Pub Date : 2025-02-20DOI: 10.1016/j.bioactmat.2025.02.017
Chubing Lin , Xin Huang , Yueguang Xue , Shasha Jiang , Chunying Chen , Ying Liu , Kuan Chen
Nanomaterials and nanotechnology are emerging as promising strategies for medical devices due to their advantageous properties, including the ability to effectively interact with biomolecules and tissues, as well as enhance therapeutic efficacy and biocompatibility. This has resulted in approved and candidate devices in fields, such as orthopedics, dentistry, wound care, and neurology. However, the overall progress in translating medical devices using nanomaterials has been relatively slow, highlighting the urgent need to advance regulatory science. Regulatory authorities and organizations, such as the National Medical Products Administration in China and the European Union, have issued essential guidance documents for these devices' safety and efficiency evaluation. These documents include special requirements and considerations for physicochemical characterization, biological evaluation, and other aspects. Although some evaluation paths have been defined, ongoing advancements in technologies and methods are expected to enhance safety evaluation practices, reduce burdens on the medical device industry, and accelerate the clinical translation of medical devices using nanomaterials. Herein, we review the current state of regulatory science related to medical devices using nanomaterials, suggest the feasibility of using in vitro alternative methods to advance regulatory science, and offer forward-looking insights to inspire new ideas and technologies for accelerating clinical translation.
{"title":"Advances in medical devices using nanomaterials and nanotechnology: Innovation and regulatory science","authors":"Chubing Lin , Xin Huang , Yueguang Xue , Shasha Jiang , Chunying Chen , Ying Liu , Kuan Chen","doi":"10.1016/j.bioactmat.2025.02.017","DOIUrl":"10.1016/j.bioactmat.2025.02.017","url":null,"abstract":"<div><div>Nanomaterials and nanotechnology are emerging as promising strategies for medical devices due to their advantageous properties, including the ability to effectively interact with biomolecules and tissues, as well as enhance therapeutic efficacy and biocompatibility. This has resulted in approved and candidate devices in fields, such as orthopedics, dentistry, wound care, and neurology. However, the overall progress in translating medical devices using nanomaterials has been relatively slow, highlighting the urgent need to advance regulatory science. Regulatory authorities and organizations, such as the National Medical Products Administration in China and the European Union, have issued essential guidance documents for these devices' safety and efficiency evaluation. These documents include special requirements and considerations for physicochemical characterization, biological evaluation, and other aspects. Although some evaluation paths have been defined, ongoing advancements in technologies and methods are expected to enhance safety evaluation practices, reduce burdens on the medical device industry, and accelerate the clinical translation of medical devices using nanomaterials. Herein, we review the current state of regulatory science related to medical devices using nanomaterials, suggest the feasibility of using <em>in vitro</em> alternative methods to advance regulatory science, and offer forward-looking insights to inspire new ideas and technologies for accelerating clinical translation.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 353-369"},"PeriodicalIF":18.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-20DOI: 10.1016/j.bioactmat.2025.01.001
Haiying Zhou , Yangwu Chen , Wu Yan , Xiao Chen , Yin Zi
Tendon and enthesis injuries are a global health problem affecting millions of people, causing huge medical expenditure and labor loss every year. However, due to their intricate tissue architecture, unique mechanical properties, and especially their sluggish and limited innate regenerative capacity, repairing these injuries remains a formidable clinical challenge. Here, we present a comprehensive review of biomaterials advances in tendon and enthesis repair recently. These biomaterials are categorized into two primary groups based on their potential clinical application conditions: biomaterials for T/E repairing and biomaterials for T/E replacement. The T/E repairing biomaterials were further divided into two groups: mechanical-enhanced biomaterials and bioactive biomaterials, according to the approaches they used to improve sutured tendon healing. We delve into the characteristics and underlying mechanisms of these various biomaterials to gain a deeper understanding of the current landscape in tendon and enthesis repair biomaterials. This review aims to highlight the prominent advancements while identifying the remaining gaps, ultimately inspiring future biomaterial design strategies.
