<div><div>The manufacturability of the cellular structure-based materials represents one of the most emerging themes in the additive manufacturing of medical implants and devices. This has been more relevant as natural bone possesses a unique porous architecture, which cannot be mimicked in conventional manufacturing. Despite recent advances, a critical knowledge gap persists in connecting scaffold topology and manufacturability with the mechano-biological responses, governed by asymmetric 3D pore structures. In this perspective, the present study focuses on laser powder bed fusion (L-PBF) of Schwarz diamond-based triply periodic minimal surface (SDW-TPMS) structures in Ti6Al4V, while varying unit cell size from 2.5 to 3.0 mm. The extensive micro-computed tomography analysis of 3D pore topology using customised design evaluation protocols established the efficacy of L-PBF-based optimised process parameters on dimensional tolerance and manufacturability of the TPMS structures. Intriguingly, an asymmetric mechanical response with a clinically relevant combination of the compressive elastic modulus (14–20 GPa), tensile elastic modulus (38 - 55 GPa), compressive strength (413–547 MPa), and tensile strength (325–475 MPa), together with unique 3D pore architecture, closely resembled the properties of human cortical bone. While correlating the anisotropic pore topology to the asymmetric mechanical response using the Gibson-Ashby model, the bendingdominated response was revealed with exponents of ∼1.5 in compression and ∼2.0 in tension. Furthermore, in vitro studies demonstrate MC3T3-E1 pre-osteoblasts' adhesion, proliferation, and maturation with modulation of early osteogenic markers and bone mineralisation, both quantitatively and qualitatively. The confocal microscopy observations revealed the cellular bridging, migration, and colonisation, indicating cytocompatibility. The present study conclusively establishes that SDW-TPMS structures offer a compelling combination of cortical bone-mimicking mechanical properties and a favourable biological response. It highlights their potential for reconstructive surgeries of load-bearing joints.</div></div><div><h3><em>Statement of Significanc</em>e</h3><div>Conventional high-modulus metallic implants can induce periprosthetic bone resorption via stress shielding. While additively manufactured porous biomaterials address this, a robust structure-property-function paradigm has remained elusive. This study presents a Ti6Al4V based TPMS scaffold that achieves the biomechanical fidelity for load-bearing applications while providing a microenvironment suitable for differentiataion of pre-osteoblasts. The central innovation is our use of quantitative pore network modeling to establish a predictive link between the as-manufactured pore topology, the scaffold's pronounced tension-compression asymmetry, and its pro-osteogenic biological response. This work provides a validated framework for the rational design of next-ge
{"title":"Asymmetric mechanical behavior and pre-osteoblast differentiation in 3D printed Ti6Al4V-based triply periodic minimal surface bone-analogues: the role of pore topology","authors":"Bijay Kumar Karali , Suresh Suthar , Sushant Banerji , Bikramjit Basu","doi":"10.1016/j.actbio.2025.10.002","DOIUrl":"10.1016/j.actbio.2025.10.002","url":null,"abstract":"<div><div>The manufacturability of the cellular structure-based materials represents one of the most emerging themes in the additive manufacturing of medical implants and devices. This has been more relevant as natural bone possesses a unique porous architecture, which cannot be mimicked in conventional manufacturing. Despite recent advances, a critical knowledge gap persists in connecting scaffold topology and manufacturability with the mechano-biological responses, governed by asymmetric 3D pore structures. In this perspective, the present study focuses on laser powder bed fusion (L-PBF) of Schwarz diamond-based triply periodic minimal surface (SDW-TPMS) structures in Ti6Al4V, while varying unit cell size from 2.5 to 3.0 mm. The extensive micro-computed tomography analysis of 3D pore topology using customised design evaluation protocols established the efficacy of L-PBF-based optimised process parameters on dimensional tolerance and manufacturability of the TPMS structures. Intriguingly, an asymmetric mechanical response with a clinically relevant combination of the compressive elastic modulus (14–20 GPa), tensile elastic modulus (38 - 55 GPa), compressive strength (413–547 MPa), and tensile strength (325–475 MPa), together with unique 3D pore architecture, closely resembled the properties of human cortical bone. While correlating the anisotropic pore topology to the asymmetric mechanical response using the Gibson-Ashby model, the bendingdominated response was revealed with exponents of ∼1.5 in compression and ∼2.0 in tension. Furthermore, in vitro studies demonstrate MC3T3-E1 pre-osteoblasts' adhesion, proliferation, and maturation with modulation of early osteogenic markers and bone mineralisation, both quantitatively and qualitatively. The confocal microscopy observations revealed the cellular bridging, migration, and colonisation, indicating cytocompatibility. The present study conclusively establishes that SDW-TPMS structures offer a compelling combination of cortical bone-mimicking mechanical properties and a favourable biological response. It highlights their potential for reconstructive surgeries of load-bearing joints.</div></div><div><h3><em>Statement of Significanc</em>e</h3><div>Conventional high-modulus metallic implants can induce periprosthetic bone resorption via stress shielding. While additively manufactured porous biomaterials address this, a robust structure-property-function paradigm has remained elusive. This study presents a Ti6Al4V based TPMS scaffold that achieves the biomechanical fidelity for load-bearing applications while providing a microenvironment suitable for differentiataion of pre-osteoblasts. The central innovation is our use of quantitative pore network modeling to establish a predictive link between the as-manufactured pore topology, the scaffold's pronounced tension-compression asymmetry, and its pro-osteogenic biological response. This work provides a validated framework for the rational design of next-ge","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"207 ","pages":"Pages 633-652"},"PeriodicalIF":9.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228258","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 : 2025-11-01DOI: 10.1016/j.actbio.2025.10.033
Hang Liu , Daniel Soo Lin Wong , Bhav Harshad Parikh , Ming Hao , Queenie Shu Woon Tan , Pei Lin Chee , Xiaowei Lou , Dan Kai , Gopal Lingam , Dejian Huang , Xinyi Su , Zengping Liu
Cell therapy is one of the most promising methods to treat retinal degenerative diseases, and crucial to its success is optimizing biomaterials to facilitate the delivery of retinal pigment epithelial (RPE) cells. This study explores the application of single-cell-pore-sized 3D printed polycaprolactone (PCL) scaffolds for cultivating human embryonic stem cell-derived RPE cell sheets. It compares them with track-etched polyethylene terephthalate (PET) membranes, the commercial products used in clinical trials for RPE cell delivery. We engineered two types of scaffolds at the microscale to optimize cell culture conditions, specifically focusing on pore size and fiber spacing. Protein expression analysis demonstrated that one scaffold with a pore size of ∼10 µm facilitated superior cellular integrity and function. Functional assessments, including barrier integrity, permeability, and phagocytosis assays, indicated that this scaffold enhanced nutrient exchange and maintained effective RPE functions akin to PET membranes. In an in vivo study, color fundus, optical coherence tomography, immunohistochemistry, and electroretinography revealed that 3D printed scaffolds exhibited biocompatibility, stability, and minimal inflammatory responses in the subretinal space of porcine models for 2 months and rabbit models for 14 months, with no adverse impact on retinal structure or function over either period. The findings suggest that 3D-printed biodegradable scaffolds present a viable alternative for RPE cell delivery, potentially advancing therapies for retinal degenerative conditions.
