Biomaterials最新文献

All-in-one design of titanium-based dental implant systems for enhanced soft and hard tissue integration

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-14 DOI: 10.1016/j.biomaterials.2025.123251

Min Xing , Wenhao Qian , Kuicai Ye , Haifeng Zhang , Jiayin Feng , Xuanyong Liu , Jiajun Qiu

Enhancing the sealing between titanium abutment and surrounding soft tissue is crucial for preventing peri-implantitis. Meanwhile, exploring non-invasive antibacterial strategies as alternatives for traditional antibiotic therapy is central to improving the effect of peri-implantitis treatment. Furthermore, facilitating effective integration between titanium implant and osteoporotic bone is the cornerstone for ensuring long-term implant stability in patients with osteoporosis. In light of this, this work innovatively constructed multifunctional vertical graphene-based coatings on titanium implants and abutments using plasma-enhanced chemical vapor deposition technology. The results demonstrated that the vertical graphene coatings promoted soft tissue sealing and exhibited inherent antibacterial activities with the bacteriostasis rates of 65.60 % against Staphylococcus aureus (S. aureus) and 43.89 % against Escherichia coli (E. coli) in vitro which could prevent early infections. Moreover, vertical graphene coatings presented photothermal antibacterial effects with the antibacterial rates of 99.99 % and 95.83 % for S. aureus in vitro and in vivo, respectively, and 92.23 % for E. coli in vitro under near-infrared irradiation, which provided a non-invasive and highly effective treatment option for peri-implantitis. Furthermore, teriparatide acetate was loaded on vertical graphene coatings which enhanced osseointegration between titanium implants and osteoporotic bone. By comprehensively considering the critical functional requirements of dental implants and abutments, this work meticulously designed vertical graphene-based coatings on titanium dental implant systems for soft and hard tissue integration. This innovative design demonstrates immense application potential, especially for dental implant restoration in patients with osteoporosis.

{"title":"All-in-one design of titanium-based dental implant systems for enhanced soft and hard tissue integration","authors":"Min Xing , Wenhao Qian , Kuicai Ye , Haifeng Zhang , Jiayin Feng , Xuanyong Liu , Jiajun Qiu","doi":"10.1016/j.biomaterials.2025.123251","DOIUrl":"10.1016/j.biomaterials.2025.123251","url":null,"abstract":"<div><div>Enhancing the sealing between titanium abutment and surrounding soft tissue is crucial for preventing peri-implantitis. Meanwhile, exploring non-invasive antibacterial strategies as alternatives for traditional antibiotic therapy is central to improving the effect of peri-implantitis treatment. Furthermore, facilitating effective integration between titanium implant and osteoporotic bone is the cornerstone for ensuring long-term implant stability in patients with osteoporosis. In light of this, this work innovatively constructed multifunctional vertical graphene-based coatings on titanium implants and abutments using plasma-enhanced chemical vapor deposition technology. The results demonstrated that the vertical graphene coatings promoted soft tissue sealing and exhibited inherent antibacterial activities with the bacteriostasis rates of 65.60 % against <em>Staphylococcus aureus</em> (<em>S. aureus</em>) and 43.89 % against <em>Escherichia coli</em> (<em>E. coli</em>) <em>in vitro</em> which could prevent early infections. Moreover, vertical graphene coatings presented photothermal antibacterial effects with the antibacterial rates of 99.99 % and 95.83 % for <em>S. aureus in vitro</em> and <em>in vivo</em>, respectively, and 92.23 % for <em>E. coli in vitro</em> under near-infrared irradiation, which provided a non-invasive and highly effective treatment option for peri-implantitis. Furthermore, teriparatide acetate was loaded on vertical graphene coatings which enhanced osseointegration between titanium implants and osteoporotic bone. By comprehensively considering the critical functional requirements of dental implants and abutments, this work meticulously designed vertical graphene-based coatings on titanium dental implant systems for soft and hard tissue integration. This innovative design demonstrates immense application potential, especially for dental implant restoration in patients with osteoporosis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123251"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642763","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}

引用次数: 0

Selective and iron-independent ferroptosis in cancer cells induced by manipulation of mitochondrial fatty acid oxidation

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-14 DOI: 10.1016/j.biomaterials.2025.123259

Yan Gao, Zilin Song, Wenxin Gan, Xue Zou, Yaning Bai, Xiuli Zhao, Dawei Chen, Mingxi Qiao

