Pub Date : 2024-10-14DOI: 10.1016/j.bioactmat.2024.09.013
Jiseong Kim , Myung Chul Lee , Jieun Jeon , Alejandra Rodríguez-delaRosa , Yori Endo , Da-Seul Kim , Andrea Donaxi Madrigal-Salazar , Jeong Wook Seo , Hyeseon Lee , Ki-Tae Kim , Jae-I Moon , Seung Gwa Park , Mariana Carolina Lopez-Pacheco , Abdulhameed F. Alkhateeb , Nebras Sobahi , Nicole Bassous , Wenpeng Liu , Jae Seo Lee , Seongsoo Kim , Dilara Yilmaz Aykut , Su Ryon Shin
In regenerative medicine, extracellular vesicles (EVs) possess the potential to repair injured cells by delivering modulatory factors. However, the therapeutic effect of EVs in large-scale tissue defects, which are subject to prolonged timelines for tissue architecture and functional restoration, remains poorly understood. In this study, we introduce EVs and cell-tethering hybrid hydrogels composed of tyramine-conjugated gelatin (GelTA) that can be in-situ crosslinked with EVs derived from human induced pluripotent stem cell-derived myofibers (hiPSC-myofibers) and hiPSC-muscle precursor cells. This hybrid hydrogel sustains the release of EVs and provides a beneficial nano-topography and mechanical properties for creating a favorable extracellular matrix. Secreted EVs from the hiPSC-myofibers contain specific microRNAs, potentially improving myogenesis and angiogenesis. Herein, we demonstrate increased myogenic markers and fusion/differentiation indexes through the combinatory effects of EVs and integrin-mediated adhesions in the 3D matrix. Furthermore, we observe a unique impact of EVs, which aid in maintaining the viability and phenotype of myofibers under harsh environments. The hybrid hydrogel in-situ crosslinked with hiPSCs and EVs is facilely used to fabricate large-scale muscle constructs by the stacking of micro-patterned hydrogel domains. Later, we confirmed a combinational effect, whereby muscle tissue regeneration and functional restoration were improved, via an in vivo murine volumetric muscle loss model.
{"title":"Combinational regenerative inductive effect of bio-adhesive hybrid hydrogels conjugated with hiPSC-derived myofibers and its derived EVs for volumetric muscle regeneration","authors":"Jiseong Kim , Myung Chul Lee , Jieun Jeon , Alejandra Rodríguez-delaRosa , Yori Endo , Da-Seul Kim , Andrea Donaxi Madrigal-Salazar , Jeong Wook Seo , Hyeseon Lee , Ki-Tae Kim , Jae-I Moon , Seung Gwa Park , Mariana Carolina Lopez-Pacheco , Abdulhameed F. Alkhateeb , Nebras Sobahi , Nicole Bassous , Wenpeng Liu , Jae Seo Lee , Seongsoo Kim , Dilara Yilmaz Aykut , Su Ryon Shin","doi":"10.1016/j.bioactmat.2024.09.013","DOIUrl":"10.1016/j.bioactmat.2024.09.013","url":null,"abstract":"<div><div>In regenerative medicine, extracellular vesicles (EVs) possess the potential to repair injured cells by delivering modulatory factors. However, the therapeutic effect of EVs in large-scale tissue defects, which are subject to prolonged timelines for tissue architecture and functional restoration, remains poorly understood. In this study, we introduce EVs and cell-tethering hybrid hydrogels composed of tyramine-conjugated gelatin (GelTA) that can be <em>in-situ</em> crosslinked with EVs derived from human induced pluripotent stem cell-derived myofibers (hiPSC-myofibers) and hiPSC-muscle precursor cells. This hybrid hydrogel sustains the release of EVs and provides a beneficial nano-topography and mechanical properties for creating a favorable extracellular matrix. Secreted EVs from the hiPSC-myofibers contain specific microRNAs, potentially improving myogenesis and angiogenesis. Herein, we demonstrate increased myogenic markers and fusion/differentiation indexes through the combinatory effects of EVs and integrin-mediated adhesions in the 3D matrix. Furthermore, we observe a unique impact of EVs, which aid in maintaining the viability and phenotype of myofibers under harsh environments. The hybrid hydrogel <em>in-situ</em> crosslinked with hiPSCs and EVs is facilely used to fabricate large-scale muscle constructs by the stacking of micro-patterned hydrogel domains. Later, we confirmed a combinational effect, whereby muscle tissue regeneration and functional restoration were improved, via an <em>in vivo</em> murine volumetric muscle loss model.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 579-602"},"PeriodicalIF":18.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433870","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 : 2024-10-14DOI: 10.1016/j.bioactmat.2024.09.035
Yuan Gao , Mengyao Mu , Yiju Wei , Bowen Yan , Hui Liu , Kai Guo , Mengmeng Zhang , Xiaohui Dai , Xiao Sun , David Tai Leong
Biodegradable two-dimensional nanomaterials could be a significant breakthrough in the field of oncology nanotheranostic agents, which are rapidly emerging as promising candidates for tumor theranostic applications. Herein, a novel biodegradable ferrous sulfide nanosheet (FeS NS) is developed. Compared to the traditional photothermal material, black phosphorus nanosheet (BP NS), FeS demonstrates superior degradability and enhanced photothermal performance, and making it ideal for efficient photothermal therapy (PTT) of tumors. In the acidic tumor microenvironment, FeS degrades and releases H2S, which inhibits mitochondrial respiration and ATP production. This process leads to a reduction in heat shock protein expression, lowering the resistance of tumor cells to photothermal stimulation, and improving the efficacy of PTT. The released Fe2+ exhibits efficient peroxidase activity, triggering ferroptosis in tumor cells. Furthermore, due to its superparamagnetic nature, FeS NSs could accumulate at the tumor site and provide a strong magnetic resonance imaging (MRI) signal for imaging-guided tumor therapy. Overall, as a promising alternative to BP, the FeS NSs are a potentially innovative nanotheranostic agent of tumors, offering a synergistic approach to ferroptosis−PTT with MRI guidance.
