Pub Date : 2026-05-01Epub Date: 2026-01-06DOI: 10.1016/j.bioactmat.2025.12.040
Hung Pang Lee , Michelle Tai , Sarah J. Jones , Xinming Tong , Sungwon Kim , Michelle M.T. Jansman , Tony Tam , Jianyi Du , Mark A. Skylar-Scott , Fan Yang
Granular microgels are attractive bioinks for bioprinting due to their injectability, printability, modularity, and enhanced macroporosity compared to conventional nanoporous hydrogels. Despite the potential of microgels for bioprinting, most previous work has relied on spherical microgels and produced isotropic tissues, whereas many native tissues are inherently anisotropic. While emerging studies have explored non-spherical microgels for bioprinting, there remains a need for bioinks that support cell alignment and tunable niche cues. Microribbons (μRB) are anisotropic ribbon-shaped microgels, but the potential of μRBs as bioinks for printing 3D anisotropic tissues remains unexplored. Here, we report the development of μRBs with tunable stiffness as bioinks for extrusion-based bioprinting and demonstrate that μRB bioinks maintain excellent printability and align during extrusion. μRB bioinks support alignment of MSCs and endothelial cells, with greater alignment as μRB stiffness increases. Increasing μRB stiffness also accelerates mesenchymal stromal cell osteogenesis in 3D. Finally, we demonstrate the potential of μRB bioinks for modeling breast cancer-bone metastasis, which features spatial patterning of multiple cell types to model cancer cell invasion at the tissue interface. Together, these results establish ribbon-shaped microgels as a new class of anisotropic bioinks, offering a versatile platform to support a broad range of bioprinting applications.
{"title":"Ribbon-shaped microgels as bioinks for 3D bioprinting of anisotropic tissue structures","authors":"Hung Pang Lee , Michelle Tai , Sarah J. Jones , Xinming Tong , Sungwon Kim , Michelle M.T. Jansman , Tony Tam , Jianyi Du , Mark A. Skylar-Scott , Fan Yang","doi":"10.1016/j.bioactmat.2025.12.040","DOIUrl":"10.1016/j.bioactmat.2025.12.040","url":null,"abstract":"<div><div>Granular microgels are attractive bioinks for bioprinting due to their injectability, printability, modularity, and enhanced macroporosity compared to conventional nanoporous hydrogels. Despite the potential of microgels for bioprinting, most previous work has relied on spherical microgels and produced isotropic tissues, whereas many native tissues are inherently anisotropic. While emerging studies have explored non-spherical microgels for bioprinting, there remains a need for bioinks that support cell alignment and tunable niche cues. Microribbons (μRB) are anisotropic ribbon-shaped microgels, but the potential of μRBs as bioinks for printing 3D anisotropic tissues remains unexplored. Here, we report the development of μRBs with tunable stiffness as bioinks for extrusion-based bioprinting and demonstrate that μRB bioinks maintain excellent printability and align during extrusion. μRB bioinks support alignment of MSCs and endothelial cells, with greater alignment as μRB stiffness increases. Increasing μRB stiffness also accelerates mesenchymal stromal cell osteogenesis in 3D. Finally, we demonstrate the potential of μRB bioinks for modeling breast cancer-bone metastasis, which features spatial patterning of multiple cell types to model cancer cell invasion at the tissue interface. Together, these results establish ribbon-shaped microgels as a new class of anisotropic bioinks, offering a versatile platform to support a broad range of bioprinting applications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 595-606"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-01Epub Date: 2026-01-02DOI: 10.1016/j.bioactmat.2025.12.015
Yutong Qian , Meng Wang , Yicong Li , Mei Zhu , Meng Pan , Xicheng Li , Wen Chen , Yujia Wei , Ran Li , Danrong Hu , Zhiyong Qian
Peritoneal metastasis of colorectal cancer (PM-CRC) represents a major therapeutic challenge in advanced disease, where aberrant tumor vasculature contributes to poor prognosis. To address the pharmacological limitations of regorafenib (REG), this study developed a dual-receptor-targeted nanoplatform (REG@LFHA NPs) that leverages the characteristic overexpression of LRP-1 and CD44 receptors in the colorectal cancer tumor microenvironment. The nanoplatform was engineered through nanoprecipitation and electrostatic self-assembly, incorporating lactoferrin for LRP-1 targeting and hyaluronic acid for CD44 recognition. REG@LFHA NPs exert multifaceted antitumor effects through three coordinated mechanisms: potent suppression of tumor vasculature through VEGF-VEGFR pathway blockade, effectively disrupting blood and oxygen supply to induce tumor necrosis; direct tumor cytotoxicity via REG-mediated apoptosis and cell cycle arrest; and immune microenvironment remodeling through macrophage repolarization from pro-tumor M2 to antitumor M1 phenotypes. In PM-CRC models, REG@LFHA NPs demonstrated significantly enhanced tumor accumulation and therapeutic efficacy compared to free REG. Furthermore, the nanoplatform showed remarkable synergy with oxaliplatin, the first-line chemotherapeutic agent for PM-CRC, producing superior treatment outcomes through complementary mechanisms of action. This study not only establishes REG@LFHA NPs as an effective dual-targeting nanomedicine but also demonstrates their strong potential for clinical translation, particularly in combination with standard chemotherapy regimens for advanced peritoneal metastatic colorectal cancer.