Despite the promise of ferroptosis in cancer therapy, selectively inducing robust ferroptosis in cancer cells remains a significant challenge. In this study, manipulation of fatty acids β-oxidation (FAO) by combination of mild photodynamic therapy (PDT) and inhibition of triglycerides (TGs) synthesis was found to induce robust and iron-independent ferroptosis in cancer cells with dysregulated lipid metabolism for the first time. To achieve that, TGs synthesis inhibitor of xanthohumol (Xan) and FAO initiator of tetrakis (4-carboxyphenyl) porphyrin (TCPP) were co-delivered by a nanoplexes composed of pH-responsive amphiphilic lipopeptide C₁₈-pHis₁₀ and DSPE-PEG₂₀₀₀. TCPP was found to rapidly increase the intracellular ROS under laser irradiation without inducing antioxidant response and apoptosis, activating the AMPK in cancer cells and accelerating mitochondrial FAO. Xan fueled the mitochondrial FAO with substrates by suppressing the conversion of fatty acids (FAs) to TGs. This also led to augmented intracellular polyunsaturated fatty acids (PUFAs) and PUFAs-phospholipids levels, increasing the intrinsic susceptibility of cancer cells to lipid peroxidization. As a result, the excessive ROS generated from the sustained mitochondrial FAO caused remarkably lipid peroxidation and ultimately ferroptosis. Collectively, our study provides a new approach to selectively induce iron-independent ferroptosis in cancer cells by taking advantage of dysregulated lipid metabolism.

{"title":"Selective and iron-independent ferroptosis in cancer cells induced by manipulation of mitochondrial fatty acid oxidation","authors":"Yan Gao, Zilin Song, Wenxin Gan, Xue Zou, Yaning Bai, Xiuli Zhao, Dawei Chen, Mingxi Qiao","doi":"10.1016/j.biomaterials.2025.123259","DOIUrl":"10.1016/j.biomaterials.2025.123259","url":null,"abstract":"<div><div>Despite the promise of ferroptosis in cancer therapy, selectively inducing robust ferroptosis in cancer cells remains a significant challenge. In this study, manipulation of fatty acids β-oxidation (FAO) by combination of mild photodynamic therapy (PDT) and inhibition of triglycerides (TGs) synthesis was found to induce robust and iron-independent ferroptosis in cancer cells with dysregulated lipid metabolism for the first time. To achieve that, TGs synthesis inhibitor of xanthohumol (Xan) and FAO initiator of tetrakis (4-carboxyphenyl) porphyrin (TCPP) were co-delivered by a nanoplexes composed of pH-responsive amphiphilic lipopeptide C<sub>18</sub>-pHis<sub>10</sub> and DSPE-PEG<sub>2000</sub>. TCPP was found to rapidly increase the intracellular ROS under laser irradiation without inducing antioxidant response and apoptosis, activating the AMPK in cancer cells and accelerating mitochondrial FAO. Xan fueled the mitochondrial FAO with substrates by suppressing the conversion of fatty acids (FAs) to TGs. This also led to augmented intracellular polyunsaturated fatty acids (PUFAs) and PUFAs-phospholipids levels, increasing the intrinsic susceptibility of cancer cells to lipid peroxidization. As a result, the excessive ROS generated from the sustained mitochondrial FAO caused remarkably lipid peroxidation and ultimately ferroptosis. Collectively, our study provides a new approach to selectively induce iron-independent ferroptosis in cancer cells by taking advantage of dysregulated lipid metabolism.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123259"},"PeriodicalIF":12.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644798","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}

引用次数: 0

Vacancies-rich Z-scheme VdW heterojunction as H2S-sensitized synergistic therapeutic nanoplatform against refractory biofilm infections

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-13 DOI: 10.1016/j.biomaterials.2025.123258

Jianwen Dong , Shuting Zhang , Yau Kei Chan , Shuangquan Lai , Yi Deng

Encapsulated in a self-produced negatively charged extracellular polymeric substance (EPS) matrix, the wound infected bacterial biofilms exhibit formidable resistance to conventional positively charged antibiotics and host's immune responses, which can undoubtedly lead to persistent infections and lethal complications. Nevertheless, developing efficacious strategies to root out stubborn biofilm and promote tissue regeneration still remains a challenge. To resolve this dilemma, a versatile vacancies-rich Z-scheme MoSSe Van der Waals heterojunction (MoSSe VdW HJ) is rationally fabricated as nanoplatform for hydrogen sulfide (H₂S)-sensitized synergistic therapy of wound bacterial biofilm infection. The rich anion vacancies and Z-scheme heterostructure make the fabricated MoSSe VdW HJ can effectively augment H₂S, localized hyperthermia, and reactive oxygen species production under the stimulation of biofilm microenvironments (BME) and irradiation of 808 nm near-infrared (NIR) light. Therefore, MoSSe VdW HJ is capable to integrate H₂S gas, chemodynamic, photothermal, and photodynamic therapies to effectively destroy eDNA and polysaccharides in the EPS matrix, thereby breaching the biofilm barrier to eradicate bacteria and facilitate wound healing. The synergistic strategy exhibits superior anti-biofilm and wound repair effects both in vivo and in vitro, thus providing guideline for the development of BME and NIR light activated synergistic therapeutics to fight against refractory biofilm infections.

