Bugra Ayan, Gaoxian Chen, Ishita Jain, Sha Chen, Gladys Chiang, Caroline Hu, Renato Reyes, Beu P Oropeza, Ngan F Huang
{"title":"Geometrically Tunable Scaffold-Free Muscle Bioconstructs for Treating Volumetric Muscle Loss.","authors":"Bugra Ayan, Gaoxian Chen, Ishita Jain, Sha Chen, Gladys Chiang, Caroline Hu, Renato Reyes, Beu P Oropeza, Ngan F Huang","doi":"10.1002/adhm.202501887","DOIUrl":"https://doi.org/10.1002/adhm.202501887","url":null,"abstract":"<p><p>Traumatic muscle injuries associated with volumetric muscle loss (VML) are characterized by muscle loss beyond intrinsic regeneration capacity, leading to permanent functional impairment. Experimental therapies to augment muscle regeneration, such as cell injection, are limited by low cell transplantation capacity, whereas conventional engineered muscle tissue transplants lack geometric customization to conform to the shape of the muscle defect. Here, a facile approach to engineer scaffold-free high-density muscle tissues in customizable geometric shapes and sizes with high cell viability and integration potential is developed. Using a facile mold-based approach to engineer scaffold-free modular units, transcriptional profiling is performed to uncover the role of pre-formed cell-cell interactions within scaffold-free muscle bioconstructs on myogenesis, an the efficacy of muscle bioconstructs in a mouse model of VML is then evaluated. RNA sequencing revealed that pre-formed cell-cell interactions supported myogenic pathways related to muscle contraction and myofibril assembly, unlike dissociated monodisperse cells. This work further demonstrates the therapeutic efficacy of 3D rectangular solid-shaped scaffold-free transplants in improving muscle function and vascular regeneration. Finally, toward clinical translation, the feasibility of this technology to integrate with medical imaging and artificial intelligence-driven customized bioconstruct design and assembly for intraoperative use is illustrated.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e01887"},"PeriodicalIF":9.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342165","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}
Ninon Möhl, Daphne Bouwens, Johanna Abele, Aline Hans, Tanja Topic, Daniel Günther, Jitske Jansen, Rafael Kramann, Laura De Laporte
{"title":"Development of a Synthetic 3D Platform for Compartmentalized Kidney In Vitro Disease Modeling.","authors":"Ninon Möhl, Daphne Bouwens, Johanna Abele, Aline Hans, Tanja Topic, Daniel Günther, Jitske Jansen, Rafael Kramann, Laura De Laporte","doi":"10.1002/adhm.202503287","DOIUrl":"https://doi.org/10.1002/adhm.202503287","url":null,"abstract":"<p><p>3D in vitro tissue and disease models have emerged as an important tool for diagnostic and therapeutic screenings, as they offer a closer approximation toward native environments than traditional 2D cell culture. Kidney disease modeling in particular has progressed to using induced pluripotent stem cells (iPSCs) and microfluidic platforms to replicate the complex microenvironment of the kidney. However, current models lack mature tissue development, scalability, tunability, and spatial organization. In this study, a fully synthetic, 3D kidney disease platform that addresses these challenges is presented. This model comprises a compartmentalized poly (ethylene glycol) (PEG)-based hydrogel matrix with anisotropic PEG-based microgels. This multiphasic hydrogel system provides control over spatially organizing a triple-co-culture of key renal cell types: tubule-epithelial cells (CD10<sup>+</sup>), endothelial cells (CD31<sup>+</sup>), and fibroblasts (PDGFRβ<sup>+</sup>). Structural control and compartmentalization are enabled through enzymatically degradable rod microgels produced using microfluidics, allowing for a modular system. This study characterizes the synthetic models and analyzes the functionality of the system by examining cell-material interactions. The use of this system as a promising disease model is demonstrated through the addition of TGFβ, inducing fibrosis. This work highlights a novel approach to building a fully synthetic, scalable, modular kidney model with a tunable microenvironment.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03287"},"PeriodicalIF":9.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353070","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 Pathophysiology-Informed, Negentropy-Oriented Strategy for Nanomedicine in MASLD.","authors":"Rui Mao, Meng Yu, Xiu-Ping Guo, Xiao-Lian Tian, Meng-Yu Zhao, Quan-Yong Yu, Gang Ren, Ming-Yu Pan, Ru Bai, Li-Ping Liu, Gui-Ling Li, Jian-Dong Jiang, Lu-Lu Wang","doi":"10.1002/adhm.202504298","DOIUrl":"https://doi.org/10.1002/adhm.202504298","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial chronic liver disorder driven by an ensemble of interrelated pathological processes, including insulin resistance, lipid accumulation, oxidative stress, immune dysregulation, gut microbiota imbalance, and hepatocyte injury-induced cell death. These overlapping mechanisms pose significant challenges for effective treatment, as conventional single-target therapies often fail to address the systemic complexity of the disease. Recent advances in functional nanomedicine have introduced promising avenues for MASLD intervention by enabling the development of nanoplatforms specifically engineered to interact with disease-specific pathophysiological features. These systems incorporate stimuli-responsive drug release, targeted hepatic accumulation, and intrinsic therapeutic activity, allowing for simultaneous modulation of multiple pathological pathways. This review presents a pathophysiology-informed framework for nanomedicine design in MASLD therapy. How diverse platforms are strategically tailored to regulate reactive oxygen species (ROS) production, modulate immune imbalance, restore insulin signaling, inhibit ferroptosis, and rebalance gut microbial dysbiosis is examined. Moreover, emerging approaches such as carrier-free, self-assembling systems and multifunctional yet intentionally minimalist architectures that enhance translational potential are highlighted. Together, these strategies exemplify a shift toward mechanism-driven, entropy-informed nanotherapeutics, wherein negentropy-oriented and leading-axis design principles offer a promising roadmap for restoring metabolic homeostasis in complex disease contexts such as MASLD.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e04298"},"PeriodicalIF":9.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353072","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}
