Cui Ma, Yaqi Cui, Bailong Liu, Min Liu, Xia Chen and Biao Dong
Malignant tumors pose a serious threat to human health with their high incidence and mortality rates. Although chemotherapeutic agents such as doxorubicin (DOX) exhibit significant antitumor efficacy, their non-specific distribution leads to toxic side effects and mono-chemotherapy fails to achieve complete tumor eradication, significantly limiting clinical applications. This study presents the development and evaluation of a multifunctional nanoplatform, Fe3O4@Ce6-DOX@liposome, which integrates magnetic targeting, chemotherapy, and photodynamic therapy (PDT) for enhanced tumor treatment. The nanoparticles (NPs) were engineered to co-deliver the chemotherapeutic drug DOX and the photosensitizer chlorin e6 (Ce6), while superparamagnetic Fe3O4 enabled external magnetic guidance. In vitro studies in MCF-7 cells demonstrated the system's light-activated cytotoxicity, with confocal microscopy revealing precise spatiotemporal control over drug release and ROS generation. In vivo evaluation in 4T1 tumor-bearing mice showed that magnetic navigation significantly enhanced tumor accumulation of NPs, leading to 73% tumor growth inhibition through synergistic chemo-PDT effects. The combination of magnetic targeting and dual therapeutic modalities resulted in superior antitumor efficacy compared to individual treatments, with minimal systemic toxicity. These findings highlight the potential of this multifunctional nanoplatform as a precise and effective strategy for solid tumor therapy, offering improved targeting and reduced off-target effects compared to conventional treatments.
{"title":"A trimodal magnetic navigation-enhanced nanoplatform for spatiotemporally controlled chemo-photodynamic synergistic cancer therapy","authors":"Cui Ma, Yaqi Cui, Bailong Liu, Min Liu, Xia Chen and Biao Dong","doi":"10.1039/D5BM00579E","DOIUrl":"10.1039/D5BM00579E","url":null,"abstract":"<p >Malignant tumors pose a serious threat to human health with their high incidence and mortality rates. Although chemotherapeutic agents such as doxorubicin (DOX) exhibit significant antitumor efficacy, their non-specific distribution leads to toxic side effects and mono-chemotherapy fails to achieve complete tumor eradication, significantly limiting clinical applications. This study presents the development and evaluation of a multifunctional nanoplatform, Fe<small><sub>3</sub></small>O<small><sub>4</sub></small>@Ce6-DOX@liposome, which integrates magnetic targeting, chemotherapy, and photodynamic therapy (PDT) for enhanced tumor treatment. The nanoparticles (NPs) were engineered to co-deliver the chemotherapeutic drug DOX and the photosensitizer chlorin e6 (Ce6), while superparamagnetic Fe<small><sub>3</sub></small>O<small><sub>4</sub></small> enabled external magnetic guidance. <em>In vitro</em> studies in MCF-7 cells demonstrated the system's light-activated cytotoxicity, with confocal microscopy revealing precise spatiotemporal control over drug release and ROS generation. <em>In vivo</em> evaluation in 4T1 tumor-bearing mice showed that magnetic navigation significantly enhanced tumor accumulation of NPs, leading to 73% tumor growth inhibition through synergistic chemo-PDT effects. The combination of magnetic targeting and dual therapeutic modalities resulted in superior antitumor efficacy compared to individual treatments, with minimal systemic toxicity. These findings highlight the potential of this multifunctional nanoplatform as a precise and effective strategy for solid tumor therapy, offering improved targeting and reduced off-target effects compared to conventional treatments.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 24","pages":" 6906-6917"},"PeriodicalIF":5.7,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145429636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michelle D. Farrelly, Nazanin Mohebali, Emma Dal Maso, Cameron J. Nowell, Denise Wootten, Patrick M. Sexton, Lisandra L. Martin and San H. Thang
Polymer nanodiscs are a research tool that allows membrane proteins (MPs) to be encapsulated by a surrounding amphipathic polymer, isolated and studied to understand their structural and physiological properties. An advantage of using polymer nanodiscs over other membrane mimetics can be found in their ability to natively solubilise membrane proteins (MPs) within an annulus of cellular phospholipids, however, potential polymer interactions with membrane constituents can hinder MP activity making the selection of a suitable polymer critical. This work demonstrates the native solubilisation of G-protein coupled A2A adenosine receptor (A2AR) by polymers with alternating units and cationic charge, poly(N-methyl-4-vinyl pyridinium iodide-co-N-alkyl-maleimides) (poly(MVP-co-AlkylMs)), and novel statistical copolymers with pseudozwitterionic charge, poly(potassium 3-sulfopropyl