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}
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}
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}
Cervical cancer is a leading cause of death in women in low‐ and middle‐income countries (LMICs) and disproportionately affects women of minority populations in the United States, primarily due to a lack of infrastructural support for specialized care. A promising treatment that meets accessibility requirements is ethyl cellulose (EC)‐ethanol ablation—inducing necrotic cell death through application of ethanol to kill precancerous cells. While previous work focused on injecting EC‐ethanol to ablate high‐grade dysplasia (which can reach depths up to 5 mm below the tissue surface), low‐grade dysplasia requires a different delivery method as it is much more superficial (reaching depths of only 1–3 mm). Here, we have developed a topical gel for local ethanol ablation of low‐grade dysplasia with minimal damage to healthy cervical tissue. We investigated several gellants, including methyl cellulose (MC), EC, and Pluronic® F‐127, to develop an ethanol gel that meets parameters for low cost and topical ease of use. Formulations with F‐127 did not form gels with ethanol. Formulations with EC and MC were gel‐forming. The MC‐based formulations formed more uniform and stable gels that hold their own weight while still being spreadable at both room and body temperatures, key criteria for local cervical application. The optimal formulation contained 70% ethanol, 20% water, and 10% MC. One gram of this formulation represents approximately 5¢ material cost, and formulated gels were stable for at least 1 week when stored at 4, 22, 30, and 37°C. Additionally, the MC gel achieved localized ablation within 5 min after application to cervical cancer cells in vitro. Taken together, we have developed a low‐cost, efficacious, MC‐based ethanol gel fit for translational testing to treat low‐grade cervical dysplasia. This gel may provide a novel treatment option for women in LMICs, without causing major side effects or loss of healthy cervical tissue.
{"title":"Development of a novel methyl cellulose hydrogel with physiologically relevant controlled ethanol release for cervical dysplasia ablation","authors":"Ashleigh M. Jankowski, Erela Imanoel, Gatha Adhikari, Jenna Mueller, Katharina Maisel","doi":"10.1002/btm2.70113","DOIUrl":"https://doi.org/10.1002/btm2.70113","url":null,"abstract":"Cervical cancer is a leading cause of death in women in low‐ and middle‐income countries (LMICs) and disproportionately affects women of minority populations in the United States, primarily due to a lack of infrastructural support for specialized care. A promising treatment that meets accessibility requirements is ethyl cellulose (EC)‐ethanol ablation—inducing necrotic cell death through application of ethanol to kill precancerous cells. While previous work focused on injecting EC‐ethanol to ablate high‐grade dysplasia (which can reach depths up to 5 mm below the tissue surface), low‐grade dysplasia requires a different delivery method as it is much more superficial (reaching depths of only 1–3 mm). Here, we have developed a topical gel for local ethanol ablation of low‐grade dysplasia with minimal damage to healthy cervical tissue. We investigated several gellants, including methyl cellulose (MC), EC, and Pluronic® F‐127, to develop an ethanol gel that meets parameters for low cost and topical ease of use. Formulations with F‐127 did not form gels with ethanol. Formulations with EC and MC were gel‐forming. The MC‐based formulations formed more uniform and stable gels that hold their own weight while still being spreadable at both room and body temperatures, key criteria for local cervical application. The optimal formulation contained 70% ethanol, 20% water, and 10% MC. One gram of this formulation represents approximately 5¢ material cost, and formulated gels were stable for at least 1 week when stored at 4, 22, 30, and 37°C. Additionally, the MC gel achieved localized ablation within 5 min after application to cervical cancer cells in vitro. Taken together, we have developed a low‐cost, efficacious, MC‐based ethanol gel fit for translational testing to treat low‐grade cervical dysplasia. This gel may provide a novel treatment option for women in LMICs, without causing major side effects or loss of healthy cervical tissue.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"396 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014346","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}
