sanjay Misra, Pankaj J. Pasricha, Dietmar W. Hutmacher
Untethered mobile milli/microrobots hold transformative potential for interventional medicine by enabling more precise and entirely non‐invasive diagnosis and therapy. Realizing this promise requires bridging the gap between groundbreaking laboratory demonstrations and successful clinical integration. Despite remarkable technical progress over the past two decades, most millirobots and microrobots remain confined to laboratory proof‐of‐concept demonstrations, with limited real‐world feasibility. Here, we identify key factors that slow translation from bench to bedside, focusing on the disconnect between technical innovation and meaningful patient outcomes. We argue that the long‐term impact and sustainability of the field depend on aligning development with unmet clinical needs, demonstrating feasibility, value and integration potential into existing clinical workflows. To foster translational research of milli/microrobots, we introduce a strategic milli/microrobot Technology Readiness Level framework (mTRL), which maps system development from initial conceptualization to clinical adoption through clearly defined milestones and their associated stepwise activities. The mTRL model provides a structured gauge of technological maturity, a common language for multi‐disciplinary collaboration and actionable guidance to accelerate translational development toward new, safer and more efficient interventions.
{"title":"How microrobots should be translated: A clinical and value‐centered readiness framework","authors":"Hakan Ceylan, Edoardo Sinibaldi, Sanjay Misra, Pankaj J. Pasricha, Dietmar W. Hutmacher","doi":"10.1002/btm2.70112","DOIUrl":"https://doi.org/10.1002/btm2.70112","url":null,"abstract":"Untethered mobile milli/microrobots hold transformative potential for interventional medicine by enabling more precise and entirely non‐invasive diagnosis and therapy. Realizing this promise requires bridging the gap between groundbreaking laboratory demonstrations and successful clinical integration. Despite remarkable technical progress over the past two decades, most millirobots and microrobots remain confined to laboratory proof‐of‐concept demonstrations, with limited real‐world feasibility. Here, we identify key factors that slow translation from bench to bedside, focusing on the disconnect between technical innovation and meaningful patient outcomes. We argue that the long‐term impact and sustainability of the field depend on aligning development with unmet clinical needs, demonstrating feasibility, value and integration potential into existing clinical workflows. To foster translational research of milli/microrobots, we introduce a strategic milli/microrobot Technology Readiness Level framework (mTRL), which maps system development from initial conceptualization to clinical adoption through clearly defined milestones and their associated stepwise activities. The mTRL model provides a structured gauge of technological maturity, a common language for multi‐disciplinary collaboration and actionable guidance to accelerate translational development toward new, safer and more efficient interventions.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"91 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcia Muerner, Junxuan Ma, Rathina V. Balasubramanian, Chencheng Feng, Julia Fernández Pérez, Aleksandr Ovsianikov, Sibylle Grad
Intervertebral disc (IVD) degeneration (IVDD) is a major cause of low back pain, yet treatment options remain limited. Robust IVDD models are essential for discovering and validating new regenerative treatments. Ex vivo whole organ bioreactor cultures using bovine IVDs are a well‐established approach, with various degeneration models developed on this platform. However, most existing models replicate only isolated aspects of IVDD, failing to reflect its complex nature. There is a critical need for in vitro models that more accurately simulate the full spectrum of degeneration phenotypes observed in patients. Combining multiple well‐established degeneration models offers a promising strategy. In this study, we investigated the combined effects of enzyme (papain) and cytokine (tumor necrosis factor alpha [TNFα]) based degeneration inducers on bioreactor loaded bovine IVDs. While papain injection led to a 5.5‐fold higher glycosaminoglycan loss and tissue void formation, TNFα induced inflammatory and catabolic changes relevant to IVDD, including significant aggrecanase‐1 (ADAMTS4) upregulation and a 2.65‐fold increase in interleukin 6 release. Both effects were evident when combined, enabling the manifestation of multiple aspects of IVDD in one model. To also explore implications on nociception, primary bovine dorsal root ganglion neurons were cultured and treated with conditioned medium from the induced degenerative IVDs. Nociceptors treated with degenerative medium showed a 1.51‐fold higher proportion of neurons with a response compared to treatment with control IVD medium. By expanding the range of degenerative changes and bridging them to pain‐associated features, this model provides a valuable platform for testing novel regenerative therapies.
