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Porcine plasma protein cold-set hydrogel crosslinked by genipin and the immunomodulatory, proliferation promoting and scar-remodeling in wound healing
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-28 DOI: 10.1016/j.bioadv.2025.214216
Hanluo Li , Meiling Wu , Zhuanzhuan Ma , Xue Wang , Junwei Fan , Kanghong Hu , Yanhong Wei , Chenguang Yao , Jinbiao Liu , Sini Kang , Xu Kang , Jianglan Yuan
Addressing the critical need for biocompatible and multifunctional wound dressings for chronic and non-healing wounds, cold-set hydrogel using natural biomacromolecules are potential candidates. This study developed a novel cold-set hydrogel of porcine plasma protein (PPP) through genipin (GP) as crosslinker and glucono delta-lactone (GDL) as acidifier. GP promoted hardness, springiness, water holding capacity (WHC) and modulus in a dose-dependent manner in the presence of GDL, and significantly enhanced microstructural density, integrity and anti-degradation, critical as wound dressing, achieving the optimal performance at 0.15 % GP and 0.2 % GDL. Subsequently, biocompatibility assessments revealed that the optimum PPP gel was low cytotoxicity and could support cell migration and proliferation, reduce apoptosis with dose-effect relationship of the filler PPP. Meanwhile, in vivo skin wound healing model indicated the efficacy in accelerating wound healing, reducing inflammation, and promoting tissue remodeling without excessive scar formation. These effects are attributed to the ability of PPP in the hydrogel to modulate local inflammatory responses, enhance angiogenesis, and balance extracellular matrix remodeling processes. In conclusion, this pioneering work establishes PPP cold-set hydrogels as promising candidates for advanced wound care solutions, combining the benefits of natural protein-based biomaterials with innovative crosslinking strategies to meet urgent clinical needs in regenerative medicine.
{"title":"Porcine plasma protein cold-set hydrogel crosslinked by genipin and the immunomodulatory, proliferation promoting and scar-remodeling in wound healing","authors":"Hanluo Li ,&nbsp;Meiling Wu ,&nbsp;Zhuanzhuan Ma ,&nbsp;Xue Wang ,&nbsp;Junwei Fan ,&nbsp;Kanghong Hu ,&nbsp;Yanhong Wei ,&nbsp;Chenguang Yao ,&nbsp;Jinbiao Liu ,&nbsp;Sini Kang ,&nbsp;Xu Kang ,&nbsp;Jianglan Yuan","doi":"10.1016/j.bioadv.2025.214216","DOIUrl":"10.1016/j.bioadv.2025.214216","url":null,"abstract":"<div><div>Addressing the critical need for biocompatible and multifunctional wound dressings for chronic and non-healing wounds, cold-set hydrogel using natural biomacromolecules are potential candidates. This study developed a novel cold-set hydrogel of porcine plasma protein (PPP) through genipin (GP) as crosslinker and glucono delta-lactone (GDL) as acidifier. GP promoted hardness, springiness, water holding capacity (WHC) and modulus in a dose-dependent manner in the presence of GDL, and significantly enhanced microstructural density, integrity and anti-degradation, critical as wound dressing, achieving the optimal performance at 0.15 % GP and 0.2 % GDL. Subsequently, biocompatibility assessments revealed that the optimum PPP gel was low cytotoxicity and could support cell migration and proliferation, reduce apoptosis with dose-effect relationship of the filler PPP. Meanwhile, <em>in vivo</em> skin wound healing model indicated the efficacy in accelerating wound healing, reducing inflammation, and promoting tissue remodeling without excessive scar formation. These effects are attributed to the ability of PPP in the hydrogel to modulate local inflammatory responses, enhance angiogenesis, and balance extracellular matrix remodeling processes. In conclusion, this pioneering work establishes PPP cold-set hydrogels as promising candidates for advanced wound care solutions, combining the benefits of natural protein-based biomaterials with innovative crosslinking strategies to meet urgent clinical needs in regenerative medicine.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"170 ","pages":"Article 214216"},"PeriodicalIF":5.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Eumelanin pigment release from photo-crosslinkable methacrylated gelatin-based cryogels: Exploring the physicochemical properties and antioxidant efficacy in wound healing
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-28 DOI: 10.1016/j.bioadv.2025.214214
Ugo D'Amora , Stefania Scialla , Ines Fasolino , Alfredo Ronca , Alessandra Soriente , Noemi De Cesare , Paola Manini , Jun Wei Phua , Alessandro Pezzella , Maria Grazia Raucci , Luigi Ambrosio
Managing wounds in certain phases of the healing process still represents a big challenge. The oxidative stress, caused by reactive oxygen species (ROS), is one of the hallmarks controlling the wound healing-related process. Multifunctional biomaterials with excellent biocompatibility, tuneable properties, and easy functionalization, may allow realizing suitable three-dimensional (3D) and extracellular matrix (ECM)-mimicking structures, to efficiently control ROS levels. This might be a promising strategy for healing severe wounds. Herein, photo-crosslinkable methacrylated gelatin (GelMA)-based spongy-like cryogels (from 5 to 20 % w/v) incorporating Eumelanin from Black Soldier Flies (BSF-Eumel, 0.5 and 1.0 mg/mL), a pigment endowed with marked antioxidant properties, were developed. GelMA-based cryogels were fabricated by an easily handled and scalable cryogelation process followed by ultraviolet (UV) photo-crosslinking. BSF-Eumel sub-micrometer particles were embedded into GelMA-based cryogels by passive permeation of the solution within the polymeric network. BSF-Eumel addition resulted in more hydrophilic and porous structures, exhibiting a good stability and a prolonged release within 14 days. Furthermore, GelMA/BSF-Eumel cryogels exhibited good antioxidant activity, confirmed by a powerful quenching effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (59 % at 1.0 mg/mL of BSF-Eumel). Moreover, GelMA/BSF-Eumel cryogels at the highest GelMA concentrations (10 and 20 % w/v) accelerated human dermal fibroblasts-adult (HDF-a) migration, promoting wound closure within 24 h. They also proved to mitigate oxidative stress, modulating the production of ROS levels and preventing superoxide dismutase (SOD) activity inhibition in HDFs stimulated by lipopolysaccharide (LPS), owing to the release of BSF-Eumel. Such remarkable outcomes make GelMA/BSF-Eumel cryogels a promising antioxidant platform for wound healing.
