Yan Luo, Chenyang Zhang, Sage Fulco, Jingyi Liu, Keyu Chen, Yuntao Hu, Yuchen Jiang, Rui Xu, Leela Rakesh, Ozer Fusun, Ottman Tertuliano, Kevin Turner, Kyle H. Vining
{"title":"Biocompatible Multifunctional Polymeric Material for Mineralized Tissue Adhesion (Adv. Healthcare Mater. 27/2025)","authors":"Yan Luo, Chenyang Zhang, Sage Fulco, Jingyi Liu, Keyu Chen, Yuntao Hu, Yuchen Jiang, Rui Xu, Leela Rakesh, Ozer Fusun, Ottman Tertuliano, Kevin Turner, Kyle H. Vining","doi":"10.1002/adhm.70262","DOIUrl":"https://doi.org/10.1002/adhm.70262","url":null,"abstract":"<p><b>Biocompatible adhesive Resin</b></p><p>A multi-functional polymeric resin system based on thiol-ene crosslinking provides a strong adhesive interface with dentin that composes the inside structures of teeth and is biocompatible with dental pulp cells residing in the dentinal tubules that extend from the dentin surface. More details can be found in the Research Article by Kyle H. Vining and co-workers (DOI: 10.1002/adhm.202501993).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":"14 27","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adhm.70262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145327749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rao Fu, Evan Jones, Ni Chen, Boyuan Sun, Biao Si, Zhenglun Alan Wei, Guillermo Ameer, Cheng Sun, Yonghui Ding
{"title":"Multiscale 3D Printing of Nanoporous Scaffolds with Surface Topography for Guiding 3D Cell Alignment.","authors":"Rao Fu, Evan Jones, Ni Chen, Boyuan Sun, Biao Si, Zhenglun Alan Wei, Guillermo Ameer, Cheng Sun, Yonghui Ding","doi":"10.1002/adhm.202504630","DOIUrl":"https://doi.org/10.1002/adhm.202504630","url":null,"abstract":"<p><p>Engineering biomaterial scaffolds with hierarchical structures that integrate macroscale architecture with micro/nanoscale features is essential for directing cellular organization and tissue regeneration. However, fabricating such multiscale scaffolds remains a challenge due to the limitations of conventional techniques and the speed-resolution trade-off in current 3D printing methods. Here, a multiscale micro-continuous liquid interface production (MµCLIP) method is presented, combined with polymerization-induced phase separation, to enable rapid, one-step 3D printing of centimeter-scale scaffolds featuring microscale surface topography and nanoscale porosity. MµCLIP achieves unprecedented structural resolution across five orders of magnitude (20 nm-1 cm) at high printing speed of up to 1.85 mm min<sup>-1</sup>. As a proof of concept, a 1cm-long tubular scaffold with interconnected nanopores (20-260 nm) and dual surface topographies: 15 µm circumferential rings on outer surface and 20 µm longitudinal grooves on luminal surface is fabricated. These topographies directed orthogonal alignment of vascular smooth muscle cells and endothelial cells, closely recapitulating the architecture of native arteries. Additionally, surface grooves significantly enhanced endothelial cell migration within scaffolds, suggesting a promising approach for accelerating re-endothelialization. This study establishes MµCLIP as a versatile platform for integrating distinct topographies into 3D scaffolds, opening new opportunities for regenerative implants and biomimetic tissue models.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e04630"},"PeriodicalIF":9.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336285","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":"Inducing In Situ Functional Maturation of Transplanted Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Establishing Strategies for Treating Myocardial Injury.","authors":"Xueqin Shi, Jianfeng Zhong, Xueting Liu, Shuai Guo, Weirun Li, Jiexin Zhang, Xiaodong Ning, Yuhua Liu, Chi Zhang, Qiujian Zhong, Zhilong Zhang, Tianwang Guan, Peier Chen, Caiwen Ou","doi":"10.1002/adhm.202503799","DOIUrl":"https://doi.org/10.1002/adhm.202503799","url":null,"abstract":"<p><p>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have demonstrated significant potential for the treatment of heart diseases. However, hiPSC-CMs generated by the current methods still exhibit structural and electrophysiological immaturity, resembling