可生物降解的二维纳米材料可能是肿瘤纳米治疗剂领域的一个重大突破，它正迅速成为肿瘤治疗应用的有前途的候选材料。本文开发了一种新型可生物降解硫化亚铁纳米片（FeS NS）。与传统的光热材料黑磷纳米片（BP NS）相比，硫化亚铁具有更优越的可降解性和更强的光热性能，是肿瘤高效光热疗法（PTT）的理想选择。在酸性肿瘤微环境中，FeS 会降解并释放出 H2S，从而抑制线粒体呼吸和 ATP 的产生。这一过程会减少热休克蛋白的表达，降低肿瘤细胞对光热刺激的抵抗力，提高 PTT 的疗效。释放出的 Fe2+ 具有高效的过氧化物酶活性，可引发肿瘤细胞的铁变态反应。此外，由于具有超顺磁性，FeS NSs 可以在肿瘤部位聚集，为成像引导的肿瘤治疗提供强大的磁共振成像（MRI）信号。总之，作为 BP 的一种有前途的替代品，FeS NSs 是一种潜在的创新性肿瘤纳米otheranostic 药剂，提供了一种具有磁共振成像引导的铁卟啉-PTT 协同方法。
{"title":"Novel ultrathin ferrous sulfide nanosheets: Towards replacing black phosphorus in anticancer nanotheranostics","authors":"Yuan Gao , Mengyao Mu , Yiju Wei , Bowen Yan , Hui Liu , Kai Guo , Mengmeng Zhang , Xiaohui Dai , Xiao Sun , David Tai Leong","doi":"10.1016/j.bioactmat.2024.09.035","DOIUrl":"10.1016/j.bioactmat.2024.09.035","url":null,"abstract":"<div><div>Biodegradable two-dimensional nanomaterials could be a significant breakthrough in the field of oncology nanotheranostic agents, which are rapidly emerging as promising candidates for tumor theranostic applications. Herein, a novel biodegradable ferrous sulfide nanosheet (FeS NS) is developed. Compared to the traditional photothermal material, black phosphorus nanosheet (BP NS), FeS demonstrates superior degradability and enhanced photothermal performance, and making it ideal for efficient photothermal therapy (PTT) of tumors. In the acidic tumor microenvironment, FeS degrades and releases H<sub>2</sub>S, which inhibits mitochondrial respiration and ATP production. This process leads to a reduction in heat shock protein expression, lowering the resistance of tumor cells to photothermal stimulation, and improving the efficacy of PTT. The released Fe<sup>2+</sup> exhibits efficient peroxidase activity, triggering ferroptosis in tumor cells. Furthermore, due to its superparamagnetic nature, FeS NSs could accumulate at the tumor site and provide a strong magnetic resonance imaging (MRI) signal for imaging-guided tumor therapy. Overall, as a promising alternative to BP, the FeS NSs are a potentially innovative nanotheranostic agent of tumors, offering a synergistic approach to ferroptosis−PTT with MRI guidance.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 564-578"},"PeriodicalIF":18.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433869","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 : 2024-10-14DOI: 10.1016/j.bioactmat.2024.09.039
Xiao Yue , Haihua Guo , Guanlin Wang , Jieyun Li , Zizhao Zhai , Zeting Wang , Wenhao Wang , Ziyu Zhao , Xiao Xia , Chuangxin Chen , Yingtong Cui , Chuanbin Wu , Zhengwei Huang , Xuejuan Zhang
With the aging of the population, the incidence of Alzheimer's disease (AD) has increased dramatically, causing severe medical, care, and economic burdens on society and families. The efficacy of rivastigmine hydrogen tartrate (RHT), the first-line clinical treatment, is severely limited by the complex and multiple pathogenesis of AD and low brain bioavailability caused by the blood-brain barrier (BBB). Confronting such two bottlenecks, the development of multi-target agents encapsulated BBB-bypassing drug delivery systems offer tremendous therapeutics possibilities for AD. In this study, a tailored phytosomes based nose-to-brain drug delivery system with appropriate plume was successfully designed and developed. On the one hand, Ginseng RG3-based phytosomes loaded with RHT was designed for the co-delivery of GRg3 and RHT, achieving the multi-target pharmacology for AD treatment. On the other hand, a tailored nose-to-brain drug delivery system was established for the satisfactory nose-to-brain delivery efficiency, avoiding the obstacle of BBB through bypassing it. In the pharmacodynamic study based on AD rat model, GRg3@RHT exhibited obviously synergic effect, effectively break the vicious cycle of AD progression, ultimately markedly ameliorating learning and memory ability as well as behavioral dysfunctions, and delaying the neurodegenerative process associated with AD. In addition, the strong correlation of viscosity-droplet size-plume geometry-olfactory deposition was also established, and further proved by the in vivo pharmacokinetic study, which is proposed to provide evidence to enhance nose-to-brain delivery efficiency. This study is anticipated to provide novel insights into AD treatment strategies while offering innovative ideas for drug delivery approaches targeting nervous system disorders.
