Pub Date : 2025-02-18DOI: 10.1016/j.mtbio.2025.101585
Hua Yu , Bin Wang , Zihao Li , Kaibo Liu , Wanying Chen , Songyun Zhao , Yu Zhou , Gaoyi Wang , Yaqin Zhou , Yanming Chen , Housheng Chen , Yunning Lai , Quan Wang , Jingping Wang , Binting Ni , Dupiao Zhang , Chuanmeng Pan , Yucang He , Liqun Li
Diabetic wounds often exhibit delayed healing due to compromised vascular function and intensified inflammation. In this study, we overexpressed Thymosin β4 (Tβ4) in Adipose-Derived Stem Cells (ADSCs) to produce Exosomes (Exos) rich in Tβ4. We then utilized a dual photopolymerizable hydrogel composed of Hyaluronic Acid Methacryloyl (HAMA) and Poly-L-lysine Methacryloyl (PLMA) for the sustained release of Tβ4-Exos on diabetic wounds. The results showed that Tβ4-Exos could stimulate angiogenesis and collagen synthesis, and mitigate inflammation in diabetic wounds by promoting the polarization of M1-type macrophages and inhibiting that of M2-type macrophages. Furthermore, Tβ4-Exos was found to activate the PI3K/AKT/mTOR/HIF-1a signaling pathway, thereby enhancing vascular proliferation. In summary, the sustained release of Tβ4-Exos in HAMA-PLMA (HP) hydrogel and the management of inflammation through the upregulation of the HIF-1a pathway and modulation of macrophage polarization in vascular proliferation significantly accelerated the healing process of diabetic wounds.
{"title":"Tβ4-exosome-loaded hemostatic and antibacterial hydrogel to improve vascular regeneration and modulate macrophage polarization for diabetic wound treatment","authors":"Hua Yu , Bin Wang , Zihao Li , Kaibo Liu , Wanying Chen , Songyun Zhao , Yu Zhou , Gaoyi Wang , Yaqin Zhou , Yanming Chen , Housheng Chen , Yunning Lai , Quan Wang , Jingping Wang , Binting Ni , Dupiao Zhang , Chuanmeng Pan , Yucang He , Liqun Li","doi":"10.1016/j.mtbio.2025.101585","DOIUrl":"10.1016/j.mtbio.2025.101585","url":null,"abstract":"<div><div>Diabetic wounds often exhibit delayed healing due to compromised vascular function and intensified inflammation. In this study, we overexpressed Thymosin β4 (Tβ4) in Adipose-Derived Stem Cells (ADSCs) to produce Exosomes (Exos) rich in Tβ4. We then utilized a dual photopolymerizable hydrogel composed of Hyaluronic Acid Methacryloyl (HAMA) and Poly-L-lysine Methacryloyl (PLMA) for the sustained release of Tβ4-Exos on diabetic wounds. The results showed that Tβ4-Exos could stimulate angiogenesis and collagen synthesis, and mitigate inflammation in diabetic wounds by promoting the polarization of M1-type macrophages and inhibiting that of M2-type macrophages. Furthermore, Tβ4-Exos was found to activate the PI3K/AKT/mTOR/HIF-1a signaling pathway, thereby enhancing vascular proliferation. In summary, the sustained release of Tβ4-Exos in HAMA-PLMA (HP) hydrogel and the management of inflammation through the upregulation of the HIF-1a pathway and modulation of macrophage polarization in vascular proliferation significantly accelerated the healing process of diabetic wounds.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101585"},"PeriodicalIF":8.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-15DOI: 10.1016/j.mtbio.2025.101580
Ruifang Han , Haiyi Zhou , Xingshan Liang , Siyi He , Xiaoming Sun , Yongge Guan , Yang Song
Endometrium plays a key role in embryo implantation and maintenance of pregnancy. However, to repair endometrial injury is still a challenge. In recent years, hydrogel materials have been widely used as effective support matrices to prevent intrauterine adhesions after endometrial injury. They can also be used as preparation scaffolds for encapsulating MSCs and certain therapeutic drugs. This study aimed to develop a preparation scaffold with high tissue affinity, high viscoelasticity and controlled release for repair of endometrial injury. The scaffold utilized heparin poloxamer (HP) as the matrix material and ε-polylysine (EPL) as the functional excipient to prepare a hydrogel that is suitable for endometrial adhesion and further encapsulate BMSCs. Furthermore, a strategy of the thermo-sensitive EPL-HP hydrogel-encapsulated BMSCs were used for better homing of BMSC after transplantation into the rat endometrial injury model, so as to exert the potential of endometrial regeneration by activating Nrf2 to regulate SDF-1/CXCR4 axis.
