{"title":"Magnesium-Impregnated Membrane Promotes Bone Regeneration in Rat Skull Defect by N-Linked Glycosylation of SPARC via MagT1.","authors":"Weisin Chen, Hongwei Lu, Wenhao Yu, Lei Huang, Mengxuan Bian, Ning Wang, Xingdong Xiang, Guokang Mo, Cheng Zhang, Yulin Li, Libo Jiang, Jian Zhang","doi":"10.1002/adhm.202402705","DOIUrl":"https://doi.org/10.1002/adhm.202402705","url":null,"abstract":"<p><p>Autograft has long been the gold standard for various bone surgeries. Nevertheless, the increasing usage of synthetic implants is taking over the operation rooms due to biosafety and standardized protocols. To fulfill such tremendous needs, a magnesium-impregnated membrane is devised that steadily releases magnesium ions to stimulate osteogenesis. The compatibility of Magnesium oxide (MgO) particles is enhanced through hydration and grafting, characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). With detailed degradation profiles, an in-depth investigation of Magnesium transporter 1 (MagT1) for magnesium intake is carried out and engaging in the N-linked glycosylation by using RNAi and inhibitors. The glycosylation of secreted protein acidic and rich in cysteine (SPARC) affected extracellular secretion and mineral deposition, demonstrated by immunostaining and density-dependent color-SEM (DDC-SEM). Skull defects are treated by implanting magnesium-impregnated membranes in rats and evaluated them by micro-CT and histological exams. This study revealed the compatible integration of grafted magnesium hydroxide (g-MH) particles is the key to functional performance and critical to applicability in vivo; meanwhile, it opens the door to a biological rationale for designing biomimetic materials.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402705"},"PeriodicalIF":10.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acute Three-Dimensional Hypoxia Regulates Angiogenesis.","authors":"Dimitris Ntekoumes, Jiyeon Song, Haohao Liu, Connor Amelung, Ya Guan, Sharon Gerecht","doi":"10.1002/adhm.202403860","DOIUrl":"https://doi.org/10.1002/adhm.202403860","url":null,"abstract":"<p><p>Hypoxia elicits a multitude of tissue responses depending on the severity and duration of the exposure. While chronic hypoxia is shown to impact development, regeneration, and cancer, the understanding of the threats of acute (i.e., short-term) hypoxia is limited mainly due to its transient nature. Here, a novel gelatin-dextran (Gel-Dex) hydrogel is established that decouples hydrogel formation and oxygen consumption and thus facilitates 3D sprouting from endothelial spheroids and, subsequently, induces hypoxia \"on-demand.\" The Gel-Dex platform rapidly achieves acute moderate hypoxic conditions without compromising its mechanical properties. Acute exposure to hypoxia leads to increased endothelial cell migration and proliferation, promoting the total length and number of vascular sprouts. This work finds that the enhanced angiogenic response is mediated by reactive oxygen species, independently of hypoxia-inducible factors. Reactive oxygen species-dependent matrix metalloproteinases activity mediated angiogenic sprouting is observed following acute hypoxia. Overall, the Gel-Dex hydrogel offers a novel platform to study how \"on-demand\" acute moderate hypoxia impacts angiogenesis, with broad applicability to the development of novel sensing technologies.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403860"},"PeriodicalIF":10.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to Tattoo Inks for Optical Biosensing in Interstitial Fluid.","authors":"","doi":"10.1002/adhm.202404550","DOIUrl":"https://doi.org/10.1002/adhm.202404550","url":null,"abstract":"","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2404550"},"PeriodicalIF":10.