{"title":"Vacancies-rich Z-scheme VdW heterojunction as H2S-sensitized synergistic therapeutic nanoplatform against refractory biofilm infections","authors":"Jianwen Dong , Shuting Zhang , Yau Kei Chan , Shuangquan Lai , Yi Deng","doi":"10.1016/j.biomaterials.2025.123258","DOIUrl":"10.1016/j.biomaterials.2025.123258","url":null,"abstract":"<div><div>Encapsulated in a self-produced negatively charged extracellular polymeric substance (EPS) matrix, the wound infected bacterial biofilms exhibit formidable resistance to conventional positively charged antibiotics and host's immune responses, which can undoubtedly lead to persistent infections and lethal complications. Nevertheless, developing efficacious strategies to root out stubborn biofilm and promote tissue regeneration still remains a challenge. To resolve this dilemma, a versatile vacancies-rich Z-scheme MoSSe Van der Waals heterojunction (MoSSe VdW HJ) is rationally fabricated as nanoplatform for hydrogen sulfide (H<sub>2</sub>S)-sensitized synergistic therapy of wound bacterial biofilm infection. The rich anion vacancies and Z-scheme heterostructure make the fabricated MoSSe VdW HJ can effectively augment H<sub>2</sub>S, localized hyperthermia, and reactive oxygen species production under the stimulation of biofilm microenvironments (BME) and irradiation of 808 nm near-infrared (NIR) light. Therefore, MoSSe VdW HJ is capable to integrate H<sub>2</sub>S gas, chemodynamic, photothermal, and photodynamic therapies to effectively destroy eDNA and polysaccharides in the EPS matrix, thereby breaching the biofilm barrier to eradicate bacteria and facilitate wound healing. The synergistic strategy exhibits superior anti-biofilm and wound repair effects both <em>in vivo</em> and <em>in vitro</em>, thus providing guideline for the development of BME and NIR light activated synergistic therapeutics to fight against refractory biofilm infections.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123258"},"PeriodicalIF":12.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629049","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}

引用次数: 0

Bioactive polymers as stimulus-responsive anti-metastatic combination agents to treat pancreatic cancer

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-13 DOI: 10.1016/j.biomaterials.2025.123255

Sudipta Panja , Ekta Kapoor , Kasturi Siddhanta , Chinmay M. Jogdeo , Diptesh Sil , Rubayat I. Khan , Neha Kumari , Ling Ding , Howard E. Gendelman , Amar B. Singh , David Oupický

The intractable and devastating nature of pancreatic ductal adenocarcinoma (PDAC) necessitates an urgent need for novel therapies. This study presents the development of a novel polymer prodrug system for the combination treatment of PDAC, based on an optimized pharmacologically active anti-metastatic macromolecular carrier, PCQ, conjugated with gemcitabine (GEM). Structure-activity relationship evaluations showed that random PCQ copolymers exhibited superior anti-migratory activity compared to the gradient PCQ analogs. GEM was incorporated into the random PCQ copolymers using disulfide linker to prepare a reduction-responsive prodrug, PCQ(r)6-SS-GEM12. The resultant therapeutic system presents a pharmacologically active delivery strategy that targets both the proliferative and the metastatic phenotype in PDAC. The PCQ(r)6-SS-GEM12 prodrug demonstrated a selective release of GEM under the reductive tumor environment leading to a significant inhibition of tumor growth with pronounced anti-metastatic effect. Collectively, our data show that the combination of anti-metastatic PCQ and cytotoxic GEM-based reduction-responsive prodrug polymer offers an innovative strategy to treat PDAC.

{"title":"Bioactive polymers as stimulus-responsive anti-metastatic combination agents to treat pancreatic cancer","authors":"Sudipta Panja , Ekta Kapoor , Kasturi Siddhanta , Chinmay M. Jogdeo , Diptesh Sil , Rubayat I. Khan , Neha Kumari , Ling Ding , Howard E. Gendelman , Amar B. Singh , David Oupický","doi":"10.1016/j.biomaterials.2025.123255","DOIUrl":"10.1016/j.biomaterials.2025.123255","url":null,"abstract":"<div><div>The intractable and devastating nature of pancreatic ductal adenocarcinoma (PDAC) necessitates an urgent need for novel therapies. This study presents the development of a novel polymer prodrug system for the combination treatment of PDAC, based on an optimized pharmacologically active anti-metastatic macromolecular carrier, PCQ, conjugated with gemcitabine (GEM). Structure-activity relationship evaluations showed that random PCQ copolymers exhibited superior anti-migratory activity compared to the gradient PCQ analogs. GEM was incorporated into the random PCQ copolymers using disulfide linker to prepare a reduction-responsive prodrug, PCQ(r)6-SS-GEM12. The resultant therapeutic system presents a pharmacologically active delivery strategy that targets both the proliferative and the metastatic phenotype in PDAC. The PCQ(r)6-SS-GEM12 prodrug demonstrated a selective release of GEM under the reductive tumor environment leading to a significant inhibition of tumor growth with pronounced anti-metastatic effect. Collectively, our data show that the combination of anti-metastatic PCQ and cytotoxic GEM-based reduction-responsive prodrug polymer offers an innovative strategy to treat PDAC.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123255"},"PeriodicalIF":12.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642764","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}