{"title":"Eumelanin pigment release from photo-crosslinkable methacrylated gelatin-based cryogels: Exploring the physicochemical properties and antioxidant efficacy in wound healing","authors":"Ugo D'Amora ,&nbsp;Stefania Scialla ,&nbsp;Ines Fasolino ,&nbsp;Alfredo Ronca ,&nbsp;Alessandra Soriente ,&nbsp;Noemi De Cesare ,&nbsp;Paola Manini ,&nbsp;Jun Wei Phua ,&nbsp;Alessandro Pezzella ,&nbsp;Maria Grazia Raucci ,&nbsp;Luigi Ambrosio","doi":"10.1016/j.bioadv.2025.214214","DOIUrl":"10.1016/j.bioadv.2025.214214","url":null,"abstract":"<div><div>Managing wounds in certain phases of the healing process still represents a big challenge. The oxidative stress, caused by reactive oxygen species (ROS), is one of the hallmarks controlling the wound healing-related process. Multifunctional biomaterials with excellent biocompatibility, tuneable properties, and easy functionalization, may allow realizing suitable three-dimensional (3D) and extracellular matrix (ECM)-mimicking structures, to efficiently control ROS levels. This might be a promising strategy for healing severe wounds. Herein, photo-crosslinkable methacrylated gelatin (GelMA)-based spongy-like cryogels (from 5 to 20 % <em>w</em>/<em>v</em>) incorporating Eumelanin from Black Soldier Flies (BSF-Eumel, 0.5 and 1.0 mg/mL), a pigment endowed with marked antioxidant properties, were developed. GelMA-based cryogels were fabricated by an easily handled and scalable cryogelation process followed by ultraviolet (UV) photo-crosslinking. BSF-Eumel sub-micrometer particles were embedded into GelMA-based cryogels by passive permeation of the solution within the polymeric network. BSF-Eumel addition resulted in more hydrophilic and porous structures, exhibiting a good stability and a prolonged release within 14 days. Furthermore, GelMA/BSF-Eumel cryogels exhibited good antioxidant activity, confirmed by a powerful quenching effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (59 % at 1.0 mg/mL of BSF-Eumel). Moreover, GelMA/BSF-Eumel cryogels at the highest GelMA concentrations (10 and 20 % <em>w</em>/<em>v</em>) accelerated human dermal fibroblasts-adult (HDF-a) migration, promoting wound closure within 24 h. They also proved to mitigate oxidative stress, modulating the production of ROS levels and preventing superoxide dismutase (SOD) activity inhibition in HDFs stimulated by lipopolysaccharide (LPS), owing to the release of BSF-Eumel. Such remarkable outcomes make GelMA/BSF-Eumel cryogels a promising antioxidant platform for wound healing.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"170 ","pages":"Article 214214"},"PeriodicalIF":5.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Construction and biocompatibility of penetrating corneal transplant substitute with cross-linked acellular porcine cornea and biopolymer polyurethane
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-27 DOI: 10.1016/j.bioadv.2025.214201
Qing Li , Fan Zhang , Haibin Zhao
In this study, acellular porcine cornea (APC) was composited with biopolymer polyurethane (PU), in which Polyethylene glycol (PEG) served as porogen, to fabricate a breathable and impermeable barrier and maintain the transparency of APC. To improve the effect of decellularization on the collagen fibrolamella of the APC, structural regularity and stability as well as postoperative corneal edema and melting, crosslinking was taken as an effective way to improve the mechanical properties and anti-enzymatic hydrolysis of APC. Chemical cross-linking in different agents, crosslink concentrations, and reaction times were conducted. The transparency, elastic modulus, oxygen permeability, crosslinking degree, and expansion thickness were examined. Furthermore, the immunogenicity, cytocompatibility, and histocompatibility of the cross-linked APC-PU composite under the optimal crosslinking parameters (GP-0.2 %-3.0, EDC-1.0 %-1.0, GD-0.8 %-0.3) were analyzed. The results showed that the GD-0.8 %-0.3 samples demonstrated cytotoxicity and significant neovascularization during subcutaneous experiments. Moreover, a proliferation membrane was formed on the PU surface in the orthotopic transplantation, suggesting immune rejection. The GP-0.2 %-3.0 group exhibited pronounced edema and delamination in the 4th week, indicating inadequate permeability and incomplete fiber cross-linking. However, the EDC-1.0 %-1.0 group promoted cell adhesion and proliferation, while maintaining graft integrity without degradation upon subcutaneous implantation. No corneal swelling or degradation was observed within 4 weeks post-transplantation. Cross-linking of EDC/NHS is an effective method for fabricating the ideal and functional APC-PU composite for penetrating keratoplasty.
