Pub Date : 2024-10-29DOI: 10.1016/j.mtbio.2024.101321
Meixuan Liu , Jing Jiang , Yiran Wang , Huan Liu , Yiping Lu , Xingang Wang
Wound healing is an ongoing concern for the medical community. The limitations of traditional dressings are being addressed by materials and manufacturing technology. Microneedles (MNs) are a novel type of drug delivery system that has been widely used in cancer therapy, dermatological treatment, and insulin and vaccine delivery. MNs locally penetrate necrotic tissue, eschar, biofilm and epidermis into deep tissues, avoiding the possibility of drug dilution and degradation and greatly improving administration efficiency with less pain. MNs represent a new direction for wound treatment and transdermal delivery. In this study, we summarise the skin wound healing process and the mechanical stimulation of MNs in the context of the wound healing process. We also introduce the structural design and manufacture of MNs. Subsequently, MNs are categorised according to the loaded drugs, where the design of the MNs according to the traumatic biological/biochemical microenvironment (pH, glucose, and bacteria) and the physical microenvironment (temperature, light, and ultrasound) is emphasised. Finally, the advantages of MNs are compared with traditional drug delivery systems and their prospects are discussed.
{"title":"Smart drug delivery and responsive microneedles for wound healing","authors":"Meixuan Liu , Jing Jiang , Yiran Wang , Huan Liu , Yiping Lu , Xingang Wang","doi":"10.1016/j.mtbio.2024.101321","DOIUrl":"10.1016/j.mtbio.2024.101321","url":null,"abstract":"<div><div>Wound healing is an ongoing concern for the medical community. The limitations of traditional dressings are being addressed by materials and manufacturing technology. Microneedles (MNs) are a novel type of drug delivery system that has been widely used in cancer therapy, dermatological treatment, and insulin and vaccine delivery. MNs locally penetrate necrotic tissue, eschar, biofilm and epidermis into deep tissues, avoiding the possibility of drug dilution and degradation and greatly improving administration efficiency with less pain. MNs represent a new direction for wound treatment and transdermal delivery. In this study, we summarise the skin wound healing process and the mechanical stimulation of MNs in the context of the wound healing process. We also introduce the structural design and manufacture of MNs. Subsequently, MNs are categorised according to the loaded drugs, where the design of the MNs according to the traumatic biological/biochemical microenvironment (pH, glucose, and bacteria) and the physical microenvironment (temperature, light, and ultrasound) is emphasised. Finally, the advantages of MNs are compared with traditional drug delivery systems and their prospects are discussed.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101321"},"PeriodicalIF":8.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571717","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 : 2024-10-29DOI: 10.1016/j.mtbio.2024.101313
Xinping Wang , Guoqing Wang , Jianfei Wang , Junqiang Xue , Gaoli Liu , Changjiang Fan
Seroma formation and poor wound healing are common complications of many surgeries that create anatomical dead space (i.e., mastectomy), often causing tissue infection and even necrosis. Although negative pressure drainage and tissue adhesives are investigated to alleviate fluid accumulation post-surgery, however, their therapeutic efficacy remains unsatisfactory in most cases. Herein, the catechol-rich chemically crosslinked gelatin microspheres (ca-CGMSs) have been developed as biodegradable reconstructive implants for preventing seroma formation and concurrently promoting subcutaneous wound healing. Compared with the most representative hydrogel adhesive, i.e. commercial porcine fibrin sealant (PFS), the loosely packed ca-CGMSs with diameters range from 50 to 350 μm, provide numerous cell-adhesive interfaces and interconnected macro-pores for enhanced cell adhesion, proliferation and migration. Subcutaneous embedding trials show the in situ swelling aggregation and wet tissue adhesion of ca-CGMSs as well as their capacity in recruiting autologous cells in rat mastectomy models. The trials in rabbit mastectomy models demonstrate that, compared with PFS gluing, the implanted dried ca-CGMSs not only significantly inhibit seroma formation, but also achieve enhanced wound healing by inducing the formation of vascularized neo-tissue. The ca-CGMSs show a great potential to be the next-generation of restorative materials for both preventing seroma formation and healing subcutaneous wounds.
