Pub Date : 2025-02-17DOI: 10.1016/j.biomaterials.2025.123194
Wumeng Yin , Xingyu Chen , Long Bai , Yong Li , Wen Chen , Yueying Jiang , Yutian He , Yichen Yang , Yunfeng Lin , Taoran Tian , Xiaoxiao Cai
Bone Morphogenetic Protein-2 (BMP-2) is a key growth factor for inducing osteogenic differentiation and promoting bone remodeling. However, the exogenous application of delivery systems for BMP-2 has been hampered by various postoperative complications, poor stability and high price. Hence, in situ enrichment of endogenous BMP-2 is promising. The discovery of a small molecule BMP-2 binding peptide (BBP) that binds specifically to BMP-2 with high affinity lays the foundation for the construction of bioactive materials that capture endogenous BMP-2. In contrast, conventional enrichment strategies have low binding efficiency due to steric hindrance caused by the disordered arrangement of BBPs. Tetrahedral framework nucleic acid (tFNA) exhibits good editability and unique three-dimensional spatial structure that enables topological control of multivalent ligands in spatial distribution. The BBPs are further designed to be stably modified on tFNA (BBPs-tFNA) via click chemistry of the azide-alkyne addition to achieve the orderly arrangement of BBPs in spatial organization, to improve the binding efficiency of BMP-2. Therefore, in this study, BBPs-tFNA is modified on biocompatible hyaluronic acid methacryloyl (HAMA) to construct the functionalized bioactive composite hydrogel scaffolds, with the aim of achieving precise and efficient capture of endogenous BMP-2, stimulating osteogenic differentiation and promoting in situ osteogenesis for bone defect repair.
{"title":"BBPs-functionalized tetrahedral framework nucleic acid hydrogel scaffold captures endogenous BMP-2 to promote bone regeneration","authors":"Wumeng Yin , Xingyu Chen , Long Bai , Yong Li , Wen Chen , Yueying Jiang , Yutian He , Yichen Yang , Yunfeng Lin , Taoran Tian , Xiaoxiao Cai","doi":"10.1016/j.biomaterials.2025.123194","DOIUrl":"10.1016/j.biomaterials.2025.123194","url":null,"abstract":"<div><div>Bone Morphogenetic Protein-2 (BMP-2) is a key growth factor for inducing osteogenic differentiation and promoting bone remodeling. However, the exogenous application of delivery systems for BMP-2 has been hampered by various postoperative complications, poor stability and high price. Hence, in situ enrichment of endogenous BMP-2 is promising. The discovery of a small molecule BMP-2 binding peptide (BBP) that binds specifically to BMP-2 with high affinity lays the foundation for the construction of bioactive materials that capture endogenous BMP-2. In contrast, conventional enrichment strategies have low binding efficiency due to steric hindrance caused by the disordered arrangement of BBPs. Tetrahedral framework nucleic acid (tFNA) exhibits good editability and unique three-dimensional spatial structure that enables topological control of multivalent ligands in spatial distribution. The BBPs are further designed to be stably modified on tFNA (BBPs-tFNA) via click chemistry of the azide-alkyne addition to achieve the orderly arrangement of BBPs in spatial organization, to improve the binding efficiency of BMP-2. Therefore, in this study, BBPs-tFNA is modified on biocompatible hyaluronic acid methacryloyl (HAMA) to construct the functionalized bioactive composite hydrogel scaffolds, with the aim of achieving precise and efficient capture of endogenous BMP-2, stimulating osteogenic differentiation and promoting in situ osteogenesis for bone defect repair.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123194"},"PeriodicalIF":12.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437804","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 : 2025-02-17DOI: 10.1016/j.biomaterials.2025.123198
Ning Wu , Ziwei Han , Wenxing Lv , Yanjuan Huang , Jingwen Zhu , Jinqi Deng , Qing Xue
Endometriosis is a chronic inflammatory disease that primarily affects women of reproductive age. The current hormonal treatments are unsuitable for women who wish to conceive, highlighting the need for non-hormonal therapeutic alternatives. In this study, we engineered outer membrane vesicle (OMV)-coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (OMV-NPs) as a potential therapy for endometriosis. These OMV-NPs were internalized by macrophages more efficiently than bacterial OMVs and preserved the immunostimulatory properties of OMVs. In vivo administration of OMV-NPs in mice achieved prolonged retention in the peritoneal cavity, with effective uptake by nearly 80 % of the peritoneal macrophages. Notably, treatment with OMV-NPs reprogrammed macrophages toward the M1 phenotype, resulting in a significant decrease in the M2 to M1 ratio within the peritoneal cavity and in endometriotic lesions. This shift from M2 to M1 was associated with reduced TGF-β1 production and suppressed myofibroblast activation, which led to substantial inhibition of endometriosis progression. Furthermore, immunohistochemical imaging of paired eutopic and ectopic endometrial tissues from endometriosis patients revealed a positive correlation between M2-polarized macrophages and fibrosis. This finding suggests that reprogramming macrophages with OMV-NPs could be a promising therapeutic approach for endometriosis.