{"title":"Construction and biocompatibility of penetrating corneal transplant substitute with cross-linked acellular porcine cornea and biopolymer polyurethane","authors":"Qing Li ,&nbsp;Fan Zhang ,&nbsp;Haibin Zhao","doi":"10.1016/j.bioadv.2025.214201","DOIUrl":"10.1016/j.bioadv.2025.214201","url":null,"abstract":"<div><div>In this study, acellular porcine cornea (APC) was composited with biopolymer polyurethane (PU), in which Polyethylene glycol (PEG) served as porogen, to fabricate a breathable and impermeable barrier and maintain the transparency of APC. To improve the effect of decellularization on the collagen fibrolamella of the APC, structural regularity and stability as well as postoperative corneal edema and melting, crosslinking was taken as an effective way to improve the mechanical properties and anti-enzymatic hydrolysis of APC. Chemical cross-linking in different agents, crosslink concentrations, and reaction times were conducted. The transparency, elastic modulus, oxygen permeability, crosslinking degree, and expansion thickness were examined. Furthermore, the immunogenicity, cytocompatibility, and histocompatibility of the cross-linked APC-PU composite under the optimal crosslinking parameters (GP-0.2 %-3.0, EDC-1.0 %-1.0, GD-0.8 %-0.3) were analyzed. The results showed that the GD-0.8 %-0.3 samples demonstrated cytotoxicity and significant neovascularization during subcutaneous experiments. Moreover, a proliferation membrane was formed on the PU surface in the orthotopic transplantation, suggesting immune rejection. The GP-0.2 %-3.0 group exhibited pronounced edema and delamination in the 4th week, indicating inadequate permeability and incomplete fiber cross-linking. However, the EDC-1.0 %-1.0 group promoted cell adhesion and proliferation, while maintaining graft integrity without degradation upon subcutaneous implantation. No corneal swelling or degradation was observed within 4 weeks post-transplantation. Cross-linking of EDC/NHS is an effective method for fabricating the ideal and functional APC-PU composite for penetrating keratoplasty.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"170 ","pages":"Article 214201"},"PeriodicalIF":5.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Immunomodulatory and bone regenerative properties of copper/procyanidins-modified titanium surfaces
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-23 DOI: 10.1016/j.bioadv.2025.214199
Rongxin Wan , Wenbo Li , Kuo Yang , Lijun Li , Shaojing Wang , Li Lei , Huiqin Tang , Hanqing Gu
The inflammatory response triggered by the interaction between implants and macrophages is essential for bone regeneration around these implants. This study presents the application of dopamine hydrochloride to develop a copper and procyanidins coating on titanium surfaces to investigate its effects on bacterial inhibition, macrophage polarization, and osteogenic differentiation. The results demonstrated that this copper/procyanidins coating significantly suppressed the growth of Escherichia coli and Staphylococcus aureus. Notably, the initial release of Cu2+ ions promoted macrophage polarization toward a pro-inflammatory phenotype while stimulating the secretion of anti-inflammatory factors. Subsequently, the reduced Cu2+ release combined with procyanidins facilitated the transition from M1 to M2 macrophages—an essential process for bacterial phagocytosis and bone regeneration. Furthermore, this coating enhanced the secretion of osteogenic factors by bone marrow mesenchymal stem cells, enhancing their osteogenic differentiation and integration with bone tissue. These findings highlight the potential of copper/procyanidins coating in developing implant surfaces with immune-modulating and sustained antibacterial properties.