{"title":"Catechol-rich gelatin microspheres as restorative medical implants intended for inhibiting seroma formation and promoting wound healing","authors":"Xinping Wang , Guoqing Wang , Jianfei Wang , Junqiang Xue , Gaoli Liu , Changjiang Fan","doi":"10.1016/j.mtbio.2024.101313","DOIUrl":"10.1016/j.mtbio.2024.101313","url":null,"abstract":"<div><div>Seroma formation and poor wound healing are common complications of many surgeries that create anatomical dead space (i.e., mastectomy), often causing tissue infection and even necrosis. Although negative pressure drainage and tissue adhesives are investigated to alleviate fluid accumulation post-surgery, however, their therapeutic efficacy remains unsatisfactory in most cases. Herein, the catechol-rich chemically crosslinked gelatin microspheres (ca-CGMSs) have been developed as biodegradable reconstructive implants for preventing seroma formation and concurrently promoting subcutaneous wound healing. Compared with the most representative hydrogel adhesive, i.e. commercial porcine fibrin sealant (PFS), the loosely packed ca-CGMSs with diameters range from 50 to 350 μm, provide numerous cell-adhesive interfaces and interconnected macro-pores for enhanced cell adhesion, proliferation and migration. Subcutaneous embedding trials show the <em>in situ</em> swelling aggregation and wet tissue adhesion of ca-CGMSs as well as their capacity in recruiting autologous cells in rat mastectomy models. The trials in rabbit mastectomy models demonstrate that, compared with PFS gluing, the implanted dried ca-CGMSs not only significantly inhibit seroma formation, but also achieve enhanced wound healing by inducing the formation of vascularized neo-tissue. The ca-CGMSs show a great potential to be the next-generation of restorative materials for both preventing seroma formation and healing subcutaneous wounds.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101313"},"PeriodicalIF":8.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560911","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 : 2024-10-28DOI: 10.1016/j.mtbio.2024.101317
Xufeng Lu , Wenhai Deng , Shuaibin Wang , Shengsheng Zhao , Bingzi Zhu , Binglong Bai , Yiwen Mao , Ji Lin , Yongdong Yi , Zuoliang Xie , Xiang Wang , Yongyong Lu , Xiufeng Huang , Tao You , Xiaolei Chen , Weijian Sun , Xian Shen
Nanozymes constitute a promising treatment strategy for antitumor therapy. However, the catalytic function of metal‒organic framework (MOF)-based nanozymes during cuproptosis remains unclear. In this study, a Cu(Ⅱ)-based MOF nanocomposite loaded with the copper ionophore elesclomol and surface modified with polyethylene glycol polymer (PEG) was developed (ES@Cu(Ⅱ)-MOF) for effective cuproptosis induction. The peroxidase (POD)-like activity of ES@Cu(Ⅱ)-MOF generated an abundance of hydroxyl radicals (•OH) via a Fenton-like reaction, and its glutathione peroxidase (GSH-Px)-like activity converted Cu2+ into more toxic Cu+ ions to efficiently consume endogenous GSH. Notably, the rapid accumulation of Cu+ and ES in tumor cells induced the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT) and the downregulation of Fe‒S cluster proteins, ultimately leading to cuproptosis. ES@Cu(Ⅱ)-MOF exhibited extraordinary cytotoxicity against breast cancer cells in vitro and significantly suppressed 4T1 breast tumor growth in vivo. Moreover, ES@Cu(Ⅱ)-MOF induced immunogenic cell death (ICD) to increase the antitumor immune response. Furthermore, combining ES@Cu(Ⅱ)-MOF with an anti-programmed cell death-ligand 1 (PD-L1) antibody converted the immunosuppressive tumor microenvironment to an immunogenic microenvironment, thus effectively inhibiting breast tumor growth. Overall, this work provides an innovative approach utilizing nanozymes to facilitate cuproptosis for cancer treatment, which potentially enhances the effectiveness of immune checkpoint inhibitor-based immunotherapy.