{"title":"A tailored phytosomes based nose-to-brain drug delivery strategy: Silver bullet for Alzheimer's disease","authors":"Xiao Yue , Haihua Guo , Guanlin Wang , Jieyun Li , Zizhao Zhai , Zeting Wang , Wenhao Wang , Ziyu Zhao , Xiao Xia , Chuangxin Chen , Yingtong Cui , Chuanbin Wu , Zhengwei Huang , Xuejuan Zhang","doi":"10.1016/j.bioactmat.2024.09.039","DOIUrl":"10.1016/j.bioactmat.2024.09.039","url":null,"abstract":"<div><div>With the aging of the population, the incidence of Alzheimer's disease (AD) has increased dramatically, causing severe medical, care, and economic burdens on society and families. The efficacy of rivastigmine hydrogen tartrate (RHT), the first-line clinical treatment, is severely limited by the complex and multiple pathogenesis of AD and low brain bioavailability caused by the blood-brain barrier (BBB). Confronting such two bottlenecks, the development of multi-target agents encapsulated BBB-bypassing drug delivery systems offer tremendous therapeutics possibilities for AD. In this study, a tailored phytosomes based nose-to-brain drug delivery system with appropriate plume was successfully designed and developed. On the one hand, Ginseng RG3-based phytosomes loaded with RHT was designed for the co-delivery of GRg3 and RHT, achieving the multi-target pharmacology for AD treatment. On the other hand, a tailored nose-to-brain drug delivery system was established for the satisfactory nose-to-brain delivery efficiency, avoiding the obstacle of BBB through bypassing it. In the pharmacodynamic study based on AD rat model, GRg3@RHT exhibited obviously synergic effect, effectively break the vicious cycle of AD progression, ultimately markedly ameliorating learning and memory ability as well as behavioral dysfunctions, and delaying the neurodegenerative process associated with AD. In addition, the strong correlation of viscosity-droplet size-plume geometry-olfactory deposition was also established, and further proved by the <em>in vivo</em> pharmacokinetic study, which is proposed to provide evidence to enhance nose-to-brain delivery efficiency. This study is anticipated to provide novel insights into AD treatment strategies while offering innovative ideas for drug delivery approaches targeting nervous system disorders.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"44 ","pages":"Pages 97-115"},"PeriodicalIF":18.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433234","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 : 2024-10-13DOI: 10.1016/j.bioactmat.2024.10.005
Takuro Shirasu , Go Urabe , Nisakorn Yodsanit , Yitao Huang , Ruosen Xie , Matthew S. Stratton , Matthew Joseph , Zhanpeng Zhang , Yuyuan Wang , Jing Li , Runze Tang , Lynn M. Marcho , Li Yin , Eric W. Kent , Kaijie Zhang , Ki Ho Park , Bowen Wang , K. Craig Kent , Shaoqin Gong , Lian-Wang Guo
Open vascular reconstructions (OVR), including bypass grafts and dialysis access, are standard treatments for cardiovascular and renal diseases. Unfortunately, OVR often fail largely due to intimal hyperplasia (IH), and there are no clinical methods to prevent this complication. Perivascular drug administration during OVR presents a promising strategy for IH suppression. However, durations of drug release from carriers are generally short whereas sustained efficacy is essential for clinical success. This raises a critical question in clinical translation: can IH suppression be realistically maintained long-term (e.g., over 6 months) with short-term perivascular interventions? To address this question, we modified a rat vein-graft model to prolong IH progression. We then applied Pericelle, a nanoparticle/hydrogel hybrid system that we developed for perivascular delivery of rapamycin, an established IH-inhibitory drug. Surprisingly, despite short (∼3-month) drug release, Pericelle demonstrated IH suppression throughout 3, 6, and 9 months with IH reduced from 115.58 ± 27.89 to 40.34 ± 5.18 at 9 months (P < 0.05, n = 6 rats), as indicated by morphometric analysis. Live animal ultrasonography showed the same trend. Consistently, histone-3 lysine-27 trimethylation, an epigenetic mark associated with IH progression, was decreased at 6 months after Pericelle treatment. Moreover, Pericelle exhibited promising efficacy in mitigating IH in a porcine model of arteriovenous fistula that mimics dialysis access. These results suggest that Pericelle-mediated suppression of IH in rat vein-grafts extends much beyond drug release, offering potential solutions to longstanding translational challenges in reducing OVR failure.