{"title":"Thermo-sensitive ε-polylysine-heparin-poloxamer hydrogel-encapsulated BMSCs promote endometrial regeneration","authors":"Ruifang Han , Haiyi Zhou , Xingshan Liang , Siyi He , Xiaoming Sun , Yongge Guan , Yang Song","doi":"10.1016/j.mtbio.2025.101580","DOIUrl":"10.1016/j.mtbio.2025.101580","url":null,"abstract":"<div><div>Endometrium plays a key role in embryo implantation and maintenance of pregnancy. However, to repair endometrial injury is still a challenge. In recent years, hydrogel materials have been widely used as effective support matrices to prevent intrauterine adhesions after endometrial injury. They can also be used as preparation scaffolds for encapsulating MSCs and certain therapeutic drugs. This study aimed to develop a preparation scaffold with high tissue affinity, high viscoelasticity and controlled release for repair of endometrial injury. The scaffold utilized heparin poloxamer (HP) as the matrix material and ε-polylysine (EPL) as the functional excipient to prepare a hydrogel that is suitable for endometrial adhesion and further encapsulate BMSCs. Furthermore, a strategy of the thermo-sensitive EPL-HP hydrogel-encapsulated BMSCs were used for better homing of BMSC after transplantation into the rat endometrial injury model, so as to exert the potential of endometrial regeneration by activating Nrf2 to regulate SDF-1/CXCR4 axis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101580"},"PeriodicalIF":8.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-15DOI: 10.1016/j.mtbio.2025.101576
Hang Liang , Jingyao Tu , Bingjin Wang , Yu Song , Kun Wang , Kangcheng Zhao , Wenbin Hua , Shuai Li , Lei Tan , Xiaobo Feng , Cao Yang
An interbody fusion cage is crucial in spine fusion procedures, serving to restore physiological vertebral alignment and reestablish spinal stability. However, conventional fusion cages often face challenges related to insufficient osteointegration and the requirement for substantial bone grafting, which may result in incomplete fusion and prolonged recovery periods. In this study, we harnessed the osteointegration advantages of tantalum (Ta), in conjunction with advanced 3D printing technology, to develop a novel non-window-type Ta cage. The mechanical and biological characteristics of the cage were comprehensively evaluated through mechanical testing, in vitro cellular assays, and in vivo sheep anterior cervical discectomy and fusion models. The results indicated that the 3D-printed porous tantalum (3D-pTa) cage, with mechanical properties analogous to those of trabecular bone, exhibited superior bone ingrowth and osseointegration performance, achieving excellent intervertebral fusion without the need for bone grafting, thereby enhancing cervical vertebra stability. Moreover, we performed a pilot clinical trial to assess the performance of non-window-type 3D-pTa cages in single-level posterior lumbar interbody fusion. The results demonstrated that 3D-pTa achieved favorable clinical outcomes up to the 12-month follow-up period. These results highlight the significant clinical potential of the 3D-pTa cage for spinal fusion applications.
{"title":"Innovative 3D-printed porous tantalum cage with non-window design to accelerate spinal fusion: A proof-of-concept study","authors":"Hang Liang , Jingyao Tu , Bingjin Wang , Yu Song , Kun Wang , Kangcheng Zhao , Wenbin Hua , Shuai Li , Lei Tan , Xiaobo Feng , Cao Yang","doi":"10.1016/j.mtbio.2025.101576","DOIUrl":"10.1016/j.mtbio.2025.101576","url":null,"abstract":"<div><div>An interbody fusion cage is crucial in spine fusion procedures, serving to restore physiological vertebral alignment and reestablish spinal stability. However, conventional fusion cages often face challenges related to insufficient osteointegration and the requirement for substantial bone grafting, which may result in incomplete fusion and prolonged recovery periods. In this study, we harnessed the osteointegration advantages of tantalum (Ta), in conjunction with advanced 3D printing technology, to develop a novel non-window-type Ta cage. The mechanical and biological characteristics of the cage were comprehensively evaluated through mechanical testing, in vitro cellular assays, and in vivo sheep anterior cervical discectomy and fusion models. The results indicated that the 3D-printed porous tantalum (3D-pTa) cage, with mechanical properties analogous to those of trabecular bone, exhibited superior bone ingrowth and osseointegration performance, achieving excellent intervertebral fusion without the need for bone grafting, thereby enhancing cervical vertebra stability. Moreover, we performed a pilot clinical trial to assess the performance of non-window-type 3D-pTa cages in single-level posterior lumbar interbody fusion. The results demonstrated that 3D-pTa achieved favorable clinical outcomes up to the 12-month follow-up period. These results highlight the significant clinical potential of the 3D-pTa cage for spinal fusion applications.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101576"},"PeriodicalIF":8.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-15DOI: 10.1016/j.mtbio.2025.101566
R. Santoro , L. Piacentini , C. Vavassori , P. Benzoni , G.I. Colombo , C. Banfi , A. Barbuti , G. Pompilio
Induced pluripotent stem cells (iPSCs), carrying the patient's genetic background, open the path to advanced in vitro modeling. The feasibility of recapitulating complex pathophysiological scenarios depends on iPSC's ability to differentiate into the plurality of specific organ resident cells, on their maturation and networking. To this end, a strong interest has arisen in organoids, 3D structures, obtained by exploiting iPSC natural capability to self-assemble and rebuild organ parts.