{"title":"PEGylated Elesclomol@Cu(Ⅱ)-based Metal‒organic framework with effective nanozyme performance and cuproptosis induction efficacy for enhanced PD-L1-based immunotherapy","authors":"Xufeng Lu , Wenhai Deng , Shuaibin Wang , Shengsheng Zhao , Bingzi Zhu , Binglong Bai , Yiwen Mao , Ji Lin , Yongdong Yi , Zuoliang Xie , Xiang Wang , Yongyong Lu , Xiufeng Huang , Tao You , Xiaolei Chen , Weijian Sun , Xian Shen","doi":"10.1016/j.mtbio.2024.101317","DOIUrl":"10.1016/j.mtbio.2024.101317","url":null,"abstract":"<div><div>Nanozymes constitute a promising treatment strategy for antitumor therapy. However, the catalytic function of metal‒organic framework (MOF)-based nanozymes during cuproptosis remains unclear. In this study, a Cu(Ⅱ)-based MOF nanocomposite loaded with the copper ionophore elesclomol and surface modified with polyethylene glycol polymer (PEG) was developed (ES@Cu(Ⅱ)-MOF) for effective cuproptosis induction. The peroxidase (POD)-like activity of ES@Cu(Ⅱ)-MOF generated an abundance of hydroxyl radicals (•OH) via a Fenton-like reaction, and its glutathione peroxidase (GSH-Px)-like activity converted Cu<sup>2+</sup> into more toxic Cu<sup>+</sup> ions to efficiently consume endogenous GSH. Notably, the rapid accumulation of Cu<sup>+</sup> and ES in tumor cells induced the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT) and the downregulation of Fe‒S cluster proteins, ultimately leading to cuproptosis. ES@Cu(Ⅱ)-MOF exhibited extraordinary cytotoxicity against breast cancer cells <em>in vitro</em> and significantly suppressed 4T1 breast tumor growth <em>in vivo</em>. Moreover, ES@Cu(Ⅱ)-MOF induced immunogenic cell death (ICD) to increase the antitumor immune response. Furthermore, combining ES@Cu(Ⅱ)-MOF with an anti-programmed cell death-ligand 1 (PD-L1) antibody converted the immunosuppressive tumor microenvironment to an immunogenic microenvironment, thus effectively inhibiting breast tumor growth. Overall, this work provides an innovative approach utilizing nanozymes to facilitate cuproptosis for cancer treatment, which potentially enhances the effectiveness of immune checkpoint inhibitor-based immunotherapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101317"},"PeriodicalIF":8.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571716","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 : 2024-10-28DOI: 10.1016/j.mtbio.2024.101318
Minghui Chen , Hanbo Xu , Pengzhao Chang , Xueqi Li , Shuang Liu , Lingyue Xu , Kai Xu , Guohui Cheng
Mitochondria-targeted photodynamic therapy (PDT) has emerged as one of the most promising antitumor therapies, as it significantly enhances the efficacy of photosensitizers. An efficient and biocompatible nanocarrier to deliver cationic photosensitizers (PSs) is vital for mitochondria-targeted PDT but still challenging. Herein, a poly-AS1411 aptamer DNA nanoclew (AS-AMD) synthesized via rolling circle amplification (RCA) is developed, incorporating mitochondria-targeted PSs (APNO) and paramagnetic Mn2+ for mitochondria-targeted PDT and magnetic resonance imaging (MRI). The AS1411 aptamer of AS-AMD has been engineered to enhance tumor targeting and cellular internalization. Paramagnetic Mn2+ released in the acidic tumor microenvironment promotes MRI performance of the tumor tissue and guides subsequent PDT. The released cationic APNO selectively targets the mitochondrial membrane and generates reactive oxygen species (ROS) that induce the apoptosis of 4T1 breast tumor cells. Additionally, AS-AMD exhibits effective tumor targeting in the 4T1-tumor-bearing mice model, significantly enhanced MRI performance and PDT efficacy. Therefore, this study introduces an interesting strategy to achieve efficient mitochondrial-targeted delivery of cationic PSs and provides a versatile biocompatible DNA nanoplatform for the development of nanotheranostic agents.