{"title":"Reprogramming peritoneal macrophages with outer membrane vesicle-coated PLGA nanoparticles for endometriosis prevention","authors":"Ning Wu , Ziwei Han , Wenxing Lv , Yanjuan Huang , Jingwen Zhu , Jinqi Deng , Qing Xue","doi":"10.1016/j.biomaterials.2025.123198","DOIUrl":"10.1016/j.biomaterials.2025.123198","url":null,"abstract":"<div><div>Endometriosis is a chronic inflammatory disease that primarily affects women of reproductive age. The current hormonal treatments are unsuitable for women who wish to conceive, highlighting the need for non-hormonal therapeutic alternatives. In this study, we engineered outer membrane vesicle (OMV)-coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (OMV-NPs) as a potential therapy for endometriosis. These OMV-NPs were internalized by macrophages more efficiently than bacterial OMVs and preserved the immunostimulatory properties of OMVs. In vivo administration of OMV-NPs in mice achieved prolonged retention in the peritoneal cavity, with effective uptake by nearly 80 % of the peritoneal macrophages. Notably, treatment with OMV-NPs reprogrammed macrophages toward the M1 phenotype, resulting in a significant decrease in the M2 to M1 ratio within the peritoneal cavity and in endometriotic lesions. This shift from M2 to M1 was associated with reduced TGF-β1 production and suppressed myofibroblast activation, which led to substantial inhibition of endometriosis progression. Furthermore, immunohistochemical imaging of paired eutopic and ectopic endometrial tissues from endometriosis patients revealed a positive correlation between M2-polarized macrophages and fibrosis. This finding suggests that reprogramming macrophages with OMV-NPs could be a promising therapeutic approach for endometriosis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123198"},"PeriodicalIF":12.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-17DOI: 10.1016/j.biomaterials.2025.123197
Qiandong Yang , Jiangling Zhou , Ming Yang , Jiayi Wei , Yingtao Gui , Fan Yang , Sihao He , Juan Cai , Bo Yu , Qijie Dai , Zhenzhen Tang , Tianyong Hou
The crosstalk between osteogenesis and angiogenesis plays an important role in promoting the formation of a microenvironment that supports bone regeneration. This suggests that the retention of endogenous osteogenic and angiogenic cells in the bone defect area can promote tissue-engineered bone (TEB) osteogenesis and cell–cell interactions. In this study, a Di-Aptamer-functionalized HA/β-TCP (Di-Aptamer-H/T) scaffold was prepared by sequential modification of APTES and sulfo-SMCC and connected with aptamer HM69 and EPC1. We confirmed that aptamers HM69 and EPC1 can specifically identify mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), respectively. This process triggers the expression of adhesion-related genes in these cells and allows these cells to selectively stay coupled to Di-Aptamer-H/T. The osteogenic differentiation ability of MSCs treated with Di-Aptamer-H/T in vitro was significantly increased. Similarly, the ability of Di-Aptamer-H/T-treated EPCs to form blood vessels was also enhanced. Notably, the osteogenic and angiogenic abilities of cocultured MSCs and EPCs treated with the Di-Aptamer-H/T scaffold were significantly better than those of cells cultured individually. In vivo, the results of micro-CT angiography, H&E staining, Masson's staining and histochemical staining further confirmed that Di-Aptamer-H/T formed new bones and vessels more readily than those treated with a single aptamer linked to HA/β-TCP or with HA/β-TCP alone. In brief, our study demonstrated that crosstalk between osteogenesis and angiogenesis is promoted by the Di-Aptamer-H/T scaffold, which serves as a potential treatment strategy for bone defects and can improve outcomes.