Statement of Significance
Cell therapy shows great promise for treating eye diseases that lead to vision loss. A crucial aspect of this therapy is delivering specialized retinal pigment epithelial (RPE) cells effectively. Our research presents a 3D-printed scaffold made from polycaprolactone (PCL), designed to carry RPE cells derived from human stem cells and dissolve after placement in the eye. We tested this scaffold in rabbits and pigs to evaluate its surgical handling, cell delivery effectiveness, and safety for human application. Our results refine implant design, paving the way for safer and more effective treatments for retinal diseases. Overall, this research enhances the application of cell therapy with scaffolds and offers valuable insights for future medical practices.
{"title":"Single-cell-pore-sized 3D printed scaffolds for retinal pigment epithelial cell therapy","authors":"Hang Liu , Daniel Soo Lin Wong , Bhav Harshad Parikh , Ming Hao , Queenie Shu Woon Tan , Pei Lin Chee , Xiaowei Lou , Dan Kai , Gopal Lingam , Dejian Huang , Xinyi Su , Zengping Liu","doi":"10.1016/j.actbio.2025.10.033","DOIUrl":"10.1016/j.actbio.2025.10.033","url":null,"abstract":"<div><div>Cell therapy is one of the most promising methods to treat retinal degenerative diseases, and crucial to its success is optimizing biomaterials to facilitate the delivery of retinal pigment epithelial (RPE) cells. This study explores the application of single-cell-pore-sized 3D printed polycaprolactone (PCL) scaffolds for cultivating human embryonic stem cell-derived RPE cell sheets. It compares them with track-etched polyethylene terephthalate (PET) membranes, the commercial products used in clinical trials for RPE cell delivery. We engineered two types of scaffolds at the microscale to optimize cell culture conditions, specifically focusing on pore size and fiber spacing. Protein expression analysis demonstrated that one scaffold with a pore size of ∼10 µm facilitated superior cellular integrity and function. Functional assessments, including barrier integrity, permeability, and phagocytosis assays, indicated that this scaffold enhanced nutrient exchange and maintained effective RPE functions akin to PET membranes. In an <em>in vivo</em> study, color fundus, optical coherence tomography, immunohistochemistry, and electroretinography revealed that 3D printed scaffolds exhibited biocompatibility, stability, and minimal inflammatory responses in the subretinal space of porcine models for 2 months and rabbit models for 14 months, with no adverse impact on retinal structure or function over either period. The findings suggest that 3D-printed biodegradable scaffolds present a viable alternative for RPE cell delivery, potentially advancing therapies for retinal degenerative conditions.</div></div><div><h3>Statement of Significance</h3><div>Cell therapy shows great promise for treating eye diseases that lead to vision loss. A crucial aspect of this therapy is delivering specialized retinal pigment epithelial (RPE) cells effectively. Our research presents a 3D-printed scaffold made from polycaprolactone (PCL), designed to carry RPE cells derived from human stem cells and dissolve after placement in the eye. We tested this scaffold in rabbits and pigs to evaluate its surgical handling, cell delivery effectiveness, and safety for human application. Our results refine implant design, paving the way for safer and more effective treatments for retinal diseases. Overall, this research enhances the application of cell therapy with scaffolds and offers valuable insights for future medical practices.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"207 ","pages":"Pages 294-310"},"PeriodicalIF":9.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145331014","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 : 2025-11-01DOI: 10.1016/j.actbio.2025.10.010
Dan Wu , Zhankui Zhang , Xinyue Li , Jie Zhou , Yibin Cao , Shaolong Qi , Lei Wang , Zhida Liu , Guocan Yu
{"title":"Corrigendum to “Dynamically assembled nanomedicine based on host−guest molecular recognition for NIR laser-excited chemotherapy and phototheranostics” [Acta Biomaterilia. Volume 168, 15 September 2023, Pages 565-579]","authors":"Dan Wu , Zhankui Zhang , Xinyue Li , Jie Zhou , Yibin Cao , Shaolong Qi , Lei Wang , Zhida Liu , Guocan Yu","doi":"10.1016/j.actbio.2025.10.010","DOIUrl":"10.1016/j.actbio.2025.10.010","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"207 ","pages":"Pages 657-659"},"PeriodicalIF":9.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356998","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 : 2025-11-01DOI: 10.1016/j.actbio.2025.10.031
Claudia Daboin , Ethan Nicklow , Donald R. Griffin
The use of biomaterials to model diseases and tissues in vitro has updated our understandings of cellular processes through the inclusion of a 3D microenvironment that better mimics physiological conditions. A major limitation that remains is the ability to probe these cultures on longer timescales while maintaining a simple, reproducible 3D-structure. Microporous annealed particle (MAP) scaffolds demonstrate potential in circumventing some drawbacks of traditional bulk hydrogels, including lowered nutrient diffusivity and early inhibition of cell-to-cell interactions, that may limit efficacy over long timescales. Previous research explored impacts of degradation and cell-adhesion ligands on MAP’s ability to promote creation of cell-mediated extracellular matrix (ECM) within its porous network over an 8-day period. This manuscript expands on this work by culturing a high density of human dermal fibroblasts in poly(ethylene glycol) (PEG) MAP scaffolds over 63 days. We evaluated mechanical maturation and viability over time between enzymatically insensitive (PEG-PEG) and sensitive (PEG-peptide) formulations of MAP. Mechanical modulus significantly increased in PEG-peptide scaffolds at 28 days, but viability was sustained for both conditions up to 63 days. Bulk RNAseq was performed on both conditions at equivalent timepoints, with many ECM-related genes highlighted as significant to the overall model and largest differences in gene profiles between conditions occurring at 28 days, corroborating mechanical data. Overall, this study demonstrates MAP’s use for long-term in vitro cultures with sustained viability and begins to optimize scaffold formulation to promote material-tissue hybridization. Future work will further analyze mechanisms for the differential behaviors, including decoupling degradability from material composition.