{"title":"An intelligent poly aptamer-encoded DNA nanoclew for tumor site activated mitochondria-targeted photodynamic therapy and MR imaging","authors":"Minghui Chen , Hanbo Xu , Pengzhao Chang , Xueqi Li , Shuang Liu , Lingyue Xu , Kai Xu , Guohui Cheng","doi":"10.1016/j.mtbio.2024.101318","DOIUrl":"10.1016/j.mtbio.2024.101318","url":null,"abstract":"<div><div>Mitochondria-targeted photodynamic therapy (PDT) has emerged as one of the most promising antitumor therapies, as it significantly enhances the efficacy of photosensitizers. An efficient and biocompatible nanocarrier to deliver cationic photosensitizers (PSs) is vital for mitochondria-targeted PDT but still challenging. Herein, a poly-AS1411 aptamer DNA nanoclew (AS-AMD) synthesized via rolling circle amplification (RCA) is developed, incorporating mitochondria-targeted PSs (APNO) and paramagnetic Mn<sup>2+</sup> for mitochondria-targeted PDT and magnetic resonance imaging (MRI). The AS1411 aptamer of AS-AMD has been engineered to enhance tumor targeting and cellular internalization. Paramagnetic Mn<sup>2+</sup> released in the acidic tumor microenvironment promotes MRI performance of the tumor tissue and guides subsequent PDT. The released cationic APNO selectively targets the mitochondrial membrane and generates reactive oxygen species (ROS) that induce the apoptosis of 4T1 breast tumor cells. Additionally, AS-AMD exhibits effective tumor targeting in the 4T1-tumor-bearing mice model, significantly enhanced MRI performance and PDT efficacy. Therefore, this study introduces an interesting strategy to achieve efficient mitochondrial-targeted delivery of cationic PSs and provides a versatile biocompatible DNA nanoplatform for the development of nanotheranostic agents.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101318"},"PeriodicalIF":8.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554985","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 : 2024-10-28DOI: 10.1016/j.mtbio.2024.101316
Jia Rui , Siyu Zhu , Xiang Xu, Yi Wang, Zulan Liu, Guotao Cheng, Dingpei Long, Lan Cheng, Fangyin Dai
The choice of suitable materials and effective structural design are crucial in influencing the therapeutic outcomes of bone tissue engineering scaffolds. This study introduces a controllable biodegradable composite scaffold composed of flat silkworm cocoon (FSC) and polylactic acid (PLA) as an innovative strategy for promoting bone healing in complex injuries. We focused on optimizing the scaffold's structural design, mechanical properties, and underlying mechanisms of osteogenesis. Initial experiments established the parameters for hot pressing the FSC, followed by mechanical performance tests to identify the optimal preparation conditions. Composite scaffolds incorporating PLA films were subsequently fabricated using these optimized parameters. The results indicate that the FSC/PLA composite scaffold exhibits outstanding biocompatibility, mechanical strength, and in vitro mineralization capabilities, alongside an appropriate degradation rate. Furthermore, the composite scaffolds demonstrated significant potential in promoting osteogenic differentiation and facilitating macrophage polarization toward an anti-inflammatory M2 phenotype. In vivo implantation of the scaffold in defective regions enhanced osteogenesis and mitigated inflammatory responses associated with degradation. This investigation presents an optimal composite scaffold that closely mimics the complex structure of bone, offering a novel approach to enhance bone regeneration and effectively address substantial bone defects.
{"title":"High-performance silk/polylactic acid composite scaffold material with immunomodulation and osteogenesis function","authors":"Jia Rui , Siyu Zhu , Xiang Xu, Yi Wang, Zulan Liu, Guotao Cheng, Dingpei Long, Lan Cheng, Fangyin Dai","doi":"10.1016/j.mtbio.2024.101316","DOIUrl":"10.1016/j.mtbio.2024.101316","url":null,"abstract":"<div><div>The choice of suitable materials and effective structural design are crucial in influencing the therapeutic outcomes of bone tissue engineering scaffolds. This study introduces a controllable biodegradable composite scaffold composed of flat silkworm cocoon (FSC) and polylactic acid (PLA) as an innovative strategy for promoting bone healing in complex injuries. We focused on optimizing the scaffold's structural design, mechanical properties, and underlying mechanisms of osteogenesis. Initial experiments established the parameters for hot pressing the FSC, followed by mechanical performance tests to identify the optimal preparation conditions. Composite scaffolds incorporating PLA films were subsequently fabricated using these optimized parameters. The results indicate that the FSC/PLA composite scaffold exhibits outstanding biocompatibility, mechanical strength, and in vitro mineralization capabilities, alongside an appropriate degradation rate. Furthermore, the composite scaffolds demonstrated significant potential in promoting osteogenic differentiation and facilitating macrophage polarization toward an anti-inflammatory M2 phenotype. In vivo implantation of the scaffold in defective regions enhanced osteogenesis and mitigated inflammatory responses associated with degradation. This investigation presents an optimal composite scaffold that closely mimics the complex structure of bone, offering a novel approach to enhance bone regeneration and effectively address substantial bone defects.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101316"},"PeriodicalIF":8.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586336","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 : 2024-10-26DOI: 10.1016/j.mtbio.2024.101314
Xuanlong Zhang , Xiaoqiong Jiang , Huiming Deng , Gaoxiang Yu , Ningning Yang , Abdullah Al Mamun , Feifei Lian , Tianling Chen , Haijuan Zhang , Yingying Lai , Jiayi Huang , Shi Xu , Fuman Cai , Xiaokun Li , Kailiang Zhou , Jian Xiao
Background
The recovery of ischemic skin flaps is a major concern in clinical settings. The purpose of this study is to evaluate the effects of engineered exosomes derived from FGF1 pre-conditioned adipose-derived stem cells (FEXO) on ischemic skin flaps.