{"title":"A Di-aptamer-functionalized scaffold promotes bone regeneration by facilitating the selective retention of MSCs and EPCs and then promoting crosstalk between osteogenesis and angiogenesis","authors":"Qiandong Yang , Jiangling Zhou , Ming Yang , Jiayi Wei , Yingtao Gui , Fan Yang , Sihao He , Juan Cai , Bo Yu , Qijie Dai , Zhenzhen Tang , Tianyong Hou","doi":"10.1016/j.biomaterials.2025.123197","DOIUrl":"10.1016/j.biomaterials.2025.123197","url":null,"abstract":"<div><div>The crosstalk between osteogenesis and angiogenesis plays an important role in promoting the formation of a microenvironment that supports bone regeneration. This suggests that the retention of endogenous osteogenic and angiogenic cells in the bone defect area can promote tissue-engineered bone (TEB) osteogenesis and cell–cell interactions. In this study, a Di-Aptamer-functionalized HA/β-TCP (Di-Aptamer-H/T) scaffold was prepared by sequential modification of APTES and sulfo-SMCC and connected with aptamer HM69 and EPC1. We confirmed that aptamers HM69 and EPC1 can specifically identify mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), respectively. This process triggers the expression of adhesion-related genes in these cells and allows these cells to selectively stay coupled to Di-Aptamer-H/T. The osteogenic differentiation ability of MSCs treated with Di-Aptamer-H/T in vitro was significantly increased. Similarly, the ability of Di-Aptamer-H/T-treated EPCs to form blood vessels was also enhanced. Notably, the osteogenic and angiogenic abilities of cocultured MSCs and EPCs treated with the Di-Aptamer-H/T scaffold were significantly better than those of cells cultured individually. In vivo, the results of micro-CT angiography, H&E staining, Masson's staining and histochemical staining further confirmed that Di-Aptamer-H/T formed new bones and vessels more readily than those treated with a single aptamer linked to HA/β-TCP or with HA/β-TCP alone. In brief, our study demonstrated that crosstalk between osteogenesis and angiogenesis is promoted by the Di-Aptamer-H/T scaffold, which serves as a potential treatment strategy for bone defects and can improve outcomes.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123197"},"PeriodicalIF":12.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453691","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 : 2025-02-15DOI: 10.1016/j.biomaterials.2025.123196
Linli Jiang , Jia Dong , Minwen Jiang , Weiwei Tan , Yiwei Zeng , Xuanqi Liu , Pu Wang , Hejin Jiang , Jiajing Zhou , Xiaojing Liu , Hui Li , Lei Liu
Full-thickness skin defects pose significant challenges to physical and psychological health while traditional skin grafting techniques are associated with limitations. Herein, we present a 3D-printed multifunctional bilayer scaffold that incorporates apoptotic extracellular vesicles (ApoEVs) and antibacterial coacervates to prevent wound infection and promote wound healing. The ApoEVs were continuously released from the lower layer of the scaffold with large pores to promote angiogenesis and collagen deposition. Meanwhile, the pH-responsive curcumin-containing coacervates were released from the upper layer of the scaffold with dense pores to exert antibacterial and reactive oxygen species scavenging ability. In vivo experiments showed that the scaffold accelerated wound healing and improved healing quality by promoting a more organized collagen arrangement and reducing hyperplastic scar tissue. Furthermore, it effectively reduced hyperplastic scar tissue, resulting in a decrease in the average scar area from 73.3 % to 19.9 %. RNA sequencing analysis revealed that the scaffold upregulated genes associated with cell proliferation and downregulated genes related to inflammation, indicating its potential therapeutic applications for wound healing. This multifunctional bilayer scaffold represents a promising candidate for the treatment of full-thickness skin defects, offering rationales for designing skin scaffolds for regenerative medicine applications.