引用次数: 0

Bioprinted high cell density liver model with improved hepatic metabolic functions 可改善肝脏代谢功能的生物打印高细胞密度肝脏模型

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-11 DOI: 10.1016/j.biomaterials.2025.123256

Ting-Yu Lu , Yichun Ji , Cheng Lyu , Erin Nicole Shen , Yazhi Sun , Yi Xiang , Tobias Meng-Saccoccio , Gen-Sheng Feng , Shaochen Chen

In vitro liver tissue models are valuable for studying liver function, understanding liver diseases, and screening candidate drugs for toxicity and efficacy. While three-dimensional (3D) bioprinting shows promise in creating various types of functional tissues, current efforts to engineer a functional liver tissue face challenges in replicating native high cell density (HCD) and maintaining long-term cell viability. HCD is crucial for establishing the cell-cell interactions necessary to mimic the liver's metabolic and detoxification functions. However, HCD bioinks exacerbate light scattering in light-based 3D bioprinting. In this study, we incorporated iodixanol into our bioink formulation to minimize light scattering, enabling the fabrication of hepatic tissue constructs with an HCD of 8 × 10⁷ cells/mL while maintaining high cell viability (∼80 %). The printed dense hepatic tissue constructs showed enhanced cell-cell interactions, as evidenced by increased expression of E-cadherin and ZO-1. Furthermore, these constructs promoted albumin secretion, urea production, and P450 metabolic activity. Additionally, HCD hepatic tissue inactivated the YAP/TAZ pathway via cell-cell interactions, preserving primary hepatocyte functions. Further screening revealed that hepatocytes in the dense model were more sensitive to drug treatments than those in a lower-density hepatic model, highlighting the importance of HCD in recapitulating the physiological drug responses. Overall, our approach represents a significant advancement in liver tissue engineering, providing a promising platform for the development of physiologically relevant in vitro liver models for drug screening and toxicity testing.

体外肝脏组织模型对于研究肝脏功能、了解肝脏疾病以及筛选候选药物的毒性和疗效非常有价值。虽然三维（3D）生物打印技术在创建各种类型的功能性组织方面大有可为，但目前在设计功能性肝脏组织方面面临着复制原生高细胞密度（HCD）和维持细胞长期存活率的挑战。高细胞密度对于建立模拟肝脏代谢和解毒功能所需的细胞间相互作用至关重要。然而，在基于光的三维生物打印中，HCD 生物墨水会加剧光散射。在本研究中，我们在生物墨水配方中加入了碘克沙醇，以最大限度地减少光散射，从而能够制造出 HCD 为 8 × 107 cells/mL 的肝组织构建体，同时保持较高的细胞存活率（∼80%）。打印出的致密肝组织构建体显示出更强的细胞间相互作用，E-cadherin 和 ZO-1 的表达增加就是证明。此外，这些构建体还促进了白蛋白分泌、尿素生成和 P450 代谢活动。此外，HCD 肝组织通过细胞间相互作用使 YAP/TAZ 通路失活，从而保留了原始肝细胞的功能。进一步筛选发现，高密度模型中的肝细胞比低密度肝脏模型中的肝细胞对药物治疗更敏感，这凸显了 HCD 在重现生理药物反应方面的重要性。总之，我们的方法代表了肝脏组织工程学的一大进步，为开发用于药物筛选和毒性测试的生理相关体外肝脏模型提供了一个前景广阔的平台。