Method
6 patients who suffered from pressure ulcer at stage 4 and underwent skin flaps surgery were recruited in this study to screen the potential targets of ischemic skin flaps in FGF family. FGF1 was co-incubated with adipose stem cells, and ultracentrifugation was applied to extract FEXO. Transcriptome sequencing analysis was used to determine the most effective microRNA in FEXO. Animal skin flaps models were established in our study to verify the effects of FEXO. Immunofluorescence (IF), western blotting (WB) and other molecular strategy were used to evaluate the effects and mechanism of FEXO.
Results
FGF1 was expected to be the therapeutic and diagnostic target of ischemic skin flaps, but there is still some deficiency in rescuing skin flaps. FEXO significantly improved the viability of RPSFs and endothelial cells by inhibiting oxidative stress and alleviating apoptosis and pyroptosis through augmenting autophagy flux. In addition, FEXO inhibited the over-activated inflammation responses. Transcriptome sequencing analysis showed that miR-183-5p was significantly elevated in FEXO, and inhibiting miR-183-5p resulted in impaired protective effects of autophagy in skin flaps. The exosomal miR-183-5p markedly enhanced cell viability, inhibited oxidative stress and alleviated apoptosis and pyroptosis in endothelial cells by targeting GPR137 through Pi3k/Akt/mTOR pathway, indicating that GPR137 could also be a therapeutic target of ischemic skin flap. It was also notabale that FGF1 increased the number of exosomes by upregulating VAMP3, which may be a promising strategy for clinical translation.
Conclusion
FEXO markedly improved the survivial rate of ischemic skin flaps through miR-183-5p/GPR137/Pi3k/Akt/mTOR axis, which would be a promising strategy to rescue ischemic skin flaps.
{"title":"Engineering exosomes from fibroblast growth factor 1 pre-conditioned adipose-derived stem cells promote ischemic skin flaps survival by activating autophagy","authors":"Xuanlong Zhang , Xiaoqiong Jiang , Huiming Deng , Gaoxiang Yu , Ningning Yang , Abdullah Al Mamun , Feifei Lian , Tianling Chen , Haijuan Zhang , Yingying Lai , Jiayi Huang , Shi Xu , Fuman Cai , Xiaokun Li , Kailiang Zhou , Jian Xiao","doi":"10.1016/j.mtbio.2024.101314","DOIUrl":"10.1016/j.mtbio.2024.101314","url":null,"abstract":"<div><h3>Background</h3><div>The recovery of ischemic skin flaps is a major concern in clinical settings. The purpose of this study is to evaluate the effects of engineered exosomes derived from FGF1 pre-conditioned adipose-derived stem cells (FEXO) on ischemic skin flaps.</div></div><div><h3>Method</h3><div>6 patients who suffered from pressure ulcer at stage 4 and underwent skin flaps surgery were recruited in this study to screen the potential targets of ischemic skin flaps in FGF family. FGF1 was co-incubated with adipose stem cells, and ultracentrifugation was applied to extract FEXO. Transcriptome sequencing analysis was used to determine the most effective microRNA in FEXO. Animal skin flaps models were established in our study to verify the effects of FEXO. Immunofluorescence (IF), western blotting (WB) and other molecular strategy were used to evaluate the effects and mechanism of FEXO.</div></div><div><h3>Results</h3><div>FGF1 was expected to be the therapeutic and diagnostic target of ischemic skin flaps, but there is still some deficiency in rescuing skin flaps. FEXO significantly improved the viability of RPSFs and endothelial cells by inhibiting oxidative stress and alleviating apoptosis and pyroptosis through augmenting autophagy flux. In addition, FEXO inhibited the over-activated inflammation responses. Transcriptome sequencing analysis showed that miR-183-5p was significantly elevated in FEXO, and inhibiting miR-183-5p resulted in impaired protective effects of autophagy in skin flaps. The exosomal miR-183-5p markedly enhanced cell viability, inhibited oxidative stress and alleviated apoptosis and pyroptosis in endothelial cells by targeting GPR137 through Pi3k/Akt/mTOR pathway, indicating that GPR137 could also be a therapeutic target of ischemic skin flap. It was also notabale that FGF1 increased the number of exosomes by upregulating VAMP3, which may be a promising strategy for clinical translation.</div></div><div><h3>Conclusion</h3><div>FEXO markedly improved the survivial rate of ischemic skin flaps through miR-183-5p/GPR137/Pi3k/Akt/mTOR axis, which would be a promising strategy to rescue ischemic skin flaps.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101314"},"PeriodicalIF":8.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554987","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 : 2024-10-26DOI: 10.1016/j.mtbio.2024.101302
Patrick Weber , Annalena Maier , David Fercher, Maryam Asadikorayem, Marcy Zenobi-Wong