Hepatocellular carcinoma (HCC) is a major cause of cancer‐related deaths. Advanced‐stage patients face poor prognosis due to chemotherapy resistance and an immunosuppressive tumor microenvironment (TME). Cellular senescence, marked by the senescence‐associated secretory phenotype, promotes tumor progression and immune evasion. Although honokiol (HKL) shows strong antitumor activity, its clinical use is limited by poor solubility, rapid clearance, and low bioavailability. Here, we report HKL‐loaded poly(ethylene glycol)‐poly(ε‐caprolactone)‐poly(ethylene glycol) triblock copolymer nanomicelles (HKL‐nm) as a multifunctional nanotherapeutic platform. HKL‐nm exhibited a uniform spherical shape with a diameter of 60.93 ± 5.7 nm, near‐neutral charge (−0.28 ± 0.1 mV), and high encapsulation efficiency (85.9 ± 4.9%). It enabled sustained drug release (70.04 ± 6.2% over 200 h) and significantly improved oral pharmacokinetics (area under the curve increased 6.26‐fold and Cmax increased 4.06‐fold). Specifically, the HKL drug concentration at the tumor site was enhanced by 3.52‐fold. Mechanistically, HKL‐nm suppressed senescence markers (p53, p16, and p21) and senescence‐associated β‐galactosidase positivity via a Sirtuin 3‐dependent pathway, inhibiting cytoplasmic mitochondrial DNA leakage and cGAS‐STING signaling. In Hepa1‐6 cells xenografts, combination therapy with HKL‐nm and the senolytic cocktail dasatinib + quercetin achieved tumor volume reduction, with transcriptomic analysis validating enrichment of immune activation pathways. This was accompanied by enhanced infiltration of CD8 + cytotoxic T cells and mature dendritic cells, coupled with profound suppression of myeloid‐derived suppressor cells. By integrating nanodelivery, senescence modulation, and immuno‐oncology, HKL‐nm represents a promising strategy to overcome therapeutic resistance in HCC, providing a preclinical basis for translation to solid tumors.
{"title":"Honokiol‐loaded nanomicelles reprogram senescence and immune evasion in hepatocellular carcinoma via SIRT3 ‐mediated mitochondrial stabilization","authors":"Wenxing Deng, Yizhi Wu, Yisheng Yin, Jing Wang","doi":"10.1002/btm2.70111","DOIUrl":"https://doi.org/10.1002/btm2.70111","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a major cause of cancer‐related deaths. Advanced‐stage patients face poor prognosis due to chemotherapy resistance and an immunosuppressive tumor microenvironment (TME). Cellular senescence, marked by the senescence‐associated secretory phenotype, promotes tumor progression and immune evasion. Although honokiol (HKL) shows strong antitumor activity, its clinical use is limited by poor solubility, rapid clearance, and low bioavailability. Here, we report HKL‐loaded poly(ethylene glycol)‐poly(ε‐caprolactone)‐poly(ethylene glycol) triblock copolymer nanomicelles (HKL‐nm) as a multifunctional nanotherapeutic platform. HKL‐nm exhibited a uniform spherical shape with a diameter of 60.93 ± 5.7 nm, near‐neutral charge (−0.28 ± 0.1 mV), and high encapsulation efficiency (85.9 ± 4.9%). It enabled sustained drug release (70.04 ± 6.2% over 200 h) and significantly improved oral pharmacokinetics (area under the curve increased 6.26‐fold and <jats:italic>C</jats:italic> <jats:sub>max</jats:sub> increased 4.06‐fold). Specifically, the HKL drug concentration at the tumor site was enhanced by 3.52‐fold. Mechanistically, HKL‐nm suppressed senescence markers (p53, p16, and p21) and senescence‐associated β‐galactosidase positivity via a Sirtuin 3‐dependent pathway, inhibiting cytoplasmic mitochondrial DNA leakage and cGAS‐STING signaling. In Hepa1‐6 cells xenografts, combination therapy with HKL‐nm and the senolytic cocktail dasatinib + quercetin achieved tumor volume reduction, with transcriptomic analysis validating enrichment of immune activation pathways. This was accompanied by enhanced infiltration of CD8 <jats:sup>+</jats:sup> cytotoxic T cells and mature dendritic cells, coupled with profound suppression of myeloid‐derived suppressor cells. By integrating nanodelivery, senescence modulation, and immuno‐oncology, HKL‐nm represents a promising strategy to overcome therapeutic resistance in HCC, providing a preclinical basis for translation to solid tumors.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"32 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000886","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}