methacrylate-co-2-(trimethyl-amino) ethyl methacrylate-co-n-butyl methacrylate) (poly(KSPMA-co-TMAEMA-co-BMA)), both synthesised using RAFT polymerisation. After surveying a library of polymers within each class, A2AR extraction was the most efficient using poly(MVP-co-BM) (1 : 1 MVP : BM) and poly(KSPMA-co-TMAEMA-co-BMA) (1 : 1 : 1 KSPMA : TMAEMA : BMA). The optimal pH, temperature, solubilisation time, polymer concentration and ionic strength conditions required for extracting A2AR were identified and enabled a large-scale A2AR-nanodisc preparation. The yield of A2AR-poly(MVP-co-BM) was superior to A2AR-poly(KSPMA-co-TMAEMA-co-BMA) nanodiscs after affinity purification. Functional assessment of the reconstituted receptors was undertaken using fluorescence correlation spectroscopy (FCS) to determine the ligand binding capacity of A2AR stabilised within an alternating cationic poly(MVP-co-BM). These native nanodiscs retained their ability to specifically bind A2AR ligand antagonists.
{"title":"Native adenosine A2A receptor solubilisation by a library of amphipathic copolymers","authors":"Michelle D. Farrelly, Nazanin Mohebali, Emma Dal Maso, Cameron J. Nowell, Denise Wootten, Patrick M. Sexton, Lisandra L. Martin and San H. Thang","doi":"10.1039/D5BM01011J","DOIUrl":"10.1039/D5BM01011J","url":null,"abstract":"<p >Polymer nanodiscs are a research tool that allows membrane proteins (MPs) to be encapsulated by a surrounding amphipathic polymer, isolated and studied to understand their structural and physiological properties. An advantage of using polymer nanodiscs over other membrane mimetics can be found in their ability to natively solubilise membrane proteins (MPs) within an annulus of cellular phospholipids, however, potential polymer interactions with membrane constituents can hinder MP activity making the selection of a suitable polymer critical. This work demonstrates the native solubilisation of G-protein coupled A<small><sub>2A</sub></small> adenosine receptor (A<small><sub>2A</sub></small>R) by polymers with alternating units and cationic charge, poly(<em>N</em>-methyl-4-vinyl pyridinium iodide-<em>co-N</em>-alkyl-maleimides) (poly(MVP-<em>co</em>-AlkylMs)), and novel statistical copolymers with pseudozwitterionic charge, poly(potassium 3-sulfopropyl methacrylate-<em>co</em>-2-(trimethyl-amino) ethyl methacrylate-<em>co-n</em>-butyl methacrylate) (poly(KSPMA-<em>co</em>-TMAEMA-<em>co</em>-BMA)), both synthesised using RAFT polymerisation. After surveying a library of polymers within each class, A<small><sub>2A</sub></small>R extraction was the most efficient using poly(MVP-<em>co</em>-BM) (1 : 1 MVP : BM) and poly(KSPMA-<em>co</em>-TMAEMA-<em>co</em>-BMA) (1 : 1 : 1 KSPMA : TMAEMA : BMA). The optimal pH, temperature, solubilisation time, polymer concentration and ionic strength conditions required for extracting A<small><sub>2A</sub></small>R were identified and enabled a large-scale A<small><sub>2A</sub></small>R-nanodisc preparation. The yield of A<small><sub>2A</sub></small>R-poly(MVP-<em>co</em>-BM) was superior to A<small><sub>2A</sub></small>R-poly(KSPMA-<em>co</em>-TMAEMA-<em>co</em>-BMA) nanodiscs after affinity purification. Functional assessment of the reconstituted receptors was undertaken using fluorescence correlation spectroscopy (FCS) to determine the ligand binding capacity of A<small><sub>2A</sub></small>R stabilised within an alternating cationic poly(MVP-<em>co</em>-BM). These native nanodiscs retained their ability to specifically bind A<small><sub>2A</sub></small>R ligand antagonists.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 24","pages":" 6837-6854"},"PeriodicalIF":5.7,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melissa Ling, Nataly Kacherovsky, Abe Y. Wu, Minjian Ni, Jessica A. Hamerman and Suzie H. Pun
Monocytes are mononuclear phagocytes crucial for tissue repair, pathogen clearance, and immune surveillance. Comprising 2–10% of all human blood peripheral leukocytes, monocytes are precursors to macrophages and dendritic cells and can be leveraged for diagnostics and treatment of various diseases, such as cancer and autoimmune conditions. Current methods of monocyte isolation for these applications, such as plastic adhesion, magnetic-activated antibody-based selection, and counterflow centrifugal elutriation are limited by either low purity and viability or costly equipment and reagents. Here, we develop and optimize an aptamer-based method for traceless isolation of monocytes from peripheral blood mononuclear cells at low cost with high purity and yield, and with minimal activation and immunogenic risks. We identify and use CD36 as a novel selection marker for monocyte isolation and confirm that monocytes isolated using our CD36-binding aptamer possess similar phenotypes to monocytes isolated from anti-CD14 and anti-CD36 antibodies with higher, unperturbed CD14 and CD36 expression.