开放式血管重建（OVR），包括旁路移植和透析通路，是心血管和肾脏疾病的标准治疗方法。遗憾的是，开放性血管重建失败的主要原因是血管内膜增生（IH），目前还没有预防这种并发症的临床方法。在 OVR 期间进行血管周围给药是抑制内膜增生的一种可行策略。然而，载体释放药物的持续时间通常很短，而持续疗效是临床成功的关键。这就提出了一个临床转化的关键问题：短期的血管周围干预能否长期（如 6 个月）维持 IH 抑制？为了解决这个问题，我们对大鼠静脉移植模型进行了改造，以延长 IH 的进展时间。然后，我们应用了 Pericelle，这是我们开发的一种纳米颗粒/水凝胶混合系统，用于在血管周围输送雷帕霉素，这是一种公认的 IH 抑制药物。令人惊讶的是，尽管药物释放时间很短（∼3 个月），但 Pericelle 在 3、6 和 9 个月期间都表现出了 IH 抑制作用，形态分析表明，IH 从 115.58 ± 27.89 降至 9 个月时的 40.34 ± 5.18（P < 0.05，n = 6 只大鼠）。活体动物超声波检查也显示了同样的趋势。一致的是，组蛋白-3 赖氨酸-27 三甲基化（一种与 IH 进展相关的表观遗传标记）在 Pericelle 治疗 6 个月后有所降低。此外，在模拟透析通路的猪动静脉瘘模型中，Pericelle 在缓解 IH 方面表现出良好的疗效。这些结果表明，Pericelle 介导的对大鼠静脉移植物 IH 的抑制远远超出了药物释放的范围，为减少 OVR 失败的长期转化挑战提供了潜在的解决方案。
{"title":"Nano-based perivascular intervention sustains a nine-month long-term suppression of intimal hyperplasia in vein grafts","authors":"Takuro Shirasu , Go Urabe , Nisakorn Yodsanit , Yitao Huang , Ruosen Xie , Matthew S. Stratton , Matthew Joseph , Zhanpeng Zhang , Yuyuan Wang , Jing Li , Runze Tang , Lynn M. Marcho , Li Yin , Eric W. Kent , Kaijie Zhang , Ki Ho Park , Bowen Wang , K. Craig Kent , Shaoqin Gong , Lian-Wang Guo","doi":"10.1016/j.bioactmat.2024.10.005","DOIUrl":"10.1016/j.bioactmat.2024.10.005","url":null,"abstract":"<div><div>Open vascular reconstructions (OVR), including bypass grafts and dialysis access, are standard treatments for cardiovascular and renal diseases. Unfortunately, OVR often fail largely due to intimal hyperplasia (IH), and there are no clinical methods to prevent this complication. Perivascular drug administration during OVR presents a promising strategy for IH suppression. However, durations of drug release from carriers are generally short whereas sustained efficacy is essential for clinical success. This raises a critical question in clinical translation: can IH suppression be realistically maintained long-term (e.g., over 6 months) with short-term perivascular interventions? To address this question, we modified a rat vein-graft model to prolong IH progression. We then applied Pericelle, a nanoparticle/hydrogel hybrid system that we developed for perivascular delivery of rapamycin, an established IH-inhibitory drug. Surprisingly, despite short (∼3-month) drug release, Pericelle demonstrated IH suppression throughout 3, 6, and 9 months with IH reduced from 115.58 ± 27.89 to 40.34 ± 5.18 at 9 months (P < 0.05, n = 6 rats), as indicated by morphometric analysis. Live animal ultrasonography showed the same trend. Consistently, histone-3 lysine-27 trimethylation, an epigenetic mark associated with IH progression, was decreased at 6 months after Pericelle treatment. Moreover, Pericelle exhibited promising efficacy in mitigating IH in a porcine model of arteriovenous fistula that mimics dialysis access. These results suggest that Pericelle-mediated suppression of IH in rat vein-grafts extends much beyond drug release, offering potential solutions to longstanding translational challenges in reducing OVR failure.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"44 ","pages":"Pages 82-96"},"PeriodicalIF":18.0,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433233","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 : 2024-10-11DOI: 10.1016/j.bioactmat.2024.09.038
Wendi Zhu , Yue Wu , Xiao Li , Hongjun Yang , Fuchu He , Jie Ma , Junying Wei , Ling Leng
Stroke is one of the top causes of death and disability worldwide, and its pathogenesis and mechanism have not been fully elucidated. Several agents have shown protective effects against stroke in animal models; however, few studies have shown obvious effects in clinical practice. This might be due to differences in brain structure and physiological function between humans and rodents. In this study, we established a hypoxic stroke model in human-induced pluripotent stem cell (hiPSC)-derived brain organoids to simulate the hypoxic stroke caused by ischemia. Then, by combining proteomics, single-cell transcriptome analysis, and histopathological analysis, a significant increase of three types of astrocytes was identified and they showed different responses to hypoxic environments; also the main type of astrocyte that cause brain tissue hyperplasia in ischemia brains was identified. In addition, the cortical excitatory neurons had signs of apoptosis and aging after hypoxia both in vivo and in vitro. Most importantly, we identified a possible role of a traditional Chinese medicine formula called DengZhanShengMai capsule in ischemic and hypoxic stroke treatment through regulation of lipid metabolism related biological functions. These results indicate that the combination of brain organoids and multiomics method is helpful for developing a new strategy to direct study stroke, and could provide a promising platform for drug screening of stroke in the future.