{"title":"Advances and challenges in biomaterials for tendon and enthesis repair","authors":"Haiying Zhou , Yangwu Chen , Wu Yan , Xiao Chen , Yin Zi","doi":"10.1016/j.bioactmat.2025.01.001","DOIUrl":"10.1016/j.bioactmat.2025.01.001","url":null,"abstract":"<div><div>Tendon and enthesis injuries are a global health problem affecting millions of people, causing huge medical expenditure and labor loss every year. However, due to their intricate tissue architecture, unique mechanical properties, and especially their sluggish and limited innate regenerative capacity, repairing these injuries remains a formidable clinical challenge. Here, we present a comprehensive review of biomaterials advances in tendon and enthesis repair recently. These biomaterials are categorized into two primary groups based on their potential clinical application conditions: biomaterials for T/E repairing and biomaterials for T/E replacement. The T/E repairing biomaterials were further divided into two groups: mechanical-enhanced biomaterials and bioactive biomaterials, according to the approaches they used to improve sutured tendon healing. We delve into the characteristics and underlying mechanisms of these various biomaterials to gain a deeper understanding of the current landscape in tendon and enthesis repair biomaterials. This review aims to highlight the prominent advancements while identifying the remaining gaps, ultimately inspiring future biomaterial design strategies.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 531-545"},"PeriodicalIF":18.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-19DOI: 10.1016/j.bioactmat.2025.02.006
Ju Young Lee , Taemin Kim , Shinil Cho , Jiho Shin , Woon-Hong Yeo , Tae Soo Kim , Ki Jun Yu
Optogenetics enables precise, cell-specific control of neural activity, surpassing traditional electrical stimulation methods that indiscriminately activate nearby cells, making it crucial for rehabilitation, neurological disorder treatment, and understanding neural circuits. Among light sources for delivering light to genetically modified cells, bio-implants integrated with Light Emitting Diodes (LEDs) have recently been the focus of extensive research due to their advantage of enabling local photogeneration. Unlike laser-based systems, which require tethered setups that hinder behavioral experiments, μ-LED-based devices allow for wireless operation, facilitating more natural movement in subjects. Furthermore, μ-LED arrays can be designed with higher spatial resolution compared to waveguide-coupled external light sources, enabling more precise control over neural activity. This paper presents design rules for implantable flexible optogenetic devices based on μ-LED, tailored to the unique anatomical and functional requirements of various regions of the nervous system. Integration of recent advancements in devices with μ-LEDs (e.g. wireless systems, optofluidic systems, multifunctionality, and closed-loop systems) enhances behavioral experiments and deepens understanding of complex neural functions in the brain, spinal cord, autonomic nervous system, and somatic nervous system. The combination of optogenetics with advanced bio-implantable devices offers promising avenues in medical science, providing more effective tools for neuromodulation research and clinical applications.
{"title":"Design considerations for optogenetic applications of soft micro-LED-based device systems across diverse nervous systems","authors":"Ju Young Lee , Taemin Kim , Shinil Cho , Jiho Shin , Woon-Hong Yeo , Tae Soo Kim , Ki Jun Yu","doi":"10.1016/j.bioactmat.2025.02.006","DOIUrl":"10.1016/j.bioactmat.2025.02.006","url":null,"abstract":"<div><div>Optogenetics enables precise, cell-specific control of neural activity, surpassing traditional electrical stimulation methods that indiscriminately activate nearby cells, making it crucial for rehabilitation, neurological disorder treatment, and understanding neural circuits. Among light sources for delivering light to genetically modified cells, bio-implants integrated with Light Emitting Diodes (LEDs) have recently been the focus of extensive research due to their advantage of enabling local photogeneration. Unlike laser-based systems, which require tethered setups that hinder behavioral experiments, μ-LED-based devices allow for wireless operation, facilitating more natural movement in subjects. Furthermore, μ-LED arrays can be designed with higher spatial resolution compared to waveguide-coupled external light sources, enabling more precise control over neural activity. This paper presents design rules for implantable flexible optogenetic devices based on μ-LED, tailored to the unique anatomical and functional requirements of various regions of the nervous system. Integration of recent advancements in devices with μ-LEDs (e.g. wireless systems, optofluidic systems, multifunctionality, and closed-loop systems) enhances behavioral experiments and deepens understanding of complex neural functions in the brain, spinal cord, autonomic nervous system, and somatic nervous system. The combination of optogenetics with advanced bio-implantable devices offers promising avenues in medical science, providing more effective tools for neuromodulation research and clinical applications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 217-241"},"PeriodicalIF":18.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-19DOI: 10.1016/j.bioactmat.2025.02.020