{"title":"Rapid and label-free isolation of human peripheral blood monocytes using a reversible CD36-binding aptamer for cell capture","authors":"Melissa Ling, Nataly Kacherovsky, Abe Y. Wu, Minjian Ni, Jessica A. Hamerman and Suzie H. Pun","doi":"10.1039/D5BM01232E","DOIUrl":"10.1039/D5BM01232E","url":null,"abstract":"<p >Monocytes are mononuclear phagocytes crucial for tissue repair, pathogen clearance, and immune surveillance. Comprising 2–10% of all human blood peripheral leukocytes, monocytes are precursors to macrophages and dendritic cells and can be leveraged for diagnostics and treatment of various diseases, such as cancer and autoimmune conditions. Current methods of monocyte isolation for these applications, such as plastic adhesion, magnetic-activated antibody-based selection, and counterflow centrifugal elutriation are limited by either low purity and viability or costly equipment and reagents. Here, we develop and optimize an aptamer-based method for traceless isolation of monocytes from peripheral blood mononuclear cells at low cost with high purity and yield, and with minimal activation and immunogenic risks. We identify and use CD36 as a novel selection marker for monocyte isolation and confirm that monocytes isolated using our CD36-binding aptamer possess similar phenotypes to monocytes isolated from anti-CD14 and anti-CD36 antibodies with higher, unperturbed CD14 and CD36 expression.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 24","pages":" 6805-6817"},"PeriodicalIF":5.7,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12557302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145372218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elvan Dogan, Ann Austin, Ayda Pourmostafa, Swaprakash Yogeshwaran, Hossein Goodarzi Hosseinabadi and Amir K. Miri
Correction for ‘Design considerations for photoinitiator selection in cell-laden gelatin methacryloyl hydrogels’ by Elvan Dogan et al., Biomater. Sci., 2025, https://doi.org/10.1039/d5bm00550g.
{"title":"Correction: Design considerations for photoinitiator selection in cell-laden gelatin methacryloyl hydrogels","authors":"Elvan Dogan, Ann Austin, Ayda Pourmostafa, Swaprakash Yogeshwaran, Hossein Goodarzi Hosseinabadi and Amir K. Miri","doi":"10.1039/D5BM90068A","DOIUrl":"10.1039/D5BM90068A","url":null,"abstract":"<p >Correction for ‘Design considerations for photoinitiator selection in cell-laden gelatin methacryloyl hydrogels’ by Elvan Dogan <em>et al.</em>, <em>Biomater. Sci.</em>, 2025, https://doi.org/10.1039/d5bm00550g.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 23","pages":" 6737-6742"},"PeriodicalIF":5.7,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/bm/d5bm90068a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The development of inorganic nanozymes has revolutionized the field of nanotechnology by providing a new class of catalytic materials that exhibit enzyme-like activities. Compared with traditional natural enzymes, nanozymes have broad application prospects in the field of biomedicine due to their higher chemical stability, stronger environmental adaptability, and ability to maintain their activity under extreme conditions. To provide a comprehensive overview of the recent progress made in this field, herein, an overview of inorganic nanozymes for biomedical applications is provided. In this review, the structure, synthesis methods, and catalytic mechanism of inorganic nanozymes are summarized. Subsequently, the latest progress of various inorganic nanozymes for the applications in biomedicine is reviewed, including diagnostic applications, therapeutic applications and drug delivery systems. Then, the recent developments in the modification and multifunctionalization of novel inorganic nanozymes are discussed. Finally, the challenges and prospects of inorganic nanozymes in the field of biomedicine are highlighted and pointed out. We hope that this timely review can further advance this promising field.