In this study, we describe the characterization of a novel iPSC-based cardiac organoid (CO) model, generated by a high-throughput and cost-effective method. Organoids were obtained by culture onto substrates of known stiffness, under geometrical confinement and inducing cardiac differentiation by small-molecule-based modulation of Wnt pathway. COs were characterized using a multi-omic approach (including bulk/single-cell RNA-sequencing, and proteomic analysis), immunofluorescence, electrophysiology (patch clamp), and optical recording-based contraction measurements.
Results showed that COs recapitulate relevant cardiac features, including spontaneous contraction, multicellularity (e.g., cardiomyocytes, fibroblasts, epicardial layer) and chamber organization. Moreover, modulation of environmental mechanical cues showed a significant effect on organoid cardiac features. In particular, culturing organoids onto substrates of low stiffness, in the range of that characterizing the embryonal surrounding, enriched the gene sets related to cardiac maturity and cardiomyocyte ultrastructure. Functionally, different cardiac-specific ionic currents and consistent spontaneous action potentials were recorded upon patch-clamp of cardiomyocytes dissociated from COs. Finally, the beating rate of the whole COs was monitored non-destructively via video recording and quantified, demonstrating their response to clinically used chronotropic compounds, supporting the feasibility of future implementation of the proposed COs as in vitro platform for drug testing.
{"title":"An in vitro model for cardiac organoid production: The combined role of geometrical confinement and substrate stiffness","authors":"R. Santoro , L. Piacentini , C. Vavassori , P. Benzoni , G.I. Colombo , C. Banfi , A. Barbuti , G. Pompilio","doi":"10.1016/j.mtbio.2025.101566","DOIUrl":"10.1016/j.mtbio.2025.101566","url":null,"abstract":"<div><div>Induced pluripotent stem cells (iPSCs), carrying the patient's genetic background, open the path to advanced <em>in vitro</em> modeling. The feasibility of recapitulating complex pathophysiological scenarios depends on iPSC's ability to differentiate into the plurality of specific organ resident cells, on their maturation and networking. To this end, a strong interest has arisen in organoids, 3D structures, obtained by exploiting iPSC natural capability to self-assemble and rebuild organ parts.</div><div>In this study, we describe the characterization of a novel iPSC-based cardiac organoid (CO) model, generated by a high-throughput and cost-effective method. Organoids were obtained by culture onto substrates of known stiffness, under geometrical confinement and inducing cardiac differentiation by small-molecule-based modulation of Wnt pathway. COs were characterized using a multi-omic approach (including bulk/single-cell RNA-sequencing, and proteomic analysis), immunofluorescence, electrophysiology (patch clamp), and optical recording-based contraction measurements.</div><div>Results showed that COs recapitulate relevant cardiac features, including spontaneous contraction, multicellularity (e.g., cardiomyocytes, fibroblasts, epicardial layer) and chamber organization. Moreover, modulation of environmental mechanical cues showed a significant effect on organoid cardiac features. In particular, culturing organoids onto substrates of low stiffness, in the range of that characterizing the embryonal surrounding, enriched the gene sets related to cardiac maturity and cardiomyocyte ultrastructure. Functionally, different cardiac-specific ionic currents and consistent spontaneous action potentials were recorded upon patch-clamp of cardiomyocytes dissociated from COs. Finally, the beating rate of the whole COs was monitored non-destructively via video recording and quantified, demonstrating their response to clinically used chronotropic compounds, supporting the feasibility of future implementation of the proposed COs as <em>in vitro</em> platform for drug testing.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101566"},"PeriodicalIF":8.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-15DOI: 10.1016/j.mtbio.2025.101582
Yunqing Pang , Lingyuan Kong , Yuanyuan Li , Jiamin Li , Qianlong Ma , Jing Qiu , Jing Wang