Rongpu Liu , Guifang Wang , Li Ma , Guangzheng Yang , Sihan Lin , Ningjia Sun , Jiajia Wang , Huijing Ma , Xinquan Jiang , Wenjie Zhang
Guided bone regeneration (GBR) is widely applied in implant dentistry, employing barrier membranes to create an osteogenic space by preventing gingival tissue ingrowth. However, this method does not enhance the osteogenic capacity of osteoblasts, limiting sufficient bone volume in larger defects. Inspired by axolotl limb regeneration, abundant soft tissue-derived stem cells mobilized to the defect may facilitate comprehensive osteogenesis within a BMP-2-enriched environment. We developed a biomimetic channel system (BCS) to promote alveolar bone regeneration, using channel structures to activate gingival-derived stem cells under a BMP-2-enriched biological barrier. In a cell-tracing mouse model, Prrx1+ stem cells demonstrated a critical role in BMP-2-induced subcutaneous osteogenesis. Sequencing and histological analyses revealed that channel structures significantly enhance soft tissue cell proliferation and migration. Attributable to the biological barrier, BCS applications markedly improved bone formation in beagle mandibular defects. These results suggest a novel osteoinductive strategy for alveolar bone regeneration that functions without a traditional barrier membrane.
{"title":"An axolotl limb regeneration-inspired strategy to enhance alveolar bone regeneration","authors":"Rongpu Liu , Guifang Wang , Li Ma , Guangzheng Yang , Sihan Lin , Ningjia Sun , Jiajia Wang , Huijing Ma , Xinquan Jiang , Wenjie Zhang","doi":"10.1016/j.bioactmat.2025.02.020","DOIUrl":"10.1016/j.bioactmat.2025.02.020","url":null,"abstract":"<div><div>Guided bone regeneration (GBR) is widely applied in implant dentistry, employing barrier membranes to create an osteogenic space by preventing gingival tissue ingrowth. However, this method does not enhance the osteogenic capacity of osteoblasts, limiting sufficient bone volume in larger defects. Inspired by axolotl limb regeneration, abundant soft tissue-derived stem cells mobilized to the defect may facilitate comprehensive osteogenesis within a BMP-2-enriched environment. We developed a biomimetic channel system (BCS) to promote alveolar bone regeneration, using channel structures to activate gingival-derived stem cells under a BMP-2-enriched biological barrier. In a cell-tracing mouse model, Prrx1<sup>+</sup> stem cells demonstrated a critical role in BMP-2-induced subcutaneous osteogenesis. Sequencing and histological analyses revealed that channel structures significantly enhance soft tissue cell proliferation and migration. Attributable to the biological barrier, BCS applications markedly improved bone formation in beagle mandibular defects. These results suggest a novel osteoinductive strategy for alveolar bone regeneration that functions without a traditional barrier membrane.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 242-256"},"PeriodicalIF":18.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-19DOI: 10.1016/j.bioactmat.2025.02.015
Haiyan Yao , Emine Sumeyra Turali Emre , Yuan Fan , Jiaolong Wang , Feng Liu , Junchao Wei
Periodontitis is a chronic inflammatory disease characterized by progressive alveolar bone resorption, and excessive reactive oxygen species (ROS) is a key factor to disease progression. Therefore, scavenging ROS to alleviate inflammation and promote bone regeneration are promising strategies to treat periodontitis. In this study, L-arginine (L-Arg) was used to modify mesoporous bioactive glass (MBG), forming L-Arg modified MBG (MBG@L-Arg), which showed effective ROS-scavenging and NO release properties in cells, and realize the protection and restoration of cell's activity in ROS-rich microenvironment. Furthermore, MBG@L-Arg can induce macrophage polarization from M1 to M2 phenotype, and promote the osteogenic differentiation of MC3T3-E1 cells and human periodontal ligament stem cells (hPDLSCs). MBG@L-Arg also regulated anti-inflammatory and antioxidant systems by inhibiting the NF-κB signaling pathway and activating the Nrf2 signaling pathway. Besides, NO-PKG signaling pathway was also activated, further promoting bone regeneration. The in vivo results demonstrated that MBG@L-Arg can efficiently inhibit inflammation-induced tissue destruction and promote osteogenesis regeneration. The quantitative bone loss in MBG@L-Arg group was 1.03 ± 0.05 mm, significantly lower than that of the periodontitis group (1.47 ± 0.13 mm), implying that MBG@L-Arg can work as multifunctional materials for periodontal tissue regeneration.