{"title":"A stroke organoids-multiomics platform to study injury mechanism and drug response","authors":"Wendi Zhu , Yue Wu , Xiao Li , Hongjun Yang , Fuchu He , Jie Ma , Junying Wei , Ling Leng","doi":"10.1016/j.bioactmat.2024.09.038","DOIUrl":"10.1016/j.bioactmat.2024.09.038","url":null,"abstract":"<div><div>Stroke is one of the top causes of death and disability worldwide, and its pathogenesis and mechanism have not been fully elucidated. Several agents have shown protective effects against stroke in animal models; however, few studies have shown obvious effects in clinical practice. This might be due to differences in brain structure and physiological function between humans and rodents. In this study, we established a hypoxic stroke model in human-induced pluripotent stem cell (hiPSC)-derived brain organoids to simulate the hypoxic stroke caused by ischemia. Then, by combining proteomics, single-cell transcriptome analysis, and histopathological analysis, a significant increase of three types of astrocytes was identified and they showed different responses to hypoxic environments; also the main type of astrocyte that cause brain tissue hyperplasia in ischemia brains was identified. In addition, the cortical excitatory neurons had signs of apoptosis and aging after hypoxia both <em>in vivo</em> and <em>in vitro</em>. Most importantly, we identified a possible role of a traditional Chinese medicine formula called DengZhanShengMai capsule in ischemic and hypoxic stroke treatment through regulation of lipid metabolism related biological functions. These results indicate that the combination of brain organoids and multiomics method is helpful for developing a new strategy to direct study stroke, and could provide a promising platform for drug screening of stroke in the future.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"44 ","pages":"Pages 68-81"},"PeriodicalIF":18.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142426322","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 : 2024-10-11DOI: 10.1016/j.bioactmat.2024.09.040
Wenbin Liu , Kai Zhang , Yan Sun , Zhenyang Xiao , Hongkun Hu , Zixuan Xiong , Yihe Hu
Bacterial infection and delayed osteointegration are two major challenges for orthopedic implants. Surface modification enables the implant have a time-sequenced biological function of effective antibacterial in the early stage and stable osteogenesis in the later stage, which is expected to achieve the purpose of preventing infection and prosthetic loosening after implant surgery. This study aims to construct a composite coating of carboxymethyl chitosan (CCS) grafted with an antibacterial (HHC36) and angiogenic (FP) fusion peptide (FP) on the surface of 3D-printed porous tantalum (Ta-CCS@FP) using alkaline treatment, electrostatic adsorption, and EDC/NHS reaction, to functionalize the surface coating while maintaining the original advantages of the material. The functionalized implants (Ta-CCS@FP) achieve sustained FP release in the initial stages, exhibiting potent antibacterial and anti-biofilm properties due to the synergistic action of the antimicrobial peptides (AMPs) HHC36 and CCS in disrupting bacterial membranes. Additionally, Ta-CCS@FP demonstrate robust osteogenic and angiogenic capabilities compared to Ta and Ta-CCS, attributed to QK and CCS. Notably, the conditioned medium intervention experiments of HUVECs and BMSCs showed that the implants had good angiogenic-osteogenic coupling properties. In vivo assays using infection bone defect models revealed that these bioactive implants effectively eradicated bacteria within 2 weeks and facilitated vascularized bone regeneration by 6 weeks. Thus, our study offers an integrated approach to address bacterial infection and enhance osseointegration for porous tantalum implants.