Diabetes and periodontitis exhibit a bidirectional relationship, posing significant challenges for the treatment of periodontitis in patients with diabetes. Our previous studies showed that the hypoglycemic agent liraglutide (LIRA), together with glycemic control, had favorable therapeutic effects on diabetic periodontitis (DP), achieving a “two birds with one stone” effect. Therefore, exploration of the topical application of LIRA for treating DP is warranted. In this study, nanoparticles were loaded with LIRA using poly (lactic-co-glycolic acid) (PLGA), and their morphology, particle size, encapsulation efficiency, drug loading, and drug release profiles were characterized. These nanoparticles were further encapsulated with hyaluronic acid (HA) to form a LIRA@PLGA/HA sustained-release system. The cytotoxicity of LIRA@PLGA/HA was analyzed using CCK-8 assays, and its anti-inflammatory and osteogenic effects on periodontitis in diabetic rats were evaluated by histology, ELISA, and micro-CT analysis, while its influence on necroptosis-related factors was assessed using qRT-PCR and Western blotting. The results indicated that LIRA@PLGA (30000 Da) exhibited an encapsulation efficiency of 86.2 %, a drug loading capacity of 4.3 %, and a cumulative release of LIRA reaching approximately 60 % after 8 days, thereby meting the requirement for sustained release. Following 24 h of stimulation with various concentrations (0–20 mg/ml) of LIRA@PLGA/HA, the viability of human periodontal ligament cells (HPDLCs) remained above 85 %. Topical application for four weeks significantly inhibited the expression of the inflammatory factors TNF-α and IL-1β in gingival crevicular fluid and serum, reduced inflammatory cell infiltration in periodontal tissues, and attenuated alveolar bone resorption while improving alveolar bone microstructure, showing therapeutic effects similar to the commercial drug PERIOCLINE® (PERIO). Furthermore, LIRA@PLGA/HA reduced the expression of necroptosis-related factors RIPK1, RIPK3, and MLKL. In conclusion, these results suggest that topical application of LIRA@PLGA/HA is effective for the treatment of DP through inhibition of necroptosis, representing a promising treatment strategy.
{"title":"PLGA/HA sustained-release system loaded with liraglutide for the treatment of diabetic periodontitis through inhibition of necroptosis","authors":"Yunqing Pang , Lingyuan Kong , Yuanyuan Li , Jiamin Li , Qianlong Ma , Jing Qiu , Jing Wang","doi":"10.1016/j.mtbio.2025.101582","DOIUrl":"10.1016/j.mtbio.2025.101582","url":null,"abstract":"<div><div>Diabetes and periodontitis exhibit a bidirectional relationship, posing significant challenges for the treatment of periodontitis in patients with diabetes. Our previous studies showed that the hypoglycemic agent liraglutide (LIRA), together with glycemic control, had favorable therapeutic effects on diabetic periodontitis (DP), achieving a “two birds with one stone” effect. Therefore, exploration of the topical application of LIRA for treating DP is warranted. In this study, nanoparticles were loaded with LIRA using poly (lactic-co-glycolic acid) (PLGA), and their morphology, particle size, encapsulation efficiency, drug loading, and drug release profiles were characterized. These nanoparticles were further encapsulated with hyaluronic acid (HA) to form a LIRA@PLGA/HA sustained-release system. The cytotoxicity of LIRA@PLGA/HA was analyzed using CCK-8 assays, and its anti-inflammatory and osteogenic effects on periodontitis in diabetic rats were evaluated by histology, ELISA, and micro-CT analysis, while its influence on necroptosis-related factors was assessed using qRT-PCR and Western blotting. The results indicated that LIRA@PLGA (30000 Da) exhibited an encapsulation efficiency of 86.2 %, a drug loading capacity of 4.3 %, and a cumulative release of LIRA reaching approximately 60 % after 8 days, thereby meting the requirement for sustained release. Following 24 h of stimulation with various concentrations (0–20 mg/ml) of LIRA@PLGA/HA, the viability of human periodontal ligament cells (HPDLCs) remained above 85 %. Topical application for four weeks significantly inhibited the expression of the inflammatory factors TNF-α and IL-1β in gingival crevicular fluid and serum, reduced inflammatory cell infiltration in periodontal tissues, and attenuated alveolar bone resorption while improving alveolar bone microstructure, showing therapeutic effects similar to the commercial drug PERIOCLINE® (PERIO). Furthermore, LIRA@PLGA/HA reduced the expression of necroptosis-related factors RIPK1, RIPK3, and MLKL. In conclusion, these results suggest that topical application of LIRA@PLGA/HA is effective for the treatment of DP through inhibition of necroptosis, representing a promising treatment strategy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101582"},"PeriodicalIF":8.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429838","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}