{"title":"L-arginine modified mesoporous bioactive glass with ROS scavenging and NO release for periodontitis treatment","authors":"Haiyan Yao , Emine Sumeyra Turali Emre , Yuan Fan , Jiaolong Wang , Feng Liu , Junchao Wei","doi":"10.1016/j.bioactmat.2025.02.015","DOIUrl":"10.1016/j.bioactmat.2025.02.015","url":null,"abstract":"<div><div>Periodontitis is a chronic inflammatory disease characterized by progressive alveolar bone resorption, and excessive reactive oxygen species (ROS) is a key factor to disease progression. Therefore, scavenging ROS to alleviate inflammation and promote bone regeneration are promising strategies to treat periodontitis. In this study, L-arginine (L-Arg) was used to modify mesoporous bioactive glass (MBG), forming L-Arg modified MBG (MBG@L-Arg), which showed effective ROS-scavenging and NO release properties in cells, and realize the protection and restoration of cell's activity in ROS-rich microenvironment. Furthermore, MBG@L-Arg can induce macrophage polarization from M1 to M2 phenotype, and promote the osteogenic differentiation of MC3T3-E1 cells and human periodontal ligament stem cells (hPDLSCs). MBG@L-Arg also regulated anti-inflammatory and antioxidant systems by inhibiting the NF-<em>κ</em>B signaling pathway and activating the Nrf2 signaling pathway. Besides, NO-PKG signaling pathway was also activated, further promoting bone regeneration. The <em>in vivo</em> results demonstrated that MBG@L-Arg can efficiently inhibit inflammation-induced tissue destruction and promote osteogenesis regeneration. The quantitative bone loss in MBG@L-Arg group was 1.03 ± 0.05 mm, significantly lower than that of the periodontitis group (1.47 ± 0.13 mm), implying that MBG@L-Arg can work as multifunctional materials for periodontal tissue regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 200-216"},"PeriodicalIF":18.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-18DOI: 10.1016/j.bioactmat.2025.02.024
Sangmin Lee , Jeongbok Lee , Hyunseok Kwon , Heungsoo Shin
Adipose tissue is highly vascularized, which is crucial for homeostasis and energy storage. Current efforts to engineer 3D vascularized adipose tissue in vitro typically involve co-culturing adipocytes and endothelial cells, but adipogenic differentiation often suppresses endothelial function. In this study, we propose a novel approach to reconstruct vascularized adipose tissues in vitro by effectively coupling adipogenesis and vasculogenesis. First, we developed adipo-inductive nanofibers (ID/F@INS) that contain indomethacin and insulin. The in vitro adipogenesis of human adipose-derived stem cells (hADSCs) in general medium was significantly enhanced in adipogenic spheroids (AS) prepared with hADSCs and ID/F@INS, which were encapsulated in a gelatin methacryloyl (GelMA) hydrogel. To further replicate clustering during de novo adipogenesis, we generated AS of varying sizes and found that larger spheroids exhibited markedly greater adipogenesis than smaller ones. At the same time, we used hADSCs and human umbilical vein endothelial cells to generate vascular spheroids (VS). The biomimetic integration of AS and VS within GelMA hydrogels enabled us to investigate the interactions between de novo adipogenesis and vascularization. The integration of the two types of spheroids (VS:AS ratio of 2:1) significantly improved vascular network formation, indicating the concurrent stimulation of adipogenesis and vasculogenesis. This system was then applied to develop an in vitro obesity-like white adipose dysfunction model characterized by reduced vascularization and the elevated expression of pro-inflammatory cytokines. In addition, we found both vascularization and adipogenesis in vivo when we implanted the engineered tissue into mice, demonstrating the potential of our tissue for therapeutic applications in tissue reconstruction.