{"title":"3D-printed multifunctional bilayer scaffold with sustained release of apoptotic extracellular vesicles and antibacterial coacervates for enhanced wound healing","authors":"Linli Jiang , Jia Dong , Minwen Jiang , Weiwei Tan , Yiwei Zeng , Xuanqi Liu , Pu Wang , Hejin Jiang , Jiajing Zhou , Xiaojing Liu , Hui Li , Lei Liu","doi":"10.1016/j.biomaterials.2025.123196","DOIUrl":"10.1016/j.biomaterials.2025.123196","url":null,"abstract":"<div><div>Full-thickness skin defects pose significant challenges to physical and psychological health while traditional skin grafting techniques are associated with limitations. Herein, we present a 3D-printed multifunctional bilayer scaffold that incorporates apoptotic extracellular vesicles (ApoEVs) and antibacterial coacervates to prevent wound infection and promote wound healing. The ApoEVs were continuously released from the lower layer of the scaffold with large pores to promote angiogenesis and collagen deposition. Meanwhile, the pH-responsive curcumin-containing coacervates were released from the upper layer of the scaffold with dense pores to exert antibacterial and reactive oxygen species scavenging ability. In vivo experiments showed that the scaffold accelerated wound healing and improved healing quality by promoting a more organized collagen arrangement and reducing hyperplastic scar tissue. Furthermore, it effectively reduced hyperplastic scar tissue, resulting in a decrease in the average scar area from 73.3 % to 19.9 %. RNA sequencing analysis revealed that the scaffold upregulated genes associated with cell proliferation and downregulated genes related to inflammation, indicating its potential therapeutic applications for wound healing. This multifunctional bilayer scaffold represents a promising candidate for the treatment of full-thickness skin defects, offering rationales for designing skin scaffolds for regenerative medicine applications.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123196"},"PeriodicalIF":12.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428792","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 : 2025-02-15DOI: 10.1016/j.biomaterials.2025.123190
Antonio R. Montaño , Anas Masillati , Dani A. Szafran , Nourhan A. Shams , Grace E. Hubbell , Connor W. Barth , Summer L. Gibbs , Lei G. Wang
The FDA's recent approval of pafolacianine, the first molecular targeted contrast agent for fluorescence-guided surgery (FGS), signifies a remarkable milestone in precision medicine. This advance offers new hope for cancer patients by enabling guided removal of cancerous tissues, where completed surgical removal remains a consistent challenge without real-time intraoperative guidance. For optimal surgical outcomes, delicate nerve tissues must be preserved to maintain patient quality of life. Despite advances in the clinical translation pipeline, the development of clinically viable nerve-specific contrast agents for FGS remains a significant challenge. Herein, a medicinal chemistry-based matrix design strategy was applied to effectively generate a synthetic roadmap permitting management of nerve-specificity within the near-infrared (NIR) oxazine fluorophore family. Many of these newly developed fluorophores demonstrated robust nerve-specificity and superior safety profiles, while also offering spectral profiles that are compatible with the clinical surgical FGS infrastructure. Notably, improving observed brightness in vivo enabled exceptional visibility of buried nerve tissue, a priority during surgical procedures. Critically, the lead probe showed a large dosage safety window capable of generating substantial contrast at doses 100x lower than the maximum tolerated dose. Following clinical translation, such NIR nerve-specific fluorophores stand poised to significantly improve outcomes for surgical patients by improving identification and visualization of surface and buried nerve tissues in real time within the surgical arena.
{"title":"Matrix-designed bright near-infrared fluorophores for precision peripheral nerve imaging","authors":"Antonio R. Montaño , Anas Masillati , Dani A. Szafran , Nourhan A. Shams , Grace E. Hubbell , Connor W. Barth , Summer L. Gibbs , Lei G. Wang","doi":"10.1016/j.biomaterials.2025.123190","DOIUrl":"10.1016/j.biomaterials.2025.123190","url":null,"abstract":"<div><div>The FDA's recent approval of pafolacianine, the first molecular targeted contrast agent for fluorescence-guided surgery (FGS), signifies a remarkable milestone in precision medicine. This advance offers new hope for cancer patients by enabling guided removal of cancerous tissues, where completed surgical removal remains a consistent challenge without real-time intraoperative guidance. For optimal surgical outcomes, delicate nerve tissues must be preserved to maintain patient quality of life. Despite advances in the clinical translation pipeline, the development of clinically viable nerve-specific contrast agents for FGS remains a significant challenge. Herein, a medicinal chemistry-based matrix design strategy was applied to effectively generate a synthetic roadmap permitting management of nerve-specificity within the near-infrared (NIR) oxazine fluorophore family. Many of these newly developed fluorophores demonstrated robust nerve-specificity and superior safety profiles, while also offering spectral profiles that are compatible with the clinical surgical FGS infrastructure. Notably, improving observed brightness <em>in vivo</em> enabled exceptional visibility of buried nerve tissue, a priority during surgical procedures. Critically, the lead probe showed a large dosage safety window capable of generating substantial contrast at doses 100x lower than the maximum tolerated dose. Following clinical translation, such NIR nerve-specific fluorophores stand poised to significantly improve outcomes for surgical patients by improving identification and visualization of surface and buried nerve tissues in real time within the surgical arena.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123190"},"PeriodicalIF":12.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-15DOI: 10.1016/j.biomaterials.2025.123195
Jiacheng Liu , Junyan Liu , Senrui Liu , Pengcheng Xiao , Chengcheng Du , Jingdi Zhan , Zhuolin Chen , Lu Chen , Ke Li , Wei Huang , Yiting Lei
Selenium (Se) deficiency is a critical factor contributing to the imbalance of redox homeostasis in chondrocytes and the progression of osteoarthritis (OA). However, traditional selenium supplements face challenges such as a narrow therapeutic window and lack of targeting. To address this, we designed hyaluronic acid (HA)-modified selenium nanoparticles (HA-SeNPs) and developed a cascade-targeted delivery system (HA-SeNPs@AHAMA-HMs) based on a nano-micron combined strategy. The system involves loading HA-SeNPs into aldehyde-functionalized hydrogel microspheres prepared via microfluidic technology. Through Schiff base reactions between the aldehyde groups of the microspheres and amino groups of the cartilage, the system selectively adheres to the surface of damaged cartilage, achieving micron-scale targeting while continuously releasing HA-SeNPs. Then, HA-SeNPs achieve nanoscale targeting by binding to CD44, which is highly expressed on OA chondrocyte membranes, via their HA surface. Once taken up by the cells, HA-SeNPs exert their effects by directly scavenging ROS and promoting selenoprotein synthesis through the generation of selenite, forming a multifaceted antioxidant defense system. This effectively alleviates oxidative stress and optimizes mitochondrial function. In vivo and in vitro results demonstrated that this system significantly improved the oxidative phosphorylation pathway associated with mitochondrial function, which markedly reduced joint space narrowing and cartilage matrix degradation, and delayed the progression of OA. In summary, this study suggests that the cascade-targeting hydrogel microspheres designed and constructed based on a nano-micron combined strategy represent a promising prospective approach for precise Se supplementation and OA treatment.