Breast reconstruction after mastectomy aims to restore breast appearance and function. Current scaffolds often fail to meet the complex clinical demands of post-mastectomy breast reconstruction, which include personalized shaping, prevention of tumor recurrence and metastasis, and promotion of adipose tissue regeneration. This study aims to address these challenges by combining a readily processable biopolymer, polycaprolactone (PCL), with a multifunctional bioactive ceramic, cobalt orthosilicate (Co2SiO4, CoSi) to form a multi-functional CoSi/PCL composite scaffold through 3D printing technology. The scaffold exhibits a controllable shape with designed macroporous architecture. Its photothermal performances are well presented in both near-infrared (NIR) I and NIR-II regions, enabling effective tumor ablation with minimal side effects. Additionally, the release of bioactive silicate and cobalt ions promotes adipogenesis and angiogenesis, thereby enhancing the integration of the scaffold with surrounding tissues. This approach offers a promising strategy for combining tumor therapy with breast reconstruction, providing a clinically relevant solution for post-mastectomy patients.
{"title":"3D-printed CoSi/PCL composite scaffold with NIR-II photothermal ability and enhanced adipogenic activity for breast reconstruction after mastectomy","authors":"Jupei Zhang , Hangbin Xia , Xuerui Zhou , Zhaoxu Meng , Qishu Jin , Dongmin Chen , Xiaojuan Xia , Yiren Jiao , Jiang Chang , Zhihong Dong , Zhen Zeng , Hongshi Ma , Chen Yang","doi":"10.1016/j.mtbio.2025.101577","DOIUrl":"10.1016/j.mtbio.2025.101577","url":null,"abstract":"<div><div>Breast reconstruction after mastectomy aims to restore breast appearance and function. Current scaffolds often fail to meet the complex clinical demands of post-mastectomy breast reconstruction, which include personalized shaping, prevention of tumor recurrence and metastasis, and promotion of adipose tissue regeneration. This study aims to address these challenges by combining a readily processable biopolymer, polycaprolactone (PCL), with a multifunctional bioactive ceramic, cobalt orthosilicate (Co<sub>2</sub>SiO<sub>4</sub>, CoSi) to form a multi-functional CoSi/PCL composite scaffold through 3D printing technology. The scaffold exhibits a controllable shape with designed macroporous architecture. Its photothermal performances are well presented in both near-infrared (NIR) I and NIR-II regions, enabling effective tumor ablation with minimal side effects. Additionally, the release of bioactive silicate and cobalt ions promotes adipogenesis and angiogenesis, thereby enhancing the integration of the scaffold with surrounding tissues. This approach offers a promising strategy for combining tumor therapy with breast reconstruction, providing a clinically relevant solution for post-mastectomy patients.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101577"},"PeriodicalIF":8.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-14DOI: 10.1016/j.mtbio.2025.101569
Qi Cheng , Qianping Guo , Xiaoyu Zhang , Yuanchen Zhu , Chengyuan Liu , Huan Wang , Caihong Zhu , Li Ni , Bin Li , Huilin Yang
The self-repair ability of articular cartilage is limited, which is one of the most difficult diseases to treat clinically. Kartogenin (KGN) induces chondrogenesis by regulating RUNX1 mRNA translation and the small molecule compound TD-198946 (TD) promotes chondrogenic differentiation of mesenchymal stem cells (MSCs) through increasing the transcription of RUNX1 mRNA. GelMA hydrogel and liposomes are respectively similar to the extracellular matrix (ECM) and extracellular vesicles (EVs). So, we developed an “EVs-in-ECM” mimicking system by incorporating GelMA and KGN/TD-loaded liposomes to investigate the repair effects of cartilage defect. First, western-blot, RNA fluorescence in situ hybridization (FISH), cellular immuno-fluorescence, co-immuno-precipitation (CO-IP), and qRT-PCR techniques showed that KGN regulated RUNX1 mRNA expression, and then promote chondrogenic differentiation of MSCs. Second, the role of RUNX1 was amplified by orchestrating RUNX1 transcription and translation through TD-198946 (TD) and KGN respectively, and the synergistic effects of TD and KGN on chondrogenesis of MSCs in vitro were discovered. Finally, an “EVs-in-ECM” mimicking system was designed for in situ cartilage repair. When GelMA loaded with KGN and TD liposomes, the hydrogel (KGN + TD@ GelMA) showed biological functions by the continuously controlled release of KGN and TD while maintaining its porous structure and mechanical strength, which enhanced the chondrogenesis of MSCs in one system. The repair performance of “EVs-in-ECM” in vivo was assessed using the articular osteochondral defect model of rat. The implantation of KGN + TD@ GelMA hydrogels effectively exerted favorable osteochondral repair effects showing structures similar to the native tissue, and prevented chondrocyte hypertrophy. The study indicate that the “EVs-in-ECM” mimicking system can act as a highly efficient and potent scaffold for osteochondral defect regeneration.