Accurately assessing cartilage tissue degradation is a big challenge in osteoarthritis (OA) research, as histology only provides information about a 2D tissue section, and currently available contrast agents for tomographic evaluation suffer from low specificity. In this study, we present a modular platform based on zwitterionic carboxybetaine (CBAA) to create multivalent polymeric contrast agents for x-ray computed tomography (CT) with high specificity towards the anionic glycosaminoglycans in the cartilage tissue. By copolymerizing CBAA with different ratios of anionic and cationic iodinated comonomers, we created a library of polymers with net charges ranging from strongly anionic to strongly cationic. The polymers were applied onto osteochondral plugs with different degradation states and the resulting CT images compared to histological stainings. In healthy tissues, the bulk contrast enhancement was strongly correlated with polymer charge, with cationic polymers reaching a 2-fold stronger contrast compared to established small molecule contrast agents. While a further increase in cationic charge slowed the penetration, it increased the polymer's specificity, thereby enabling the most cationic polymer C40 (40 mol% cationic iodinated comonomer) to discriminate accurately between tissues treated with IL-1β for 0, 1, 2 and 3 weeks. Moreover, this polymer also showed a strong local specificity, visualizing local differences in GAG distribution with significantly increased accuracy compared to the controls. Our polymer contrast agents show the importance of multivalency and charge control for the accurate, volumetric detection of GAGs in the cartilage tissue and paves the way towards new contrast agents in- and outside of the clinic.
{"title":"Modular iodinated carboxybetaine copolymers as charge-sensitive contrast agents for the detection of cartilage degradation","authors":"Patrick Weber , Annalena Maier , David Fercher, Maryam Asadikorayem, Marcy Zenobi-Wong","doi":"10.1016/j.mtbio.2024.101302","DOIUrl":"10.1016/j.mtbio.2024.101302","url":null,"abstract":"<div><div>Accurately assessing cartilage tissue degradation is a big challenge in osteoarthritis (OA) research, as histology only provides information about a 2D tissue section, and currently available contrast agents for tomographic evaluation suffer from low specificity. In this study, we present a modular platform based on zwitterionic carboxybetaine (CBAA) to create multivalent polymeric contrast agents for x-ray computed tomography (CT) with high specificity towards the anionic glycosaminoglycans in the cartilage tissue. By copolymerizing CBAA with different ratios of anionic and cationic iodinated comonomers, we created a library of polymers with net charges ranging from strongly anionic to strongly cationic. The polymers were applied onto osteochondral plugs with different degradation states and the resulting CT images compared to histological stainings. In healthy tissues, the bulk contrast enhancement was strongly correlated with polymer charge, with cationic polymers reaching a 2-fold stronger contrast compared to established small molecule contrast agents. While a further increase in cationic charge slowed the penetration, it increased the polymer's specificity, thereby enabling the most cationic polymer C40 (40 mol% cationic iodinated comonomer) to discriminate accurately between tissues treated with IL-1β for 0, 1, 2 and 3 weeks. Moreover, this polymer also showed a strong local specificity, visualizing local differences in GAG distribution with significantly increased accuracy compared to the controls. Our polymer contrast agents show the importance of multivalency and charge control for the accurate, volumetric detection of GAGs in the cartilage tissue and paves the way towards new contrast agents in- and outside of the clinic.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101302"},"PeriodicalIF":8.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571715","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 : 2024-10-26DOI: 10.1016/j.mtbio.2024.101309
Jing Zhao , Liyun Chen , Aiwei Ma , Xujue Bai , Yating Zeng , Daojun Liu , Bo Liu , Wancong Zhang , Shijie Tang
The skin is the body's primary immune barrier, defending it against pathogenic invasion. Skin injuries impose a significant physiological burden on patients, making effective wound management essential. Dressings are commonly employed in wound care, and electrospun nanofiber dressings are a research hotspot owing to their ease of fabrication, cost-effectiveness, and structural similarity to the extracellular matrix. Coaxial electrospinning offers considerable advantages in drug delivery, fiber structure transformation, and enhanced interaction with the host. These attributes make coaxial electrospun materials promising candidates for precision and personalized wound dressings in medical treatments. This review provides a comprehensive overview of wound healing and its influencing factors. It also outlines coaxial electrospinning's production principles and benefits in wound dressings. Guided by the factors affecting wound healing, coaxial electrospun nanofiber dressings have different application modalities. Furthermore, we discuss the current limitations and future directions for enhancing the current coaxial electrospun dressing technologies.