{"title":"Cascade targeting selenium nanoparticles-loaded hydrogel microspheres for multifaceted antioxidant defense in osteoarthritis","authors":"Jiacheng Liu , Junyan Liu , Senrui Liu , Pengcheng Xiao , Chengcheng Du , Jingdi Zhan , Zhuolin Chen , Lu Chen , Ke Li , Wei Huang , Yiting Lei","doi":"10.1016/j.biomaterials.2025.123195","DOIUrl":"10.1016/j.biomaterials.2025.123195","url":null,"abstract":"<div><div>Selenium (Se) deficiency is a critical factor contributing to the imbalance of redox homeostasis in chondrocytes and the progression of osteoarthritis (OA). However, traditional selenium supplements face challenges such as a narrow therapeutic window and lack of targeting. To address this, we designed hyaluronic acid (HA)-modified selenium nanoparticles (HA-SeNPs) and developed a cascade-targeted delivery system (HA-SeNPs@AHAMA-HMs) based on a nano-micron combined strategy. The system involves loading HA-SeNPs into aldehyde-functionalized hydrogel microspheres prepared via microfluidic technology. Through Schiff base reactions between the aldehyde groups of the microspheres and amino groups of the cartilage, the system selectively adheres to the surface of damaged cartilage, achieving micron-scale targeting while continuously releasing HA-SeNPs. Then, HA-SeNPs achieve nanoscale targeting by binding to CD44, which is highly expressed on OA chondrocyte membranes, via their HA surface. Once taken up by the cells, HA-SeNPs exert their effects by directly scavenging ROS and promoting selenoprotein synthesis through the generation of selenite, forming a multifaceted antioxidant defense system. This effectively alleviates oxidative stress and optimizes mitochondrial function. In vivo and in vitro results demonstrated that this system significantly improved the oxidative phosphorylation pathway associated with mitochondrial function, which markedly reduced joint space narrowing and cartilage matrix degradation, and delayed the progression of OA. In summary, this study suggests that the cascade-targeting hydrogel microspheres designed and constructed based on a nano-micron combined strategy represent a promising prospective approach for precise Se supplementation and OA treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123195"},"PeriodicalIF":12.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428791","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 : 2025-02-13DOI: 10.1016/j.biomaterials.2025.123192
Qifeng Guan , Sen Hou , Kai Wang , Linhao Li , Yating Cheng , Mingxia Zheng , Chen Liu , Xinbin Zhao , Jin Zhou , Ping Li , Xufeng Niu , Lizhen Wang , Yubo Fan
Biomaterials can play a crucial role in facilitating tissue regeneration, but their application is often limited by that they induce scarring rather than complete tissue restoration. Hydrogels with microporous architectures, engineered via 3D printing techniques or particle packing (granular hydrogels), have shown promise in providing a conducive microenvironment for cellular infiltration and favorable immune response. Nonetheless, there is a notably lacking in studies that demonstrate scarless regeneration solely through pore structure engineering. In this study, we demonstrate that optimizing micropore structure of injectable granular hydrogels via controlled liquid-liquid phase separation facilitates scarless wound healing. The building block particles are fabricated by precisely controlling the separation kinetics of two immiscible aqueous phases (gelling and porogenic) and timely arresting phase separation, to generate bicontinuous, hollow or closed porous structure. Employing a murine model, we reveal that the optimized pore structure significantly facilitates mature vascular network boosts pro-regenerative macrophage polarization (M2/M1) and CD4+/Foxp3+ regulatory T cells, culminating in scarless skin regeneration enriched with hair follicles. Moreover, our hydrogels outperform the clinical gold-standard collagen/proteoglycan scaffolds in a porcine model, showcasing superior cell infiltration, epidermal integration, and dermal regeneration. Micropore structure engineering of biomaterials presents a promising and biologics free pathway for tissue regeneration.