{"title":"Bioprinted high cell density liver model with improved hepatic metabolic functions","authors":"Ting-Yu Lu , Yichun Ji , Cheng Lyu , Erin Nicole Shen , Yazhi Sun , Yi Xiang , Tobias Meng-Saccoccio , Gen-Sheng Feng , Shaochen Chen","doi":"10.1016/j.biomaterials.2025.123256","DOIUrl":"10.1016/j.biomaterials.2025.123256","url":null,"abstract":"<div><div><em>In vitro</em> liver tissue models are valuable for studying liver function, understanding liver diseases, and screening candidate drugs for toxicity and efficacy. While three-dimensional (3D) bioprinting shows promise in creating various types of functional tissues, current efforts to engineer a functional liver tissue face challenges in replicating native high cell density (HCD) and maintaining long-term cell viability. HCD is crucial for establishing the cell-cell interactions necessary to mimic the liver's metabolic and detoxification functions. However, HCD bioinks exacerbate light scattering in light-based 3D bioprinting. In this study, we incorporated iodixanol into our bioink formulation to minimize light scattering, enabling the fabrication of hepatic tissue constructs with an HCD of 8 × 10<sup>7</sup> cells/mL while maintaining high cell viability (∼80 %). The printed dense hepatic tissue constructs showed enhanced cell-cell interactions, as evidenced by increased expression of E-cadherin and ZO-1. Furthermore, these constructs promoted albumin secretion, urea production, and P450 metabolic activity. Additionally, HCD hepatic tissue inactivated the YAP/TAZ pathway via cell-cell interactions, preserving primary hepatocyte functions. Further screening revealed that hepatocytes in the dense model were more sensitive to drug treatments than those in a lower-density hepatic model, highlighting the importance of HCD in recapitulating the physiological drug responses. Overall, our approach represents a significant advancement in liver tissue engineering, providing a promising platform for the development of physiologically relevant <em>in vitro</em> liver models for drug screening and toxicity testing.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123256"},"PeriodicalIF":12.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637637","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}

引用次数: 0

Phase-adapted metal ion supply for spinal cord repair with a Mg–Zn incorporated chimeric microsphere

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-11 DOI: 10.1016/j.biomaterials.2025.123253

Xiangyu Liu , Biao Ma , Sihan Hu , Dandan Li , Chun Pan , Zhuobin Xu , Hao Chen , Yongxiang Wang , Huihui Wang

Dynamic alterations in metal ion concentrations are observed in the pathological process of spinal cord injury (SCI). Hence, strategically supplying metal ions in a phase-adapted manner is promising to facilitate injured spinal cord repair by preventing pathological damage. To achieve this, a chimeric hydrogel microsphere with Mg²⁺-crosslinked methacrylate gelatin as the "shell" and Zn²⁺-loaded poly (lactic-co-glycolic acid) (PLGA) as the "core" was designed. The chimeric microspheres allow continuous delivery of Mg²⁺ or Zn²⁺ at the exact required phase in SCI pathological process. Early release of Mg²⁺ reduced inflammation by diminishing the secretion of proinflammatory cytokines due to changes in macrophage polarization, which further suppressed scar formation to create an ideal space for neural regeneration. The subsequently released Zn²⁺ at the late phase effectively promoted neural cell proliferation and regeneration, which was accompanied by activation of mature neurons, interneurons, and motor neurons, leading to significant behavioral recovery. Thus, this study underscores the critical role of metal ions at different phases of injured spinal cord repair and describes the construction of an injectable chimeric hydrogel microsphere carrying distinct metal ions with a core-shell structure. Chimeric microspheres overcome the discrepancy between the inflammatory response and neural regeneration and are a promising therapeutic strategy for injured spinal cord repair.

{"title":"Phase-adapted metal ion supply for spinal cord repair with a Mg–Zn incorporated chimeric microsphere","authors":"Xiangyu Liu , Biao Ma , Sihan Hu , Dandan Li , Chun Pan , Zhuobin Xu , Hao Chen , Yongxiang Wang , Huihui Wang","doi":"10.1016/j.biomaterials.2025.123253","DOIUrl":"10.1016/j.biomaterials.2025.123253","url":null,"abstract":"<div><div>Dynamic alterations in metal ion concentrations are observed in the pathological process of spinal cord injury (SCI). Hence, strategically supplying metal ions in a phase-adapted manner is promising to facilitate injured spinal cord repair by preventing pathological damage. To achieve this, a chimeric hydrogel microsphere with Mg<sup>2+</sup>-crosslinked methacrylate gelatin as the \"shell\" and Zn<sup>2+</sup>-loaded poly (lactic-co-glycolic acid) (PLGA) as the \"core\" was designed. The chimeric microspheres allow continuous delivery of Mg<sup>2+</sup> or Zn<sup>2+</sup> at the exact required phase in SCI pathological process. Early release of Mg<sup>2+</sup> reduced inflammation by diminishing the secretion of proinflammatory cytokines due to changes in macrophage polarization, which further suppressed scar formation to create an ideal space for neural regeneration. The subsequently released Zn<sup>2+</sup> at the late phase effectively promoted neural cell proliferation and regeneration, which was accompanied by activation of mature neurons, interneurons, and motor neurons, leading to significant behavioral recovery. Thus, this study underscores the critical role of metal ions at different phases of injured spinal cord repair and describes the construction of an injectable chimeric hydrogel microsphere carrying distinct metal ions with a core-shell structure. Chimeric microspheres overcome the discrepancy between the inflammatory response and neural regeneration and are a promising therapeutic strategy for injured spinal cord repair.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123253"},"PeriodicalIF":12.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642765","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}