{"title":"Multidimensional treatment of periprosthetic joint infection using fusion peptide-grafted chitosan coated porous tantalum scaffold","authors":"Wenbin Liu , Kai Zhang , Yan Sun , Zhenyang Xiao , Hongkun Hu , Zixuan Xiong , Yihe Hu","doi":"10.1016/j.bioactmat.2024.09.040","DOIUrl":"10.1016/j.bioactmat.2024.09.040","url":null,"abstract":"<div><div>Bacterial infection and delayed osteointegration are two major challenges for orthopedic implants. Surface modification enables the implant have a time-sequenced biological function of effective antibacterial in the early stage and stable osteogenesis in the later stage, which is expected to achieve the purpose of preventing infection and prosthetic loosening after implant surgery. This study aims to construct a composite coating of carboxymethyl chitosan (CCS) grafted with an antibacterial (HHC36) and angiogenic (FP) fusion peptide (FP) on the surface of 3D-printed porous tantalum (Ta-CCS@FP) using alkaline treatment, electrostatic adsorption, and EDC/NHS reaction, to functionalize the surface coating while maintaining the original advantages of the material. The functionalized implants (Ta-CCS@FP) achieve sustained FP release in the initial stages, exhibiting potent antibacterial and anti-biofilm properties due to the synergistic action of the antimicrobial peptides (AMPs) HHC36 and CCS in disrupting bacterial membranes. Additionally, Ta-CCS@FP demonstrate robust osteogenic and angiogenic capabilities compared to Ta and Ta-CCS, attributed to QK and CCS. Notably, the conditioned medium intervention experiments of HUVECs and BMSCs showed that the implants had good angiogenic-osteogenic coupling properties. <em>In vivo</em> assays using infection bone defect models revealed that these bioactive implants effectively eradicated bacteria within 2 weeks and facilitated vascularized bone regeneration by 6 weeks. Thus, our study offers an integrated approach to address bacterial infection and enhance osseointegration for porous tantalum implants.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"44 ","pages":"Pages 15-33"},"PeriodicalIF":18.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142426383","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 : 2024-10-11DOI: 10.1016/j.bioactmat.2024.10.002
WonJin Kim , Dong Rak Kwon , Hyeongjin Lee , JaeYoon Lee , Yong Suk Moon , Sang Chul Lee , Geun Hyung Kim
Rotator cuff tears are common among physically active individuals and often require surgical intervention owing to their limited self-healing capacity. This study proposes a new bioprinting approach using bone- and tendon tissue-specific bioinks derived from decellularized extracellular matrix, supplemented with hydroxyapatite and TGF-β/poly(vinyl alcohol) to fabricate engineered tendon-to-bone complex tissue. To achieve this goal, a core-shell nozzle system attached to a bioprinter enables the effective and simultaneous fabrication of aligned tendon tissue, a gradient tendon-bone interface (TBI), and a mechanically improved bone region, mimicking the native tendon-to-bone structure. In vitro evaluation demonstrated the well-directed differentiation of human adipose stem cells towards osteogenic and tenogenic lineages in the bone and tendon constructs. In the graded TBI structure, further facilitated fibrocartilage formation and enhanced the integration of tendon-to-bone tissues compared to non-graded structures in vitro. Furthermore, using a rabbit rotator cuff tear model, implantation of the biologically graded constructs significantly promoted the rapid regeneration of full-thickness tendon-to-bone tissue, including the formation of a high-quality TBI in vivo. This bioprinting approach not only improved mechanical properties and tissue integration but also enhanced angiogenesis and extracellular matrix (ECM) formation, demonstrating its potential as a promising platform for the regeneration of tendon-to-bone complex tissues.
{"title":"3D bioprinted multi-layered cell constructs with gradient core-shell interface for tendon-to-bone tissue regeneration","authors":"WonJin Kim , Dong Rak Kwon , Hyeongjin Lee , JaeYoon Lee , Yong Suk Moon , Sang Chul Lee , Geun Hyung Kim","doi":"10.1016/j.bioactmat.2024.10.002","DOIUrl":"10.1016/j.bioactmat.2024.10.002","url":null,"abstract":"<div><div>Rotator cuff tears are common among physically active individuals and often require surgical intervention owing to their limited self-healing capacity. This study proposes a new bioprinting approach using bone- and tendon tissue-specific bioinks derived from decellularized extracellular matrix, supplemented with hydroxyapatite and TGF-β/poly(vinyl alcohol) to fabricate engineered tendon-to-bone complex tissue. To achieve this goal, a core-shell nozzle system attached to a bioprinter enables the effective and simultaneous fabrication of aligned tendon tissue, a gradient tendon-bone interface (TBI), and a mechanically improved bone region, mimicking the native tendon-to-bone structure. <em>In vitro</em> evaluation demonstrated the well-directed differentiation of human adipose stem cells towards osteogenic and tenogenic lineages in the bone and tendon constructs. In the graded TBI structure, further facilitated fibrocartilage formation and enhanced the integration of tendon-to-bone tissues compared to non-graded structures <em>in vitro</em>. Furthermore, using a rabbit rotator cuff tear model, implantation of the biologically graded constructs significantly promoted the rapid regeneration of full-thickness tendon-to-bone tissue, including the formation of a high-quality TBI <em>in vivo</em>. This bioprinting approach not only improved mechanical properties and tissue integration but also enhanced angiogenesis and extracellular matrix (ECM) formation, demonstrating its potential as a promising platform for the regeneration of tendon-to-bone complex tissues.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 471-490"},"PeriodicalIF":18.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142427640","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 : 2024-10-11DOI: 10.1016/j.bioactmat.2024.10.001
Xiaoqi Lin , Ye Zhang , Jiarong Li , Brian G. Oliver , Bin Wang , Haiyan Li , Ken-Tye Yong , Jiao Jiao Li
Chondral and osteochondral injuries are frequently encountered in clinical practice. However, articular cartilage has limited self-healing capacity due to its sophisticated zonal structure and avascular nature, introducing significant challenges to the restoration of chondral and osteochondral tissues after injury. Improperly repaired articular cartilage can lead to irreversible joint damage and increase the risk of osteoarthritis progression. Cartilage tissue engineering using stratified scaffolds with multizonal design to match the zonal structure of articular cartilage may help to meet the complex regeneration requirements of chondral and osteochondral tissues, and address the drawbacks experienced with single-phase scaffolds. Navigating the heterogeneity in matrix organisation and cellular composition across cartilage zones is a central consideration in multizonal scaffold design. With emphasis on recent advances in scaffold design and fabrication strategies, this review captures emerging approaches on biomimetic multizonal scaffolds for the reconstruction of zonal articular cartilage, including strategies on replicating native tissue structure through variations in fibre orientation, porous structure, and cell types. Exciting progress in this dynamic field has highlighted the tremendous potential of multizonal scaffolding strategies for regenerative medicine in the recreation of functional tissues.