{"title":"Micropore structure engineering of injectable granular hydrogels via controlled liquid-liquid phase separation facilitates regenerative wound healing in mice and pigs","authors":"Qifeng Guan , Sen Hou , Kai Wang , Linhao Li , Yating Cheng , Mingxia Zheng , Chen Liu , Xinbin Zhao , Jin Zhou , Ping Li , Xufeng Niu , Lizhen Wang , Yubo Fan","doi":"10.1016/j.biomaterials.2025.123192","DOIUrl":"10.1016/j.biomaterials.2025.123192","url":null,"abstract":"<div><div>Biomaterials can play a crucial role in facilitating tissue regeneration, but their application is often limited by that they induce scarring rather than complete tissue restoration. Hydrogels with microporous architectures, engineered via 3D printing techniques or particle packing (granular hydrogels), have shown promise in providing a conducive microenvironment for cellular infiltration and favorable immune response. Nonetheless, there is a notably lacking in studies that demonstrate scarless regeneration solely through pore structure engineering. In this study, we demonstrate that optimizing micropore structure of injectable granular hydrogels via controlled liquid-liquid phase separation facilitates scarless wound healing. The building block particles are fabricated by precisely controlling the separation kinetics of two immiscible aqueous phases (gelling and porogenic) and timely arresting phase separation, to generate bicontinuous, hollow or closed porous structure. Employing a murine model, we reveal that the optimized pore structure significantly facilitates mature vascular network boosts pro-regenerative macrophage polarization (M2/M1) and CD4+/Foxp3+ regulatory T cells, culminating in scarless skin regeneration enriched with hair follicles. Moreover, our hydrogels outperform the clinical gold-standard collagen/proteoglycan scaffolds in a porcine model, showcasing superior cell infiltration, epidermal integration, and dermal regeneration. Micropore structure engineering of biomaterials presents a promising and biologics free pathway for tissue regeneration.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123192"},"PeriodicalIF":12.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419222","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 : 2025-02-13DOI: 10.1016/j.biomaterials.2025.123187
Min Liu , Yiwen Tang , Mijia Yan , Jiale Zhang , Hangrong Chen , Qiuhong Zhang
Cancer thermal immunotherapeutic strategy has garnered tremendous attention in nanomedicine frontier. Photothermal therapy (PTT) within the second near-infrared (NIR-II) window is popular hyperthermia technique, but the effect of NIR-II PTT on antitumor immunity remains extensive exploration. Here, we first reveal the inflammatory immunosuppressive tumor microenvironment (TME) characterized by high-influx of myeloid-derived suppressor cells (MDSCs) following NIR-II PTT. For this issue, we develop biomineralized copper sulfide nanoparticles (BCS NPs) as NIR-II photothermal agents (PTAs), and found for the first time that they are superior electron-donor antioxidants with pronounced anti-inflammatory activities. Impressively, the excessive inflammation triggered by BCS NPs-mediated NIR-II PTT can be self-alleviated to minimize the high-influx of MDSCs, and the immunosuppression-related reactive oxygen species produced by MDSCs can also be self-scavenged. Such reprogramming of TME facilitates the activation of systemic adaptive antitumor immunity and the strengthened tumour-infiltrating of cytotoxic T lymphocytes, thereby realizing self-reinforcing immunotherapy synergy with cancer NIR-II PTT. More importantly, a robust abscopal effect against distant tumors is also observed in bilateral tumor models. This work provides the first example to underscore the potential of PTAs with antioxidant and anti-inflammatory functions as innovative thermal immuno-nanomedicines.