Statement of Significance
Three-dimensional in vitro cultures better mimic the physiological environment compared to traditional 2D cultures, but extending their lifetime remains challenging. Microporous annealed particle (MAP) scaffolds address limitations of bulk hydrogels by providing a porous microenvironment that enables immediate cell migration and proliferation without extensive polymer breakdown. This study demonstrates sustained viability and mechanical maturation of human dermal fibroblasts in MAP scaffolds for over 63 days – significantly longer than previous reports. We demonstrate that protease-sensitive peptide crosslinkers, compared to protease-insensitive alternatives, lead to enhanced ECM deposition and mechanical maturation, supported by transcriptomic evidence. These findings establish MAP scaffolds as a platform for long-term in vitro modeling of tissue development and potential engineering of tissues for transplantation.
{"title":"Mechanical maturation of human dermal fibroblast-laden microporous annealed particle scaffolds during long-term in vitro culture","authors":"Claudia Daboin , Ethan Nicklow , Donald R. Griffin","doi":"10.1016/j.actbio.2025.10.031","DOIUrl":"10.1016/j.actbio.2025.10.031","url":null,"abstract":"<div><div>The use of biomaterials to model diseases and tissues <em>in vitro</em> has updated our understandings of cellular processes through the inclusion of a 3D microenvironment that better mimics physiological conditions. A major limitation that remains is the ability to probe these cultures on longer timescales while maintaining a simple, reproducible 3D-structure. Microporous annealed particle (MAP) scaffolds demonstrate potential in circumventing some drawbacks of traditional bulk hydrogels, including lowered nutrient diffusivity and early inhibition of cell-to-cell interactions, that may limit efficacy over long timescales. Previous research explored impacts of degradation and cell-adhesion ligands on MAP’s ability to promote creation of cell-mediated extracellular matrix (ECM) within its porous network over an 8-day period. This manuscript expands on this work by culturing a high density of human dermal fibroblasts in poly(ethylene glycol) (PEG) MAP scaffolds over 63 days. We evaluated mechanical maturation and viability over time between enzymatically insensitive (PEG-PEG) and sensitive (PEG-peptide) formulations of MAP. Mechanical modulus significantly increased in PEG-peptide scaffolds at 28 days, but viability was sustained for both conditions up to 63 days. Bulk RNAseq was performed on both conditions at equivalent timepoints, with many ECM-related genes highlighted as significant to the overall model and largest differences in gene profiles between conditions occurring at 28 days, corroborating mechanical data. Overall, this study demonstrates MAP’s use for long-term <em>in vitro</em> cultures with sustained viability and begins to optimize scaffold formulation to promote material-tissue hybridization. Future work will further analyze mechanisms for the differential behaviors, including decoupling degradability from material composition.</div></div><div><h3>Statement of Significance</h3><div>Three-dimensional <em>in vitro</em> cultures better mimic the physiological environment compared to traditional 2D cultures, but extending their lifetime remains challenging. Microporous annealed particle (MAP) scaffolds address limitations of bulk hydrogels by providing a porous microenvironment that enables immediate cell migration and proliferation without extensive polymer breakdown. This study demonstrates sustained viability and mechanical maturation of human dermal fibroblasts in MAP scaffolds for over 63 days – significantly longer than previous reports. We demonstrate that protease-sensitive peptide crosslinkers, compared to protease-insensitive alternatives, lead to enhanced ECM deposition and mechanical maturation, supported by transcriptomic evidence. These findings establish MAP scaffolds as a platform for long-term <em>in vitro</em> modeling of tissue development and potential engineering of tissues for transplantation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"207 ","pages":"Pages 353-363"},"PeriodicalIF":9.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357153","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 : 2025-11-01DOI: 10.1016/j.actbio.2025.09.040
Sarah Ford , Kerstin Tiedemann , Rachel Shapiro , Svetlana V. Komarova , Katharina Jähn-Rickert , Elizabeth A. Zimmermann
Bone modeling and remodeling by osteoblasts and osteoclasts has been considered the primary mechanism of bone metabolism; however, osteocyte bone cells resorb their surrounding perilacunar bone matrix. It is unknown whether perilacunar remodeling contributes to bone formation in the absence of disease, disorder, or other external stimuli. Here, fluorescently labeled bone formation was quantified in femoral cortical bone and vertebral trabecular bone of skeletally mature female C57BL/6 mice (a commonly used mouse strain) using confocal microscopy. To explore whether the osteoblasts, pre-osteocytes, and mature osteocytes equally contributed to bone formation, the number density of lacunae with bone formation and bone formation rate were quantified. Bone formation was observed at both pre-osteocyte and mature osteocyte lacunae. In femoral cortical bone, 89 % of lacunae with bone formation were mature osteocyte lacunae, while in vertebral trabecular bone, 32 % of lacunae with bone formation were mature osteocyte lacunae. Bone formation rate at osteocyte lacunae was 1–2 orders of magnitude lower compared to osteoblast bone formation. Even though perilacunar (re)modeling has a smaller contribution to bone formation, it is an important process that shapes the LCN in pre-osteocyte lacunae during the osteoblast-to-osteocyte transition and maintains bone quality in mature osteocyte lacunae.