{"title":"Immunomodulatory and bone regenerative properties of copper/procyanidins-modified titanium surfaces","authors":"Rongxin Wan ,&nbsp;Wenbo Li ,&nbsp;Kuo Yang ,&nbsp;Lijun Li ,&nbsp;Shaojing Wang ,&nbsp;Li Lei ,&nbsp;Huiqin Tang ,&nbsp;Hanqing Gu","doi":"10.1016/j.bioadv.2025.214199","DOIUrl":"10.1016/j.bioadv.2025.214199","url":null,"abstract":"<div><div>The inflammatory response triggered by the interaction between implants and macrophages is essential for bone regeneration around these implants. This study presents the application of dopamine hydrochloride to develop a copper and procyanidins coating on titanium surfaces to investigate its effects on bacterial inhibition, macrophage polarization, and osteogenic differentiation. The results demonstrated that this copper/procyanidins coating significantly suppressed the growth of <em>Escherichia coli</em> and <em>Staphylococcus aureus</em>. Notably, the initial release of Cu<sup>2+</sup> ions promoted macrophage polarization toward a pro-inflammatory phenotype while stimulating the secretion of anti-inflammatory factors. Subsequently, the reduced Cu<sup>2+</sup> release combined with procyanidins facilitated the transition from M1 to M2 macrophages—an essential process for bacterial phagocytosis and bone regeneration. Furthermore, this coating enhanced the secretion of osteogenic factors by bone marrow mesenchymal stem cells, enhancing their osteogenic differentiation and integration with bone tissue. These findings highlight the potential of copper/procyanidins coating in developing implant surfaces with immune-modulating and sustained antibacterial properties.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"169 ","pages":"Article 214199"},"PeriodicalIF":5.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Mechanically robust, mouldable, dynamically crosslinked hydrogel flap with multiple functionalities for accelerated deep skin wound healing
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-20 DOI: 10.1016/j.bioadv.2025.214195
Hitasha Vithalani , Harshil Dave , Hemant Singh , Dinesh Sharma , Archana Navale , Mukesh Dhanka
Deep cutaneous wounds, which are difficult to heal and specifically occur on dynamic body surfaces, remain a substantial healthcare challenge in clinical practice because of multiple underlying factors, including excessive reactive oxygen species, potential bacterial infection, and extensive degradation of the extracellular matrix (ECM) which further leads to the progressive deterioration of the wound microenvironment. Any available individual wound therapy, such as antibiotic-loaded cotton gauze, cannot address all these issues. Engineering an advanced multifunctional wound dressing is the current need to promote the overall healing process of such wounds. Here, we report a multifunctional hydrogel flap primarily composed of biodegradable polymers gelatin (G) and poly-methyl vinyl ether-alt-maleic acid (MA) as the base material. The hydrogel physically incorporates tannic acid (TA) and vancomycin (V), for added functionality. The resulting hydrogel flap, gelatin- poly-methyl vinyl ether-alt-maleic acid-tannic acid-vancomycin (G-MA-TA-V/E-N), is formed through a chemical crosslinking process using EDC (E) and NHS (N). Thus, the hydrogel flap reveals multiple ideal properties that support its ease of application, including stretchability, porous microstructure (honey-comb structure), mouldability, and adhesiveness to multiple surfaces, including wet biological surfaces. The in vitro studies demonstrated strong antioxidant, antibacterial, and absorption properties essential for accelerated wound-healing applications. In vivo studies further reveal accelerated wound contraction and enhanced healing kinetics, promoting re-epithelialization, angiogenesis, and formation of apocrine glands. These findings underscore the efficacy and cost-effectiveness of fabricated hydrogel flaps as viable therapeutic options for treating deep skin wounds and make it worthwhile to integrate them with medical devices for tissue adhesion.
{"title":"Mechanically robust, mouldable, dynamically crosslinked hydrogel flap with multiple functionalities for accelerated deep skin wound healing","authors":"Hitasha Vithalani ,&nbsp;Harshil Dave ,&nbsp;Hemant Singh ,&nbsp;Dinesh Sharma ,&nbsp;Archana Navale ,&nbsp;Mukesh Dhanka","doi":"10.1016/j.bioadv.2025.214195","DOIUrl":"10.1016/j.bioadv.2025.214195","url":null,"abstract":"<div><div>Deep cutaneous wounds, which are difficult to heal and specifically occur on dynamic body surfaces, remain a substantial healthcare challenge in clinical practice because of multiple underlying factors, including excessive reactive oxygen species, potential bacterial infection, and extensive degradation of the extracellular matrix (ECM) which further leads to the progressive deterioration of the wound microenvironment. Any available individual wound therapy, such as antibiotic-loaded cotton gauze, cannot address all these issues. Engineering an advanced multifunctional wound dressing is the current need to promote the overall healing process of such wounds. Here, we report a multifunctional hydrogel flap primarily composed of biodegradable polymers gelatin (G) and poly-methyl vinyl ether-<em>alt</em>-maleic acid (MA) as the base material. The hydrogel physically incorporates tannic acid (TA) and vancomycin (V), for added functionality. The resulting hydrogel flap, gelatin- poly-methyl vinyl ether-<em>alt</em>-maleic acid-tannic acid-vancomycin (G-MA-TA-V/E-N), is formed through a chemical crosslinking process using EDC (E) and NHS (N). Thus, the hydrogel flap reveals multiple ideal properties that support its ease of application, including stretchability, porous microstructure (honey-comb structure), mouldability, and adhesiveness to multiple surfaces, including wet biological surfaces. The <em>in vitro</em> studies demonstrated strong antioxidant, antibacterial, and absorption properties essential for accelerated wound-healing applications. <em>In vivo</em> studies further reveal accelerated wound contraction and enhanced healing kinetics, promoting re-epithelialization, angiogenesis, and formation of apocrine glands. These findings underscore the efficacy and cost-effectiveness of fabricated hydrogel flaps as viable therapeutic options for treating deep skin wounds and make it worthwhile to integrate them with medical devices for tissue adhesion.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"169 ","pages":"Article 214195"},"PeriodicalIF":5.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Enhanced cellular viability and osteogenic activity in oxygen-self-generating and magnetically responsive alginate microgels as advanced cell carriers