{"title":"LRP-1/CD44-targeted regorafenib nano-delivery system leveraging anti-angiogenesis and synergistic cytotoxicity against peritoneal metastasis of colorectal cancer","authors":"Yutong Qian , Meng Wang , Yicong Li , Mei Zhu , Meng Pan , Xicheng Li , Wen Chen , Yujia Wei , Ran Li , Danrong Hu , Zhiyong Qian","doi":"10.1016/j.bioactmat.2025.12.015","DOIUrl":"10.1016/j.bioactmat.2025.12.015","url":null,"abstract":"<div><div>Peritoneal metastasis of colorectal cancer (PM-CRC) represents a major therapeutic challenge in advanced disease, where aberrant tumor vasculature contributes to poor prognosis. To address the pharmacological limitations of regorafenib (REG), this study developed a dual-receptor-targeted nanoplatform (REG@LFHA NPs) that leverages the characteristic overexpression of LRP-1 and CD44 receptors in the colorectal cancer tumor microenvironment. The nanoplatform was engineered through nanoprecipitation and electrostatic self-assembly, incorporating lactoferrin for LRP-1 targeting and hyaluronic acid for CD44 recognition. REG@LFHA NPs exert multifaceted antitumor effects through three coordinated mechanisms: potent suppression of tumor vasculature through VEGF-VEGFR pathway blockade, effectively disrupting blood and oxygen supply to induce tumor necrosis; direct tumor cytotoxicity via REG-mediated apoptosis and cell cycle arrest; and immune microenvironment remodeling through macrophage repolarization from pro-tumor M2 to antitumor M1 phenotypes. In PM-CRC models, REG@LFHA NPs demonstrated significantly enhanced tumor accumulation and therapeutic efficacy compared to free REG. Furthermore, the nanoplatform showed remarkable synergy with oxaliplatin, the first-line chemotherapeutic agent for PM-CRC, producing superior treatment outcomes through complementary mechanisms of action. This study not only establishes REG@LFHA NPs as an effective dual-targeting nanomedicine but also demonstrates their strong potential for clinical translation, particularly in combination with standard chemotherapy regimens for advanced peritoneal metastatic colorectal cancer.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 337-354"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-01Epub Date: 2026-01-02DOI: 10.1016/j.bioactmat.2025.12.032
Tuya Naren , Weikang Lv , Abdellah Aazmi , Yujun Wang , Haoran Yu , Jie Ying Lee , Huixiang Yang , Mengfei Yu , Xiuxiu Jiang , Huayong Yang , Liang Ma
Organ-on-a-chip (OoC) technology offers a transformative approach to modeling the human renal barrier, overcoming limitations of traditional animal and two-dimensional cell models. This review systematically outlines the construction and evaluation of renal barrier biochips, focusing on the glomerular filtration barrier (GFB), tubular reabsorption barrier (TRB), and collecting duct regulatory barrier (CDRB). OoC platforms integrate biomimetic materials, simulate dynamic microenvironments, and use multicellular co-culture strategies. This enables them to closely replicate the structural and functional characteristics of renal barriers. Key evaluation metrics—including structural biomimicry, barrier integrity, and active transport functions—are discussed to validate model performance. The technology demonstrates significant potential in drug nephrotoxicity prediction, disease mechanism investigation, and regenerative medicine. Despite challenges in material properties and long-term functional maintenance, ongoing advancements in OoC design and integration are poised to enhance its application in precision medicine and kidney disease research.