{"title":"A multifactorial intervertebral disc degeneration model: Integrating inflammation, structural disruption, biomechanical parameters, and neural sensitization","authors":"Marcia Muerner, Junxuan Ma, Rathina V. Balasubramanian, Chencheng Feng, Julia Fernández Pérez, Aleksandr Ovsianikov, Sibylle Grad","doi":"10.1002/btm2.70120","DOIUrl":"https://doi.org/10.1002/btm2.70120","url":null,"abstract":"Intervertebral disc (IVD) degeneration (IVDD) is a major cause of low back pain, yet treatment options remain limited. Robust IVDD models are essential for discovering and validating new regenerative treatments. <jats:italic>Ex vivo</jats:italic> whole organ bioreactor cultures using bovine IVDs are a well‐established approach, with various degeneration models developed on this platform. However, most existing models replicate only isolated aspects of IVDD, failing to reflect its complex nature. There is a critical need for <jats:italic>in vitro</jats:italic> models that more accurately simulate the full spectrum of degeneration phenotypes observed in patients. Combining multiple well‐established degeneration models offers a promising strategy. In this study, we investigated the combined effects of enzyme (papain) and cytokine (tumor necrosis factor alpha [TNFα]) based degeneration inducers on bioreactor loaded bovine IVDs. While papain injection led to a 5.5‐fold higher glycosaminoglycan loss and tissue void formation, TNFα induced inflammatory and catabolic changes relevant to IVDD, including significant aggrecanase‐1 (ADAMTS4) upregulation and a 2.65‐fold increase in interleukin 6 release. Both effects were evident when combined, enabling the manifestation of multiple aspects of IVDD in one model. To also explore implications on nociception, primary bovine dorsal root ganglion neurons were cultured and treated with conditioned medium from the induced degenerative IVDs. Nociceptors treated with degenerative medium showed a 1.51‐fold higher proportion of neurons with a response compared to treatment with control IVD medium. By expanding the range of degenerative changes and bridging them to pain‐associated features, this model provides a valuable platform for testing novel regenerative therapies.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"87 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abhinav P. Acharya, Matthew A. Borrelli, Michael J. Jurczak, Jonathan Krakoff, Steven R. Little
Controlling the molecular transport of nutrients through the gut is an attractive strategy to modulate host metabolism. Herein, a technique of stress‐based evolution of an individual's own microbiota to enhance lipid metabolism is presented, which is based on sequential culture of these bacteria in higher concentrations of lipids. Using this technique, a probiotic formulation of bacterial colonies that exhibit increased lipid metabolism was generated from oral microbiota samples from mice, canine, and human sources. Mice fed a high‐fat diet (HFD) and administered lipid stress evolved (LSE) probiotics excreted increased lipids in stool and reduced triglyceride transport into the blood by three‐fold till 3 h post‐oral gavage of soybean oil, as compared to controls. In addition, these enhanced probiotics prevented weight gain in mice fed a HFD five‐fold better than controls and induced weight loss in mice with diet change three‐fold faster than diet change alone. In these mice, there was a marked change in appearance with a more healthy, less oily coat. Controlled metabolic cage experiments demonstrated that the total movement, food intake, and water intake were not significantly different between mice receiving LSE probiotic versus a control probiotic formulation, suggesting that important health measures are unchanged with LSE probiotic administration. Overall, this facile stress‐based culture technique can be utilized to modulate bacterial metabolism and applied to different industrial processes of probiotic generation and to affect different disease outcomes such as obesity.