{"title":"Biomimetic multizonal scaffolds for the reconstruction of zonal articular cartilage in chondral and osteochondral defects","authors":"Xiaoqi Lin , Ye Zhang , Jiarong Li , Brian G. Oliver , Bin Wang , Haiyan Li , Ken-Tye Yong , Jiao Jiao Li","doi":"10.1016/j.bioactmat.2024.10.001","DOIUrl":"10.1016/j.bioactmat.2024.10.001","url":null,"abstract":"<div><div>Chondral and osteochondral injuries are frequently encountered in clinical practice. However, articular cartilage has limited self-healing capacity due to its sophisticated zonal structure and avascular nature, introducing significant challenges to the restoration of chondral and osteochondral tissues after injury. Improperly repaired articular cartilage can lead to irreversible joint damage and increase the risk of osteoarthritis progression. Cartilage tissue engineering using stratified scaffolds with multizonal design to match the zonal structure of articular cartilage may help to meet the complex regeneration requirements of chondral and osteochondral tissues, and address the drawbacks experienced with single-phase scaffolds. Navigating the heterogeneity in matrix organisation and cellular composition across cartilage zones is a central consideration in multizonal scaffold design. With emphasis on recent advances in scaffold design and fabrication strategies, this review captures emerging approaches on biomimetic multizonal scaffolds for the reconstruction of zonal articular cartilage, including strategies on replicating native tissue structure through variations in fibre orientation, porous structure, and cell types. Exciting progress in this dynamic field has highlighted the tremendous potential of multizonal scaffolding strategies for regenerative medicine in the recreation of functional tissues.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"43 ","pages":"Pages 510-549"},"PeriodicalIF":18.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142427647","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 : 2024-10-11DOI: 10.1016/j.bioactmat.2024.09.030
Vasiliki Kolliopoulos , Maxwell Polanek , Melisande Wong Yan Ling , Aleczandria Tiffany , Kara L. Spiller , Brendan A.C. Harley
Mesenchymal stem cells (MSCs) are highly plastic, with the capacity to differentiate into a spectrum of tissue-specific stromal cells. In the field of bone regeneration, MSCs have largely been considered for their osteogenic differentiation capacity. MSCs are increasingly being appreciated for their immunomodulatory potential following exposure to pro-inflammatory stimuli (licensing). Pro-inflammatory environments arise following bone injury via activation of resident immune cells like macrophages. We describe the use of a mineralized collagen scaffold as a bone-mimetic in vitro model to study the influence of paracrine versus direct cell-to-cell contact of THP-1 macrophages on MSC osteogenic and immunomodulatory potential. Paracrine stimuli from macrophages enhance MSC osteogenic and immunomodulatory potential via upregulation of key transcriptomic markers as well as via soluble biomolecule production. Direct co-culture of MSCs and macrophages decreased immunomodulatory potential in MSCs, especially for licensed MSCs, but enhanced matrix remodeling and expression of genes related to macrophage chemotaxis. These data demonstrate the significant effect macrophage-derived paracrine factors and direct contact have on MSC activity in a biomaterial model of bone regeneration. This work illuminates a critical need to further understand these processes in more clinically relevant cell models to inform biomaterial design.