{"title":"Biomimetic integration of functionally controlled modular tissue building blocks for engineering 3D vascularized adipose tissue","authors":"Sangmin Lee , Jeongbok Lee , Hyunseok Kwon , Heungsoo Shin","doi":"10.1016/j.bioactmat.2025.02.024","DOIUrl":"10.1016/j.bioactmat.2025.02.024","url":null,"abstract":"<div><div>Adipose tissue is highly vascularized, which is crucial for homeostasis and energy storage. Current efforts to engineer 3D vascularized adipose tissue <em>in vitro</em> typically involve co-culturing adipocytes and endothelial cells, but adipogenic differentiation often suppresses endothelial function. In this study, we propose a novel approach to reconstruct vascularized adipose tissues <em>in vitro</em> by effectively coupling adipogenesis and vasculogenesis. First, we developed adipo-inductive nanofibers (ID/F@INS) that contain indomethacin and insulin. The <em>in vitro</em> adipogenesis of human adipose-derived stem cells (hADSCs) in general medium was significantly enhanced in adipogenic spheroids (AS) prepared with hADSCs and ID/F@INS, which were encapsulated in a gelatin methacryloyl (GelMA) hydrogel. To further replicate clustering during <em>de novo</em> adipogenesis, we generated AS of varying sizes and found that larger spheroids exhibited markedly greater adipogenesis than smaller ones. At the same time, we used hADSCs and human umbilical vein endothelial cells to generate vascular spheroids (VS). The biomimetic integration of AS and VS within GelMA hydrogels enabled us to investigate the interactions between <em>de novo</em> adipogenesis and vascularization. The integration of the two types of spheroids (VS:AS ratio of 2:1) significantly improved vascular network formation, indicating the concurrent stimulation of adipogenesis and vasculogenesis. This system was then applied to develop an <em>in vitro</em> obesity-like white adipose dysfunction model characterized by reduced vascularization and the elevated expression of pro-inflammatory cytokines. In addition, we found both vascularization and adipogenesis <em>in vivo</em> when we implanted the engineered tissue into mice, demonstrating the potential of our tissue for therapeutic applications in tissue reconstruction.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 171-188"},"PeriodicalIF":18.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-18DOI: 10.1016/j.bioactmat.2025.01.028
Yuan Luo , Shiqi Zhou , Yiting Song , Wei-Chiao Huang , Gregory E. Wilding , James Jablonski , Breandan Quinn , Jonathan F. Lovell
A challenge for cancer vaccines is to elicit immune responses of sufficient magnitude to control malignant tumor growth and spread. In this study, we iteratively screened a panel of 22 lipid-phase vaccine adjuvants in mice for the elicitation of neoantigen-specific CD8⁺ T cell responses, using an integrated peptide-lipid nanoparticle approach. CL401, a dual Toll-like receptor 2/7 (TLR2/7) adjuvant rapidly induced neoantigen-specific T cell responses and improved lymphatic drainage and uptake of the particle. Additional rounds of in vivo screening identified complementary adjuvants which targeted TLR4 (3D6A-PHAD adjuvant), TLR8 (motolimod), and inflammasome (QS-21) pathways and synergized to enhance cytokine secretion in antigen presenting cells and vaccine-elicited neoantigen-specific CD8⁺ T cells. Co-delivery of adjuvants and antigens led to effective immune responses which regressed large established tumors, synergized with immune checkpoint blockade, and inhibited lung nodules in an experimental metastasis model, without overt toxicity or reactogenicity. We conclude that iterative adjuvant screening, performed in mice in vivo, can identify useful adjuvant combinations that hold potential for therapeutic cancer vaccine research.