{"title":"Lipid stress evolved, microbiome‐based probiotics reduce lipid uptake in mice","authors":"Abhinav P. Acharya, Matthew A. Borrelli, Michael J. Jurczak, Jonathan Krakoff, Steven R. Little","doi":"10.1002/btm2.70122","DOIUrl":"https://doi.org/10.1002/btm2.70122","url":null,"abstract":"Controlling the molecular transport of nutrients through the gut is an attractive strategy to modulate host metabolism. Herein, a technique of stress‐based evolution of an individual's own microbiota to enhance lipid metabolism is presented, which is based on sequential culture of these bacteria in higher concentrations of lipids. Using this technique, a probiotic formulation of bacterial colonies that exhibit increased lipid metabolism was generated from oral microbiota samples from mice, canine, and human sources. Mice fed a high‐fat diet (HFD) and administered lipid stress evolved (LSE) probiotics excreted increased lipids in stool and reduced triglyceride transport into the blood by three‐fold till 3 h post‐oral gavage of soybean oil, as compared to controls. In addition, these enhanced probiotics prevented weight gain in mice fed a HFD five‐fold better than controls and induced weight loss in mice with diet change three‐fold faster than diet change alone. In these mice, there was a marked change in appearance with a more healthy, less oily coat. Controlled metabolic cage experiments demonstrated that the total movement, food intake, and water intake were not significantly different between mice receiving LSE probiotic versus a control probiotic formulation, suggesting that important health measures are unchanged with LSE probiotic administration. Overall, this facile stress‐based culture technique can be utilized to modulate bacterial metabolism and applied to different industrial processes of probiotic generation and to affect different disease outcomes such as obesity.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"56 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jordyn M. Wyse, Monica Prieto Nieto, Jinmin Zhang, Chia George Hsu, Marissa E. Wechsler
Elevated levels of reactive oxygen species play an integral role in chronic inflammation. Current treatments for chronic inflammation often ignore reactive oxygen species and instead focus on symptom control or immunosuppression. However, by controlling reactive oxygen species in inflammatory environments, cyclic inflammation can be reduced. Combining reactive oxygen species scavenging delivery systems with stealth coatings can help avoid the innate immune system and enable targeted delivery to sites of inflammation without causing further oxidative stress. For this purpose, poly(propylene sulfide) nanoparticles were synthesized utilizing two different surfactants, Pluronic F‐127 and sucrose monolaurate, adding stealth properties to the coatings of the reactive oxygen species scavenging nanoparticles. Characterization of the nanoparticles demonstrated the surfactant coatings did not affect the scavenging abilities nor the cytocompatibility of the materials. Degradation of the nanoparticles related to the sulfide groups and disulfide bond interactions with reactive oxygen species was also analyzed. Moreover, proinflammatory cytokine secretion from macrophages exposed to the nanoparticles was investigated to determine immune response evasion. Results obtained showed little to no activation of macrophages exposed to nanoparticle formulations in regard to MCP‐1 cytokine release. However, there is room for improvement using glycerol‐based coatings with regard to protecting cells from reactive oxygen species exposure and reducing macrophage activation in relation to IL‐6 and TNF‐alpha. Overall, the nanoparticles investigated have the capabilities to improve inflammatory disease treatments by not only targeting delivery of therapeutics to the site of inflammation, but also avoiding excess immune response recruitment due to incorporation of stealth coatings.