Statement of significance
Osteoclast and osteoblast bone cells have long been considered the cells responsible for bone remodeling. Here, we quantify the contributions of osteoblasts, pre-osteocytes, and mature osteocytes to bone metabolism in a common mouse strain. We find that perilacunar bone formation occurs at pre-osteocytes and mature osteocytes. In trabecular bone, a greater proportion of lacunae with bone formation were pre-osteocytes because trabecular bone has a high bone turnover. In cortical bone, a greater proportion of lacunae with bone formation were mature osteocytes. In the absence of disease or external stimuli, osteoblasts produce an order of magnitude more bone than at the perilacunar regions. However, perilacunar remodeling is still an important process regulating lacuno-canalicular network morphology and bone quality.
{"title":"Fluorescent mapping of osteocyte-driven bone formation at pre-osteocyte and mature osteocyte lacunae","authors":"Sarah Ford , Kerstin Tiedemann , Rachel Shapiro , Svetlana V. Komarova , Katharina Jähn-Rickert , Elizabeth A. Zimmermann","doi":"10.1016/j.actbio.2025.09.040","DOIUrl":"10.1016/j.actbio.2025.09.040","url":null,"abstract":"<div><div>Bone modeling and remodeling by osteoblasts and osteoclasts has been considered the primary mechanism of bone metabolism; however, osteocyte bone cells resorb their surrounding perilacunar bone matrix. It is unknown whether perilacunar remodeling contributes to bone formation in the absence of disease, disorder, or other external stimuli. Here, fluorescently labeled bone formation was quantified in femoral cortical bone and vertebral trabecular bone of skeletally mature female C57BL/6 mice (a commonly used mouse strain) using confocal microscopy. To explore whether the osteoblasts, pre-osteocytes, and mature osteocytes equally contributed to bone formation, the number density of lacunae with bone formation and bone formation rate were quantified. Bone formation was observed at both pre-osteocyte and mature osteocyte lacunae. In femoral cortical bone, 89 % of lacunae with bone formation were mature osteocyte lacunae, while in vertebral trabecular bone, 32 % of lacunae with bone formation were mature osteocyte lacunae. Bone formation rate at osteocyte lacunae was 1–2 orders of magnitude lower compared to osteoblast bone formation. Even though perilacunar (re)modeling has a smaller contribution to bone formation, it is an important process that shapes the LCN in pre-osteocyte lacunae during the osteoblast-to-osteocyte transition and maintains bone quality in mature osteocyte lacunae.</div></div><div><h3>Statement of significance</h3><div>Osteoclast and osteoblast bone cells have long been considered the cells responsible for bone remodeling. Here, we quantify the contributions of osteoblasts, pre-osteocytes, and mature osteocytes to bone metabolism in a common mouse strain. We find that perilacunar bone formation occurs at pre-osteocytes and mature osteocytes. In trabecular bone, a greater proportion of lacunae with bone formation were pre-osteocytes because trabecular bone has a high bone turnover. In cortical bone, a greater proportion of lacunae with bone formation were mature osteocytes. In the absence of disease or external stimuli, osteoblasts produce an order of magnitude more bone than at the perilacunar regions. However, perilacunar remodeling is still an important process regulating lacuno-canalicular network morphology and bone quality.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"207 ","pages":"Pages 444-455"},"PeriodicalIF":9.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202436","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 : 2025-11-01DOI: 10.1016/j.actbio.2025.10.013
Huiming Chen , Jinpei Mei , Jie Chen , Taju Wu , Tao Ma , Yutian Su , Ninglin Zhou , Baohong Sun
Over the past few decades, the field of phototherapy has undergone a significant transition. Covalent organic frameworks (COFs), with their structural design, biocompatibility, and photostability, have emerged as key materials in phototherapy advancement. Photoactive COFs have demonstrated potential in treating various diseases. However, traditional single-modal COF-based phototherapy, relying on thermal imbalance and oxidative stress, struggles with complex diseases, limiting therapeutic efficacy. This review systematically summarizes the synergistic strategies and innovative applications of COFs in phototherapy from a multimodal perspective. It focuses on designs enhancing COF photoactivity, including topological structure transformation, bandgap structures, and chemical bonding modes. These optimized designs enhance photothermal conversion efficiency and reactive oxygen species (ROS) generation by fine-tuning the electronic structures and photophysical properties. The review emphasizes COF-based phototherapy combination strategies, including light-responsive delivery, photo-immunological activation, metabolic regulation, gas molecule release, starvation intervention, and biological modification. These multimodal and synergistic therapeutic systems promote complex disease treatment. Finally, it evaluates clinical translation challenges, including regulatory barriers, toxicological assessment, and metabolic fates, while outlining artificial intelligence (AI)-based design prospects in precision medicine and photo-vaccine development strategies for long-term immunotherapy.