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Constructing a Metal-Organic Frameworks-Based Long-Acting Sequential Release System for the Treatment of Alzheimer's Disease.","authors":"Qi Ding, Yun Zhao, Enpeng Xi, Kangning Liu, Nan Gao, Guangshan Zhu","doi":"10.1002/adhm.202402425","DOIUrl":"https://doi.org/10.1002/adhm.202402425","url":null,"abstract":"<p><p>Due to the unclear pathogenesis of Alzheimer's disease (AD) and the lack of a completely cured medication, AD patients need to take medication in order and on time every day all one's life, which is difficult for severe memory impairment patients to strictly follow on time. Traditional AD drug carriers, such as sugar coating and capsules, rely on dissolution or fragmentation to achieve drug release, which lacks the interaction between drug molecules and carriers, thus they cannot achieve sufficient long-acting and sequential drug release. Herein, Mn-MOF-74, which ligand structure is similar to two antioxidants dihydroquercetin (DHQ) and resveratrol (Res) is chosen as the carrier. Due to the differences in adsorption energy between DHQ/MOF and Res/MOF, the release speed of DHQ is much faster than Res. Therefore, Mn-MOF-74 loaded with DHQ and Res (DR@MOF) showed sequential drug release and a long-term antioxidant effect for ≈72 h, with an efficacy time six times longer than that of vitamin E. In 5×FAD transgenic mice, DR@MOF exhibited excellent capacity in maintaining oxidative balance in the brain, ameliorating spatial learning and memory deficits, and showed the potential of an AD agent for long-acting and sequential treatment.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402425"},"PeriodicalIF":10.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Layered Double Hydroxides for Radium-223 Targeted Alpha Therapy with Elicitation of the Immune Response.","authors":"Mengdie Yang, Jianguo Li, Zongtai Han, Xiaohui Luan, Xiaoyi Zhang, Jie Gao, Shanshan Qin, Fei Yu","doi":"10.1002/adhm.202403175","DOIUrl":"https://doi.org/10.1002/adhm.202403175","url":null,"abstract":"<p><p>Targeted Alpha therapy (TAT) has promising application prospects in tumor therapy. It is very appealing to design alpha-emitting radiopharmaceuticals that can modulate the immune microenvironment to overcome the limitations of immunotherapy. Herein, Mg/Al layered double hydroxide nanomaterials (LDH) are utilized to load the alpha-emitting nuclide Radium-223 (<sup>223</sup>Ra), achieving precise delivery of <sup>223</sup>Ra to the tumor microenvironment. Dual-modal imaging is employed to dynamically monitor the in vivo distribution of <sup>223</sup>Ra-LDH, ensuring its prolonged retention at the tumor site. In vitro experimentsshowed that ionizing radiation from alpha-emitting nuclides effectively reduced glutathione (GSH) and produced large amounts of reactive oxygen species (ROS), which damaged mitochondria and released free calcium (Ca<sup>2+</sup>), thereby aggravating tumor cell death. Additionally, DNA double-strand breaks induced by alpha-emitting radiation triggered the STING signaling pathway, which in turn effectively induced immunogenic cell death (ICD) and promoted immune cell maturation and activation. The synergistic effect with immunotherapy triggered a powerful systemic antitumor immune response. Overall, this study develops a novel TAT therapeutic strategy with sufficient antitumor immunity.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403175"},"PeriodicalIF":10.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pingping Niu, Liman Zhao, Jing Yang, Yanan Ding, Xiaoqiao Xu, Sijin Li, Lige Song, Guosong Chen, Yao Sun
{"title":"Self-Assembled Nanoparticles with Well-Defined Oligosaccharide Promote Osteogenesis by Regulating Golgi Stress Response.","authors":"Pingping Niu, Liman Zhao, Jing Yang, Yanan Ding, Xiaoqiao Xu, Sijin Li, Lige Song, Guosong Chen, Yao Sun","doi":"10.1002/adhm.202402976","DOIUrl":"https://doi.org/10.1002/adhm.202402976","url":null,"abstract":"<p><p>Osteoporosis, a prevalent disease characterized by low bone density and increased fracture risk, poses significant health challenges for the elderly. Current treatments offer short-term benefits but are limited by long-term efficacy and adverse effects, highlighting the need for new strategies. Chondroitin sulfate polysaccharides (CS), a major component of