{"title":"Stealth polymer coatings of reactive oxygen species scavenging nanoparticles for immune response mitigation","authors":"Jordyn M. Wyse, Monica Prieto Nieto, Jinmin Zhang, Chia George Hsu, Marissa E. Wechsler","doi":"10.1002/btm2.70115","DOIUrl":"https://doi.org/10.1002/btm2.70115","url":null,"abstract":"Elevated levels of reactive oxygen species play an integral role in chronic inflammation. Current treatments for chronic inflammation often ignore reactive oxygen species and instead focus on symptom control or immunosuppression. However, by controlling reactive oxygen species in inflammatory environments, cyclic inflammation can be reduced. Combining reactive oxygen species scavenging delivery systems with stealth coatings can help avoid the innate immune system and enable targeted delivery to sites of inflammation without causing further oxidative stress. For this purpose, poly(propylene sulfide) nanoparticles were synthesized utilizing two different surfactants, Pluronic F‐127 and sucrose monolaurate, adding stealth properties to the coatings of the reactive oxygen species scavenging nanoparticles. Characterization of the nanoparticles demonstrated the surfactant coatings did not affect the scavenging abilities nor the cytocompatibility of the materials. Degradation of the nanoparticles related to the sulfide groups and disulfide bond interactions with reactive oxygen species was also analyzed. Moreover, proinflammatory cytokine secretion from macrophages exposed to the nanoparticles was investigated to determine immune response evasion. Results obtained showed little to no activation of macrophages exposed to nanoparticle formulations in regard to MCP‐1 cytokine release. However, there is room for improvement using glycerol‐based coatings with regard to protecting cells from reactive oxygen species exposure and reducing macrophage activation in relation to IL‐6 and TNF‐alpha. Overall, the nanoparticles investigated have the capabilities to improve inflammatory disease treatments by not only targeting delivery of therapeutics to the site of inflammation, but also avoiding excess immune response recruitment due to incorporation of stealth coatings.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"12 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146070239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marco Mammana, Alessandro Gandin, Giovanni Zambello, Margherita Pelosin, Alberto Elmi, Domenico Ventrella, Silvia Todros, Veronica Torresan, Federica Pezzuto, Marco Pietra, Noemi Romagnoli, Andrea Dell'Amore, Maria Laura Bacci, Fiorella Calabrese, Giovanna Brusatin, Federico Rea
Tracheal replacement is an unmet clinical need, as patients with long or complex airway defects are managed with tracheostomy or permanent stents. Experimental and clinical research is ongoing in order to find safe airway substitutes; however, the strategies under investigation suffer from major limitations, such as unsatisfactory re‐epithelialization, insufficient long‐term mechanical support, and complex ex vivo procedures. A ready‐to‐use and stable patch, able to support airway functionality and tissue regeneration, remains a significant challenge. Here we present the development of an off‐the‐shelf composite patch consisting of a resorbable polymer to aid epithelial restoration and a 3D‐printed multimaterial structure to guarantee effective mechanical stability. To evaluate the prosthesis performance, we designed a pilot study on a large animal setting, monitoring postoperative survival and airway healing for up to 60 days. An anterior cervical tracheal defect was created on four domestic pigs and patched with the prosthesis. The results were satisfactory in terms of postoperative survival, as only one animal died before the end of the study. However, endoscopic findings revealed a worsening stenosis due to wound contraction, granulation tissue formation, and partial displacement of the prosthesis. These findings were confirmed at histology, where a prominent inflammatory infiltrate was evident. Blood tests performed during follow‐up did not reveal any systemic inflammatory reaction. Overall, we believe that further optimization of the prosthesis design and materials is necessary in order to create an ideal “off‐the‐shelf” tracheal substitute. Nevertheless, this pilot study provides promising results and novel insights into a clinically relevant research area.