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-20 DOI: 10.1016/j.bioadv.2025.214198
Yifan Zhang , Min Fang , Lanqin Yu , Xinshuo Liu , Jizhuang Wang , Na Li , Lihua Li , Changren Zhou
Improving the accuracy of in vitro three-dimensional (3D) cellular cultures more closely replicates the in vivo microenvironment by mimicking the complex tissue structures, enhancing cell-cell interactions, and increasing differentiation potential along with functional capabilities. Natural materials aid in cell adhesion and proliferation within the 3D matrix, providing a more realistic growth environment. Oxygen availability is also critical for cell survival in 3D cultures, as a lack of oxygen can impede proliferation, reduce functionality, and ultimately result in cell death. To address the issue of oxygen supply in such systems, a novel magnetic alginate-based microcarrier that generates oxygen autonomously has been developed. This microcarrier contains calcium peroxide encapsulated within polylactic acid microspheres (CP), which act as an internal oxygen reservoir. The release of calcium ions results in weak interactions with alginate, thus improving structural integrity while also supporting bone marrow stromal cells (BMSCs) and creating a more in vivo-like microenvironment. Notably, when exposed to an external magnetic field, BMSCs on these CP/Fe3O4/SA microcarriers show improved viability, a marked decrease in hypoxia-inducible factor-1α (HIF-1α), and increased osteogenic gene expression. Therefore, the CP/Fe3O4/SA microcarriers represent a promising approach for enhancing in vitro 3D culture methods and offer significant potential for tissue repair and regeneration.
{"title":"Enhanced cellular viability and osteogenic activity in oxygen-self-generating and magnetically responsive alginate microgels as advanced cell carriers","authors":"Yifan Zhang ,&nbsp;Min Fang ,&nbsp;Lanqin Yu ,&nbsp;Xinshuo Liu ,&nbsp;Jizhuang Wang ,&nbsp;Na Li ,&nbsp;Lihua Li ,&nbsp;Changren Zhou","doi":"10.1016/j.bioadv.2025.214198","DOIUrl":"10.1016/j.bioadv.2025.214198","url":null,"abstract":"<div><div>Improving the accuracy of <em>in vitro</em> three-dimensional (3D) cellular cultures more closely replicates the <em>in vivo</em> microenvironment by mimicking the complex tissue structures, enhancing cell-cell interactions, and increasing differentiation potential along with functional capabilities. Natural materials aid in cell adhesion and proliferation within the 3D matrix, providing a more realistic growth environment. Oxygen availability is also critical for cell survival in 3D cultures, as a lack of oxygen can impede proliferation, reduce functionality, and ultimately result in cell death. To address the issue of oxygen supply in such systems, a novel magnetic alginate-based microcarrier that generates oxygen autonomously has been developed. This microcarrier contains calcium peroxide encapsulated within polylactic acid microspheres (CP), which act as an internal oxygen reservoir. The release of calcium ions results in weak interactions with alginate, thus improving structural integrity while also supporting bone marrow stromal cells (BMSCs) and creating a more <em>in vivo</em>-like microenvironment. Notably, when exposed to an external magnetic field, BMSCs on these CP/Fe<sub>3</sub>O<sub>4</sub>/SA microcarriers show improved viability, a marked decrease in hypoxia-inducible factor-1α (HIF-1α), and increased osteogenic gene expression. Therefore, the CP/Fe<sub>3</sub>O<sub>4</sub>/SA microcarriers represent a promising approach for enhancing <em>in vitro</em> 3D culture methods and offer significant potential for tissue repair and regeneration.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"170 ","pages":"Article 214198"},"PeriodicalIF":5.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Electrically conductive and photocurable MXene-modulated hydrogel conduits for peripheral nerve regeneration: In vitro and in vivo studies
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-20 DOI: 10.1016/j.bioadv.2025.214197
Roya Lotfi , Banafsheh Dolatyar , Nooshin Zandi , Elnaz Tamjid , Ali Pourjavadi , Abdolreza Simchi
Electroconductive biomaterials, as advanced nerve guidance conduits (NGCs), have shown great promise to accelerate the rate of peripheral nerve repair and regeneration (PNR) but remain among the greatest challenges in regenerative medicine because of frail recovery. Herein, we introduce injectable nanocomposite nerve conduits based on gelatin methacrylate (GelMa) and MXene nanosheets (MX) for PNR. Microstructural studies determine that the addition of MX increases the mean pore size of GelMa NH from 5.8 ± 1.2 μm to 8.4 ± 1.6 μm for the hydrogel containing 0.25 mg/mL MX, for example, leading to higher swelling and degradation rates. The highest electrical conductivity (∼910 μS/cm) is attained for the GelMa-based nanocomposite composed MX with the concentration of 0.125 mg/mL, for the reason that at higher concentrations, agglomeration of the MXs happens. In vitro investigations, including metabolic activity and live-dead assessments by PC12 cells, reveal the biocompatibility of developed nanocomposite hydrogels (NHs) containing different concentrations of MX nanosheets in the range of 0.025–0.25 mg/mL. Implantation of GelMa-MX conduits in a rat model of peripheral nerve injury (PNI) leads to the impressive recovery of the injured sciatic nerve's sensory, motor, and sensory-motor function. Electrophysiological analysis also indicates a significant increase in compound muscle action potential and nerve conduction velocity with a decrease in terminal latency in animals implanted with GelMa-MX conduits compared to control groups (animals implanted with GelMa and animals without implantation). Moreover, histological analysis exhibits a notable absence of fibrous connective tissue in the regenerated nerve fibers with a substantial increase in more organized myelinated axons. Our results demonstrate that GelMa-MX conduits promote regeneration of the injured sciatic nerve and could be promising for peripheral nerve tissue engineering.