引用次数: 0

An injectable hydrogel loaded with miRNA nanocarriers promotes vessel-associated osteoclast (VAO)-mediated angiogenesis and bone regeneration in osteonecrosis of the rat femoral head

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-10 DOI: 10.1016/j.biomaterials.2025.123252

Hongyu Quan , Chencan Ren , Hongkun Xie , Zibo He , Haibin Ding , Jinbao Li , Taiyang Li , Fuyou Wang , Shiwu Dong , Hong Jiang

Osteonecrosis of the femoral head (ONFH) remains a significant clinical challenge. Despite various strategies aimed at promoting bone repair and halting disease progression, an effective cure remains elusive. Recent studies have identified a non-bone-resorbing osteoclast subtype, vessel-associated osteoclasts (VAOs), distinct from classical bone-associated osteoclasts (BAOs), offering new therapeutic opportunities for ONFH. Notably, we observed alterations in the populations and distributions of VAOs and BAOs in the femoral head of ONFH patients, suggesting that the imbalance between these two osteoclast subtypes contributes to ONFH pathology. Here, we developed an injectable alginate/hydroxyapatite hydrogel (AHH) loaded with graphene oxide-based miR-7b nanocarriers (GPC@miR) for ONFH treatment. The controlled release of GPC@miR from AHH/GPC@miR inhibited BAO formation by suppressing dendritic cell-specific transmembrane protein (DC-STAMP), thereby reducing bone resorption. Meanwhile, mono-/bi-nucleated VAOs were preserved and increased in number, promoting angiogenesis of type H vessels and osteogenesis via platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor-A (VEGF-A) secretion. Intraosseous administration of AHH/GPC@miR rebalanced VAOs and BAOs, restored the femoral head microenvironment, and enhanced vascularization and bone regeneration in ONFH rat models. This study introduces a novel biomaterial-based strategy for ONFH repair by regulating osteoclast subtypes, providing insights into VAO-mediated angiogenesis and osteogenesis for bone regeneration.

{"title":"An injectable hydrogel loaded with miRNA nanocarriers promotes vessel-associated osteoclast (VAO)-mediated angiogenesis and bone regeneration in osteonecrosis of the rat femoral head","authors":"Hongyu Quan , Chencan Ren , Hongkun Xie , Zibo He , Haibin Ding , Jinbao Li , Taiyang Li , Fuyou Wang , Shiwu Dong , Hong Jiang","doi":"10.1016/j.biomaterials.2025.123252","DOIUrl":"10.1016/j.biomaterials.2025.123252","url":null,"abstract":"<div><div>Osteonecrosis of the femoral head (ONFH) remains a significant clinical challenge. Despite various strategies aimed at promoting bone repair and halting disease progression, an effective cure remains elusive. Recent studies have identified a non-bone-resorbing osteoclast subtype, vessel-associated osteoclasts (VAOs), distinct from classical bone-associated osteoclasts (BAOs), offering new therapeutic opportunities for ONFH. Notably, we observed alterations in the populations and distributions of VAOs and BAOs in the femoral head of ONFH patients, suggesting that the imbalance between these two osteoclast subtypes contributes to ONFH pathology. Here, we developed an injectable alginate/hydroxyapatite hydrogel (AHH) loaded with graphene oxide-based miR-7b nanocarriers (GPC@miR) for ONFH treatment. The controlled release of GPC@miR from AHH/GPC@miR inhibited BAO formation by suppressing dendritic cell-specific transmembrane protein (DC-STAMP), thereby reducing bone resorption. Meanwhile, mono-/bi-nucleated VAOs were preserved and increased in number, promoting angiogenesis of type H vessels and osteogenesis via platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor-A (VEGF-A) secretion. Intraosseous administration of AHH/GPC@miR rebalanced VAOs and BAOs, restored the femoral head microenvironment, and enhanced vascularization and bone regeneration in ONFH rat models. This study introduces a novel biomaterial-based strategy for ONFH repair by regulating osteoclast subtypes, providing insights into VAO-mediated angiogenesis and osteogenesis for bone regeneration.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123252"},"PeriodicalIF":12.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610273","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}

引用次数: 0

Acid and phosphatase-triggered release and trapping of a prodrug on cancer cell enhance its chemotherapy

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-10 DOI: 10.1016/j.biomaterials.2025.123254