the bone matrix, are crucial for bone and cartilage health. However, their role in osteoporosis is understudied due to the heterogeneity of natural CS. we found reduced CS levels in osteoporosis patients and developed CS4-NP, a self-assembled tetrasaccharide nanoparticle that mimics CS's structure. CS4-NP, which efficiently delivers the active CS4, significantly improves bone mass in ovariectomized osteoporosis models. It activates the Activating Transcription Factor 4-Cystathionine gamma-Lyase signaling axis in pre-osteoblasts, enhancing osteogenesis. our findings suggest that CS4-NP, an oligosaccharide-based nanomaterial, could address the limitations of current treatments and provide a viable strategy for osteoporosis.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402976"},"PeriodicalIF":10.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineered Nanoparticles for Theranostic Applications in Kidney Repair.","authors":"Can Jin, Lingling Xue, Leilei Zhang, Lixia Yu, Peipei Wu, Hui Qian","doi":"10.1002/adhm.202402480","DOIUrl":"https://doi.org/10.1002/adhm.202402480","url":null,"abstract":"<p><p>Kidney diseases are characterized by their intricate nature and complexity, posing significant challenges in their treatment and diagnosis. Nanoparticles (NPs), which can be further classified as synthetic and biomimetic NPs, have emerged as promising candidates for treating various diseases. In recent years, the development of engineered nanotherapeutics has focused on targeting damaged tissues and serving as drug delivery vehicles. Additionally, these NPs have shown superior sensitivity and specificity in diagnosis and imaging, thus providing valuable insights for the early detection of diseases. This review aims to focus on the application of engineered synthetic and biomimetic NPs in kidney diseases in the aspects of treatment, diagnosis, and imaging. Notably, the current perspectives and challenges are evaluated, which provide inspiration for future research directions, and encourage the clinical application of NPs in this field.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402480"},"PeriodicalIF":10.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gas Empowered Dual-Cascade Strategy for Augmented Single-Atom Nanotherapies.","authors":"Yong Liu, Xiao-Qiong Li, Qiao Yu, Bin Kang, Xueli Zhao, Jing-Juan Xu","doi":"10.1002/adhm.202404001","DOIUrl":"https://doi.org/10.1002/adhm.202404001","url":null,"abstract":"<p><p>Single-atom nanotherapies have received numerous attention in malignant oncotherapy. However, the insufficient enzyme substrate and the upregulation of heat shock proteins during therapeutic interventions are seldom concurrently noticed. Herein, a novel gas empowered dual-cascade synergistic treatment strategy is demonstrated with domino effect, which can sequentially reinforce single-atom nanozyme (SAzyme)-based enzymatic therapeutics and mild photothermal therapy (PTT) (< 45 °C). In the proof-of-concept study, Fe single atom nanozyme (Fe/SAzyme) loaded with hydrogen sulfide (H<sub>2</sub>S) donor NaHS is developed for HSPs-silencing mediated mild PTT. The generated H<sub>2</sub>S suppresses the catalase activity to achieve \"intracellular H<sub>2</sub>O<sub>2</sub> conservation\", thereby furnishing the enzyme substrate to Fe/SAzyme to produce abundant cytotoxic hydroxyl radicals (·OH) for augmented enzymatic therapeutics. Then, excess ·OH induced mitochondrial dysfunction blocks adenosine triphosphate (ATP) energy supply to realize cellular energy remodeling, which hinders overexpression of HSPs and enhances mild PTT of Fe/SAzyme both in vitro and vivo. Consequently, the gas-triggered dual-cascade strategy achieves domino H<sub>2</sub>S/·OH/mitochondrial dysfunction synergistic effect, endowing SAzymes with maximum antitumor efficacy via enzymatic therapeutics combined with mild PTT. This dual-cascaded gas/enzymatic/mild PTT synergistic oncotherapy not only exhibits a new pathway for gas-facilitated mild PTT, but also offers a valuable paradigm for the application of \"1 + 1 + 1 > 3\" multimodal synergistic tumor therapy.