{"title":"Construction, evaluation, and applications of renal barrier-on-a-chip system","authors":"Tuya Naren , Weikang Lv , Abdellah Aazmi , Yujun Wang , Haoran Yu , Jie Ying Lee , Huixiang Yang , Mengfei Yu , Xiuxiu Jiang , Huayong Yang , Liang Ma","doi":"10.1016/j.bioactmat.2025.12.032","DOIUrl":"10.1016/j.bioactmat.2025.12.032","url":null,"abstract":"<div><div>Organ-on-a-chip (OoC) technology offers a transformative approach to modeling the human renal barrier, overcoming limitations of traditional animal and two-dimensional cell models. This review systematically outlines the construction and evaluation of renal barrier biochips, focusing on the glomerular filtration barrier (GFB), tubular reabsorption barrier (TRB), and collecting duct regulatory barrier (CDRB). OoC platforms integrate biomimetic materials, simulate dynamic microenvironments, and use multicellular co-culture strategies. This enables them to closely replicate the structural and functional characteristics of renal barriers. Key evaluation metrics—including structural biomimicry, barrier integrity, and active transport functions—are discussed to validate model performance. The technology demonstrates significant potential in drug nephrotoxicity prediction, disease mechanism investigation, and regenerative medicine. Despite challenges in material properties and long-term functional maintenance, ongoing advancements in OoC design and integration are poised to enhance its application in precision medicine and kidney disease research.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 421-449"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-01Epub Date: 2025-12-30DOI: 10.1016/j.bioactmat.2025.12.042
Sungwoo Cho , Hyun-Su Ha , Sangmin Lee , Hyunjae Kim , Seok Joon Lee , Jueun Kim , Yerin Lee , Kang Suk Lee , Hyun-Chel Joo , Hak-Joon Sung
The vascular wall regulates the pattern and pressure of blood flow. In cardiovascular interventions, catheters are deployed by puncturing the vessel wall, without exception. Despite continuous progress, the outcomes remain highly operator-dependent, and large punctures with high-pressure bleeding continue to pose clinical challenges. As a translatable solution, this study introduces a shape memory vascular wall plug (VWP) that automates both the Body and Wing functions within a single component, supported by a Ring assembly to maximize pressure resistance. The VWP is deployed into a 6-mm puncture in a porcine thoracic aorta under peak blood pressure, and shape recovery is triggered by a 45°C saline flush to enable automated activation. Upon recovery, Body expansion combined with Ring compression tightly seals the puncture tract. The curved Wing induces hemostatic sealing and then flattens to maintain healthy blood flow and physiologic pressures. The VWP achieves suturing-level performance in aortic puncture closure, demonstrating effective hemostasis, patency, and endothelialization. The flow-blockage ratio required to balance hemostasis with hemodynamics is computationally modeled and validated using whole-blood microfluidics. Pressure resistance is maximized by tuning Ring strain through polymer blending, indicating multi-level strategies in polymer, device design, and memory function to advance the vascular closure technology.
{"title":"A large puncture closer of aortic wall by multi-memory actions with thrombo-hemodynamic control","authors":"Sungwoo Cho , Hyun-Su Ha , Sangmin Lee , Hyunjae Kim , Seok Joon Lee , Jueun Kim , Yerin Lee , Kang Suk Lee , Hyun-Chel Joo , Hak-Joon Sung","doi":"10.1016/j.bioactmat.2025.12.042","DOIUrl":"10.1016/j.bioactmat.2025.12.042","url":null,"abstract":"<div><div>The vascular wall regulates the pattern and pressure of blood flow. In cardiovascular interventions, catheters are deployed by puncturing the vessel wall, without exception. Despite continuous progress, the outcomes remain highly operator-dependent, and large punctures with high-pressure bleeding continue to pose clinical challenges. As a translatable solution, this study introduces a shape memory vascular wall plug (VWP) that automates both the Body and Wing functions within a single component, supported by a Ring assembly to maximize pressure resistance. The VWP is deployed into a 6-mm puncture in a porcine thoracic aorta under peak blood pressure, and shape recovery is triggered by a 45°C saline flush to enable automated activation. Upon recovery, Body expansion combined with Ring compression tightly seals the puncture tract. The curved Wing induces hemostatic sealing and then flattens to maintain healthy blood flow and physiologic pressures. The VWP achieves suturing-level performance in aortic puncture closure, demonstrating effective hemostasis, patency, and endothelialization. The flow-blockage ratio required to balance hemostasis with hemodynamics is computationally modeled and validated using whole-blood microfluidics. Pressure resistance is maximized by tuning Ring strain through polymer blending, indicating multi-level strategies in polymer, device design, and memory function to advance the vascular closure technology.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 288-304"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-01Epub Date: 2025-12-29DOI: 10.1016/j.bioactmat.2025.12.013
Aliaa S. Karam , Gabriela S. Kronemberger , Kaoutar Chattahy , Daniel J. Kelly