{"title":"An “EVs-in-ECM” mimicking system orchestrates transcription and translation of RUNX1 for in-situ cartilage regeneration","authors":"Qi Cheng , Qianping Guo , Xiaoyu Zhang , Yuanchen Zhu , Chengyuan Liu , Huan Wang , Caihong Zhu , Li Ni , Bin Li , Huilin Yang","doi":"10.1016/j.mtbio.2025.101569","DOIUrl":"10.1016/j.mtbio.2025.101569","url":null,"abstract":"<div><div>The self-repair ability of articular cartilage is limited, which is one of the most difficult diseases to treat clinically. Kartogenin (KGN) induces chondrogenesis by regulating RUNX1 mRNA translation and the small molecule compound TD-198946 (TD) promotes chondrogenic differentiation of mesenchymal stem cells (MSCs) through increasing the transcription of RUNX1 mRNA. GelMA hydrogel and liposomes are respectively similar to the extracellular matrix (ECM) and extracellular vesicles (EVs). So, we developed an “EVs-in-ECM” mimicking system by incorporating GelMA and KGN/TD-loaded liposomes to investigate the repair effects of cartilage defect. First, western-blot, RNA fluorescence in situ hybridization (FISH), cellular immuno-fluorescence, co-immuno-precipitation (CO-IP), and qRT-PCR techniques showed that KGN regulated RUNX1 mRNA expression, and then promote chondrogenic differentiation of MSCs. Second, the role of RUNX1 was amplified by orchestrating RUNX1 transcription and translation through TD-198946 (TD) and KGN respectively, and the synergistic effects of TD and KGN on chondrogenesis of MSCs in vitro were discovered. Finally, an “EVs-in-ECM” mimicking system was designed for in situ cartilage repair. When GelMA loaded with KGN and TD liposomes, the hydrogel (KGN + TD@ GelMA) showed biological functions by the continuously controlled release of KGN and TD while maintaining its porous structure and mechanical strength, which enhanced the chondrogenesis of MSCs in one system. The repair performance of “EVs-in-ECM” in vivo was assessed using the articular osteochondral defect model of rat. The implantation of KGN + TD@ GelMA hydrogels effectively exerted favorable osteochondral repair effects showing structures similar to the native tissue, and prevented chondrocyte hypertrophy. The study indicate that the “EVs-in-ECM” mimicking system can act as a highly efficient and potent scaffold for osteochondral defect regeneration.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101569"},"PeriodicalIF":8.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-14DOI: 10.1016/j.mtbio.2025.101578
Li Miao , Xue Lu , Yaoyao Wei , Jie Zhou , Yuanyuan Liu , Yang Zhang , Changle Meng , Mingyang Li , Hua Zhang , Wen Chen , Han Zhang
In diabetic wounds, the presence of hyperglycemia is often accompanied by a persistent inflammatory response, oxidative stress damage, impaired angiogenesis and bacterial infections around the wound, resulting in impaired proliferation of dermal and epidermal cells and impaired skin regeneration in diabetic wounds. To solve the above problems, this study designed a near-infrared (NIR) light-responsive multifunctional poloxamer hydrogel (EGF/PDA-MXene Gel). The Gel is composed of two-dimensional nanomaterials (2D NMs) MXene as the core, modified by polymer, further loaded with epidermal growth factor (EGF), and has antibacterial, antioxidant, photothermal properties. Meanwhile, EGF/PDA-MXene Gel can be used as a drug repository, alleviating the problem of short half-life, and realizing the sustained release of EGF. The NIR photothermal property induces protein denaturation leading to the death of pathogenic bacteria, avoiding the common clinical problem of antibiotic resistance. In addition, EGF/PDA-MXene Gel promotes diabetic chronic wound healing by promoting epidermal regeneration, collagen deposition, angiogenesis, and several other mechanisms. Therefore, the Gel preparation strategies that combine bioactive molecules with 2D NMs, which maintains the activity of EGF while exploiting the antimicrobial advantages of 2D NMs photothermally, provide a new and promising therapeutic approach for accelerating the repair of chronic infected wounds.