fetal cardiomyocytes. Although various strategies have been developed to promote in vitro maturation, cell loss and death remain persistent challenges during transplantation. Therefore, a multipronged approach is developed to induce in situ hiPSC-CMs functional maturation and enhance the cell transplantation rate, not only allowing cells carried within to have lower automatism, but also retaining the ability to restore systolic function. Chitosan is used as the matrix backbone to form a unique 3D network structure for cell encapsulation and delivery, whereas anionic lipid-based carriers derived from negatively charged liposomes enabled pH-responsive release of the mammalian target of rapamycin (mTOR) inhibitor within the weakly acidic microenvironment in myocardial infarction. Inhibition of the mTOR-signaling pathway can promote the functional maturation of hiPSC-CMs by bringing them into a quiescent state, allowing the cells not only to have lower automatism but also to resume pulsation under slight stimulation. This approach promotes the functional recovery of injured hearts by enhancing more robust gap junctions and angiogenesis in infarcted mouse hearts.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03799"},"PeriodicalIF":9.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342236","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}
Se-Hwan Lee, Ali Kiapour, Brendan D. Stoeckl, Ellen Y. Zhang, Matthew R. Begley, Jarod Oldham, Lewis Harrison, Jessee Hunt, Robert L. Mauck, Su Chin Heo
{"title":"Therapeutic Implants: Mechanobiologic Enhancement of Osteogenic, Angiogenic, and Myogenic Responses in Human Mesenchymal Stem Cells on 3D-Printed Titanium Truss (Adv. Healthcare Mater. 27/2025)","authors":"Se-Hwan Lee, Ali Kiapour, Brendan D. Stoeckl, Ellen Y. Zhang, Matthew R. Begley, Jarod Oldham, Lewis Harrison, Jessee Hunt, Robert L. Mauck, Su Chin Heo","doi":"10.1002/adhm.70265","DOIUrl":"https://doi.org/10.1002/adhm.70265","url":null,"abstract":"<p><b>The Paradigm Shift to Orthopedic Implants with Therapeutic Effect</b></p><p>Legacy manufacturing technology limited the sophistication of orthopedic implant design and function. Additive manufacturing now provides the ability to produce implants with advanced structural designs. In contrast to the performance limitations of yesterday's static implants, today, kinetic implants can be produced that are programmed to provide a mechanical mode of action that converts physiologic load into therapeutic strain at the surgical site, amplifying osteogenic activity. The authors identify the synergistic effect between surface features, implant architecture, and mechanical environment, offering insights for optimizing next-generation orthopedic implants that provide a therapeutic effect and accelerate healing. More details can be found in the Research Article by Se-Hwan Lee, Ali Kiapour, and co-workers (DOI: 10.1002/adhm.202501856).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":"14 27","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adhm.70265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145327763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Remodeling Cellular Uptake via Inducing Clustering of Urokinase Receptors in Hydrogel Microspheres for Alleviating Cartilage Senescence.","authors":"Zhiqi Lin, Chenliang Wu, Yawei Du, Ding Zhao, Yihan Li, Liren Wang, Yuhao Kang, Ziyun Li, Rongtai Zuo, Wenguo Cui, Jinzhong Zhao","doi":"10.1002/adhm.202504034","DOIUrl":"https://doi.org/10.1002/adhm.202504034","url":null,"abstract":"<p><p>Cellular senescence impairs clathrin-mediated endocytosis (CME), partly due to reduced membrane fluidity and disrupted lipid raft composition, which hinder receptor clustering and limit drug uptake. To overcome this, a urokinase receptor (µPAR) antibody-modified cationic liposome was developed loaded with plasmid of DNA-repairing enzyme Sirt6 (anti-µPAR@Lipo-Sirt6), targeting the overexpressed µPAR on senescent chondrocytes to promote receptor clustering and enhance CME. Compared to Lipo-Sirt6, anti-µPAR@Lipo-Sirt6 induced µPAR clustering and enhanced cellular uptake via the CME pathway. The results showed 1.7-2-fold higher uptake efficiency