Statement of significance
This review highlights the transformative role of covalent organic frameworks (COFs) in advancing multimodal phototherapy, addressing critical limitations of traditional single-modal approaches. By systematically summarizing structural engineering strategies to enhance COF photoactivity—including, but not limited to, topological modulation, bandgap tuning, and stacking mode design—and integrating these with synergistic therapeutic systems (e.g., photo-responsive delivery, immune activation, and metabolic regulation), a comprehensive framework is provided for combating complex diseases. Notably, the work bridges material design with clinical translation, discussing regulatory and toxicological challenges while outlining the prospects of AI-driven precision medicine and photovaccines. This synthesis not only advances the fundamental understanding of COF-based phototherapy but also accelerates its transition from the lab to the clinic, offering novel solutions for cancer, infectious diseases, and beyond.
{"title":"Innovative applications and synergistic strategies for covalent organic frameworks in multimodal phototherapy","authors":"Huiming Chen , Jinpei Mei , Jie Chen , Taju Wu , Tao Ma , Yutian Su , Ninglin Zhou , Baohong Sun","doi":"10.1016/j.actbio.2025.10.013","DOIUrl":"10.1016/j.actbio.2025.10.013","url":null,"abstract":"<div><div>Over the past few decades, the field of phototherapy has undergone a significant transition. Covalent organic frameworks (COFs), with their structural design, biocompatibility, and photostability, have emerged as key materials in phototherapy advancement. Photoactive COFs have demonstrated potential in treating various diseases. However, traditional single-modal COF-based phototherapy, relying on thermal imbalance and oxidative stress, struggles with complex diseases, limiting therapeutic efficacy. This review systematically summarizes the synergistic strategies and innovative applications of COFs in phototherapy from a multimodal perspective. It focuses on designs enhancing COF photoactivity, including topological structure transformation, bandgap structures, and chemical bonding modes. These optimized designs enhance photothermal conversion efficiency and reactive oxygen species (ROS) generation by fine-tuning the electronic structures and photophysical properties. The review emphasizes COF-based phototherapy combination strategies, including light-responsive delivery, photo-immunological activation, metabolic regulation, gas molecule release, starvation intervention, and biological modification. These multimodal and synergistic therapeutic systems promote complex disease treatment. Finally, it evaluates clinical translation challenges, including regulatory barriers, toxicological assessment, and metabolic fates, while outlining artificial intelligence (AI)-based design prospects in precision medicine and photo-vaccine development strategies for long-term immunotherapy.</div></div><div><h3>Statement of significance</h3><div>This review highlights the transformative role of covalent organic frameworks (COFs) in advancing multimodal phototherapy, addressing critical limitations of traditional single-modal approaches. By systematically summarizing structural engineering strategies to enhance COF photoactivity—including, but not limited to, topological modulation, bandgap tuning, and stacking mode design—and integrating these with synergistic therapeutic systems (<em>e.g.</em>, photo-responsive delivery, immune activation, and metabolic regulation), a comprehensive framework is provided for combating complex diseases. Notably, the work bridges material design with clinical translation, discussing regulatory and toxicological challenges while outlining the prospects of AI-driven precision medicine and photovaccines. This synthesis not only advances the fundamental understanding of COF-based phototherapy but also accelerates its transition from the lab to the clinic, offering novel solutions for cancer, infectious diseases, and beyond.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"207 ","pages":"Pages 515-545"},"PeriodicalIF":9.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282047","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 : 2025-11-01DOI: 10.1016/j.actbio.2025.10.024
Valeryi K. Lishko, Aibek Mursalimov, Nataly P. Podolnikova, Tatiana P. Ugarova
Adsorption of fibrinogen on various surfaces, including biomaterials, significantly reduces adhesion of leukocytes and platelets. The mechanism by which fibrinogen renders surfaces nonadhesive involves its surface-induced self-assembly, resulting in the formation of a nanoscale multilayer matrix. Under static conditions, when tensile forces exerted by cellular integrins pull on the fibrinogen multilayer, it extends due to the separation of layers, preventing efficient mechanotransduction and leading to weak intracellular signaling and cell adhesion. Furthermore, a weak association between fibrinogen molecules in the superficial layers of the matrix allows integrins to pull fibrinogen molecules out of the matrix, causing the detachment of adherent cells. It remains unclear whether this process contributes to the anti-adhesive mechanism under flow when cells transiently contact the fibrinogen matrix. In the present study, using several flow systems, we demonstrated that various cells, including isolated blood cells, strip superficial fibrinogen molecules from the matrix, preventing their adhesion. Fibrinogen desorption in a cell-free buffer was significantly lower than that with cells. Surprisingly, the integrin fibrinogen receptors on cultured and primary leukocytes and platelets had minimal impact on fibrinogen detachment, as function-blocking anti-integrin antibodies did not significantly inhibit this process. Additionally, erythrocytes, which are not known to express specific fibrinogen receptors and even naked liposomes that can interact with fibrinogen with minimal affinity, caused fibrinogen detachment, suggesting that the stripping of superficial layers may arise from the low-affinity interactions of cells with the matrix. These results indicate that the peeling effect on the fibrinogen matrix exerted by cells under flow contributes to the anti-adhesive mechanism.