{"title":"Electrically conductive and photocurable MXene-modulated hydrogel conduits for peripheral nerve regeneration: In vitro and in vivo studies","authors":"Roya Lotfi ,&nbsp;Banafsheh Dolatyar ,&nbsp;Nooshin Zandi ,&nbsp;Elnaz Tamjid ,&nbsp;Ali Pourjavadi ,&nbsp;Abdolreza Simchi","doi":"10.1016/j.bioadv.2025.214197","DOIUrl":"10.1016/j.bioadv.2025.214197","url":null,"abstract":"<div><div>Electroconductive biomaterials, as advanced nerve guidance conduits (NGCs), have shown great promise to accelerate the rate of peripheral nerve repair and regeneration (PNR) but remain among the greatest challenges in regenerative medicine because of frail recovery. Herein, we introduce injectable nanocomposite nerve conduits based on gelatin methacrylate (GelMa) and MXene nanosheets (MX) for PNR. Microstructural studies determine that the addition of MX increases the mean pore size of GelMa NH from 5.8 ± 1.2 μm to 8.4 ± 1.6 μm for the hydrogel containing 0.25 mg/mL MX, for example, leading to higher swelling and degradation rates. The highest electrical conductivity (∼910 μS/cm) is attained for the GelMa-based nanocomposite composed MX with the concentration of 0.125 mg/mL, for the reason that at higher concentrations, agglomeration of the MXs happens. In vitro investigations, including metabolic activity and live-dead assessments by PC12 cells, reveal the biocompatibility of developed nanocomposite hydrogels (NHs) containing different concentrations of MX nanosheets in the range of 0.025–0.25 mg/mL. Implantation of GelMa-MX conduits in a rat model of peripheral nerve injury (PNI) leads to the impressive recovery of the injured sciatic nerve's sensory, motor, and sensory-motor function. Electrophysiological analysis also indicates a significant increase in compound muscle action potential and nerve conduction velocity with a decrease in terminal latency in animals implanted with GelMa-MX conduits compared to control groups (animals implanted with GelMa and animals without implantation). Moreover, histological analysis exhibits a notable absence of fibrous connective tissue in the regenerated nerve fibers with a substantial increase in more organized myelinated axons. Our results demonstrate that GelMa-MX conduits promote regeneration of the injured sciatic nerve and could be promising for peripheral nerve tissue engineering.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"170 ","pages":"Article 214197"},"PeriodicalIF":5.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Synergistic photothermal and chemo-therapeutic platform utilizing Cu2-xSe/PDA/AIPH nanoparticles for targeted tumor eradication
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-19 DOI: 10.1016/j.bioadv.2025.214196
Haoyan Cheng , Beng Ma , Wanting Xia , Ying Yu , Jiayi Li , Keke Zhang , Linlin Shi , Hao Hu , Shegan Gao , Zhihong Zhu
In this study, we developed an innovative Cu2-xSe/PDA/AIPH nanoparticle platform that combines photothermal therapy and chemotherapy for effective tumor treatment. The Cu2-xSe nanoparticles, known for their strong near-infrared (NIR) absorption, were encapsulated within a polydopamine (PDA) and 2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) matrix. Upon NIR irradiation, the platform triggers localized heating and subsequent thermal decomposition of AIPH, releasing ROS to induce significant oxidative damage in tumor cells. In vitro and in vivo experiments demonstrated that Cu2-xSe/PDA/AIPH nanoparticles exhibit excellent biocompatibility, effective photothermal conversion, and potent anticancer efficacy. This multifunctional nanosystem offers a promising approach for enhancing tumor therapy by combining PTT with ROS-mediated chemotherapy.