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2404001"},"PeriodicalIF":10.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NIR-II Photoacoustic Imaging-Guided Chemo-Photothermal Therapy Using PA1094T Combined with Anti-CD47 Antibody: Activating Pyroptosis against Orthotopic Glioblastoma.","authors":"Shiying Li, Fanchu Zeng, Qi Zhou, Lanqing Li, Hsuan Lo, Jiali Chen, Zhijin Fan, Guojia Huang, Liming Nie","doi":"10.1002/adhm.202403108","DOIUrl":"https://doi.org/10.1002/adhm.202403108","url":null,"abstract":"<p><p>Treating glioblastoma (GBM) with single-agent chemotherapy is often ineffective due to inefficient drug delivery and the immunosuppressive tumor microenvironment, which leads to drug resistance. Strategies that activate programmed cell death mechanisms and repolarized tumor-associated macrophages toward an antitumoral M1-like phenotype can help reverse the immunosuppressive tumor microenvironment. In this study, a novel approach using NIR-II (1000-1700 nm) photoacoustic imaging (PAI)-guided chemo-photothermal therapy is presented. NIR-II imaging, with its superior tissue penetration and reduced background noise, enables precise tumor targeting. A targeted nano prodrug is developed using poly (lactic-co-glycolic acid) nanoparticles loaded with A1094 dye and temozolomide (TMZ), coupled with an anti-CD47 antibody. This system employs synergistic chemo-photothermal therapy activated by NIR-II light, inducing apoptosis, pyroptosis, and T-cell activation. PAI provides rapid, point-of-care GBM diagnosis, and highlighted the effective targeting of the PA1094T nanoplatform. In a recurrent GBM model, the combination of PA1094T and anti-CD47 antibody significantly enhances cancer cell phagocytosis and effectively remodels the immunosuppressive microenvironment, resulting in better therapeutic outcomes compared to conventional therapies. These results indicate that this NIR-II PAI-guided drug cocktail therapy is a promising strategy for treating GBM, potentially addressing drug resistance and improving treatment efficacy through enhanced targeting and immunomodulation.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403108"},"PeriodicalIF":10.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Localized Hydrogel Microspheres for Osteoarthritis Treatment: Recruitment and Differentiation of Stem Cells.","authors":"Qiming Pang, Zhuolin Chen, Jingdi Zhan, Jiacheng Liu, Junyan Liu, Weikang Zhao, Wei Huang, Lili Dong","doi":"10.1002/adhm.202403490","DOIUrl":"https://doi.org/10.1002/adhm.202403490","url":null,"abstract":"<p><p>Osteoarthritis (OA) represents a common degenerative joint disorder marked by progressive cartilage degradation, necessitating innovative therapeutic approaches beyond symptom management. Here, this study introduces a novel strategy leveraging the regenerative capabilities of mesenchymal stem cells (MSCs) by utilizing a bioactive extracellular matrix (ECM) derived from IFN-γ-stimulated MSCs, encapsulated within aldehyde- and methacrylic anhydride-modified hyaluronic acid hydrogel microspheres (AH). This engineered scaffold effectively mimics the native cartilage microenvironment, promoting targeted adhesion and retention at damaged sites via spontaneous Schiff base reactions. Notably, the IFN-γ-ECM@AH microspheres facilitate the localized release of key chemokines, such as CXCL12, enhancing endogenous stem cell recruitment, and bioactive factors (e.g., TGF-βI and TGF-β3) to drive chondrogenic differentiation. Additionally, the scaffold possesses binding sites for cellular integrins, further augmenting the regenerative potential of stem cells. Collectively, the approach presents a dual-action mechanism that supports efficient cartilage repair and regeneration, positioning this engineered microenvironment as a promising therapeutic avenue for OA and potentially other degenerative conditions.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403490"},"PeriodicalIF":10.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}