{"title":"Recent developments and prospects of inorganic nanozymes for biomedical applications","authors":"Siqi Zhan, Yan Fu, Hong Yu Yang and Doo Sung Lee","doi":"10.1039/D5BM01151E","DOIUrl":"10.1039/D5BM01151E","url":null,"abstract":"<p >The development of inorganic nanozymes has revolutionized the field of nanotechnology by providing a new class of catalytic materials that exhibit enzyme-like activities. Compared with traditional natural enzymes, nanozymes have broad application prospects in the field of biomedicine due to their higher chemical stability, stronger environmental adaptability, and ability to maintain their activity under extreme conditions. To provide a comprehensive overview of the recent progress made in this field, herein, an overview of inorganic nanozymes for biomedical applications is provided. In this review, the structure, synthesis methods, and catalytic mechanism of inorganic nanozymes are summarized. Subsequently, the latest progress of various inorganic nanozymes for the applications in biomedicine is reviewed, including diagnostic applications, therapeutic applications and drug delivery systems. Then, the recent developments in the modification and multifunctionalization of novel inorganic nanozymes are discussed. Finally, the challenges and prospects of inorganic nanozymes in the field of biomedicine are highlighted and pointed out. We hope that this timely review can further advance this promising field.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 24","pages":" 6755-6774"},"PeriodicalIF":5.7,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Konrad Kozlowski, Animesh Ghosh, Zong Yao Liu, Zhonghan Zhang, Shuzhou Li and Terry W. J. Steele
While catechol chemistry is widely known, the selection of catechols applied for resins and adhesive purposes has relied almost exclusively on L-dopamine variants. Herein five catechol isomers evaluate ortho, meta, and para dihydroxybenzene (DHB) structures on adhesion related mechanical properties, including organic/aqueous stability, gelation time, and adhesion strength on soft substrates. A model system evaluates the catechol–aldehyde isomers through Schiff base grafting to an amine rich macromolecule, branched polyethylenimine. This work evaluates how grafted-catechol isomers can be exploited to tune reactivity to both solvent and external stimuli. The formulations allow a range of sensitivity, from designs that observe gelation time within minutes of water exposure, to water-stable formulations that can be cured through via voltage stimulation.
{"title":"Catechol isomers for moisture initiated bioadhesives","authors":"Konrad Kozlowski, Animesh Ghosh, Zong Yao Liu, Zhonghan Zhang, Shuzhou Li and Terry W. J. Steele","doi":"10.1039/D5BM01338K","DOIUrl":"10.1039/D5BM01338K","url":null,"abstract":"<p >While catechol chemistry is widely known, the selection of catechols applied for resins and adhesive purposes has relied almost exclusively on <small>L</small>-dopamine variants. Herein five catechol isomers evaluate <em>ortho</em>, <em>meta</em>, and <em>para</em> dihydroxybenzene (DHB) structures on adhesion related mechanical properties, including organic/aqueous stability, gelation time, and adhesion strength on soft substrates. A model system evaluates the catechol–aldehyde isomers through Schiff base grafting to an amine rich macromolecule, branched polyethylenimine. This work evaluates how grafted-catechol isomers can be exploited to tune reactivity to both solvent and external stimuli. The formulations allow a range of sensitivity, from designs that observe gelation time within minutes of water exposure, to water-stable formulations that can be cured through <em>via</em> voltage stimulation.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 24","pages":" 6897-6905"},"PeriodicalIF":5.7,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenjie Zhang, Yuchen Gu, Xinxin Zou, Ziyi Huang, Juan Ding, Jinlong Liao, Jingrong Yu, Jie Zhao, Shuo Zhang and Fengjie Huang
The etiology of oral ulcers is complex, primarily comprising external physical and chemical stimuli, immune imbalances, and various diseases. Pressure ulcers are mainly caused by continuous or intermittent pressure that damages the skin and underlying tissues. The healing process for both types of ulcers is similar to wound healing, including stages such as inflammation, proliferation, and remodeling. However, some clinically used treatments have issues such as significant side effects, high costs, low adhesion, and insufficient mechanical strength, which can negatively affect the patient's physical and mental health. In this study, we designed a mussel-inspired hydrogel (GD3M4), which consists of dopamine-grafted gelatin (GelDA), aldehyde-modified hyaluronic acid (OHA), and methacrylate gelatin (GelMA). This hydrogel can sustain adhesion for 48 hours in artificial saliva. In compression tests, the GD3M4 hydrogel showed a compression modulus of nearly 1.26 MPa, demonstrating excellent compressive strength to adapt to complex in vivo and in vitro environments. The DCFH-DA experiments showed that the GD3M4 hydrogel has good antioxidant properties. In both the mouse oral ulcer model and pressure ulcer model, the GD3M4 hydrogel exhibited excellent ulcer-healing effects by modulating the expression of inflammatory factors and epidermal growth. In conclusion, the GD3M4 hydrogel provides a promising therapeutic strategy for promoting the healing of oral ulcers and pressure ulcers.