Liangxi Zhu , Zixiu Shen , Xiaoyang Liu , Runqun Tang , Ziyi Zhang , Furong Zhao , Jue Wang , Wenjun Zhan , Lei Zhou , Gaolin Liang , Rui Wang

Using anticancer drug-encapsulated nanocarriers to actively target tumors is a promising chemotherapy strategy. Nevertheless, premature release of the drugs in tumor microenvironment (TME) or low tumor targeting efficiency of the nanocarriers significantly reduces its therapeutic efficiency. Herein, we propose a release-and-trapping strategy that significantly enhances the chemotherapeutic efficiency of an anticancer drug camptothecin. TME acid triggers the release of its prodrug from the nanocarrier and thereafter phosphatase instructs the prodrug to form hydrogel to trap the nanocarrier on cancer cell membrane. As trapped nanocarrier facilitates cell uptake of the prodrug and its intracellular carboxylesterase-mediated hydrolysis to release camptothecin. In vitro studies showed that the prodrug release from nanocarrier was maximized at pH 6.5. In tumor-bearing mice, our release-and-trapping strategy significantly prolonged the retention of the nanocarrier in tumor and significantly enhanced the anticancer efficacy of camptothecin. We propose that our release-and-trapping strategy be applied for more efficient cancer treatment in the future.

{"title":"Acid and phosphatase-triggered release and trapping of a prodrug on cancer cell enhance its chemotherapy","authors":"Liangxi Zhu , Zixiu Shen , Xiaoyang Liu , Runqun Tang , Ziyi Zhang , Furong Zhao , Jue Wang , Wenjun Zhan , Lei Zhou , Gaolin Liang , Rui Wang","doi":"10.1016/j.biomaterials.2025.123254","DOIUrl":"10.1016/j.biomaterials.2025.123254","url":null,"abstract":"<div><div>Using anticancer drug-encapsulated nanocarriers to actively target tumors is a promising chemotherapy strategy. Nevertheless, premature release of the drugs in tumor microenvironment (TME) or low tumor targeting efficiency of the nanocarriers significantly reduces its therapeutic efficiency. Herein, we propose a release-and-trapping strategy that significantly enhances the chemotherapeutic efficiency of an anticancer drug camptothecin. TME acid triggers the release of its prodrug from the nanocarrier and thereafter phosphatase instructs the prodrug to form hydrogel to trap the nanocarrier on cancer cell membrane. As trapped nanocarrier facilitates cell uptake of the prodrug and its intracellular carboxylesterase-mediated hydrolysis to release camptothecin. In vitro studies showed that the prodrug release from nanocarrier was maximized at pH 6.5. In tumor-bearing mice, our release-and-trapping strategy significantly prolonged the retention of the nanocarrier in tumor and significantly enhanced the anticancer efficacy of camptothecin. We propose that our release-and-trapping strategy be applied for more efficient cancer treatment in the future.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123254"},"PeriodicalIF":12.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620482","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}

引用次数: 0

SDF-1α/BMP-12 loaded biphasic sustained-release SIS hydrogel/SA microspheres composite for tendon regeneration

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-08 DOI: 10.1016/j.biomaterials.2025.123246

Bo-Quan Qin , Shi-Zhou Wu , Rong Nie , Qing-Yi Zhang , Jie Tan , Hui Zhang , Hui-Qi Xie

Due to the inherent limited regenerative capacity of tendons, rendering countermeasures for tendon injury remains challenging. The pathophysiology of tendon healing is complex and contains three sequential phases including inflammation, proliferation and remodeling. Aiming at the treatment of different stages of tendon injury, in our work, an injectable small intestinal submucosa hydrogel/sodium alginate microspheres (SIS/SA) composite co-encapsulating stromal cell derived factor-1α (SDF-1α) and bone morphogenetic protein-12 (BMP-12) was developed for effective tendon regeneration. BMP-12 was initially embedded into SA microspheres by microfluid method, and then, microspheres were subsequently encapsulated into the SDF-1α loaded SIS hydrogel. The two bioactive molecules were released in a biphasic and controlled manner to facilitate cell recruitment in the early stage and tendon differentiation in the long-time stage, respectively. Meanwhile, with the degradation of hydrogel/microspheres composite, the regeneration process was accelerated through multiple pathways encompassing immune regulation, angiogenesis, and extracellular matrix (ECM) synthesis. The findings of this study present a compelling translational strategy with significant clinical potential for advancing tendon regeneration therapies.