{"title":"Self-regulating immunosuppressive tumor microenvironment by NIR-II photothermal agent with anti-inflammatory activity for self-reinforcing immunotherapy synergy with cancer photothermal ablation","authors":"Min Liu , Yiwen Tang , Mijia Yan , Jiale Zhang , Hangrong Chen , Qiuhong Zhang","doi":"10.1016/j.biomaterials.2025.123187","DOIUrl":"10.1016/j.biomaterials.2025.123187","url":null,"abstract":"<div><div>Cancer thermal immunotherapeutic strategy has garnered tremendous attention in nanomedicine frontier. Photothermal therapy (PTT) within the second near-infrared (NIR-II) window is popular hyperthermia technique, but the effect of NIR-II PTT on antitumor immunity remains extensive exploration. Here, we first reveal the inflammatory immunosuppressive tumor microenvironment (TME) characterized by high-influx of myeloid-derived suppressor cells (MDSCs) following NIR-II PTT. For this issue, we develop biomineralized copper sulfide nanoparticles (BCS NPs) as NIR-II photothermal agents (PTAs), and found for the first time that they are superior electron-donor antioxidants with pronounced anti-inflammatory activities. Impressively, the excessive inflammation triggered by BCS NPs-mediated NIR-II PTT can be self-alleviated to minimize the high-influx of MDSCs, and the immunosuppression-related reactive oxygen species produced by MDSCs can also be self-scavenged. Such reprogramming of TME facilitates the activation of systemic adaptive antitumor immunity and the strengthened tumour-infiltrating of cytotoxic T lymphocytes, thereby realizing self-reinforcing immunotherapy synergy with cancer NIR-II PTT. More importantly, a robust abscopal effect against distant tumors is also observed in bilateral tumor models. This work provides the first example to underscore the potential of PTAs with antioxidant and anti-inflammatory functions as innovative thermal immuno-nanomedicines.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123187"},"PeriodicalIF":12.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419272","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 : 2025-02-13DOI: 10.1016/j.biomaterials.2025.123186
Shirun Chu , Linlong Li , Jiahao Zhang , Jing You , Xiaolan Li , Yuanyuan Zhou , Xiao Huang , Qiaoli Wu , Fang Chen , Xue Bai , Huan Tan , Jie Weng
Novel interconnected porous scaffolds featuring suitable micro-interface structures hold significance in bone regeneration. Therefore, a hierarchical interconnected porous scaffold with nanotopography interface of pores, mimicking natural bone structure and extracellular matrix microenvironment, are designed to enhance bone regeneration by improving cell adhesion, proliferation, alleviate inflammation, and tissue integration capabilities. The scaffold is fabricated through Pickering emulsion templating method, with aminated gelatin and copper-hydroxyapatite nanoparticles serving as co-stabilizers. This process results in a dual nanoparticles-decorated interface, which could provide ample anchoring points for cells. Adjusting the ratio of the two nanoparticles leads to scaffold with different interfacial roughness. The resultant scaffold increases the number of cellular focal adhesions, enhancing cell adhesion, while its high porosity supports cell recruitment, proliferation and immunomodulation. Copper-hydroxyapatite adsorption at the pore interface reduces copper ion usage and exposes nanoparticles for direct cell contact, endowing the scaffold with enhanced antibacterial and angiogenic properties. An initial burst release phase of copper ions exerts inhibitory effects on mRNA expression, followed by a sustained and optimal release phase that promotes osteogenesis. The molecular mechanism underlying the scaffold of osteogenic potential has been elucidated through RNA sequencing analysis, along with the regulation of inflammatory cytokine expression. In vitro and in vivo studies alike verify its neovascularization-promoting capacity. The efficacy shown in a rat model with critical cranial defects underscores its clinical promise for bone regeneration, as Cu-doped scaffolds retain osteoinductive qualities after 10 weeks in vivo. This study innovates a manufacturing method for a novel scaffold in bone tissue engineering.