Statement of significance
Adsorption of the blood protein fibrinogen on implanted vascular grafts is crucial for their clinical performance. Recent research shows that fibrinogen adsorption triggers its self-assembly, forming a nonadhesive multilayer matrix. The nonadhesive properties of this matrix under static conditions arise from layer separation, which occurs when cellular integrins pull on the matrix, reducing the mechanotransduction response and weakening cell adhesion. In this study, we reveal a new mechanism explaining why fibrinogen multilayer fails to support cell adhesion under flow. We demonstrate that flowing cells detach fibrinogen molecules that are loosely associated with the upper surface of the matrix, thereby preventing platelet and leukocyte adhesion. This work enhances our understanding of protective anti-adhesive mechanisms that the host develops after the implantation of biomaterials, which could inform the design of improved vascular grafts.
{"title":"Structural instability of the superficial layers of the fibrinogen matrix contributes to its nonadhesive properties","authors":"Valeryi K. Lishko, Aibek Mursalimov, Nataly P. Podolnikova, Tatiana P. Ugarova","doi":"10.1016/j.actbio.2025.10.024","DOIUrl":"10.1016/j.actbio.2025.10.024","url":null,"abstract":"<div><div>Adsorption of fibrinogen on various surfaces, including biomaterials, significantly reduces adhesion of leukocytes and platelets. The mechanism by which fibrinogen renders surfaces nonadhesive involves its surface-induced self-assembly, resulting in the formation of a nanoscale multilayer matrix. Under static conditions, when tensile forces exerted by cellular integrins pull on the fibrinogen multilayer, it extends due to the separation of layers, preventing efficient mechanotransduction and leading to weak intracellular signaling and cell adhesion. Furthermore, a weak association between fibrinogen molecules in the superficial layers of the matrix allows integrins to pull fibrinogen molecules out of the matrix, causing the detachment of adherent cells. It remains unclear whether this process contributes to the anti-adhesive mechanism under flow when cells transiently contact the fibrinogen matrix. In the present study, using several flow systems, we demonstrated that various cells, including isolated blood cells, strip superficial fibrinogen molecules from the matrix, preventing their adhesion. Fibrinogen desorption in a cell-free buffer was significantly lower than that with cells. Surprisingly, the integrin fibrinogen receptors on cultured and primary leukocytes and platelets had minimal impact on fibrinogen detachment, as function-blocking anti-integrin antibodies did not significantly inhibit this process. Additionally, erythrocytes, which are not known to express specific fibrinogen receptors and even naked liposomes that can interact with fibrinogen with minimal affinity, caused fibrinogen detachment, suggesting that the stripping of superficial layers may arise from the low-affinity interactions of cells with the matrix. These results indicate that the peeling effect on the fibrinogen matrix exerted by cells under flow contributes to the anti-adhesive mechanism.</div></div><div><h3>Statement of significance</h3><div>Adsorption of the blood protein fibrinogen on implanted vascular grafts is crucial for their clinical performance. Recent research shows that fibrinogen adsorption triggers its self-assembly, forming a nonadhesive multilayer matrix. The nonadhesive properties of this matrix under static conditions arise from layer separation, which occurs when cellular integrins pull on the matrix, reducing the mechanotransduction response and weakening cell adhesion. In this study, we reveal a new mechanism explaining why fibrinogen multilayer fails to support cell adhesion under flow. We demonstrate that flowing cells detach fibrinogen molecules that are loosely associated with the upper surface of the matrix, thereby preventing platelet and leukocyte adhesion. This work enhances our understanding of protective anti-adhesive mechanisms that the host develops after the implantation of biomaterials, which could inform the design of improved vascular grafts.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"207 ","pages":"Pages 281-293"},"PeriodicalIF":9.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314300","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 : 2025-11-01DOI: 10.1016/j.actbio.2025.10.027
Wenhuan Bu , Jonathan I. Dawson , Richard O.C. Oreffo , Matteo D'Este , David Eglin , Hongchen Sun , Alvaro Mata
The extracellular matrix (ECM) of tissues progressively changes its mechanical properties in processes such as tissue development, repair, and disease progression. While stiffness has become a key design parameter of biomaterials, most synthetic biomaterials employed in cell culture or tissue regeneration do not display these gradual changes in mechanical properties. Here, we report on a hydrogel platform with the capacity to exhibit progressive stiffening from 0.8 to 7.4 kPa within a ∼48 h time period. The material integrates the tyramine derivative of hyaluronic acid (HAT) and Laponite® (Lap) and harnesses the diffusion of cations from culture media to trigger gradual secondary Lap-HAT cross-linking, resulting in the progressive stiffening of the hydrogel. We assessed the applicability of the hydrogel by first using it as a substrate for in vitro culture to investigate cross-talk between human bone marrow stromal cells (HBMSCs) and human umbilical vein endothelial cells (HUVECs). The progressively stiffening hydrogel led to changes in cell morphology and enhanced differentiation and communication compared to control substrates. In addition, we also tested the potential of the progressively stiffening hydrogels for bone regeneration using a critical-size rat cranial defect model and found that the hydrogel construct promoted vascularized bone regeneration. The current study introduces a hydrogel material that offers a more physiologically relevant environment for in vitro and in vivo applications and provides insight into the mechanical complexity of the ECM and its role in tissue physiology.
Statement of significance
This study presents a dynamic hydrogel platform that imitates the progressive mechanical changes of the native extracellular matrix (ECM), transitioning from soft (0.8 kPa) to stiff (7.4 kPa) over 48 h. By co-assembling HAT and Lap, the hydrogel achieves gradual stiffening through cation diffusion - mediated gradual secondary Lap-HAT cross-linking, offering a physiologically relevant microenvironment. In vitro, it enhances HBMSC and HUVEC cross-talk, improving differentiation and morphology. In vivo, it promotes vascularized bone regeneration in a critical-size cranial defect model. This innovation bridges the gap between static synthetic biomaterials and dynamic ECM mechanics, advancing applications in tissue engineering, disease modeling, and regenerative medicine.