{"title":"Near-infrared light-responsive nanocomposite hydrogels loaded with epidermal growth factor for diabetic wound healing","authors":"Li Miao , Xue Lu , Yaoyao Wei , Jie Zhou , Yuanyuan Liu , Yang Zhang , Changle Meng , Mingyang Li , Hua Zhang , Wen Chen , Han Zhang","doi":"10.1016/j.mtbio.2025.101578","DOIUrl":"10.1016/j.mtbio.2025.101578","url":null,"abstract":"<div><div>In diabetic wounds, the presence of hyperglycemia is often accompanied by a persistent inflammatory response, oxidative stress damage, impaired angiogenesis and bacterial infections around the wound, resulting in impaired proliferation of dermal and epidermal cells and impaired skin regeneration in diabetic wounds. To solve the above problems, this study designed a near-infrared (NIR) light-responsive multifunctional poloxamer hydrogel (EGF/PDA-MXene Gel). The Gel is composed of two-dimensional nanomaterials (2D NMs) MXene as the core, modified by polymer, further loaded with epidermal growth factor (EGF), and has antibacterial, antioxidant, photothermal properties. Meanwhile, EGF/PDA-MXene Gel can be used as a drug repository, alleviating the problem of short half-life, and realizing the sustained release of EGF. The NIR photothermal property induces protein denaturation leading to the death of pathogenic bacteria, avoiding the common clinical problem of antibiotic resistance. In addition, EGF/PDA-MXene Gel promotes diabetic chronic wound healing by promoting epidermal regeneration, collagen deposition, angiogenesis, and several other mechanisms. Therefore, the Gel preparation strategies that combine bioactive molecules with 2D NMs, which maintains the activity of EGF while exploiting the antimicrobial advantages of 2D NMs photothermally, provide a new and promising therapeutic approach for accelerating the repair of chronic infected wounds.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101578"},"PeriodicalIF":8.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-14DOI: 10.1016/j.mtbio.2025.101575
Guoqing Wei , Tiantian Xiao , Yufeng Xi, Rong Ju
The innate immune system's inactivation and microbial biofilm-induced antibiotic resistance are the main causes of implant-associated infections (IAIs), which frequently result in implant surgical failure. Refractory recolonization is the consequence of standard therapies that are unable to consistently suppress escaping planktonic bacteria from biofilm, thereby enabling IAIs to thrive. Here, we specifically designed a macrophage-like biomimetic nanoparticle (F/R@PM) for a biofilm microenvironment (BME), which was fabricated by coating the cell membrane derived from macrophage onto poly (lactic-co-glycolic acid) (PLGA) namoparticles (NPs) loaded with FOT (NO donor) and R837 (TLR7 agonist). After injecting F/R@PM into mice with implant-associated infections, it was able to selectively target macrophages through macrophage membrane proteins on its surface and effectively release FOT and R837. Then, FOT that spreads outside the cell could react with glutathione (GSH) in the BEM to rapidly produce a large amount of NO inside biofilms to destroy the biofilm and kill bacteria. At the same time, R837 would encourage macrophages to scavenge planktonic bacteria that had escaped biofilm disintegration through improved phagocytosis. Overall, this work shows that NO treatment and immunotherapy together have promising potential for the long-term and efficient control and eradication of IAIs.