{"title":"Mussel-inspired hydrogels with wet adhesion and anti-inflammatory properties for oral and pressure ulcers","authors":"Wenjie Zhang, Yuchen Gu, Xinxin Zou, Ziyi Huang, Juan Ding, Jinlong Liao, Jingrong Yu, Jie Zhao, Shuo Zhang and Fengjie Huang","doi":"10.1039/D5BM01231G","DOIUrl":"10.1039/D5BM01231G","url":null,"abstract":"<p >The etiology of oral ulcers is complex, primarily comprising external physical and chemical stimuli, immune imbalances, and various diseases. Pressure ulcers are mainly caused by continuous or intermittent pressure that damages the skin and underlying tissues. The healing process for both types of ulcers is similar to wound healing, including stages such as inflammation, proliferation, and remodeling. However, some clinically used treatments have issues such as significant side effects, high costs, low adhesion, and insufficient mechanical strength, which can negatively affect the patient's physical and mental health. In this study, we designed a mussel-inspired hydrogel (GD3M4), which consists of dopamine-grafted gelatin (GelDA), aldehyde-modified hyaluronic acid (OHA), and methacrylate gelatin (GelMA). This hydrogel can sustain adhesion for 48 hours in artificial saliva. In compression tests, the GD3M4 hydrogel showed a compression modulus of nearly 1.26 MPa, demonstrating excellent compressive strength to adapt to complex <em>in vivo</em> and <em>in vitro</em> environments. The DCFH-DA experiments showed that the GD3M4 hydrogel has good antioxidant properties. In both the mouse oral ulcer model and pressure ulcer model, the GD3M4 hydrogel exhibited excellent ulcer-healing effects by modulating the expression of inflammatory factors and epidermal growth. In conclusion, the GD3M4 hydrogel provides a promising therapeutic strategy for promoting the healing of oral ulcers and pressure ulcers.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 23","pages":" 6689-6708"},"PeriodicalIF":5.7,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amid the rising toll of war-associated deaths and injuries and escalating conflicts between countries, there is a strong need to manage complex battlefield injuries by preventing further deterioration and accelerating the repair of damaged tissues. Global military powers, including the USA and China, have established scientific facilities for dedicated research into military regenerative medicine. However, there remains a gap, as most reported medical devices created for tissue repair are unsuitable for use on battlefields. In this perspective, we argue why now is the golden time for countries to invest in military regenerative medicine, and we propose the use of RIPE (Restorative, Individualized, Portable and Emergency) criteria to optimize technologies for tackling battlefield injuries, including rapid hemostasis, immobilization, tissue repair, and functional reconstruction. Similar to technologies such as blood plasma transfusion and portable ultrasound, which were originally developed through military investment and later found highly valuable for civilian medical use, timely investment in military regenerative medicine, as we argue, will have a positive spillover impact on public healthcare programs in the future.