{"title":"Ion-mediated progressively stiffening hydrogels for vascularized bone regeneration","authors":"Wenhuan Bu , Jonathan I. Dawson , Richard O.C. Oreffo , Matteo D'Este , David Eglin , Hongchen Sun , Alvaro Mata","doi":"10.1016/j.actbio.2025.10.027","DOIUrl":"10.1016/j.actbio.2025.10.027","url":null,"abstract":"<div><div>The extracellular matrix (ECM) of tissues progressively changes its mechanical properties in processes such as tissue development, repair, and disease progression. While stiffness has become a key design parameter of biomaterials, most synthetic biomaterials employed in cell culture or tissue regeneration do not display these gradual changes in mechanical properties. Here, we report on a hydrogel platform with the capacity to exhibit progressive stiffening from 0.8 to 7.4 kPa within a ∼48 h time period. The material integrates the tyramine derivative of hyaluronic acid (HAT) and Laponite® (Lap) and harnesses the diffusion of cations from culture media to trigger gradual secondary Lap-HAT cross-linking, resulting in the progressive stiffening of the hydrogel. We assessed the applicability of the hydrogel by first using it as a substrate for in vitro culture to investigate cross-talk between human bone marrow stromal cells (HBMSCs) and human umbilical vein endothelial cells (HUVECs). The progressively stiffening hydrogel led to changes in cell morphology and enhanced differentiation and communication compared to control substrates. In addition, we also tested the potential of the progressively stiffening hydrogels for bone regeneration using a critical-size rat cranial defect model and found that the hydrogel construct promoted vascularized bone regeneration. The current study introduces a hydrogel material that offers a more physiologically relevant environment for in vitro and in vivo applications and provides insight into the mechanical complexity of the ECM and its role in tissue physiology.</div></div><div><h3>Statement of significance</h3><div>This study presents a dynamic hydrogel platform that imitates the progressive mechanical changes of the native extracellular matrix (ECM), transitioning from soft (0.8 kPa) to stiff (7.4 kPa) over 48 h. By co-assembling HAT and Lap, the hydrogel achieves gradual stiffening through cation diffusion - mediated gradual secondary Lap-HAT cross-linking, offering a physiologically relevant microenvironment. In vitro, it enhances HBMSC and HUVEC cross-talk, improving differentiation and morphology. In vivo, it promotes vascularized bone regeneration in a critical-size cranial defect model. This innovation bridges the gap between static synthetic biomaterials and dynamic ECM mechanics, advancing applications in tissue engineering, disease modeling, and regenerative medicine.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"207 ","pages":"Pages 189-204"},"PeriodicalIF":9.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314350","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 : 2025-11-01DOI: 10.1016/j.actbio.2025.08.053
Boyang Wan , Chi Wu , Ziyan Man , Zhongpu Zhang , Michael V Swain , Qing Li
Load-bearing ceramic structures have gained significant attention in biomedical applications attributable to their favourable mechanical and biological properties. However, their inherent brittleness and material defects compromise reliability and lead to premature, and catastrophic failure in vivo. To address these limitations, computational modelling has emerged as a powerful tool for predicting and analysing the fracture behaviour of various ceramic biostructures, elucidating failure mechanisms, and guiding the design of more robust ceramic implantable systems. This review provides a comprehensive overview of modelling techniques and fracture criteria relevant to load-bearing ceramic biostructures. It encompasses a range of clinical applications, including dental, orthopaedic and bone tissue engineering, and explores how modelling strategies can identify critical regions prone to crack initiation and evaluate the impact of anatomical, material, and loading factors on structural integrity. By highlighting the predictive capabilities of computational approaches, this review underscores the modelling roles in enhancing the biomechanical performance and safety of bioceramic implants. Finally, it outlines current challenges and future perspectives in computational fracture modelling, providing a foundation for advancing simulation-based design and clinical translation of ceramic-based biomaterials.
Statement of significance
While prior reviews have discussed ceramic biomaterials and general applications of finite element analysis (FEA) in dentistry and orthopedics, a focused synthesis on damage and fracture modeling of implantable, load-bearing bioceramic structures remains lacking. This review fills that gap by systematically exploring a broad range of computational strategies, including FEA, XFEM, phase field, cohesive zone models, descrete element method, and peridynamics, alongside relevant fracture criteria and modeling workflows. With a particular emphasis on dental, orthopedic, and bone regeneration applications, the review highlights the critical role of numerical simulation in predicting fracture behavior and informing prosthetic design of bioceramics. By linking modeling techniques with clinical relevance, this work supports the development of more reliable, durable, and patient-specific implantable ceramic devices for translational biomedical applications.