in vitro and 1.5-fold higher in vivo, leading to improved Sirt6 gene delivery. In vitro, treatment with anti-µPAR@Lipo-Sirt6 promoted DNA damage repair, significantly reduced the expression of senescence markers cyclin dependent kinase inhibitor 1a (Cdkn1a) and cyclin dependent kinase inhibitor 2a (Cdkn2a), and restored the expression of cartilage functional molecules type II collagen (Col2) and aggrecan (Acan). Encapsulation within hyaluronic acid-methacrylate (HAMA) hydrogel microspheres (anti-µPAR@Lipo-Sirt6@HMs) further prolonged retention and efficacy in vivo, significantly reducing p53 expression, preserving cartilage matrix molecules such as Col2 and Acan, delaying cartilage degradation, and restoring gait function in osteoarthritis (OA) mice. This study demonstrates that receptor clustering can be harnessed to enhance drug uptake in senescent cells, offering a promising strategy for anti-senescence therapy.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e04034"},"PeriodicalIF":9.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145335993","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":"A Sandwich-Like Coating for Dynamic Cerium Oxide Nanoparticles Delivery: Enhancing Osseointegration of Titanium Implants in Oxidative Microenvironment.","authors":"Ya-Nan Yao, Ya-Wen Zhu, Yu-Wen Wei, Xuan Zhou, Shu-di Li, Jing-Yi Ma, Jing Qiu","doi":"10.1002/adhm.202502889","DOIUrl":"https://doi.org/10.1002/adhm.202502889","url":null,"abstract":"<p><p>Excessive reactive oxygen species (ROS) around titanium implants under pathological conditions can cause mitochondrial dysfunction, potentially resulting in implant failure or related complications. This study designs a titanium implant functionalized with cerium oxide nanoparticles (CeNPs) using phenylboronic acid-modified hyaluronic acid (HA-PBA) and carboxylated chitosan (CCS) as polyelectrolytes, with the primary objective of modulating the local microenvironment around the implant. Owing to the responsive properties of HA-PBA, the embedded CeNPs are released in an on-demand manner as the coating degrades under different conditions. The Ti-HAPBA/CCS-CeNPs implants not only directly stimulate osteoblast differentiation under physiological conditions but also mitigate oxidative stress-induced mitochondrial dynamics imbalance and dysfunction. This protective effect is achieved by scavenging intracellular ROS, downregulating DRP1 expression, and restoring mitochondrial membrane potential (MMP). The osteoinductive efficacy of the Ti-HAPBA/CCS-CeNPs implants is further assessed using a femoral implantation model in diabetic rats, which demonstrates significantly enhanced bone remodeling and osseointegration at four and eight weeks post-implantation compared to the Ti-SLA group. Collectively, this study demonstrates the therapeutic potential of Ti-HAPBA/CCS-CeNPs implants under both physiological and pathological conditions, and provides a novel biopolymer-based strategy for improving dental implant outcomes.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02889"},"PeriodicalIF":9.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336308","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}
Yulu Yang, Tiantian Yuan, Wuzhe Fan, Pengfei Gao, Yao Yang, Ruqing Bai, Weihu Yang, Kaiyong Cai
{"title":"Enhancing Vascularized Bone Regeneration Through Oscillatory Fluid Flow-Regulated Gradient Lattice Gradient Lattice Implants Porous Titanium Alloy.","authors":"Yulu Yang, Tiantian Yuan, Wuzhe Fan, Pengfei Gao, Yao Yang, Ruqing Bai, Weihu Yang, Kaiyong Cai","doi":"10.1002/adhm.202502853","DOIUrl":"https://doi.org/10.1002/adhm.202502853","url":null,"abstract":"<p><p>Natural bone has anisotropic mechanical properties. However, most existing 3D printed porous titanium alloy implants are limited by isotropic mechanical behavior and a simple through-hole structure, which cannot fully replicate natural bone structure. This study develops a 3D printed porous titanium alloy scaffold whose truss-based microstructure is designed to simulate the anisotropic characteristics of natural bone. Finite element analysis (FEA) is used to optimize the structural parameters of the scaffold, which enhances