{"title":"Military regenerative medicine","authors":"Ang Li, João F. Mano, Laurent David and Andy Tay","doi":"10.1039/D5BM01098E","DOIUrl":"10.1039/D5BM01098E","url":null,"abstract":"<p >Amid the rising toll of war-associated deaths and injuries and escalating conflicts between countries, there is a strong need to manage complex battlefield injuries by preventing further deterioration and accelerating the repair of damaged tissues. Global military powers, including the USA and China, have established scientific facilities for dedicated research into military regenerative medicine. However, there remains a gap, as most reported medical devices created for tissue repair are unsuitable for use on battlefields. In this perspective, we argue why <em>now</em> is the golden time for countries to invest in military regenerative medicine, and we propose the use of RIPE (Restorative, Individualized, Portable and Emergency) criteria to optimize technologies for tackling battlefield injuries, including rapid hemostasis, immobilization, tissue repair, and functional reconstruction. Similar to technologies such as blood plasma transfusion and portable ultrasound, which were originally developed through military investment and later found highly valuable for civilian medical use, timely investment in military regenerative medicine, as we argue, will have a positive spillover impact on public healthcare programs in the future.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 23","pages":" 6562-6571"},"PeriodicalIF":5.7,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanna Solomon, Julie Gordon, Maddie Hasson, Hannah Arnade, Jordan Parker, Beatriz Dias, Amogh Magesh, William X Patton, John F Peroni, Jay M Patel
Cartilage injuries present a significant clinical burden due to the tissue's limited regenerative capacity. Microfracture (Mfx) remains the gold standard of cartilage repair but often results in inadequate defect fill and inferior tissue formation. Point-of-care augmentations to the Mfx environment represent implementable and cost-effective methods to enhance outcomes. The objective of this study was to evaluate platelet lysate (PL) as an adjuvant to microfracture-based cartilage repair, with the goal of maintaining tissue volume and promoting functional repair. The impact of PL on the activity of marrow-derived cells (MDCs) was first evaluated in monolayer culture, which demonstrated an increase in cellular area and proliferation. Next, PL was incorporated into fibrin gels (to mimic fibrin-rich Mfx), and MDCs encapsulated within PL-containing fibrin gels exhibited increased proliferation, increased cellular area, and reduced fibrosis markers. PL incorporation into fibrin gels led to clear changes to initial nanostructure and an increase in initial mechanical properties, which resulted in less MDC-mediated contraction during culture. These findings suggested that time-zero augmentation of Mfx with PL may alter both cellular signaling and Mfx clot structure/remodeling. Finally, PL-augmented Mfx was evaluated in a pig trochlear osteochondral defect model (t = 5 weeks). While PL-treated defects exhibited reduced contraction and improved macroscopic appearance over Mfx alone, micro-CT and mechanical testing revealed no significant differences in subchondral bone remodeling or repair tissue stiffness. Histological analysis and grading showed no significant improvements in cartilage repair quality across treatment groups, suggesting that while PL may influence early clot stability, its effects on long-term tissue maturation remain uncertain. "Future studies are needed to determine whether PL-based augmentation provides sustained functional benefits, potentially in combination with additional biological or mechanical strategies".
{"title":"The evaluation of platelet lysate incorporation into the microfracture clot in a pig model.","authors":"Hanna Solomon, Julie Gordon, Maddie Hasson, Hannah Arnade, Jordan Parker, Beatriz Dias, Amogh Magesh, William X Patton, John F Peroni, Jay M Patel","doi":"10.1039/d5bm00372e","DOIUrl":"10.1039/d5bm00372e","url":null,"abstract":"<p><p>Cartilage injuries present a significant clinical burden due to the tissue's limited regenerative capacity. Microfracture (Mfx) remains the gold standard of cartilage repair but often results in inadequate defect fill and inferior tissue formation. Point-of-care augmentations to the Mfx environment represent implementable and cost-effective methods to enhance outcomes. The objective of this study was to evaluate platelet lysate (PL) as an adjuvant to microfracture-based cartilage repair, with the goal of maintaining tissue volume and promoting functional repair. The impact of PL on the activity of marrow-derived cells (MDCs) was first evaluated in monolayer culture, which demonstrated an increase in cellular area and proliferation. Next, PL was incorporated into fibrin gels (to mimic fibrin-rich