Engineering functional articular cartilage (AC) grafts is one of the greatest challenges in tissue engineering. Recapitulating the arcade-like collagen organisation of AC, which is integral to the tissues’ strength and stiffness, is necessary to engineer truly functional grafts. This motivates the need for innovative strategies to control collagen alignment in engineered tissues in a programmable manner. Emerging 3D bioprinting strategies can provide spatially defined cues to guide tissue growth. Therefore, the goal of this study was to use embedded bioprinting to provide spatially defined boundary conditions to AC progenitor cells (ACP) to direct collagen organization and support the development of biomimetic cartilage tissues. ACPs were isolated through differential adhesion to fibronectin and demonstrated superior chondrogenesis to donor matched chondrocytes. Two different approaches (casting and 3D bioprinting) were used to physically constrain ACPs with external boundaries of differing widths (250, 500, or 750 μm). For both approaches, thinner boundaries promoted greater collagen alignment along the long axis of the developing tissue. Building on this, ACPs were bioprinted into a sheet, with collagen fibers aligning parallel to the print direction. Finally, a multi-layered graft was bioprinted with horizontal filaments (XY plane) overlaying vertical filaments (Z-axis). The bioprinted tissue had an arcade-like collagen organization with horizontal collagen fibres overlaying vertical collagen fibres. These findings demonstrate how support baths can be used to provide spatially defined physical boundary conditions to bioprinted cells to guide matrix organization, enabling the engineering of anisotropic AC grafts.
{"title":"Cell-only bioprinting of articular cartilage progenitor cells within a physically constraining support bath to engineer structurally organized grafts","authors":"Aliaa S. Karam , Gabriela S. Kronemberger , Kaoutar Chattahy , Daniel J. Kelly","doi":"10.1016/j.bioactmat.2025.12.013","DOIUrl":"10.1016/j.bioactmat.2025.12.013","url":null,"abstract":"<div><div>Engineering functional articular cartilage (AC) grafts is one of the greatest challenges in tissue engineering. Recapitulating the arcade-like collagen organisation of AC, which is integral to the tissues’ strength and stiffness, is necessary to engineer truly functional grafts. This motivates the need for innovative strategies to control collagen alignment in engineered tissues in a programmable manner. Emerging 3D bioprinting strategies can provide spatially defined cues to guide tissue growth. Therefore, the goal of this study was to use embedded bioprinting to provide spatially defined boundary conditions to AC progenitor cells (ACP) to direct collagen organization and support the development of biomimetic cartilage tissues. ACPs were isolated through differential adhesion to fibronectin and demonstrated superior chondrogenesis to donor matched chondrocytes. Two different approaches (casting and 3D bioprinting) were used to physically constrain ACPs with external boundaries of differing widths (250, 500, or 750 μm). For both approaches, thinner boundaries promoted greater collagen alignment along the long axis of the developing tissue. Building on this, ACPs were bioprinted into a sheet, with collagen fibers aligning parallel to the print direction. Finally, a multi-layered graft was bioprinted with horizontal filaments (XY plane) overlaying vertical filaments (Z-axis). The bioprinted tissue had an arcade-like collagen organization with horizontal collagen fibres overlaying vertical collagen fibres. These findings demonstrate how support baths can be used to provide spatially defined physical boundary conditions to bioprinted cells to guide matrix organization, enabling the engineering of anisotropic AC grafts.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 251-265"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-01Epub Date: 2025-12-25DOI: 10.1016/j.bioactmat.2025.12.041
Qing Zhao, Mingli He, Jing Shu, Yao Huang, Jin Chen, Weihua Guo
Enzyme-regulated biomineralization offers precise spatiotemporal control over tissue mineralization, overcoming key limitations of conventional regenerative therapies. This review systematically examines the underlying biological mechanisms, focusing on enzymatic regulation of phosphate metabolism, mineralization regulators, and matrix stabilization that orchestrate hierarchical mineral deposition. Organic matrices facilitate nanoconfinement-driven nucleation and spatially controlled mineralization through biochemical functionalization. These fundamental mechanisms have inspired the development of advanced enzyme-functionalized biomaterials, such as covalently immobilized hydrogels, physically entrapped nanocomposites, bioaffinity scaffolds, and stimuli-responsive 3D-printed constructs, which enable precisely tunable in situ mineralization. In clinical applications, such biomaterial systems demonstrate significant therapeutic potential, with critical-sized bone defects showing accelerated healing through biomimetic mineral-collagen alignment and enzyme-mediated enamel restoration achieving both hardness recovery and reduced secondary caries incidence. Current limitations primarily involve enzymatic stability, immunogenicity, and manufacturing scalability. Emerging solutions focus on gene-enzyme hybrid platforms and intelligent responsive systems for personalized regenerative approaches. The synergistic integration of biological principles with materials science provides a transformative foundation for developing next-generation therapeutic strategies.