{"title":"Recent advances in coaxial electrospun nanofibers for wound healing","authors":"Jing Zhao , Liyun Chen , Aiwei Ma , Xujue Bai , Yating Zeng , Daojun Liu , Bo Liu , Wancong Zhang , Shijie Tang","doi":"10.1016/j.mtbio.2024.101309","DOIUrl":"10.1016/j.mtbio.2024.101309","url":null,"abstract":"<div><div>The skin is the body's primary immune barrier, defending it against pathogenic invasion. Skin injuries impose a significant physiological burden on patients, making effective wound management essential. Dressings are commonly employed in wound care, and electrospun nanofiber dressings are a research hotspot owing to their ease of fabrication, cost-effectiveness, and structural similarity to the extracellular matrix. Coaxial electrospinning offers considerable advantages in drug delivery, fiber structure transformation, and enhanced interaction with the host. These attributes make coaxial electrospun materials promising candidates for precision and personalized wound dressings in medical treatments. This review provides a comprehensive overview of wound healing and its influencing factors. It also outlines coaxial electrospinning's production principles and benefits in wound dressings. Guided by the factors affecting wound healing, coaxial electrospun nanofiber dressings have different application modalities. Furthermore, we discuss the current limitations and future directions for enhancing the current coaxial electrospun dressing technologies.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101309"},"PeriodicalIF":8.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593161","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 : 2024-10-25DOI: 10.1016/j.mtbio.2024.101311
Jialu Weng , Shiyi Wu , Yating Pan , Yifan Lai , Jinrong Zhu , Wenzhang Jin , Deyu Lu , Yizhang Chen , Zhijie Yu , Xinjie Zan , Jinglin Xia
Chemotherapy is the primary palliative treatment for advanced hepatocellular carcinoma (HCC). However, the systemic delivery is associated with the drawbacks including a high risk of adverse effects and a low efficacy. Therefore, local injection therapy may be beneficial. Nevertheless, the existing local drug-carrying microspheres(DOBM)have the characteristics of low loading and abrupt release, can not simultaneously load two drugs, and may cause unnecessary toxicity. In this study, we created the dual-loaded bovine serum albumin (BSA) microspheres (also known as DOBM), which were hollow and contained both oxaliplatin (OXA) and Adriamycin hydrochloride (DOX). In addition, this pH-sensitive drug delivery method exhibited a high drug loading capacity and was promising in breaking through biological barriers, making it a viable option for the treatment of HCC through local implantation. Based on physiochemical evaluation of BSA microspheres, they had a porous structure which was close to the surface. Adriamycin and oxaliplatin were successfully added to the surface of BSA microspheres. According to in vitro experimental results, the growth of human HCC (HCC-LM3 and PLC/PRF/5) cell lines was significantly inhibited by DOBM. Furthermore, in the subcutaneous PLC/PRF/5 HCC model, DOBM played an essential role in tumor development and change in the tumor microenvironment.