{"title":"Iterative selection of lipid nanoparticle vaccine adjuvants for rapid elicitation of tumoricidal CD8⁺ T cells","authors":"Yuan Luo , Shiqi Zhou , Yiting Song , Wei-Chiao Huang , Gregory E. Wilding , James Jablonski , Breandan Quinn , Jonathan F. Lovell","doi":"10.1016/j.bioactmat.2025.01.028","DOIUrl":"10.1016/j.bioactmat.2025.01.028","url":null,"abstract":"<div><div>A challenge for cancer vaccines is to elicit immune responses of sufficient magnitude to control malignant tumor growth and spread. In this study, we iteratively screened a panel of 22 lipid-phase vaccine adjuvants in mice for the elicitation of neoantigen-specific CD8⁺ T cell responses, using an integrated peptide-lipid nanoparticle approach. CL401, a dual Toll-like receptor 2/7 (TLR2/7) adjuvant rapidly induced neoantigen-specific T cell responses and improved lymphatic drainage and uptake of the particle. Additional rounds of <em>in vivo</em> screening identified complementary adjuvants which targeted TLR4 (3D6A-PHAD adjuvant), TLR8 (motolimod), and inflammasome (QS-21) pathways and synergized to enhance cytokine secretion in antigen presenting cells and vaccine-elicited neoantigen-specific CD8⁺ T cells. Co-delivery of adjuvants and antigens led to effective immune responses which regressed large established tumors, synergized with immune checkpoint blockade, and inhibited lung nodules in an experimental metastasis model, without overt toxicity or reactogenicity. We conclude that iterative adjuvant screening, performed in mice <em>in vivo</em>, can identify useful adjuvant combinations that hold potential for therapeutic cancer vaccine research.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 189-199"},"PeriodicalIF":18.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-18DOI: 10.1016/j.bioactmat.2025.02.018
Sirui Li , Lan Zhou , Yu Huang , Shupei Tang
Acute kidney injury (AKI) remains a prevalent and critical clinical condition. Although considerable advancements have been achieved in clinical and fundamental research in recent decades, the enhancements in AKI diagnosis and therapeutic approaches, such as the development of emerging biomarkers including neutrophil gelatinase-associated lipocalin (NGAL) and liver fatty acid-binding protein (FABP1) for early detection of AKI and the exploration of “goal-directed" hemodynamic treatment methods and renal replacement therapies, have yet to fulfill the demands of modern medicine. Extracellular vesicles (EVs) serve as pivotal messengers in cell-to-cell communication, exerting a vital impact on both physiological and pathological processes. They exhibit immense potential as disease regulators, innovative biomarkers, therapeutic agents, and drug delivery vehicles. In recent times, the diagnostic and therapeutic potential of EVs in AKI has garnered widespread recognition and exploration, making them a focal point in clinical research. Consequently, a comprehensive overview of EVs' role in AKI is of great importance. This review delves into the multifaceted roles of EVs from diverse cellular sources, including tubular epithelial cells (TECs), mesenchymal stem cells (MSCs), progenitor cells, platelets and macrophages, within the context of AKI. It scrutinizes their contributions to disease progression and mitigation, their diagnostic marker potential, and encompasses a variety of conventional and novel EVs extraction techniques suitable for AKI clinical applications. Moreover, it underscores four innovative strategies for engineering EVs to boost production efficiency, targeting precision, circulatory stability and therapeutic potency. These advancements pave the way for novel approaches in the diagnosis and treatment of AKI. We are optimistic that as research into EVs progresses, the future will bring about earlier detection, more tailored treatments, and a more holistic management of AKI.
{"title":"Emerging Frontiers in acute kidney injury: The role of extracellular vesicles","authors":"Sirui Li , Lan Zhou , Yu Huang , Shupei Tang","doi":"10.1016/j.bioactmat.2025.02.018","DOIUrl":"10.1016/j.bioactmat.2025.02.018","url":null,"abstract":"<div><div>Acute kidney injury (AKI) remains a prevalent and critical clinical condition. Although considerable advancements have been achieved in clinical and fundamental research in recent decades, the enhancements in AKI diagnosis and therapeutic approaches, such as the development of emerging biomarkers including neutrophil gelatinase-associated lipocalin (NGAL) and liver fatty acid-binding protein (FABP1) for early detection of AKI and the exploration of “goal-directed\" hemodynamic treatment methods and renal replacement therapies, have yet to fulfill the demands of modern medicine. Extracellular vesicles (EVs) serve as pivotal messengers in cell-to-cell communication, exerting a vital impact on both physiological and pathological processes. They exhibit immense potential as disease regulators, innovative