{"title":"Enzyme-regulated biomineralization: Biological functions and advanced biomaterials for tissue regeneration","authors":"Qing Zhao, Mingli He, Jing Shu, Yao Huang, Jin Chen, Weihua Guo","doi":"10.1016/j.bioactmat.2025.12.041","DOIUrl":"10.1016/j.bioactmat.2025.12.041","url":null,"abstract":"<div><div>Enzyme-regulated biomineralization offers precise spatiotemporal control over tissue mineralization, overcoming key limitations of conventional regenerative therapies. This review systematically examines the underlying biological mechanisms, focusing on enzymatic regulation of phosphate metabolism, mineralization regulators, and matrix stabilization that orchestrate hierarchical mineral deposition. Organic matrices facilitate nanoconfinement-driven nucleation and spatially controlled mineralization through biochemical functionalization. These fundamental mechanisms have inspired the development of advanced enzyme-functionalized biomaterials, such as covalently immobilized hydrogels, physically entrapped nanocomposites, bioaffinity scaffolds, and stimuli-responsive 3D-printed constructs, which enable precisely tunable in situ mineralization. In clinical applications, such biomaterial systems demonstrate significant therapeutic potential, with critical-sized bone defects showing accelerated healing through biomimetic mineral-collagen alignment and enzyme-mediated enamel restoration achieving both hardness recovery and reduced secondary caries incidence. Current limitations primarily involve enzymatic stability, immunogenicity, and manufacturing scalability. Emerging solutions focus on gene-enzyme hybrid platforms and intelligent responsive systems for personalized regenerative approaches. The synergistic integration of biological principles with materials science provides a transformative foundation for developing next-generation therapeutic strategies.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 135-160"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-01Epub Date: 2026-01-09DOI: 10.1016/j.bioactmat.2026.01.007
Yanyang Chen , Wei He , Shifeng Ling , Yang Zhou , Jie Chen , Yawei Du , Ran Mo , Wenguo Cui
mRNA therapy holds immense promise for regenerative medicine; however, localized endoplasmic reticulum stress (ERS) in damaged tissues can impair the critical process of ribosomal translation. Here, we developed an in situ injectable lipid nanoparticle (LNP)/microsphere complex, also referred to as a lipid-hydrogel microplex (iLMP), with ERS-alleviating functionality to increase ribosomal translation. A vitamin E-derived ionizable lipid was synthesized to replace conventional ionizable lipids in LNPs, whereas porous hydrogel microspheres stabilized the LNPs via physical adsorption. In vitro studies revealed that the iLMPs codelivered vitamin E and mRNA, mitigating ERS and reducing eIF2α phosphorylation, a key translational barrier. Additionally, iLMPs injected in situ rapidly reconstructed the extracellular matrix, promoting tissue repair. In a bone defect animal model, iLMPs significantly enhanced BMP-2 mRNA translation, promoting osteogenesis. In summary, we present a novel in situ injectable mRNA delivery platform that enhances ribosomal translation, offering a promising strategy for tissue regeneration.