{"title":"Synergistic photothermal and chemo-therapeutic platform utilizing Cu2-xSe/PDA/AIPH nanoparticles for targeted tumor eradication","authors":"Haoyan Cheng ,&nbsp;Beng Ma ,&nbsp;Wanting Xia ,&nbsp;Ying Yu ,&nbsp;Jiayi Li ,&nbsp;Keke Zhang ,&nbsp;Linlin Shi ,&nbsp;Hao Hu ,&nbsp;Shegan Gao ,&nbsp;Zhihong Zhu","doi":"10.1016/j.bioadv.2025.214196","DOIUrl":"10.1016/j.bioadv.2025.214196","url":null,"abstract":"<div><div>In this study, we developed an innovative Cu<sub>2-x</sub>Se/PDA/AIPH nanoparticle platform that combines photothermal therapy and chemotherapy for effective tumor treatment. The Cu<sub>2-x</sub>Se nanoparticles, known for their strong near-infrared (NIR) absorption, were encapsulated within a polydopamine (PDA) and 2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) matrix. Upon NIR irradiation, the platform triggers localized heating and subsequent thermal decomposition of AIPH, releasing ROS to induce significant oxidative damage in tumor cells. <em>In vitro</em> and <em>in vivo</em> experiments demonstrated that Cu<sub>2-x</sub>Se/PDA/AIPH nanoparticles exhibit excellent biocompatibility, effective photothermal conversion, and potent anticancer efficacy. This multifunctional nanosystem offers a promising approach for enhancing tumor therapy by combining PTT with ROS-mediated chemotherapy.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"169 ","pages":"Article 214196"},"PeriodicalIF":5.5,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Intervening with nanozymes in aging-related diseases: Strategies for restoring mitochondrial function 纳米酶干预衰老相关疾病:恢复线粒体功能的策略
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-18 DOI: 10.1016/j.bioadv.2025.214193
Fanyong Yan , Dongyang Liu , Baojuan Zhao , Yu Wang , Yidi Wang , Shangpeng Yang , Shanshan Li
The decline in mitochondrial function has been identified as one of the central pathological mechanisms underlying a variety of aging-related diseases. Nanozymes are nanomaterials with intrinsic enzyme-like properties and are important alternatives to natural enzymes. As emerging biocatalysts, nanozymes exhibit significant potential in mimicking the activity of natural enzymes, enhancing mitochondrial function, and offering novel therapeutic strategies for aging-related conditions. This review provides an overview of various approaches to modulate the catalytic activity of nanozymes, considering factors such as particle size, shape, surface modifications, and constituent elements. It then examines the role of nanozymes in mitigating aging-related diseases by preserving mitochondrial health, with a particular focus on their ability to regulate three critical aspects: mitochondrial energy metabolism, quality control, and antioxidant capacity. By improving mitochondrial energy generation, supporting mitochondrial integrity, and eliminating excess reactive oxygen species (ROS), nanozymes offer new therapeutic possibilities for neurodegenerative diseases, bone-related disorders, and diabetes. Finally, this article discusses the major challenges faced in this field, including issues such as the scalability, biocompatibility, and targeting ability of nanozymes. It also emphasizes that future research should focus on enhancing clinical translation to ensure that nanozymes can play an effective role in practical therapeutic applications.
线粒体功能的下降已被确定为多种衰老相关疾病的核心病理机制之一。纳米酶是一种具有内在酶样特性的纳米材料,是天然酶的重要替代品。作为新兴的生物催化剂,纳米酶在模拟天然酶的活性、增强线粒体功能以及为衰老相关疾病提供新的治疗策略方面显示出巨大的潜力。本文综述了调节纳米酶催化活性的各种方法,考虑了诸如粒径、形状、表面修饰和组成元素等因素。然后研究纳米酶在通过保持线粒体健康来减轻衰老相关疾病中的作用,特别关注它们调节三个关键方面的能力:线粒体能量代谢、质量控制和抗氧化能力。通过改善线粒体能量生成、支持线粒体完整性和消除过量活性氧(ROS),纳米酶为神经退行性疾病、骨相关疾病和糖尿病提供了新的治疗可能性。最后,本文讨论了该领域面临的主要挑战,包括纳米酶的可扩展性、生物相容性和靶向性等问题。未来的研究应着眼于加强临床转化,以确保纳米酶在实际治疗应用中发挥有效作用。
{"title":"Intervening with nanozymes in aging-related diseases: Strategies for restoring mitochondrial function","authors":"Fanyong Yan ,&nbsp;Dongyang Liu ,&nbsp;Baojuan Zhao ,&nbsp;Yu Wang ,&nbsp;Yidi Wang ,&nbsp;Shangpeng Yang ,&nbsp;Shanshan Li","doi":"10.1016/j.bioadv.2025.214193","DOIUrl":"10.1016/j.bioadv.2025.214193","url":null,"abstract":"<div><div>The decline in mitochondrial function has been identified as one of the central pathological mechanisms underlying a variety of aging-related diseases. Nanozymes are nanomaterials with intrinsic enzyme-like properties and are important alternatives to natural enzymes. As emerging biocatalysts, nanozymes exhibit significant potential in mimicking the activity of natural enzymes, enhancing mitochondrial function, and offering novel therapeutic strategies for aging-related conditions. This review provides an overview of various approaches to modulate the catalytic activity of nanozymes, considering factors such as particle size, shape, surface modifications, and constituent elements. It then examines the role of nanozymes in mitigating aging-related diseases by preserving mitochondrial health, with a particular focus on their ability to regulate three critical aspects: mitochondrial energy metabolism, quality control, and antioxidant capacity. By improving mitochondrial energy generation, supporting mitochondrial integrity, and eliminating excess reactive oxygen species (ROS), nanozymes offer new therapeutic possibilities for neurodegenerative diseases, bone-related disorders, and diabetes. Finally, this article discusses the major challenges faced in this field, including issues such as the scalability, biocompatibility, and targeting ability of nanozymes. It also emphasizes that future research should focus on enhancing clinical translation to ensure that nanozymes can play an effective role in practical therapeutic applications.