Wearable biosensors have the potential to revolutionize health monitoring, yet reliable, time‐resolved hormone and cytokine tracking remains elusive. This study introduces a dual‐framework approach to enable circadian and immune profiling through perspired sweat sensing. First, sweat–saliva thresholds were calibrated for cortisol, melatonin, interleukin‐6 and tumor necrosis factor‐alpha, achieving significant classification performance (Area Under the Curve >0.80) for physiologically relevant salivary benchmarks. Second, circadian rhythmicity of each biomarker was modeled using circaCompare, revealing distinct oscillatory patterns stratified by age, gender, and stress. Young adults exhibited robust melatonin–cortisol phase separation and rhythmic immune signals. Older participants showed dampened amplitudes, phase shifts, and inflammatory dominance. Notably, stress exposure induced earlier cortisol peaks (Δ ≈ 6.7 h), suppressed melatonin rhythms, and heightened immune amplitude variability—hallmarks of circadian misalignment. These findings establish sweat as a valid, real‐time medium for capturing endocrine and immune cycles, with analytical tools capable of uncovering early physiological strain. This work lays a foundation for personalized chronobiological monitoring and stress‐risk screening in naturalistic settings.
{"title":"A wearable biosensing platform for continuous monitoring of inflammatory and metabolic biomarkers for real‐time health tracking and personalized care","authors":"Annapoorna Ramasubramanya, Preeti Singh, Akash Kumar, Kai‐Chun Lin, Shalini Prasad, Sriram Muthukumar","doi":"10.1002/btm2.70104","DOIUrl":"https://doi.org/10.1002/btm2.70104","url":null,"abstract":"Wearable biosensors have the potential to revolutionize health monitoring, yet reliable, time‐resolved hormone and cytokine tracking remains elusive. This study introduces a dual‐framework approach to enable circadian and immune profiling through perspired sweat sensing. First, sweat–saliva thresholds were calibrated for cortisol, melatonin, interleukin‐6 and tumor necrosis factor‐alpha, achieving significant classification performance (Area Under the Curve >0.80) for physiologically relevant salivary benchmarks. Second, circadian rhythmicity of each biomarker was modeled using circaCompare, revealing distinct oscillatory patterns stratified by age, gender, and stress. Young adults exhibited robust melatonin–cortisol phase separation and rhythmic immune signals. Older participants showed dampened amplitudes, phase shifts, and inflammatory dominance. Notably, stress exposure induced earlier cortisol peaks (Δ ≈ 6.7 h), suppressed melatonin rhythms, and heightened immune amplitude variability—hallmarks of circadian misalignment. These findings establish sweat as a valid, real‐time medium for capturing endocrine and immune cycles, with analytical tools capable of uncovering early physiological strain. This work lays a foundation for personalized chronobiological monitoring and stress‐risk screening in naturalistic settings.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"47 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993215","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}
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, subchondral bone remodeling, and joint microenvironment imbalance. Emerging evidence identifies pathological osteoclast–chondrocyte crosstalk as a key OA driver, mediated through RANKL/RANK/OPG, NF‐κB, HIF‐2α, and VEGF signaling pathways that create a destructive bone–cartilage feedback loop. This review examines: (1) molecular mechanisms underlying this cellular communication, (2) therapeutic small‐molecule inhibitors targeting CatK, MMP‐13, NFATc1, and Runx2, and (3) innovative nanomedicine approaches including tissue‐specific nanoparticles, smart delivery systems, and combination therapies. We evaluate these strategies' preclinical validation in animal and organoid models while addressing translational challenges in biosafety, tissue targeting, and personalized delivery. By integrating intercellular signaling knowledge with advanced therapeutic technologies, we provide a framework for developing disease‐modifying OA treatments that bridges basic research with clinical precision medicine applications.