{"title":"On fracture modelling of implantable load-bearing bioceramic structures and its state of the art","authors":"Boyang Wan , Chi Wu , Ziyan Man , Zhongpu Zhang , Michael V Swain , Qing Li","doi":"10.1016/j.actbio.2025.08.053","DOIUrl":"10.1016/j.actbio.2025.08.053","url":null,"abstract":"<div><div>Load-bearing ceramic structures have gained significant attention in biomedical applications attributable to their favourable mechanical and biological properties. However, their inherent brittleness and material defects compromise reliability and lead to premature, and catastrophic failure <em>in vivo.</em> To address these limitations, computational modelling has emerged as a powerful tool for predicting and analysing the fracture behaviour of various ceramic biostructures, elucidating failure mechanisms, and guiding the design of more robust ceramic implantable systems. This review provides a comprehensive overview of modelling techniques and fracture criteria relevant to load-bearing ceramic biostructures. It encompasses a range of clinical applications, including dental, orthopaedic and bone tissue engineering, and explores how modelling strategies can identify critical regions prone to crack initiation and evaluate the impact of anatomical, material, and loading factors on structural integrity. By highlighting the predictive capabilities of computational approaches, this review underscores the modelling roles in enhancing the biomechanical performance and safety of bioceramic implants. Finally, it outlines current challenges and future perspectives in computational fracture modelling, providing a foundation for advancing simulation-based design and clinical translation of ceramic-based biomaterials.</div></div><div><h3>Statement of significance</h3><div>While prior reviews have discussed ceramic biomaterials and general applications of finite element analysis (FEA) in dentistry and orthopedics, a focused synthesis on damage and fracture modeling of implantable, load-bearing bioceramic structures remains lacking. This review fills that gap by systematically exploring a broad range of computational strategies, including FEA, XFEM, phase field, cohesive zone models, descrete element method, and peridynamics, alongside relevant fracture criteria and modeling workflows. With a particular emphasis on dental, orthopedic, and bone regeneration applications, the review highlights the critical role of numerical simulation in predicting fracture behavior and informing prosthetic design of bioceramics. By linking modeling techniques with clinical relevance, this work supports the development of more reliable, durable, and patient-specific implantable ceramic devices for translational biomedical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"207 ","pages":"Pages 83-119"},"PeriodicalIF":9.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982083","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 : 2025-11-01DOI: 10.1016/j.actbio.2025.10.005
Yuxiang Ning , Aokang Yang , Shujun Zhou , Yunhao Wang , Ziguo Lin , Xiaojuan Xu , Yanfeng Wang
Hepatocellular carcinoma (HCC) is a significant global health challenge with limited treatment options, particularly for patients in advanced stages. Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising treatment modalities; however, their efficacy is often limited when used individually. Using the photothermal and photosensitive properties of iron diselenide (FeSe2), this study evaluates β-glucan nanotubes loaded with BFP-FeSe2 nanocomposites for enhanced HCC treatment combining PTT and PDT. We evaluated cellular uptake and in vitro therapeutic effects, as well as in vivo antitumor efficacy and biosafety in a liver cancer mouse model of the loaded nanocomposites were evaluated. In vitro experiments demonstrated that BFP-FeSe2 was efficiently internalized by liver cancer cells. Its antitumor efficacy was significantly enhanced under near-infrared light irradiation (NIR), inducing immunogenic cell death. In vivo experiments further revealed that BFP-FeSe2 achieved a high tumor inhibition rate (92–98 %) while maintaining biosafety by activating immune responses and promoting T-cell infiltration into tumor tissues. These findings highlight BFP-FeSe2 nanocomposites as an original phototherapeutic agent for HCC treatment, offering high therapeutic efficacy with minimal systemic toxicity.
Statement of significance
Liver cancer remains a major global health burden with limited treatment options, particularly in advanced stages. Photothermal and photodynamic therapies (PTT/PDT) offer promising alternatives, but their efficacy is often restricted when used alone. Our study introduces β-glucan nanotubes loaded with BFP-FeSe2 nanocomposites, leveraging the superior photothermal and photosensitive properties of FeSe₂ for synergistic PTT/PDT treatment. We demonstrate significant tumor inhibition (92–98 %) and immune activation with minimal toxicity in a liver cancer model. This work highlights a novel nanoplatform that enhances therapeutic outcomes while ensuring biosafety, offering new possibilities for HCC treatment. Our findings contribute to the growing field of nanomedicine and immunotherapy, with broad implications for cancer treatment strategies.
{"title":"β-Glucan nanotubes loaded with iron diselenide for enhanced photothermal and photodynamic therapy in hepatocellular carcinoma","authors":"Yuxiang Ning , Aokang Yang , Shujun Zhou , Yunhao Wang , Ziguo Lin , Xiaojuan Xu , Yanfeng Wang","doi":"10.1016/j.actbio.2025.10.005","DOIUrl":"10.1016/j.actbio.2025.10.005","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a significant global health challenge with limited treatment options, particularly for patients in advanced stages. Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising treatment modalities; however, their efficacy is often limited when used individually. Using the photothermal and photosensitive properties of iron diselenide (FeSe<sub>2</sub>), this study evaluates β-glucan nanotubes loaded with BFP-FeSe<sub>2</sub> nanocomposites for enhanced HCC treatment combining PTT and PDT. We evaluated cellular uptake and in vitro therapeutic effects, as well as in vivo antitumor efficacy and biosafety in a liver cancer mouse model of the loaded nanocomposites were evaluated. In vitro experiments demonstrated that BFP-FeSe2 was efficiently internalized by liver cancer cells. Its antitumor efficacy was significantly enhanced under near-infrared light irradiation (NIR), inducing immunogenic cell death. In vivo experiments further revealed that BFP-FeSe<sub>2</sub> achieved a high tumor inhibition rate (92–98 %) while maintaining biosafety by activating immune responses and promoting T-cell infiltration into tumor tissues. These findings highlight BFP-FeSe<sub>2</sub> nanocomposites as an original phototherapeutic agent for HCC treatment, offering high therapeutic efficacy with minimal systemic toxicity.</div></div><div><h3>Statement of significance</h3><div>Liver cancer remains a major global health burden with limited treatment options, particularly in advanced stages. Photothermal and photodynamic therapies (PTT/PDT) offer promising alternatives, but their efficacy is often restricted when used alone. Our study introduces β-glucan nanotubes loaded with BFP-FeSe<sub>2</sub> nanocomposites, leveraging the superior photothermal and photosensitive properties of FeSe₂ for synergistic PTT/PDT treatment. We demonstrate significant tumor inhibition (92–98 %) and immune activation with minimal toxicity in a liver cancer model. This work highlights a novel nanoplatform that enhances therapeutic outcomes while ensuring biosafety, offering new possibilities for HCC treatment. Our findings contribute to the growing field of nanomedicine and immunotherapy, with broad implications for cancer treatment strategies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"207 ","pages":"Pages 577-590"},"PeriodicalIF":9.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260190","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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