the elastic modulus matching with the host bone and improves the cell migration potential. Computational fluid dynamics (CFD) simulations further show that the gradient lattice implant promotes superior fluid dynamics and facilitates interstitial flow in the transport of cellular nutrients. Under oscillating fluid flow (OFF) conditions, bone marrow mesenchymal stem cells (BMSCs) grow along the truss rod with enhanced osteogenic differentiation. BMSCs also promote vascularization through paracrine signaling mechanisms. This bionic scaffold design mitigates the stress shielding effect while optimizing the flow of interstitial fluid to enhance bone regeneration.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02853"},"PeriodicalIF":9.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342147","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":"pH-Responsive Multicomponent Nanocomposite for Enhanced Reactive Oxygen Species Generation and Targeted Apoptosis-Induced Synergistic Cancer Treatment (Adv. Healthcare Mater. 27/2025)","authors":"Chang Hyeon Ha, Do Hyeon Kim, Gi Hun Seong","doi":"10.1002/adhm.70263","DOIUrl":"https://doi.org/10.1002/adhm.70263","url":null,"abstract":"<p><b>Cancer-Targeted Drug Delivery System</b></p><p>The HA-CS@Pt-GOx can be easily introduced into cells via specific endocytosis through the CD44 receptor. Subsequently, it can effectively induce cell death by forming toxic reactive oxygen species and lipid peroxides using excess intracellular glucose and hydrogen peroxide. More details can be found in the Research Article by Gi Hun Seong and co-workers (DOI: 10.1002/adhm.202502370).\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":"14 27","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adhm.70263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145327761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Cui, Chen Ni, Mengmeng Wang, Jie Huang, Danyang Qu, Jinfeng Yang, Xingqi Pan, Zhenbao Liu, Meilin Shi
{"title":"Smart Tumor Oxygen Supply Strategy Enables Dual-Modality Fluorescence/MR Imaging and Synergistic Therapy of Triple-Negative Breast Cancer.","authors":"Hao Cui, Chen Ni, Mengmeng Wang, Jie Huang, Danyang Qu, Jinfeng Yang, Xingqi Pan, Zhenbao Liu, Meilin Shi","doi":"10.1002/adhm.202503886","DOIUrl":"https://doi.org/10.1002/adhm.202503886","url":null,"abstract":"<p><p>Breast cancer progression is closely associated with hypoxia, which severely limits the efficacy of conventional therapy. In addition, the lack of real-time imaging hampers accurate monitoring of therapeutic processes, further reducing treatment precision and efficacy. Here, the rational design of a multifunctional nanoplatform that integrates hypoxia relief, dual-modality imaging, and synergistic therapy to overcome these barriers is reported. Mesoporous polydopamine nanoparticles are engineered and sequentially functionalized with the sonosensitizer chlorin e6 (Ce6), oxygen-generating manganese dioxide, and the targeting antibody cetuximab, yielding MPDA-Ce6@MnO<sub>2</sub>-C225 (MCMC NPs). This construct exhibits a uniform nanoflower-like architecture, high Ce6 encapsulation efficiency, and robust oxygen supply capacity. By simultaneously enhancing reactive oxygen species generation and chemodynamic activity, MCMC NPs achieve potent SDT/CDT synergy under ultrasound activation. Importantly, they provide sensitive dual-modality fluorescence and magnetic resonance (MR) imaging, enabling real-time monitoring of nanoparticle distribution and therapeutic response. In vitro studies confirm excellent biocompatibility, targeted uptake by 4T1 breast cancer cells, and significant MRI signal enhancement. In vivo, MCMC NPs effectively alleviate tumor hypoxia, markedly suppress tumor growth, and prolong therapeutic response. This study establishes MCMC NPs as a versatile nanotheranostic platform that integrates imaging with oxygen-augmented SDT/CDT, offering a promising strategy for precise and effective breast cancer treatment.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03886"},"PeriodicalIF":9.6,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145335970","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}