{"title":"A macrophage-like biomimetic nanoparticle with high-efficiency biofilm disruption and innate immunity activation for implant-related infection therapy","authors":"Guoqing Wei , Tiantian Xiao , Yufeng Xi, Rong Ju","doi":"10.1016/j.mtbio.2025.101575","DOIUrl":"10.1016/j.mtbio.2025.101575","url":null,"abstract":"<div><div>The innate immune system's inactivation and microbial biofilm-induced antibiotic resistance are the main causes of implant-associated infections (IAIs), which frequently result in implant surgical failure. Refractory recolonization is the consequence of standard therapies that are unable to consistently suppress escaping planktonic bacteria from biofilm, thereby enabling IAIs to thrive. Here, we specifically designed a macrophage-like biomimetic nanoparticle (F/R@PM) for a biofilm microenvironment (BME), which was fabricated by coating the cell membrane derived from macrophage onto poly (lactic-co-glycolic acid) (PLGA) namoparticles (NPs) loaded with FOT (NO donor) and R837 (TLR7 agonist). After injecting F/R@PM into mice with implant-associated infections, it was able to selectively target macrophages through macrophage membrane proteins on its surface and effectively release FOT and R837. Then, FOT that spreads outside the cell could react with glutathione (GSH) in the BEM to rapidly produce a large amount of NO inside biofilms to destroy the biofilm and kill bacteria. At the same time, R837 would encourage macrophages to scavenge planktonic bacteria that had escaped biofilm disintegration through improved phagocytosis. Overall, this work shows that NO treatment and immunotherapy together have promising potential for the long-term and efficient control and eradication of IAIs.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101575"},"PeriodicalIF":8.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-12DOI: 10.1016/j.mtbio.2025.101567
Wenzhu Yin , Zeyu Xu , Fang Ma , Bihua Deng , Yanhong Zhao , Xiaoxin Zuo , Haiyan Wang , Yu Lu
Excellent adjuvants and proper immunization routes play pivotal roles in activating a robust immune response. Nano-adjuvants have the advantages of enhancing immunogenicity, targeting delivery, and improving stability to provide a new solution for vaccine delivery. In this work, we designed and synthesized a pro-immunostimulant of liposolubility imiquimod derivative IMQP, which was synthesized by reaction of palmitoyl chloride with parent imiquimod (IMQ). Using an inactivated foot-and-mouth disease virus (FMDV) as antigen, and the as-synthesized IMQP containing long carbon chain as nano-adjuvant, we formulated a self-assembled foot-and-mouth disease nano-vaccine (IMQP@FMDV) by re-precipitation method for intradermal (I.D.) immunity vaccination. Because of its small size (∼131.75 ± 41.70 nm) and fat-soluble, the as-fabricated lipid nanoparticles (LNPs) showed promising potential for efficient delivery of antigens to immune cells. Also, lysosomal escape was confirmed by co-localization dendritic cells (DCs). Our findings demonstrated that IMQP nano-adjuvant greatly promoted the expression and secretion of cytokines and chemokines with a balance Th1/Th2 immune response via the I.D. administration. Meanwhile, due to the slowly releasing of IMQ by the hydrolysis of IMQP, IMQP persistently stimulated antigen-presenting cells (APCs) maturation and promoted antigen presentation, and subsequently induced the activation of the related downstream NF-кB and MAPK pathways of the TLR7 signaling pathway, thereby stimulated a robust both humoral and cellular immune response.
{"title":"Nano-adjuvant based on lipo-imiquimod self-assembly for enhanced foot-and-mouth disease virus vaccine immune responses via intradermal immunization","authors":"Wenzhu Yin , Zeyu Xu , Fang Ma , Bihua Deng , Yanhong Zhao , Xiaoxin Zuo , Haiyan Wang , Yu Lu","doi":"10.1016/j.mtbio.2025.101567","DOIUrl":"10.1016/j.mtbio.2025.101567","url":null,"abstract":"<div><div>Excellent adjuvants and proper immunization routes play pivotal roles in activating a robust immune response. Nano-adjuvants have the advantages of enhancing immunogenicity, targeting delivery, and improving stability to provide a new solution for vaccine delivery. In this work, we designed and synthesized a pro-immunostimulant of liposolubility imiquimod derivative IMQP, which was synthesized by reaction of palmitoyl chloride with parent imiquimod (IMQ). Using an inactivated foot-and-mouth disease virus (FMDV) as antigen, and the as-synthesized IMQP containing long carbon chain as nano-adjuvant, we formulated a self-assembled foot-and-mouth disease nano-vaccine (IMQP@FMDV) by re-precipitation method for intradermal (I.D.) immunity vaccination. Because of its small size (∼131.75 ± 41.70 nm) and fat-soluble, the as-fabricated lipid nanoparticles (LNPs) showed promising potential for efficient delivery of antigens to immune cells. Also, lysosomal escape was confirmed by co-localization dendritic cells (DCs). Our findings demonstrated that IMQP nano-adjuvant greatly promoted the expression and secretion of cytokines and chemokines with a balance Th1/Th2 immune response <em>via</em> the I.D. administration. Meanwhile, due to the slowly releasing of IMQ by the hydrolysis of IMQP, IMQP persistently stimulated antigen-presenting cells (APCs) maturation and promoted antigen presentation, and subsequently induced the activation of the related downstream NF-кB and MAPK pathways of the TLR7 signaling pathway, thereby stimulated a robust both humoral and cellular immune response.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"31 ","pages":"Article 101567"},"PeriodicalIF":8.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429836","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号