Vahid Naeini, Emilio A Mendiola, Ahmad Rafsanjani, Fergal B Coulter, Qian Xiang, Jianyi Zhang, Peter Vanderslice, Vahid Serpooshan, Reza Avazmohammadi
{"title":"A Computational Journey Toward an Optimal Design for Metamaterial Epicardial Passive Sleeves.","authors":"Vahid Naeini, Emilio A Mendiola, Ahmad Rafsanjani, Fergal B Coulter, Qian Xiang, Jianyi Zhang, Peter Vanderslice, Vahid Serpooshan, Reza Avazmohammadi","doi":"10.1002/adhm.202501369","DOIUrl":"https://doi.org/10.1002/adhm.202501369","url":null,"abstract":"<p><p>Heart failure (HF) following myocardial infarction (MI) is a major clinical challenge with severe complications. Epicardial sleeves and patches are increasingly investigated to improve heart function post-MI, yet their passive mechanical effects remain underexplored. This has resulted in limited insight into how sleeves mechanically interact with the infarct and remote myocardium. This study used 3-D in-silico cardiac models to examine how sleeve shape, material properties, and architecture affect global and regional mechanics. A high-fidelity biventricular model is used to investigate how a continuum cardiac sleeve alters function. Designs that improve regional mechanics successfully limited pathological bulging, modulated fiber strains, and influenced torsional behavior without over-constraining remote tissue, whereas overly restrictive and stiff sleeves penalized healthy myocardium and reduced the intended relief of infarct bulging. These findings highlight the importance of considering regional biomechanical markers when developing sleeve designs. Building on these continuum sleeve insights, a spheroidal left ventricle model demonstrated the proof-of-concept advantage of an \"auxetic\" metamaterial sleeve, engineered with a negative Poisson ratio. This programmed architecture provided region-specific benefits beyond those of conventional continuum sleeves. Ultimately, this work contributes to an improved understanding of passive sleeve-heart interactions and improves the targeted biomechanical support therapies following MI.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e01369"},"PeriodicalIF":9.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353122","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}
Qiannan Chen, Chengpan Li, Weiping Ding, Derun Kong
{"title":"Liver Organoid and Liver-On-A-Chip Platforms for Modeling Alcoholic Liver Disease: A Comparative Review.","authors":"Qiannan Chen, Chengpan Li, Weiping Ding, Derun Kong","doi":"10.1002/adhm.202503273","DOIUrl":"https://doi.org/10.1002/adhm.202503273","url":null,"abstract":"<p><p>Alcoholic liver disease (ALD) encompasses a spectrum of progressive liver injuries caused by chronic alcohol consumption, including steatosis, hepatitis, fibrosis, and cirrhosis. The development of physiologically relevant preclinical models remains critical for elucidating the pathogenesis of ALD and evaluating therapeutic strategies. Recent advances in liver organoid and liver-on-a-chip (LOC) technologies offer complementary platforms for modeling distinct aspects of ALD. Organoids recapitulate liver tissue architecture with multicellular composition, enabling the study of chronic pathological processes such as lipid accumulation and early fibrogenesis. Conversely, LOC systems replicate dynamic microenvironments such as fluid flow and oxygen gradients, enabling studies of inflammation and vascular injury. In this review, the first comprehensive comparison of liver organoids and LOC systems specifically in the context of ALD is provided. Emerging liver organoid-on-a-chip (OoC) strategies and their potential to model the full spectrum of ALD pathology are also discussed. Finally, key technical challenges are identified, and future directions are proposed targeting patient-specific, multiorgan, and high-throughput platforms to advance ALD-related research and precision medicine.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03273"},"PeriodicalIF":9.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353097","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}
Anna Burgstaller, Tamara Nink, Niklas Walter, Erick Angel Lopez Lopez, Hsin-Fang Chang, Oskar Staufer
{"title":"Synthetic Cell-Based Tissues for Bottom-Up Assembly of Artificial Lymphatic Organs.","authors":"Anna Burgstaller, Tamara Nink, Niklas Walter, Erick Angel Lopez Lopez, Hsin-Fang Chang, Oskar Staufer","doi":"10.1002/adhm.202503498","DOIUrl":"https://doi.org/10.1002/adhm.202503498","url":null,"abstract":"<p><p>Synthetic cells have emerged as a novel biomimetic approach for studying fundamental cellular functions and enabling new therapeutic interventions. However, the potential to program synthetic cells into self-organized 3D collectives to replicate the structure and function of tissues has remained largely untapped. Here, self-assembly properties are engineered into synthetic cells to form millimeter-sized 3D lymphatic bottom-up tissues (lymphBUTs) with mechanical adaptability, metabolic activity, and hierarchical microstructural organization. It is demonstrated that primary human immune cells spontaneously infiltrate and functionally integrate into these synthetic lymph nodes to form living tissue hybrids. Applying lymphBUTs, it is shown that structured 3D organization and mechanical support drives T cell activation and the application of lymphBUTs for ex vivo expansion of regulatory CD8<sup>+</sup> T cells is demonstrated. The study highlights the functional integration of living and non-living matter, advancing synthetic cell engineering toward 3D tissue structures.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03498"},"PeriodicalIF":9.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342214","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}
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":"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}