biomarkers, therapeutic agents, and drug delivery vehicles. In recent times, the diagnostic and therapeutic potential of EVs in AKI has garnered widespread recognition and exploration, making them a focal point in clinical research. Consequently, a comprehensive overview of EVs' role in AKI is of great importance. This review delves into the multifaceted roles of EVs from diverse cellular sources, including tubular epithelial cells (TECs), mesenchymal stem cells (MSCs), progenitor cells, platelets and macrophages, within the context of AKI. It scrutinizes their contributions to disease progression and mitigation, their diagnostic marker potential, and encompasses a variety of conventional and novel EVs extraction techniques suitable for AKI clinical applications. Moreover, it underscores four innovative strategies for engineering EVs to boost production efficiency, targeting precision, circulatory stability and therapeutic potency. These advancements pave the way for novel approaches in the diagnosis and treatment of AKI. We are optimistic that as research into EVs progresses, the future will bring about earlier detection, more tailored treatments, and a more holistic management of AKI.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 149-170"},"PeriodicalIF":18.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-15DOI: 10.1016/j.bioactmat.2025.02.007
Mariana Gameiro, José Almeida-Pinto, Beatriz S. Moura, João F. Mano, Vítor M. Gaspar
Emerging genome editing and synthetic biology toolboxes can accurately program mammalian cells behavior from the inside-out. Such engineered living units can be perceived as key building blocks for bioengineering mammalian cell-dense materials, with promising features to be used as living therapeutics for tissue engineering or disease modeling applications. Aiming to reach full control over the code that governs cell behavior, inside-out engineering approaches have potential to fully unlock user-defined living materials encoded with tailored cellular functionalities and spatial arrangements. Dwelling on this, herein, we discuss the most recent advances and opportunities unlocked by genetic engineering strategies, and on their use for the assembly of next-generation cell-rich or cell-based materials, with an unprecedent control over cellular arrangements and customizable therapeutic capabilities. We envision that the continuous synergy between inside-out and outside-in cell engineering approaches will potentiate the future development of increasingly sophisticated cell assemblies that may operate with augmented biofunctionalities.
{"title":"Designer mammalian living materials through genetic engineering","authors":"Mariana Gameiro, José Almeida-Pinto, Beatriz S. Moura, João F. Mano, Vítor M. Gaspar","doi":"10.1016/j.bioactmat.2025.02.007","DOIUrl":"10.1016/j.bioactmat.2025.02.007","url":null,"abstract":"<div><div>Emerging genome editing and synthetic biology toolboxes can accurately program mammalian cells behavior from the inside-out. Such engineered living units can be perceived as key building blocks for bioengineering mammalian cell-dense materials, with promising features to be used as living therapeutics for tissue engineering or disease modeling applications. Aiming to reach full control over the code that governs cell behavior, inside-out engineering approaches have potential to fully unlock user-defined living materials encoded with tailored cellular functionalities and spatial arrangements. Dwelling on this, herein, we discuss the most recent advances and opportunities unlocked by genetic engineering strategies, and on their use for the assembly of next-generation cell-rich or cell-based materials, with an unprecedent control over cellular arrangements and customizable therapeutic capabilities. We envision that the continuous synergy between inside-out and outside-in cell engineering approaches will potentiate the future development of increasingly sophisticated cell assemblies that may operate with augmented biofunctionalities.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 135-148"},"PeriodicalIF":18.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-15DOI: 10.1016/j.bioactmat.2025.02.001
Longbao Feng , Qing Peng , Li Miao , Chenghao Cai , Franklin R. Tay , Shuqin Zhou , Ying Zhang , Zonghua Liu , Xingang Wang , Yang Jiao , Rui Guo