{"title":"Use of a composite, 3D ‐printed patch as a partial airway replacement: A pilot study on the porcine model","authors":"Marco Mammana, Alessandro Gandin, Giovanni Zambello, Margherita Pelosin, Alberto Elmi, Domenico Ventrella, Silvia Todros, Veronica Torresan, Federica Pezzuto, Marco Pietra, Noemi Romagnoli, Andrea Dell'Amore, Maria Laura Bacci, Fiorella Calabrese, Giovanna Brusatin, Federico Rea","doi":"10.1002/btm2.70103","DOIUrl":"https://doi.org/10.1002/btm2.70103","url":null,"abstract":"Tracheal replacement is an unmet clinical need, as patients with long or complex airway defects are managed with tracheostomy or permanent stents. Experimental and clinical research is ongoing in order to find safe airway substitutes; however, the strategies under investigation suffer from major limitations, such as unsatisfactory re‐epithelialization, insufficient long‐term mechanical support, and complex ex vivo procedures. A ready‐to‐use and stable patch, able to support airway functionality and tissue regeneration, remains a significant challenge. Here we present the development of an off‐the‐shelf composite patch consisting of a resorbable polymer to aid epithelial restoration and a 3D‐printed multimaterial structure to guarantee effective mechanical stability. To evaluate the prosthesis performance, we designed a pilot study on a large animal setting, monitoring postoperative survival and airway healing for up to 60 days. An anterior cervical tracheal defect was created on four domestic pigs and patched with the prosthesis. The results were satisfactory in terms of postoperative survival, as only one animal died before the end of the study. However, endoscopic findings revealed a worsening stenosis due to wound contraction, granulation tissue formation, and partial displacement of the prosthesis. These findings were confirmed at histology, where a prominent inflammatory infiltrate was evident. Blood tests performed during follow‐up did not reveal any systemic inflammatory reaction. Overall, we believe that further optimization of the prosthesis design and materials is necessary in order to create an ideal “off‐the‐shelf” tracheal substitute. Nevertheless, this pilot study provides promising results and novel insights into a clinically relevant research area.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"397 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily Barnett, Joey Lavalla, Pranavi Thatavarthi, Isabel Ray, Taylor Hamas, Jessica Jager, Vaishnavi Kanduri, Jasmine White, Elizabeth Singleton, Jordan Drinks, Megan Pitz, Angela Alexander‐Bryant, Jessica Larsen
Glioblastoma (GBM) is one of the most aggressive and rapidly progressing brain tumors, characterized by a low survival rate, in part due to insufficient diagnostic tools. Computed tomography (CT), although widely available, is limited in use for GBM diagnosis by the suboptimal performance of current clinically approved contrast agents. This study focuses on the development of gold nanoparticle (AuNP)‐loaded polymersomes (AuPs) to improve the detection of GBM. We synthesized polyethylene glycol‐b‐polylactic acid (PEG‐b‐PLA) polymersomes with high AuNP loading. Increasing the concentrations of AuNPs in polymersomes resulted in enhanced contrast using clinical CT. Furthermore, AuPs bound to cell‐penetrating peptide TAT were cytocompatible with U87‐MG GBM cells at concentrations up to 100 mg/mL. Uptake studies using both fluorescence microscopy and flow cytometry confirmed the internalization of AuPs into GBM cells, with a direct correlation between AuP concentration and uptake efficiency. MicroCT imaging also confirmed a similar trend; >300% enhanced contrast compared to PBS controls was observed with increasing concentrations of AuPs and was maintained in vivo at 337–863 HU. Overall, these results demonstrate that a polymersome‐based system for AuNPs enhances CT image contrast, suggesting that this approach could be feasible for improving GBM detection via CT.