{"title":"Hierarchical interconnected porous scaffolds with regulated interfacial nanotopography exhibit antimicrobial, alleviate inflammation, neovascularization, and tissue integration for bone regeneration","authors":"Shirun Chu , Linlong Li , Jiahao Zhang , Jing You , Xiaolan Li , Yuanyuan Zhou , Xiao Huang , Qiaoli Wu , Fang Chen , Xue Bai , Huan Tan , Jie Weng","doi":"10.1016/j.biomaterials.2025.123186","DOIUrl":"10.1016/j.biomaterials.2025.123186","url":null,"abstract":"<div><div>Novel interconnected porous scaffolds featuring suitable micro-interface structures hold significance in bone regeneration. Therefore, a hierarchical interconnected porous scaffold with nanotopography interface of pores, mimicking natural bone structure and extracellular matrix microenvironment, are designed to enhance bone regeneration by improving cell adhesion, proliferation, alleviate inflammation, and tissue integration capabilities. The scaffold is fabricated through Pickering emulsion templating method, with aminated gelatin and copper-hydroxyapatite nanoparticles serving as co-stabilizers. This process results in a dual nanoparticles-decorated interface, which could provide ample anchoring points for cells. Adjusting the ratio of the two nanoparticles leads to scaffold with different interfacial roughness. The resultant scaffold increases the number of cellular focal adhesions, enhancing cell adhesion, while its high porosity supports cell recruitment, proliferation and immunomodulation. Copper-hydroxyapatite adsorption at the pore interface reduces copper ion usage and exposes nanoparticles for direct cell contact, endowing the scaffold with enhanced antibacterial and angiogenic properties. An initial burst release phase of copper ions exerts inhibitory effects on mRNA expression, followed by a sustained and optimal release phase that promotes osteogenesis. The molecular mechanism underlying the scaffold of osteogenic potential has been elucidated through RNA sequencing analysis, along with the regulation of inflammatory cytokine expression. <em>In vitro</em> and <em>in vivo</em> studies alike verify its neovascularization-promoting capacity. The efficacy shown in a rat model with critical cranial defects underscores its clinical promise for bone regeneration, as Cu-doped scaffolds retain osteoinductive qualities after 10 weeks <em>in vivo</em>. This study innovates a manufacturing method for a novel scaffold in bone tissue engineering.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"318 ","pages":"Article 123186"},"PeriodicalIF":12.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429014","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 : 2025-02-13DOI: 10.1016/j.biomaterials.2025.123180
Zhenyu Gong , Dairan Zhou , Dejun Wu , Yaguang Han , Hao Yu , Haotian Shen , Wei Feng , Lijun Hou , Yu Chen , Tao Xu
Central nervous system (CNS) tumors, encompassing a diverse array of neoplasms in the brain and spinal cord, pose significant therapeutic challenges due to their intricate anatomy and the protective presence of the blood-brain barrier (BBB). The primary treatment obstacle is the effective delivery of therapeutics to the tumor site, which is hindered by multiple physiological, biological, and technical barriers, including the BBB. This comprehensive review highlights recent advancements in material science and nanotechnology aimed at surmounting these delivery challenges, with a focus on the development and application of nanomaterials. Nanomaterials emerge as potent tools in designing innovative drug delivery systems that demonstrate the potential to overcome the limitations posed by CNS tumors. The review delves into various strategies, including the use of lipid nanoparticles, polymeric nanoparticles, and inorganic nanoparticles, all of which are engineered to enhance drug stability, BBB penetration, and targeted tumor delivery. Additionally, this review highlights the burgeoning role of theranostic nanoparticles, integrating therapeutic and diagnostic functionalities to optimize treatment efficacy. The exploration extends to biocompatible materials like biodegradable polymers, liposomes, and advanced material-integrated delivery systems such as implantable drug-eluting devices and microfabricated devices. Despite promising preclinical results, the translation of these material-based strategies into clinical practice necessitates further research and optimization.
{"title":"Challenges and material innovations in drug delivery to central nervous system tumors","authors":"Zhenyu Gong , Dairan Zhou , Dejun Wu , Yaguang Han , Hao Yu , Haotian Shen , Wei Feng , Lijun Hou , Yu Chen , Tao Xu","doi":"10.1016/j.biomaterials.2025.123180","DOIUrl":"10.1016/j.biomaterials.2025.123180","url":null,"abstract":"<div><div>Central nervous system (CNS) tumors, encompassing a diverse array of neoplasms in the brain and spinal cord, pose significant therapeutic challenges due to their intricate anatomy and the protective presence of the blood-brain barrier (BBB). The primary treatment obstacle is the effective delivery of therapeutics to the tumor site, which is hindered by multiple physiological, biological, and technical barriers, including the BBB. This comprehensive review highlights recent advancements in material science and nanotechnology aimed at surmounting these delivery challenges, with a focus on the development and application of nanomaterials. Nanomaterials emerge as potent tools in designing innovative drug delivery systems that demonstrate the potential to overcome the limitations posed by CNS tumors. The review delves into various strategies, including the use of lipid nanoparticles, polymeric nanoparticles, and inorganic nanoparticles, all of which are engineered to enhance drug stability, BBB penetration, and targeted tumor delivery. Additionally, this review highlights the burgeoning role of theranostic nanoparticles, integrating therapeutic and diagnostic functionalities to optimize treatment efficacy. The exploration extends to biocompatible materials like biodegradable polymers, liposomes, and advanced material-integrated delivery systems such as implantable drug-eluting devices and microfabricated devices. Despite promising preclinical results, the translation of these material-based strategies into clinical practice necessitates further research and optimization.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"319 ","pages":"Article 123180"},"PeriodicalIF":12.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463477","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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