Wound infections are one of the major threats to human health, accounting for millions of deaths annually. Real-time monitoring, accurate diagnosis, and on-demand therapy are crucial to minimizing complications and saving lives. Herein, we propose a “monitor-and-treat” strategy for infected wound management by integrating the emerging development of bacterio-therapeutics and bio-optics. The upper layer consists of gelatin methacryloyl (GelMA)-collagen III methacryloyl (Col3MA) (GC), Reuterin (Reu) isolated from the probiotic Lactobacillus reuteri (L. reuteri) and microfluidic safflower polysaccharide (SPS)@GelMA microspheres using 3D printing technology. The lower layer is made of acryloylated glycine (ACG) hydrogel with tissue adhesion capability, which enables the hydrogel to adapt to the movement and stretching of the skin. By integrating temperature-sensitive polydimethylsiloxane (PDMS) optical fibers, the ACG-GC/Reu/SPS-PDMS hydrogel could accurately and steadily sense and send wound temperature information to intelligent devices for real-time monitoring of the healing status (“monitor”). The double-layered hydrogel not only inhibited bacterial survival and colonization (97.4 % against E. coli and 99 % against S. aureus), but also exhibited remarkable hemostatic properties. Furthermore, it was conducive to L929 cell proliferation and pro-angiogenesis, and promoted the polarization of pro‐inflammatory M1 macrophages to the anti‐inflammatory M2‐phenotype, therefore creating a favorable immune microenvironment at the wound site. Animal experiments using SD rats and Bama minipigs demonstrated that this hydrogel promoted wound closure, directed polarization to M2 macrophages, alleviated inflammation, enhanced neovascularization, therefore accelerating infected wound healing (“treat”). In addition, RNA-Seq analysis revealed the mechanism of action of ACG-GC/Reu/SPS-PDMS hydrogel in modulating key signaling pathways, including down-regulation of AMPK, IL-17, and NF-κB signaling pathways, activation of NLRP3 inflammatory vesicles, and enrichment of MAPK, TGF-β, PI3K-Akt, TNF, and VEGF signaling pathways. The modulation of these signaling pathways suggests that hydrogels play an important role in the molecular mechanisms that promote wound healing and tissue regeneration. Therefore, the design of this study provides an innovative and multifunctional bandage strategy that can significantly improve pathologic diagnosis and wound treatment.
{"title":"“Monitor-and-treat” that integrates bacterio-therapeutics and bio-optics for infected wound management","authors":"Longbao Feng , Qing Peng , Li Miao , Chenghao Cai , Franklin R. Tay , Shuqin Zhou , Ying Zhang , Zonghua Liu , Xingang Wang , Yang Jiao , Rui Guo","doi":"10.1016/j.bioactmat.2025.02.001","DOIUrl":"10.1016/j.bioactmat.2025.02.001","url":null,"abstract":"<div><div>Wound infections are one of the major threats to human health, accounting for millions of deaths annually. Real-time monitoring, accurate diagnosis, and on-demand therapy are crucial to minimizing complications and saving lives. Herein, we propose a “monitor-and-treat” strategy for infected wound management by integrating the emerging development of bacterio-therapeutics and bio-optics. The upper layer consists of gelatin methacryloyl (GelMA)-collagen III methacryloyl (Col<sub>3</sub>MA) (GC), Reuterin (Reu) isolated from the probiotic <em>Lactobacillus reuteri</em> (L. reuteri) and microfluidic safflower polysaccharide (SPS)@GelMA microspheres using 3D printing technology. The lower layer is made of acryloylated glycine (ACG) hydrogel with tissue adhesion capability, which enables the hydrogel to adapt to the movement and stretching of the skin. By integrating temperature-sensitive polydimethylsiloxane (PDMS) optical fibers, the ACG-GC/Reu/SPS-PDMS hydrogel could accurately and steadily sense and send wound temperature information to intelligent devices for real-time monitoring of the healing status (“monitor”). The double-layered hydrogel not only inhibited bacterial survival and colonization (97.4 % against <em>E. coli</em> and 99 % against <em>S. aureus</em>), but also exhibited remarkable hemostatic properties. Furthermore, it was conducive to L929 cell proliferation and pro-angiogenesis, and promoted the polarization of pro‐inflammatory M1 macrophages to the anti‐inflammatory M2‐phenotype, therefore creating a favorable immune microenvironment at the wound site. Animal experiments using SD rats and Bama minipigs demonstrated that this hydrogel promoted wound closure, directed polarization to M2 macrophages, alleviated inflammation, enhanced neovascularization, therefore accelerating infected wound healing (“treat”). In addition, RNA-Seq analysis revealed the mechanism of action of ACG-GC/Reu/SPS-PDMS hydrogel in modulating key signaling pathways, including down-regulation of AMPK, IL-17, and NF-κB signaling pathways, activation of NLRP3 inflammatory vesicles, and enrichment of MAPK, TGF-β, PI3K-Akt, TNF, and VEGF signaling pathways. The modulation of these signaling pathways suggests that hydrogels play an important role in the molecular mechanisms that promote wound healing and tissue regeneration. Therefore, the design of this study provides an innovative and multifunctional bandage strategy that can significantly improve pathologic diagnosis and wound treatment.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 118-134"},"PeriodicalIF":18.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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