{"title":"Boosting ribosomal translation via ionizable lipid-hydrogel microplexes for localized mRNA therapy","authors":"Yanyang Chen , Wei He , Shifeng Ling , Yang Zhou , Jie Chen , Yawei Du , Ran Mo , Wenguo Cui","doi":"10.1016/j.bioactmat.2026.01.007","DOIUrl":"10.1016/j.bioactmat.2026.01.007","url":null,"abstract":"<div><div>mRNA therapy holds immense promise for regenerative medicine; however, localized endoplasmic reticulum stress (ERS) in damaged tissues can impair the critical process of ribosomal translation. Here, we developed an <em>in situ</em> injectable lipid nanoparticle (LNP)/microsphere complex, also referred to as a lipid-hydrogel microplex (iLMP), with ERS-alleviating functionality to increase ribosomal translation. A vitamin E-derived ionizable lipid was synthesized to replace conventional ionizable lipids in LNPs, whereas porous hydrogel microspheres stabilized the LNPs <em>via</em> physical adsorption. <em>In vitro</em> studies revealed that the iLMPs codelivered vitamin E and mRNA, mitigating ERS and reducing eIF2α phosphorylation, a key translational barrier. Additionally, iLMPs injected <em>in situ</em> rapidly reconstructed the extracellular matrix, promoting tissue repair. In a bone defect animal model, iLMPs significantly enhanced BMP-2 mRNA translation, promoting osteogenesis. In summary, we present a novel <em>in situ</em> injectable mRNA delivery platform that enhances ribosomal translation, offering a promising strategy for tissue regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 678-696"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-01Epub Date: 2026-01-02DOI: 10.1016/j.bioactmat.2025.12.049
Dong Mo , Meng Pan , Yujia Wei , Yun Yang , Wen Chen , Qingya Liu , Xicheng Li , Jianan Li , Tianying Luo , Fan Yang , Hanzi Deng , Zhenpeng Zhang , Zhaolin Xiao , Kang Li , Zhiyong Qian
The development of wound dressings with tunable antibacterial activity and controllable self-shrinkage remains an intractable medical task for treating drug-resistant bacterial biofilm-infected wounds. Herein, we prepared a near-infrared-light (NIR)-controlled hydrogel (Co-BOS@C/F Gel) using an oxygen vacancy (OV)-rich cobalt (Co)-doped bismuth oxysulfide (Co-Bi2O2-XS, Co-BOS) photocatalyst as the guest molecule and a hydrazide-modified chondroitin sulfate/aldehyde-terminated Pluronic F127 hydrogel (C/F Gel) as the host carrier. First, the two-dimensional Co-BOS photocatalysts were synthesized via a one-step liquid-phase ion-exchange method. Co doping decreased the band gap, increased the number of OVs, and promoted charge transfer. Co-BOS also exhibited excellent photothermal performance (η = 34.09 %) and strong photocatalytic reactive oxygen species (ROS)-generating ability. The Co-BOS@C/F Gel formed via a dynamic Schiff reaction showed good temperature sensitivity, adhesion, hemostasis, and electrical conductivity and unique NIR-light-driven self-shrinkage. It exhibited broad-spectrum antibacterial activity against various bacteria and eliminated 95 % of the methicillin-resistant Staphylococcus aureus (MRSA) biofilm using photothermal therapy/antibacterial photocatalytic therapy. Integrated transcriptomic analyses revealed that the Gel operates via multiple antibacterial mechanisms, including the regulation of oxidative stress pathways and metabolic networks. Furthermore, this Gel significantly promoted cell proliferation and migration. In a mouse model of MRSA biofilm-infected wounds, the Co-BOS@C/F Gel under NIR light adaptively covered irregular wounds, eliminated MRSA biofilms, and accelerated wound closure. Without NIR light, the gel effectively promoted collagen deposition and angiogenesis. This study provides an innovative “kill four birds with one stone” strategy to treat drug-resistant bacteria-infected wounds and promotes the application of hybrid hydrogels in the biomedical field.