Mfx), and MDCs encapsulated within PL-containing fibrin gels exhibited increased proliferation, increased cellular area, and reduced fibrosis markers. PL incorporation into fibrin gels led to clear changes to initial nanostructure and an increase in initial mechanical properties, which resulted in less MDC-mediated contraction during culture. These findings suggested that time-zero augmentation of Mfx with PL may alter both cellular signaling and Mfx clot structure/remodeling. Finally, PL-augmented Mfx was evaluated in a pig trochlear osteochondral defect model (<i>t</i> = 5 weeks). While PL-treated defects exhibited reduced contraction and improved macroscopic appearance over Mfx alone, micro-CT and mechanical testing revealed no significant differences in subchondral bone remodeling or repair tissue stiffness. Histological analysis and grading showed no significant improvements in cartilage repair quality across treatment groups, suggesting that while PL may influence early clot stability, its effects on long-term tissue maturation remain uncertain. \"Future studies are needed to determine whether PL-based augmentation provides sustained functional benefits, potentially in combination with additional biological or mechanical strategies\".</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The cells co-culture approach, involving endothelial cells and supporting stromal cells, such as fibroblasts, is commonly used for engineering microvascular networks. While this approach effectively promotes vascular morphogenesis through paracrine signaling and matrix remodeling, it often leads to excessive fibroblast proliferation. This uncontrolled growth can disrupt the structural organization of the developing vasculature, making it challenging to achieve reproducible and physiologically relevant microtissue architectures. In this work, we introduce an alternative monoculture method that uses only endothelial cells (HUVECs) in a fibrin gel matrix. To promote the formation of structured capillary-like networks without stromal support, we optimized vasculogenesis by supplementing exogenous vascular endothelial growth factor (VEGF), fine-tuning matrix stiffness, and applying it in a hypoxic environment (1% O2). This approach was also applied to brain microvascular endothelial cells (BMEC) and liver sinusoidal endothelial cells (SEC). This innovation addresses the limitations of traditional methods, overcomes rapid matrix degradation caused by fibroblast-mediated remodeling, identifies ∼2.56 kPa as the optimal stiffness for blood capillary growth, and demonstrates that capillary development is significantly enhanced at VEGF concentrations above 50 ng ml−1.
细胞共培养方法,包括内皮细胞和支持基质细胞,如成纤维细胞,通常用于工程微血管网络。虽然这种方法通过旁分泌信号和基质重塑有效地促进血管形态发生,但往往导致成纤维细胞过度增殖。这种不受控制的生长可以破坏正在发育的脉管系统的结构组织,使其难以实现可复制和生理相关的微组织结构。在这项工作中,我们介绍了一种替代的单一培养方法,该方法仅使用纤维蛋白凝胶基质中的内皮细胞(HUVECs)。为了在没有基质支持的情况下促进结构化毛细血管样网络的形成,我们通过补充外源性血管内皮生长因子(VEGF)、微调基质刚度并将其应用于低氧环境(1% O2)来优化血管发生。该方法也适用于脑微血管内皮细胞(BMEC)和肝窦内皮细胞(SEC)。这一创新解决了传统方法的局限性,克服了由成纤维细胞介导的重塑引起的基质快速降解,确定了2.56 kPa为毛细血管生长的最佳刚度,并证明了VEGF浓度高于50 ng ml-1时毛细血管发育显著增强。
{"title":"Fabrication of blood capillary microtissues without fibroblast support via growth factors and matrix stiffness modulation","authors":"He Li, Fiona Louis and Michiya Matsusaki","doi":"10.1039/D5BM00981B","DOIUrl":"10.1039/D5BM00981B","url":null,"abstract":"<p >The cells co-culture approach, involving endothelial cells and supporting stromal cells, such as fibroblasts, is commonly used for engineering microvascular networks. While this approach effectively promotes vascular morphogenesis through paracrine signaling and matrix remodeling, it often leads to excessive fibroblast proliferation. This uncontrolled growth can disrupt the structural organization of the developing vasculature, making it challenging to achieve reproducible and physiologically relevant microtissue architectures. In this work, we introduce an alternative monoculture method that uses only endothelial cells (HUVECs) in a fibrin gel matrix. To promote the formation of structured capillary-like networks without stromal support, we optimized vasculogenesis by supplementing exogenous vascular endothelial growth factor (VEGF), fine-tuning matrix stiffness, and applying it in a hypoxic environment (1% O<small><sub>2</sub></small>). This approach was also applied to brain microvascular endothelial cells (BMEC) and liver sinusoidal endothelial cells (SEC). This innovation addresses the limitations of traditional methods, overcomes rapid matrix degradation caused by fibroblast-mediated remodeling, identifies ∼2.56 kPa as the optimal stiffness for blood capillary growth, and demonstrates that capillary development is significantly enhanced at VEGF concentrations above 50 ng ml<small><sup>−1</sup></small>.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" 24","pages":" 6865-6878"},"PeriodicalIF":5.7,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}