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"169 ","pages":"Article 214193"},"PeriodicalIF":5.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Nanosheet-shaped WS2/ICG nanocomposite for photodynamic/photothermal synergistic bacterial clearance and cutaneous regeneration on infectious wounds
IF 5.5 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-01-16 DOI: 10.1016/j.bioadv.2025.214192
Zhiling Chen , Rui Zhang , Tao Wang , Yanan Peng , Qionglin Zhou , Peipei Cao , Xinxin Xiao , Fengling Li , Ziming Wei , Yuanyuan Wang , Dan Xu , Bin Qiao , Shaowen Cheng , Qiang Wu , Lina Niu
Bacterial infections present a significant threat to human health, a challenge that is intensified by the slow pace of novel antibiotic development and the swift emergence of bacterial resistance. The development of novel antibacterial agents is crucial. Indocyanine green (ICG), a widely used imaging dye, efficiently generates reactive oxygen species (ROS) and heat for treating bacterial infections but suffers from aggregation and instability, limiting its efficacy. In this study, tungsten disulfide (WS₂) nanosheet with a high surface area was used to load ICG, creating a multifunctional nanocomposite, WS2/ICG, aimed at treating bacteria-infected wounds. The two-dimensional surface structure of WS₂ provides dispersible binding sites for ICG, and the synthesized nanocomposite exhibits excellent stability. Under near-infrared (NIR) laser excitation, the generated heat further synergistically enhances the yield of singlet oxygen. Additionally, the WS₂/ICG nanoplatform synergistically combines photothermal effect with photodynamic effect, achieving a “1 + 1 > 2” enhancement. Upon NIR laser excitation, the nanocomposite disrupts bacterial cell membranes through localized heating and ROS accumulation, leading to energy metabolism system disruption and subsequent bacterial lysis and death. The findings demonstrate WS₂/ICG's outstanding antibacterial properties and biocompatibility, effectively treating skin infections and promoting tissue regeneration, providing a simple and promising solution for bacteria-infected wounds.
{"title":"Nanosheet-shaped WS2/ICG nanocomposite for photodynamic/photothermal synergistic bacterial clearance and cutaneous regeneration on infectious wounds","authors":"Zhiling Chen ,&nbsp;Rui Zhang ,&nbsp;Tao Wang ,&nbsp;Yanan Peng ,&nbsp;Qionglin Zhou ,&nbsp;Peipei Cao ,&nbsp;Xinxin Xiao ,&nbsp;Fengling Li ,&nbsp;Ziming Wei ,&nbsp;Yuanyuan Wang ,&nbsp;Dan Xu ,&nbsp;Bin Qiao ,&nbsp;Shaowen Cheng ,&nbsp;Qiang Wu ,&nbsp;Lina Niu","doi":"10.1016/j.bioadv.2025.214192","DOIUrl":"10.1016/j.bioadv.2025.214192","url":null,"abstract":"<div><div>Bacterial infections present a significant threat to human health, a challenge that is intensified by the slow pace of novel antibiotic development and the swift emergence of bacterial resistance. The development of novel antibacterial agents is crucial. Indocyanine green (ICG), a widely used imaging dye, efficiently generates reactive oxygen species (ROS) and heat for treating bacterial infections but suffers from aggregation and instability, limiting its efficacy. In this study, tungsten disulfide (WS₂) nanosheet with a high surface area was used to load ICG, creating a multifunctional nanocomposite, WS<sub>2</sub>/ICG, aimed at treating bacteria-infected wounds. The two-dimensional surface structure of WS₂ provides dispersible binding sites for ICG, and the synthesized nanocomposite exhibits excellent stability. Under near-infrared (NIR) laser excitation, the generated heat further synergistically enhances the yield of singlet oxygen. Additionally, the WS₂/ICG nanoplatform synergistically combines photothermal effect with photodynamic effect, achieving a “1 + 1 &gt; 2” enhancement. Upon NIR laser excitation, the nanocomposite disrupts bacterial cell membranes through localized heating and ROS accumulation, leading to energy metabolism system disruption and subsequent bacterial lysis and death. The findings demonstrate WS₂/ICG's outstanding antibacterial properties and biocompatibility, effectively treating skin infections and promoting tissue regeneration, providing a simple and promising solution for bacteria-infected wounds.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"169 ","pages":"Article 214192"},"PeriodicalIF":5.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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Materials Science & Engineering C-Materials for Biological Applications
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