{"title":"Near-infrared light-driven photocatalytic reactive oxygen species-generating antibacterial and self-shrinking hybrid hydrogels for combating drug-resistant bacterial biofilm infection and accelerating wound healing","authors":"Dong Mo , Meng Pan , Yujia Wei , Yun Yang , Wen Chen , Qingya Liu , Xicheng Li , Jianan Li , Tianying Luo , Fan Yang , Hanzi Deng , Zhenpeng Zhang , Zhaolin Xiao , Kang Li , Zhiyong Qian","doi":"10.1016/j.bioactmat.2025.12.049","DOIUrl":"10.1016/j.bioactmat.2025.12.049","url":null,"abstract":"<div><div>The development of wound dressings with tunable antibacterial activity and controllable self-shrinkage remains an intractable medical task for treating drug-resistant bacterial biofilm-infected wounds. Herein, we prepared a near-infrared-light (NIR)-controlled hydrogel (Co-BOS@C/F Gel) using an oxygen vacancy (OV)-rich cobalt (Co)-doped bismuth oxysulfide (Co-Bi<sub>2</sub>O<sub>2-X</sub>S, Co-BOS) photocatalyst as the guest molecule and a hydrazide-modified chondroitin sulfate/aldehyde-terminated Pluronic F127 hydrogel (C/F Gel) as the host carrier. First, the two-dimensional Co-BOS photocatalysts were synthesized <em>via</em> a one-step liquid-phase ion-exchange method. Co doping decreased the band gap, increased the number of OVs, and promoted charge transfer. Co-BOS also exhibited excellent photothermal performance (<em>η</em> = 34.09 %) and strong photocatalytic reactive oxygen species (ROS)-generating ability. The Co-BOS@C/F Gel formed via a dynamic Schiff reaction showed good temperature sensitivity, adhesion, hemostasis, and electrical conductivity and unique NIR-light-driven self-shrinkage. It exhibited broad-spectrum antibacterial activity against various bacteria and eliminated 95 % of the methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) biofilm using photothermal therapy/antibacterial photocatalytic therapy. Integrated transcriptomic analyses revealed that the Gel operates <em>via</em> multiple antibacterial mechanisms, including the regulation of oxidative stress pathways and metabolic networks. Furthermore, this Gel significantly promoted cell proliferation and migration. In a mouse model of MRSA biofilm-infected wounds, the Co-BOS@C/F Gel under NIR light adaptively covered irregular wounds, eliminated MRSA biofilms, and accelerated wound closure. Without NIR light, the gel effectively promoted collagen deposition and angiogenesis. This study provides an innovative “kill four birds with one stone” strategy to treat drug-resistant bacteria-infected wounds and promotes the application of hybrid hydrogels in the biomedical field.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 396-420"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-01Epub Date: 2026-02-04DOI: 10.1016/j.bioactmat.2026.01.039
Weimin Qi , Jue Wang , Shuya Wang , Xiaojing Shi , Tingli Xiong , Ruishi Li , Wenxuan Zheng , Min Liu , Shusheng Deng , Qiong Huang , Jianhua Liu , Kelong Ai
In myocardial infarction (MI), mitochondrial dysfunction acts as a core mechanism linking energy failure to multiple downstream pathological processes, ultimately determining cardiomyocyte fate and cardiac function. However, the rapid and safe restoration of cardiomyocyte mitochondrial function remains a major challenge in MI therapy. Herein, we present a heart-homed fast acting mitochondrial-function enhancer (H-FAME), rationally engineered to achieve sequential targeting from ischemic myocardial tissue to cardiomyocyte mitochondria. By synergistically modulating mitochondrial membrane potential (MMP) and oxidative stress, H-FAME stabilizes mitochondrial function, thereby attenuating cardiomyocyte loss, inflammation, and fibrosis and ultimately promoting functional recovery after MI. In summary, H-FAME provides a robust approach for energy homeostasis restoration, and lays the foundation for the development of related mitochondrial protective drugs to treat MI.
