Jun Ren, Chaoli Wang, Hao Gao, Shuaikun Lu, Congxiao Fu, Hu Wang, Guoliang Wang, Zhenfeng Zhu, Hong Wu, Wen Luo, Yunfei Zhang
{"title":"Multitasking Asynchronous Collaborative Nanosystem for Diabetic Wound Healing Based on Hypoglycemic, Antimicrobial, and Angiogenesis-Promoting Effects.","authors":"Jun Ren, Chaoli Wang, Hao Gao, Shuaikun Lu, Congxiao Fu, Hu Wang, Guoliang Wang, Zhenfeng Zhu, Hong Wu, Wen Luo, Yunfei Zhang","doi":"10.1002/adhm.202403282","DOIUrl":"https://doi.org/10.1002/adhm.202403282","url":null,"abstract":"<p><p>A diabetic foot ulcer (DFU) is a common and serious complication of diabetes. This complication can result in amputation and death because of the several challenges associated with wound healing that can be attributed to the complex wound microenvironment, including biofilm infection, hyperglycemia, and diabetic angiopathy. Existing investigations on the wound-healing rate consider only one or two pathogenic factors, and therefore, despite the extensive research on these pathological microenvironments, there is an urgent need to optimize the wound-healing rate in patients with diabetic foot ulcers. To this end, a multitasking asynchronous collaborative nanosystem is designed in this study. The designed nanosystem can efficiently clear biofilm infections using optimized photodynamic therapy based on a poly photosensitizer ionic liquid (i.e., Ce6IL), reduce local blood glucose concentration using glucose oxidase, and reconstruct blood vessels by stimulating endothelial cell proliferation and migration using nitric oxide. The experimental results indicate that the three-step sequential collaboration strategy for clearing biofilm infections, reducing glucose concentrations, and reconstructing damaged blood vessels can help significantly accelerate wound healing rate in patients with diabetic foot ulcers.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403282"},"PeriodicalIF":10.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833224","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}
Qing Wang, Ya Gao, Yanzheng Chen, Xuan Wang, Qingguo Pei, Taiyu Zhang, Changping Wang, Jinsong Pan
{"title":"Synergistic Enhancement of Antibacterial and Osteo-Immunomodulatory Activities of Titanium Implants via Dual-Responsive Multifunctional Surfaces.","authors":"Qing Wang, Ya Gao, Yanzheng Chen, Xuan Wang, Qingguo Pei, Taiyu Zhang, Changping Wang, Jinsong Pan","doi":"10.1002/adhm.202404260","DOIUrl":"https://doi.org/10.1002/adhm.202404260","url":null,"abstract":"<p><p>Bone implant-associated infections and inflammations, primarily caused by bacteria colonization, frequently result in unsuccessful procedures and pose significant health risks to patients. To mitigate these challenges, the development of engineered implants with spatiotemporal regulation capabilities, designed to inhibit bacterial survival and modulate immune responses in the early stage, while promoting bone defect healing in the late stage is proposed. The implants are functionalized with ε-poly-l-lysine-phenylboronic acid (PP) via dynamic boronic ester bonds, which facilitate its release through a reactive oxygen species (ROS) and pH-responsive strategy, thereby establishing an antibacterial microenvironment on and around the implants. Additionally, the dynamic metal coordination interaction facilitates the loading and sustained release of Sr<sup>2+</sup> under an acidic environment, providing immunomodulatory and osteogenic effects. The ROS/pH-responsive feature, coupled with the implant-bone tissue integration process, affords precise spatiotemporal regulation of the Ti-TA-Sr-PP implants. This strategy represents a promising approach for the preparation of advanced bone implants.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2404260"},"PeriodicalIF":10.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845394","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":"TP8, A Novel Chondroinductive Peptide, Significantly Promoted Neo-Cartilage Repair without Activating Bone Formation.","authors":"Mingjing Zhu, Siqing Jiang, Xingyang Li, Wenchao Zhong, Wei Cao, Qianting Luo, Antong Wu, Gang Wu, Qingbin Zhang","doi":"10.1002/adhm.202401752","DOIUrl":"https://doi.org/10.1002/adhm.202401752","url":null,"abstract":"<p><p>The repair of large cartilage defects remains highly challenging in the fields of orthopedics and oral and maxillofacial surgery. A chondroinductive agent is promising to activate endogenous mesenchymal stem cells (MSCs) so as to facilitate cartilage regeneration. In this study, we analyze the crystallographic data of the critical binding domain of transforming growth factor β3 (TGF-β3) with its type II receptor and successfully develop a novel chondroinductive peptide - TGF-β3-derived peptide No. 8 (TP8) that can induce an ectopic cartilage formation without obvious bone formation. TP8 shows a comparable capacity as TGF-β3 in enhancing glycosaminoglycans (GAGs) and proteoglycans (PGs) secretion in the micromass of bone marrow MSCs (BMSCs) and promoting the expression of chondrogenic markers in comparison with the Control group. TP8 induces a significantly higher expression of the SRY-box transcription factor 9 (Sox9) gene than TGF-β3. Moreover, TP8 significantly upregulates the phosphorylation of Smad1/5 but not MAPK/JNK or Smad 2/3. The knockdown of low-density lipoprotein receptor (LDLR) -related protein-1 (Lrp1), a transmembrane endocytosis receptor, nullifies the TP8-induced Sox9 expression. In the critical-size cartilage defects in rabbit medial femoral condyles, TP8 can induce neo-cartilage formation with a significantly thicker deep zone in comparison with the TGF-β3 and Control. These findings suggest a promising application potential of TP8 in cartilage tissue engineering.