胶质母细胞瘤（GBM）是最具侵袭性和快速进展的脑肿瘤之一，其特点是生存率低，部分原因是诊断工具不足。计算机断层扫描（CT）虽然广泛使用，但由于目前临床批准的造影剂性能不佳，在GBM诊断中的应用受到限制。本研究的重点是开发负载金纳米颗粒（AuNP）的聚合体（AuPs）来提高GBM的检测。我们合成了高AuNP负载的聚乙二醇- b -聚乳酸（PEG - b - PLA）聚合体。增加聚合体中AuNPs的浓度导致临床CT造影增强。此外，与细胞穿透肽TAT结合的AuPs在浓度高达100 MG /mL时与U87 - MG GBM细胞具有细胞相容性。利用荧光显微镜和流式细胞术进行摄取研究，证实了AuP能内化到GBM细胞中，且AuP浓度与摄取效率直接相关。微ct成像也证实了类似的趋势；与PBS对照相比，随着AuPs浓度的增加，对比增强了300%，并在体内维持在337-863 HU。总之，这些结果表明，基于聚合物的AuNPs系统增强了CT图像对比度，表明该方法可以通过CT提高GBM检测。
{"title":"Enabling in vivo imaging in low‐resource settings: Computed tomography imaging of gold‐loaded polymersomes for the detection of glioblastoma","authors":"Emily Barnett, Joey Lavalla, Pranavi Thatavarthi, Isabel Ray, Taylor Hamas, Jessica Jager, Vaishnavi Kanduri, Jasmine White, Elizabeth Singleton, Jordan Drinks, Megan Pitz, Angela Alexander‐Bryant, Jessica Larsen","doi":"10.1002/btm2.70109","DOIUrl":"https://doi.org/10.1002/btm2.70109","url":null,"abstract":"Glioblastoma (GBM) is one of the most aggressive and rapidly progressing brain tumors, characterized by a low survival rate, in part due to insufficient diagnostic tools. Computed tomography (CT), although widely available, is limited in use for GBM diagnosis by the suboptimal performance of current clinically approved contrast agents. This study focuses on the development of gold nanoparticle (AuNP)‐loaded polymersomes (AuPs) to improve the detection of GBM. We synthesized polyethylene glycol‐b‐polylactic acid (PEG‐b‐PLA) polymersomes with high AuNP loading. Increasing the concentrations of AuNPs in polymersomes resulted in enhanced contrast using clinical CT. Furthermore, AuPs bound to cell‐penetrating peptide TAT were cytocompatible with U87‐MG GBM cells at concentrations up to 100 mg/mL. Uptake studies using both fluorescence microscopy and flow cytometry confirmed the internalization of AuPs into GBM cells, with a direct correlation between AuP concentration and uptake efficiency. MicroCT imaging also confirmed a similar trend; >300% enhanced contrast compared to PBS controls was observed with increasing concentrations of AuPs and was maintained in vivo at 337–863 HU. Overall, these results demonstrate that a polymersome‐based system for AuNPs enhances CT image contrast, suggesting that this approach could be feasible for improving GBM detection via CT.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"58 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rachel E. Young, Tara Vijayakumar, Logan J. Reilley, Krisha Darji, Diya Patel, Samuel Hofbauer, Mohamad‐Gabriel Alameh, Drew Weissman, Rachel Riley
Placental dysfunction leads to pregnancy‐related disorders that affect up to 15% of pregnancies. Several of these, such as preeclampsia, are symptomatically managed but have no curative treatments other than preterm delivery. Placental dysfunction arises from improper placental development, leading to restricted blood vessel formation and a hypoxic placental microenvironment. The development of placental therapeutics is challenging due to the complex physiology that enables the placenta to control uptake and transport. Here, we use a simple culture system that combines hypoxia and trophoblast syncytialization to model the functional syncytiotrophoblast layer of the placenta under hypoxic stress. Using this model, we evaluate the impact of hypoxia on lipid nanoparticle (LNP)‐mediated mRNA delivery. Our data show that hypoxia hinders syncytiotrophoblast formation in vitro. Despite this, LNP delivery to syncytiotrophoblasts increases protein translation and secretion, particularly under hypoxic conditions. Further, we show delivery of a therapeutic mRNA, placental growth factor (PlGF), to syncytiotrophoblasts in hypoxia, which restored diminished PlGF levels back to normoxic controls. These findings provide an LNP platform for efficient mRNA delivery to hypoxic trophoblasts and demonstrate the importance of considering hypoxia towards the development of drug delivery platforms for placental therapeutics.