{"title":"Heart-homed nanomedicine induces fast mitochondrial rescue to enhance cardiac function post-myocardial infarction","authors":"Weimin Qi , Jue Wang , Shuya Wang , Xiaojing Shi , Tingli Xiong , Ruishi Li , Wenxuan Zheng , Min Liu , Shusheng Deng , Qiong Huang , Jianhua Liu , Kelong Ai","doi":"10.1016/j.bioactmat.2026.01.039","DOIUrl":"10.1016/j.bioactmat.2026.01.039","url":null,"abstract":"<div><div>In myocardial infarction (MI), mitochondrial dysfunction acts as a core mechanism linking energy failure to multiple downstream pathological processes, ultimately determining cardiomyocyte fate and cardiac function. However, the rapid and safe restoration of cardiomyocyte mitochondrial function remains a major challenge in MI therapy. Herein, we present a heart-homed fast acting mitochondrial-function enhancer (H-FAME), rationally engineered to achieve sequential targeting from ischemic myocardial tissue to cardiomyocyte mitochondria. By synergistically modulating mitochondrial membrane potential (MMP) and oxidative stress, H-FAME stabilizes mitochondrial function, thereby attenuating cardiomyocyte loss, inflammation, and fibrosis and ultimately promoting functional recovery after MI. In summary, H-FAME provides a robust approach for energy homeostasis restoration, and lays the foundation for the development of related mitochondrial protective drugs to treat MI.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 796-815"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146185098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-05-01Epub Date: 2025-12-27DOI: 10.1016/j.bioactmat.2025.12.026
Carla Arca-Garcia , Maria Godoy-Gallardo , Maria-Pau Ginebra
Despite advances in bone graft design and surgical techniques, bacterial infection remains a major cause of graft failure, exacerbated by the global rise in antimicrobial resistance. This has intensified the pursuit of antibiotic-free strategies to prevent bacterial colonization. Among these, antibacterial surface nanotopographies have emerged as promising tools, leveraging nanoscale geometries to physically disrupt bacteria upon contact. In this study, we engineered the surface of a calcium phosphate bone graft to confer antimicrobial functionality through a dual approach: the creation of high-aspect-ratio nanotopographies and ionic doping with fluoride. Through controlled hydrolysis of α-tricalcium phosphate by biomimetic and hydrothermal treatments, we generated calcium deficient hydroxyapatite nanoneedle structures whose morphology and biofunctionality were tuned via fluoride incorporation. XRD and Raman spectroscopy confirmed the formation of hydroxy-fluorapatite, with phase composition and surface morphology dependent on fluoride concentration and processing parameters. Fluoride doping significantly altered nanoneedle dimensions and spacing and enhanced bactericidal activity, particularly against P. aeruginosa, and to a lesser extent S. aureus. Notably, fluoride-doping alone showed no antibacterial effects; however, when combined with nanotopography, a synergistic increase in efficacy was observed. Importantly, the antimicrobial surfaces supported the proliferation and osteogenic differentiation of SaOS-2 cells. Co-culture assays modeling pre- and post-implantation infection scenarios demonstrated robust cell adhesion and markedly reduced bacterial colonization. In conclusion, our findings present a multifunctional, synthetic bone graft with both physical and chemical antibacterial properties, offering a promising strategy to mitigate infection risks while supporting osteointegration.
{"title":"Tailoring nanotopography and antibacterial properties of calcium phosphate bone grafts via fluoride incorporation","authors":"Carla Arca-Garcia , Maria Godoy-Gallardo , Maria-Pau Ginebra","doi":"10.1016/j.bioactmat.2025.12.026","DOIUrl":"10.1016/j.bioactmat.2025.12.026","url":null,"abstract":"<div><div>Despite advances in bone graft design and surgical techniques, bacterial infection remains a major cause of graft failure, exacerbated by the global rise in antimicrobial resistance. This has intensified the pursuit of antibiotic-free strategies to prevent bacterial colonization. Among these, antibacterial surface nanotopographies have emerged as promising tools, leveraging nanoscale geometries to physically disrupt bacteria upon contact. In this study, we engineered the surface of a calcium phosphate bone graft to confer antimicrobial functionality through a dual approach: the creation of high-aspect-ratio nanotopographies and ionic doping with fluoride. Through controlled hydrolysis of α-tricalcium phosphate by biomimetic and hydrothermal treatments, we generated calcium deficient hydroxyapatite nanoneedle structures whose morphology and biofunctionality were tuned via fluoride incorporation. XRD and Raman spectroscopy confirmed the formation of hydroxy-fluorapatite, with phase composition and surface morphology dependent on fluoride concentration and processing parameters. Fluoride doping significantly altered nanoneedle dimensions and spacing and enhanced bactericidal activity, particularly against <em>P. aeruginosa</em>, and to a lesser extent <em>S. aureus</em>. Notably, fluoride-doping alone showed no antibacterial effects; however, when combined with nanotopography, a synergistic increase in efficacy was observed. Importantly, the antimicrobial surfaces supported the proliferation and osteogenic differentiation of SaOS-2 cells. Co-culture assays modeling pre- and post-implantation infection scenarios demonstrated robust cell adhesion and markedly reduced bacterial colonization. In conclusion, our findings present a multifunctional, synthetic bone graft with both physical and chemical antibacterial properties, offering a promising strategy to mitigate infection risks while supporting osteointegration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 205-223"},"PeriodicalIF":18.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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