{"title":"Crosstalk between macrophages and mesenchymal stem cells shape patterns of osteogenesis and immunomodulation in mineralized collagen scaffolds","authors":"Vasiliki Kolliopoulos , Maxwell Polanek , Melisande Wong Yan Ling , Aleczandria Tiffany , Kara L. Spiller , Brendan A.C. Harley","doi":"10.1016/j.bioactmat.2024.09.030","DOIUrl":"10.1016/j.bioactmat.2024.09.030","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) are highly plastic, with the capacity to differentiate into a spectrum of tissue-specific stromal cells. In the field of bone regeneration, MSCs have largely been considered for their osteogenic differentiation capacity. MSCs are increasingly being appreciated for their immunomodulatory potential following exposure to pro-inflammatory stimuli (licensing). Pro-inflammatory environments arise following bone injury via activation of resident immune cells like macrophages. We describe the use of a mineralized collagen scaffold as a bone-mimetic <em>in vitro</em> model to study the influence of paracrine versus direct cell-to-cell contact of THP-1 macrophages on MSC osteogenic and immunomodulatory potential. Paracrine stimuli from macrophages enhance MSC osteogenic and immunomodulatory potential via upregulation of key transcriptomic markers as well as via soluble biomolecule production. Direct co-culture of MSCs and macrophages decreased immunomodulatory potential in MSCs, especially for licensed MSCs, but enhanced matrix remodeling and expression of genes related to macrophage chemotaxis. These data demonstrate the significant effect macrophage-derived paracrine factors and direct contact have on MSC activity in a biomaterial model of bone regeneration. This work illuminates a critical need to further understand these processes in more clinically relevant cell models to inform biomaterial design.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"44 ","pages":"Pages 34-45"},"PeriodicalIF":18.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142426384","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 : 2024-10-11DOI: 10.1016/j.bioactmat.2024.09.041
Junyu Qian , Haotian Qin , En Su , Jiaming Hou , Hui Zeng , Tianbing Wang , Deli Wang , Guojiang Wan , Yingqi Chen
Osteoporotic (OP) fractures remain a tough clinical challenge owing to their impaired healing outcome, which requires novel biomaterials with osteogenicity for effective healing. Metallic zinc (Zn) is attracting increasing attention for biodegradable intramedullary nails (IMNs) for OP fracture healing thanks to their comprehensive mechanical properties, biosafety, and bioactivity. However, the multiple biofunctions required for OP fracture healing have not been fully met by Zn. Herein, a zoledronate (ZA)-mediated calcium-zinc silicate (Ca(Zn)Si) metal-organic/inorganic hybrid coating was fabricated on Zn-based IMN by coordination chemistry driven via interactions between ZA and Ca2+/Zn2+ as well as in-situ directional growth of Ca(Zn)Si phase. The ZA&Ca(Zn)Si hybrid coating exhibited a homogeneous micro/nanostructure with a granular morphology, which prevented premature fracture failure of IMN in rat femur by ameliorating corrosion mode and decreasing degradation rate of the Zn matrix. More importantly, this hybrid coating enabled sustained release of Zn2+/Ca2+/Si4+ and ZA in the long term, achieving a remarkable effect on vascularized bone regeneration. The coated IMN enhanced angiogenesis–osteogenesis coupling through autocrine and paracrine effects between endothelial cells and bone marrow mesenchymal stem cells. Osteoclastogenesis was repressed by Zn2+ and ZA. This approach offers a new strategy for surface-engineering of biodegradable metals for bone fracture healing.
{"title":"Angiogenesis-osteogenesis coupling and anti-osteoclastogenesis zoledronate intermixed calcium silicate metal-organic/inorganic hybrid coating on biodegradable zinc-based intramedullary nails for osteoporotic fracture healing","authors":"Junyu Qian , Haotian Qin , En Su , Jiaming Hou , Hui Zeng , Tianbing Wang , Deli Wang , Guojiang Wan , Yingqi Chen","doi":"10.1016/j.bioactmat.2024.09.041","DOIUrl":"10.1016/j.bioactmat.2024.09.041","url":null,"abstract":"<div><div>Osteoporotic (OP) fractures remain a tough clinical challenge owing to their impaired healing outcome, which requires novel biomaterials with osteogenicity for effective healing. Metallic zinc (Zn) is attracting increasing attention for biodegradable intramedullary nails (IMNs) for OP fracture healing thanks to their comprehensive mechanical properties, biosafety, and bioactivity. However, the multiple biofunctions required for OP fracture healing have not been fully met by Zn. Herein, a zoledronate (ZA)-mediated calcium-zinc silicate (Ca(Zn)Si) metal-organic/inorganic hybrid coating was fabricated on Zn-based IMN by coordination chemistry driven via interactions between ZA and Ca<sup>2+</sup>/Zn<sup>2+</sup> as well as <em>in-situ</em> directional growth of Ca(Zn)Si phase. The ZA&Ca(Zn)Si hybrid coating exhibited a homogeneous micro/nanostructure with a granular morphology, which prevented premature fracture failure of IMN in rat femur by ameliorating corrosion mode and decreasing degradation rate of the Zn matrix. More importantly, this hybrid coating enabled sustained release of Zn<sup>2+</sup>/Ca<sup>2+</sup>/Si<sup>4+</sup> and ZA in the long term, achieving a remarkable effect on vascularized bone regeneration. The coated IMN enhanced angiogenesis–osteogenesis coupling through autocrine and paracrine effects between endothelial cells and bone marrow mesenchymal stem cells. Osteoclastogenesis was repressed by Zn<sup>2+</sup> and ZA. This approach offers a new strategy for surface-engineering of biodegradable metals for bone fracture healing.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"44 ","pages":"Pages 46-67"},"PeriodicalIF":18.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142426385","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}
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