{"title":"SDF-1α/BMP-12 loaded biphasic sustained-release SIS hydrogel/SA microspheres composite for tendon regeneration","authors":"Bo-Quan Qin , Shi-Zhou Wu , Rong Nie , Qing-Yi Zhang , Jie Tan , Hui Zhang , Hui-Qi Xie","doi":"10.1016/j.biomaterials.2025.123246","DOIUrl":"10.1016/j.biomaterials.2025.123246","url":null,"abstract":"<div><div>Due to the inherent limited regenerative capacity of tendons, rendering countermeasures for tendon injury remains challenging. The pathophysiology of tendon healing is complex and contains three sequential phases including inflammation, proliferation and remodeling. Aiming at the treatment of different stages of tendon injury, in our work, an injectable small intestinal submucosa hydrogel/sodium alginate microspheres (SIS/SA) composite co-encapsulating stromal cell derived factor-1α (SDF-1α) and bone morphogenetic protein-12 (BMP-12) was developed for effective tendon regeneration. BMP-12 was initially embedded into SA microspheres by microfluid method, and then, microspheres were subsequently encapsulated into the SDF-1α loaded SIS hydrogel. The two bioactive molecules were released in a biphasic and controlled manner to facilitate cell recruitment in the early stage and tendon differentiation in the long-time stage, respectively. Meanwhile, with the degradation of hydrogel/microspheres composite, the regeneration process was accelerated through multiple pathways encompassing immune regulation, angiogenesis, and extracellular matrix (ECM) synthesis. The findings of this study present a compelling translational strategy with significant clinical potential for advancing tendon regeneration therapies.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123246"},"PeriodicalIF":12.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143591522","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}

引用次数: 0

Ultrasound-triggered lysosomal alkalinization to block autophagy in tumor therapy

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-03-08 DOI: 10.1016/j.biomaterials.2025.123250

Yong Liu , Bowen Li , Run Yang , Chenxu Shang , Yang Bai , Bin Zheng , Liang Zhao

Lysosomes play a crucial role in regulating cancer progression and drug resistance. However, there is a pressing need for the development of drugs that can safely and effectively modulate the pH of cancerous lysosomes in a controlled manner. In this study, we propose a novel strategy for lysosomal alkalinization triggered by piezoelectricity. Our findings indicate that the electrons generated by (BaTiO₃/Zr/Ca) BCZT under sonication effectively alkalinize the lysosomes. Molecular dynamics simulations further demonstrate that alterations in lysosomal pH lead to modifications in the conformation of V-ATPase (proton pump), enhancing its interaction with sodium ions while partially excluding hydrogen ions from entering the lysosomes. This mechanism helps maintain lysosomal alkalization, resulting in reduced hydrolase activity and preventing the degradation of proteins and damaged organelles. The accumulation of nanoparticles within the lysosomes causes swelling and gradual destruction of the lysosomal membrane. Consequently, this lysosomal dysfunction hampers the fusion with autophagosomes, inhibiting autophagy in tumor cells and promoting apoptosis in various tumor types. Our strategy significantly inhibited tumor volume growth in mice during animal studies. In conclusion, our piezoelectric-triggered lysosomal alkalinization strategy holds promise for innovative breakthroughs in the treatment of multiple cancers.

{"title":"Ultrasound-triggered lysosomal alkalinization to block autophagy in tumor therapy","authors":"Yong Liu , Bowen Li , Run Yang , Chenxu Shang , Yang Bai , Bin Zheng , Liang Zhao","doi":"10.1016/j.biomaterials.2025.123250","DOIUrl":"10.1016/j.biomaterials.2025.123250","url":null,"abstract":"<div><div>Lysosomes play a crucial role in regulating cancer progression and drug resistance. However, there is a pressing need for the development of drugs that can safely and effectively modulate the pH of cancerous lysosomes in a controlled manner. In this study, we propose a novel strategy for lysosomal alkalinization triggered by piezoelectricity. Our findings indicate that the electrons generated by (BaTiO<sub>3</sub>/Zr/Ca) BCZT under sonication effectively alkalinize the lysosomes. Molecular dynamics simulations further demonstrate that alterations in lysosomal pH lead to modifications in the conformation of V-ATPase (proton pump), enhancing its interaction with sodium ions while partially excluding hydrogen ions from entering the lysosomes. This mechanism helps maintain lysosomal alkalization, resulting in reduced hydrolase activity and preventing the degradation of proteins and damaged organelles. The accumulation of nanoparticles within the lysosomes causes swelling and gradual destruction of the lysosomal membrane. Consequently, this lysosomal dysfunction hampers the fusion with autophagosomes, inhibiting autophagy in tumor cells and promoting apoptosis in various tumor types. Our strategy significantly inhibited tumor volume growth in mice during animal studies. In conclusion, our piezoelectric-triggered lysosomal alkalinization strategy holds promise for innovative breakthroughs in the treatment of multiple cancers.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"320 ","pages":"Article 123250"},"PeriodicalIF":12.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600509","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}

引用次数: 0