{"title":"PH-sensitive adriamycin hydrochloride and oxaliplatin dual-loaded microspheres synergistically enhance local injections effect of hepatocellular carcinoma","authors":"Jialu Weng , Shiyi Wu , Yating Pan , Yifan Lai , Jinrong Zhu , Wenzhang Jin , Deyu Lu , Yizhang Chen , Zhijie Yu , Xinjie Zan , Jinglin Xia","doi":"10.1016/j.mtbio.2024.101311","DOIUrl":"10.1016/j.mtbio.2024.101311","url":null,"abstract":"<div><div>Chemotherapy is the primary palliative treatment for advanced hepatocellular carcinoma (HCC). However, the systemic delivery is associated with the drawbacks including a high risk of adverse effects and a low efficacy. Therefore, local injection therapy may be beneficial. Nevertheless, the existing local drug-carrying microspheres(DOBM)have the characteristics of low loading and abrupt release, can not simultaneously load two drugs, and may cause unnecessary toxicity. In this study, we created the dual-loaded bovine serum albumin (BSA) microspheres (also known as DOBM), which were hollow and contained both oxaliplatin (OXA) and Adriamycin hydrochloride (DOX). In addition, this pH-sensitive drug delivery method exhibited a high drug loading capacity and was promising in breaking through biological barriers, making it a viable option for the treatment of HCC through local implantation. Based on physiochemical evaluation of BSA microspheres, they had a porous structure which was close to the surface. Adriamycin and oxaliplatin were successfully added to the surface of BSA microspheres. According to in vitro experimental results, the growth of human HCC (HCC-LM3 and PLC/PRF/5) cell lines was significantly inhibited by DOBM. Furthermore, in the subcutaneous PLC/PRF/5 HCC model, DOBM played an essential role in tumor development and change in the tumor microenvironment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101311"},"PeriodicalIF":8.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538517","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 : 2024-10-24DOI: 10.1016/j.mtbio.2024.101308
Ziqiao Zhong , Lu Gan , Ziyi Feng , Wenhao Wang , Xin Pan , Chuanbin Wu , Ying Huang
Surgery is one of the primary treatments for solid tumors. However, the incomplete resection of tumor cells and the immunosuppressive microenvironment make the issue of postsurgical tumor recurrence a great challenge. Furthermore, a wide range of requirements, including ensuring effective hemostasis, implementing prophylactic measures against infection, and promoting wound healing, were also raised in the postsurgical management of tumors. To fulfill these demands, multiple hydrogel local drug delivery systems (HLDDS) were developed recently. These HLDDS are expected to offer numerous advantages in the postsurgical management of tumors, such as achieving high local drug concentrations at the lesion, efficient delivery to surgical microcavities, mitigating systemic side effects, and addressing the diverse demand. Thus, in this review, a detailed discussion of the diverse demands of postsurgical management of tumors is provided. And the current publication trend on HLDDS in the postsurgical management of tumors is analyzed and discussed. Then, the applications of different types of HLDDS, in-situ HLDDS and non-in-situ HLDDS, in postsurgical management of tumors were introduced and summarized. Besides, the current problems and future perspectives are discussed. The review is expected to provide an overview of HLDDS in postsurgical management of tumors and promote their clinical application.
{"title":"Hydrogel local drug delivery systems for postsurgical management of tumors: Status Quo and perspectives","authors":"Ziqiao Zhong , Lu Gan , Ziyi Feng , Wenhao Wang , Xin Pan , Chuanbin Wu , Ying Huang","doi":"10.1016/j.mtbio.2024.101308","DOIUrl":"10.1016/j.mtbio.2024.101308","url":null,"abstract":"<div><div>Surgery is one of the primary treatments for solid tumors. However, the incomplete resection of tumor cells and the immunosuppressive microenvironment make the issue of postsurgical tumor recurrence a great challenge. Furthermore, a wide range of requirements, including ensuring effective hemostasis, implementing prophylactic measures against infection, and promoting wound healing, were also raised in the postsurgical management of tumors. To fulfill these demands, multiple hydrogel local drug delivery systems (HLDDS) were developed recently. These HLDDS are expected to offer numerous advantages in the postsurgical management of tumors, such as achieving high local drug concentrations at the lesion, efficient delivery to surgical microcavities, mitigating systemic side effects, and addressing the diverse demand. Thus, in this review, a detailed discussion of the diverse demands of postsurgical management of tumors is provided. And the current publication trend on HLDDS in the postsurgical management of tumors is analyzed and discussed. Then, the applications of different types of HLDDS, <em>in-situ</em> HLDDS and <em>non-in-situ</em> HLDDS, in postsurgical management of tumors were introduced and summarized. Besides, the current problems and future perspectives are discussed. The review is expected to provide an overview of HLDDS in postsurgical management of tumors and promote their clinical application.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101308"},"PeriodicalIF":8.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538876","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}