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2401752"},"PeriodicalIF":10.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845424","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}
Tong Zhang, Melanie Berghaus, Yuan Li, Qingmei Song, Maria M Stollenwerk, Jenny Persson, Kenneth J Shea, Börje Sellergren, Yongqin Lv
{"title":"PSMA-Targeting Imprinted Nanogels for Prostate Tumor Localization and Imaging.","authors":"Tong Zhang, Melanie Berghaus, Yuan Li, Qingmei Song, Maria M Stollenwerk, Jenny Persson, Kenneth J Shea, Börje Sellergren, Yongqin Lv","doi":"10.1002/adhm.202401929","DOIUrl":"https://doi.org/10.1002/adhm.202401929","url":null,"abstract":"<p><p>Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer cells and tumor vasculature, making it an important biomarker. However, conventional PSMA-targeting agents like antibodies and small molecules have limitations. Antibodies exhibit instability and complex production, while small molecules show lower specificity and higher toxicity. Herein, this work develops a novel PSMA-targeting synthetic antibody to address prior limitations. This work synthesizes fluorescently labelled, N-isopropylacrylamide-based epitope imprinted nanogels (MIP-M) using a dispersion of magnetic nanoparticles as template carriers with a linear epitope from PSMA's extracellular apical domain as the template. MIP-M demonstrates high binding affinities for both the epitope template (apparent K<sub>D</sub> = 6 × 10<sup>-10</sup> м) and PSMA (apparent K<sub>D</sub> = 2.5 × 10<sup>-9</sup> м). Compared to reference peptides and human serum albumin, MIP-M indicates high specificity. Flow cytometry and confocal laser scanning microscopy comparing cell lines displaying normal (PC3) and enhanced (LNCaP) PSMA expression levels, revealed that MIP-M and a PSMA antibody exhibits comparable binding preferences for the latter cell line. Moreover, MIP-M demonstrates selectivity on par with the PSMA antibody for targeting PSMA-positive prostate tumor over normal tissue, enabling discrimination. This MIP-M addresses stability, production, specificity and toxicity limitations of prior targeting agents and offer a promising alternative for PSMA-directed cancer diagnosis and treatment.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2401929"},"PeriodicalIF":10.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845380","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}
Yichen Dai, Peter Wang, Apurva Mishra, Kui You, Yuheng Zong, Wen Feng Lu, Edward Kai-Hua Chow, Philip M Preshaw, Dejian Huang, Jacob Ren Jie Chew, Dean Ho, Gopu Sriram
{"title":"3D Bioprinting and Artificial Intelligence-Assisted Biofabrication of Personalized Oral Soft Tissue Constructs.","authors":"Yichen Dai, Peter Wang, Apurva Mishra, Kui You, Yuheng Zong, Wen Feng Lu, Edward Kai-Hua Chow, Philip M Preshaw, Dejian Huang, Jacob Ren Jie Chew, Dean Ho, Gopu Sriram","doi":"10.1002/adhm.202402727","DOIUrl":"https://doi.org/10.1002/adhm.202402727","url":null,"abstract":"<p><p>Regeneration of oral soft tissue defects, including mucogingival defects associated with the recession or loss of gingival and/or mucosal tissues around teeth and implants, is crucial for restoring oral tissue form, function, and health. This study presents a novel approach using three-dimensional (3D) bioprinting to fabricate individualized grafts with precise size, shape, and layer-by-layer cellular organization. A multicomponent polysaccharide/fibrinogen-based bioink is developed, and bioprinting parameters are optimized to create shape-controlled oral soft tissue (gingival) constructs. Rheological, printability, and shape-fidelity assays, demonstrated the influence of thickener concentration and print parameters on print resolution and shape fidelity. Artificial intelligence (AI)-derived tool enabled streamline the iterative bioprinting parameter optimization and analysis of the interaction between the bioprinting parameters. The cell-laden polysaccharide/fibrinogen-based bioinks exhibited excellent cellular viability and shape fidelity of shape-controlled, full-thickness gingival tissue constructs over the 18-day culture period. While variations in thickener concentrations within the bioink minimally impact the cellular organization and morphogenesis (gingival epithelial, connective tissue, and basement membrane markers), they influence the shape fidelity of the bioprinted constructs. This study represents a significant step toward the biofabrication of personalized soft tissue grafts, offering potential applications in the repair and regeneration of mucogingival defects associated with periodontal disease and dental implants.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402727"},"PeriodicalIF":10.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845444","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}