{"title":"Investigating the impact of hypoxia and syncytialization on lipid nanoparticle‐mediated mRNA delivery to placental cells","authors":"Rachel E. Young, Tara Vijayakumar, Logan J. Reilley, Krisha Darji, Diya Patel, Samuel Hofbauer, Mohamad‐Gabriel Alameh, Drew Weissman, Rachel Riley","doi":"10.1002/btm2.70114","DOIUrl":"https://doi.org/10.1002/btm2.70114","url":null,"abstract":"Placental dysfunction leads to pregnancy‐related disorders that affect up to 15% of pregnancies. Several of these, such as preeclampsia, are symptomatically managed but have no curative treatments other than preterm delivery. Placental dysfunction arises from improper placental development, leading to restricted blood vessel formation and a hypoxic placental microenvironment. The development of placental therapeutics is challenging due to the complex physiology that enables the placenta to control uptake and transport. Here, we use a simple culture system that combines hypoxia and trophoblast syncytialization to model the functional syncytiotrophoblast layer of the placenta under hypoxic stress. Using this model, we evaluate the impact of hypoxia on lipid nanoparticle (LNP)‐mediated mRNA delivery. Our data show that hypoxia hinders syncytiotrophoblast formation in vitro. Despite this, LNP delivery to syncytiotrophoblasts increases protein translation and secretion, particularly under hypoxic conditions. Further, we show delivery of a therapeutic mRNA, placental growth factor (PlGF), to syncytiotrophoblasts in hypoxia, which restored diminished PlGF levels back to normoxic controls. These findings provide an LNP platform for efficient mRNA delivery to hypoxic trophoblasts and demonstrate the importance of considering hypoxia towards the development of drug delivery platforms for placental therapeutics.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"49 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael Yilma Yitayew, Alexandre Bay, Ling Li, Ciriaco A. Piccirillo, Maryam Tabrizian
Encapsulation of pancreatic islet transplants with nano‐thin conformal coatings has been reported to maintain islet cell function and minimize immune rejection in type 1 diabetes (T1D) treatment. Our work investigated a novel combination of non‐immunogenic polyelectrolytes, tetrahydropyran triazole phenyl‐alginate (TZ‐AL) and quaternized phosphocholine‐chitosan (PC‐QCH), for layer‐by‐layer self‐assembly onto the surface of mouse islets. Building on previous work validating coating characteristics and biocompatibility using cell‐derived spheroids, we assessed the immunoprotective properties of the polyelectrolyte coating. This was done through in vitro co‐culture of the polyelectrolytes with mouse‐derived splenocytes enriched for antigen‐presenting cells (APCs) and syngeneic transplantation of coated mouse islets into STZ‐induced diabetic mice. Results indicated that the polyelectrolytes may downregulate APC activation and maturation in vitro. In addition, coated islets successfully restored normoglycemia in syngeneic transplants, as demonstrated by blood glucose measurements, intraperitoneal glucose tolerance tests, and graft immunostaining. These results suggest that the polyelectrolyte coating may modulate APC activation and that coated islets exhibit therapeutic efficacy for glycemic control in T1D.
{"title":"Evaluation of a functionalized chitosan and alginate multilayer conformal nanocoating toward improving islet survival in syngeneic mouse islet transplantation","authors":"Michael Yilma Yitayew, Alexandre Bay, Ling Li, Ciriaco A. Piccirillo, Maryam Tabrizian","doi":"10.1002/btm2.70039","DOIUrl":"https://doi.org/10.1002/btm2.70039","url":null,"abstract":"Encapsulation of pancreatic islet transplants with nano‐thin conformal coatings has been reported to maintain islet cell function and minimize immune rejection in type 1 diabetes (T1D) treatment. Our work investigated a novel combination of non‐immunogenic polyelectrolytes, tetrahydropyran triazole phenyl‐alginate (TZ‐AL) and quaternized phosphocholine‐chitosan (PC‐QCH), for layer‐by‐layer self‐assembly onto the surface of mouse islets. Building on previous work validating coating characteristics and biocompatibility using cell‐derived spheroids, we assessed the immunoprotective properties of the polyelectrolyte coating. This was done through in vitro co‐culture of the polyelectrolytes with mouse‐derived splenocytes enriched for antigen‐presenting cells (APCs) and syngeneic transplantation of coated mouse islets into STZ‐induced diabetic mice. Results indicated that the polyelectrolytes may downregulate APC activation and maturation in vitro. In addition, coated islets successfully restored normoglycemia in syngeneic transplants, as demonstrated by blood glucose measurements, intraperitoneal glucose tolerance tests, and graft immunostaining. These results suggest that the polyelectrolyte coating may modulate APC activation and that coated islets exhibit therapeutic efficacy for glycemic control in T1D.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"58 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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