{"title":"Bridging the gap in OA therapeutics: Bioengineered strategies to target osteoclast–chondrocyte crosstalk","authors":"Enbo Zhang, Chi Ma, Xiaohe Fan, Bowen Gu, Bo Li","doi":"10.1002/btm2.70107","DOIUrl":"https://doi.org/10.1002/btm2.70107","url":null,"abstract":"Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, subchondral bone remodeling, and joint microenvironment imbalance. Emerging evidence identifies pathological osteoclast–chondrocyte crosstalk as a key OA driver, mediated through RANKL/RANK/OPG, NF‐κB, HIF‐2α, and VEGF signaling pathways that create a destructive bone–cartilage feedback loop. This review examines: (1) molecular mechanisms underlying this cellular communication, (2) therapeutic small‐molecule inhibitors targeting CatK, MMP‐13, NFATc1, and Runx2, and (3) innovative nanomedicine approaches including tissue‐specific nanoparticles, smart delivery systems, and combination therapies. We evaluate these strategies' preclinical validation in animal and organoid models while addressing translational challenges in biosafety, tissue targeting, and personalized delivery. By integrating intercellular signaling knowledge with advanced therapeutic technologies, we provide a framework for developing disease‐modifying OA treatments that bridges basic research with clinical precision medicine applications.","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"38 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955091","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}
Kyung Soo Park, Yong In Cho, Samir Mitragotri, Zongmin Zhao
Gene therapy has advanced considerably in recent years, driven by innovations in vector engineering and a more advanced understanding of virology for clinical translation. Since 2021, the U.S. Food and Drug Administration (FDA) has approved seven new viral vector-based gene therapies, five of which use adeno-associated virus (AAV) vectors, reinforcing their status as the leading platform for in vivo gene delivery. These approvals encompassed hematologic, neuromuscular, dermatologic, and neurogenetic diseases, using diverse serotypes and delivery routes tailored to the therapeutic context. Disease-specific patterns of capsid usage reveal advancement in tailored capsid engineering based on anatomical targeting needs. Beyond AAV, non-AAV vectors, such as herpes simplex virus (HSV) and adenovirus, are actively explored in cancer trials, while lentiviral vectors support applications in oncology and immune-related disorders. This review provides an updated analysis of the clinical landscape of viral vector-based gene therapies, highlighting new FDA-approved products and ongoing clinical trials by vector type, disease indication, and clinical phase since our original review in 2021. Our analysis highlights advances in viral vector technologies that reflect a maturing field, transitioning from proof-of-concept studies to precision platforms increasingly capable of addressing rare monogenic disorders and more prevalent, complex diseases.
{"title":"Viral vector-based gene therapies in the clinic: An update","authors":"Kyung Soo Park, Yong In Cho, Samir Mitragotri, Zongmin Zhao","doi":"10.1002/btm2.70106","DOIUrl":"10.1002/btm2.70106","url":null,"abstract":"<p>Gene therapy has advanced considerably in recent years, driven by innovations in vector engineering and a more advanced understanding of virology for clinical translation. Since 2021, the U.S. Food and Drug Administration (FDA) has approved seven new viral vector-based gene therapies, five of which use adeno-associated virus (AAV) vectors, reinforcing their status as the leading platform for in vivo gene delivery. These approvals encompassed hematologic, neuromuscular, dermatologic, and neurogenetic diseases, using diverse serotypes and delivery routes tailored to the therapeutic context. Disease-specific patterns of capsid usage reveal advancement in tailored capsid engineering based on anatomical targeting needs. Beyond AAV, non-AAV vectors, such as herpes simplex virus (HSV) and adenovirus, are actively explored in cancer trials, while lentiviral vectors support applications in oncology and immune-related disorders. This review provides an updated analysis of the clinical landscape of viral vector-based gene therapies, highlighting new FDA-approved products and ongoing clinical trials by vector type, disease indication, and clinical phase since our original review in 2021. Our analysis highlights advances in viral vector technologies that reflect a maturing field, transitioning from proof-of-concept studies to precision platforms increasingly capable of addressing rare monogenic disorders and more prevalent, complex diseases.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"11 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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