Xiaomei Wu, Shuo Zhang, Mei Feng, Haoya Sun, Xiaopeng Lan, Wenlong Liang, Chunzhao Liu, Yongxin Li
{"title":"Glutathione Induced In Situ Activation of Dual-Locked Cuproptosis Nanoamplifier with Glycolysis Metabolism Inhibition to Boost Cancer Immunotherapy.","authors":"Xiaomei Wu, Shuo Zhang, Mei Feng, Haoya Sun, Xiaopeng Lan, Wenlong Liang, Chunzhao Liu, Yongxin Li","doi":"10.1002/adhm.202403380","DOIUrl":"https://doi.org/10.1002/adhm.202403380","url":null,"abstract":"<p><p>Interference with glycolysis metabolism not only promotes the efficient sensitization of cuproptosis, but also amplifies cytotoxic T cell functions and proliferations, thus contributing to relieve immunosuppressive tumor microenvironment. However, the synergistic mechanism and the design of multicomponent nanoformulations involving these three pathways have not yet been explored. a copper-coordinated nanoassembly (designated as Cu-GM) is reported here that integrates a lactate dehydrogenase inhibitor, galloflavin (GF), with an immune checkpoint inhibitor, myricetin (MY), to boost cancer cuproptosis-immunotherapy. These results suggest that Cu-GM can be activated by the endogenous overexpressed glutathione to release Cu<sup>+</sup>, leading to the abnormal aggregation of lipoylated proteins and iron-sulfur cluster proteins loss, which triggers proteotoxic stress and cell cuproptosis. Meanwhile, the released GF not only inhibits the glycolysis to amplify cuproptosis efficacy but also achieves effective lactate depletion, thus alleviating immunosuppressive effects of lactate. Notably, the killed tumor cells can induce immunogenic cell death to evoke the anti-tumor immunity, which further augmented by the MY-mediated immune checkpoint blockade. Taken together, the first anticancer synergy of glycolysis metabolism, cuproptosis, and immunotherapy is presented, showcasing remarkable in vivo antitumor effects and encouraging further exploration of a rational multimodal treatment approach.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403380"},"PeriodicalIF":10.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833222","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}
Bo Zhang, Hao Zhang, Yani Sun, Lei Chen, Kaixin Sun, Yuming Zhang, Xiaofan Hu, Kang Zhao, Zixiang Wu, Yufei Tang
{"title":"Functionalized Bone Implant Inspired by Lattice Defense Strategy: Grid Management, Precise and Effective Multiple-Prevention of Osteomyelitis Recurrence and Promote Bone Regeneration.","authors":"Bo Zhang, Hao Zhang, Yani Sun, Lei Chen, Kaixin Sun, Yuming Zhang, Xiaofan Hu, Kang Zhao, Zixiang Wu, Yufei Tang","doi":"10.1002/adhm.202403058","DOIUrl":"https://doi.org/10.1002/adhm.202403058","url":null,"abstract":"<p><p>Osteomyelitis with a high recurrence rate. Timely-prevention can avoid severe consequence and death. However, conventional drug response-release has the disadvantages of unnecessary release and waste, causing ineffective prevention. Inspired by \"Lattice-defense technology\", gridding lesion areas and constructing a \"Triggered-precise response-release system\" may be an effective multiple-prevention method. Here, a new strict pH-triggered response drug controlled-release mechanism was proposed innovatively to construct a \"Triggered-precise response-release system\" and achieve multiple-effective prevention. PO<sub>4</sub> <sup>3-</sup>-Ce<sup>3+</sup> strict pH responsive release system is prepared through simultaneous hydration reaction of solution-polymerization and compounded in bone-implant. The dispersed system only targets micro-interface contact areas, achieving gridded management of the lesion site. In a normal environment, Ce<sup>3+</sup> is captured by PO<sub>4</sub> <sup>3-</sup> and kept electrostatic-attraction balance, ensuring the zero-concentration Ce<sup>3+</sup> release continuously. Once osteomyelitis recurs and pH decrease, H+ at the interface will combine with PO<sub>4</sub> <sup>3-</sup> under electrostatic drive and disrupt potential balance, achieving the release of Ce<sup>3+</sup> only when the infection recurs. In vivo experiments was confirmed effective prevention and excellent promote bone regeneration. The adoption of \"Lattice defense technology\" has achieved accuracy spatiotemporal of drug delivery. Even if other lesion sites unfortunately recur again, effective-prevention can be guaranteed. Bone-implant show great potential in preventing osteomyelitis.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403058"},"PeriodicalIF":10.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845373","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}