Yuanhui Song, Michael Seitz, Andrew Kowalczewski, Nhu Y Mai, Era Jain, Huaxiao Yang, Zhen Ma
{"title":"Mechanically and Chemically Defined PEG Hydrogels Improve Reproducibility in Human Cardioid Development.","authors":"Yuanhui Song, Michael Seitz, Andrew Kowalczewski, Nhu Y Mai, Era Jain, Huaxiao Yang, Zhen Ma","doi":"10.1002/adhm.202403997","DOIUrl":"https://doi.org/10.1002/adhm.202403997","url":null,"abstract":"<p><p>Cardioids are 3D self-organized heart organoids directly derived from induced pluripotent stem cells (hiPSCs) aggregates. The growth and culture of cardioids is either conducted in suspension culture or heavily relies on Matrigel encapsulation. Despite the significant advancements in cardioid technology, reproducibility remains a major challenge, limiting their widespread use in both basic research and translational applications. Here, for the first time, we employed synthetic, matrix metalloproteinase (MMP)-degradable polyethylene glycol (PEG)-based hydrogels to define the effect of mechanical and biochemical cues on cardioid development. Successful cardiac differentiation is demonstrated in all the hydrogel conditions, while cardioid cultured in optimized PEG hydrogel (3 wt.% PEG-2mM RGD) underwent similar morphological development and comparable tissue functions to those cultured in Matrigel. Matrix stiffness and cell adhesion motif play a critical role in cardioid development, nascent chamber formation, contractile physiology, and endothelial cell gene enrichment. More importantly, synthetic hydrogel improved the reproducibility in cardioid properties compared to traditional suspension culture and Matrigel encapsulation. Therefore, PEG-based hydrogel has the potential to be used as an alternative to Matrigel for human cardioid culture in a variety of clinical applications including cell therapy and tissue engineering.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403997"},"PeriodicalIF":10.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075199","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":"Development-Inspired Biomimetic Cell-Niche Coaggregates Safeguard Tooth Stem Cell-Based Functional Tissue Regeneration.","authors":"Xiao-Hui Zhang, Yi-De He, Hao Wang, Yuan Cao, Si-Qi Ying, Jia-Ning Liu, Xiao Lei, Lu Liu, Xin-Yue Cai, Shi-Han Mu, Kai-Chao Zhang, Yuan Yuan, Yi-Han Liu, Hao-Kun Xu, Ji Chen, Jian-Fei Liang, Yan Jin, Fang Jin, Bing-Dong Sui, Chen-Xi Zheng","doi":"10.1002/adhm.202501550","DOIUrl":"https://doi.org/10.1002/adhm.202501550","url":null,"abstract":"<p><p>Harnessing natural developmental programs to repair and replace damaged organs represents promising approaches in regenerative medicine. However, effective strategies are still lacking for tissue regeneration in complicated conditions, such as the periodontal bone defect. Here, human dental follicle stem cells (hDFSCs) and their aggregates (hDFSCA) are cultured and characterized, which are formed based on the inherent property of these stem cells self-assembly into compact spheroid-like structures, mimicking mesenchymal condensation in development. A periodontal tissue-specific microenvironment simulation material is then established, human decellularized alveolar bone matrix particles (hDABMPs), which possess favorable physicochemical and biological properties for regenerative use. hDFSCs co-cultured with hDABMPs exhibit improved cell function, and hDFSCA-hDABMP co-aggregates are subsequently constructed, which activate the developmental gene expression in hDFSCA and initiate hypoxic adaptation mechanisms for tissue regeneration. Indeed, hDFSCA-hDABMP co-aggregates significantly promote regeneration after implantation in alveolar bone defects with good biosafety. Interestingly, during the early stages of implantation, hDABMPs enhance hDFSC survival and expansion, thereby providing a sufficient source of cells for tissue regeneration. Collectively, this study reveals a development-inspired, engineered cell-niche co-aggregation strategy for enhancing CA therapeutic potential by simulating tissue-specific microenvironments, offering novel insights for functional tissue regeneration.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501550"},"PeriodicalIF":10.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075192","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}
Jimin Lee, Allison Bateman, Mi Hyeon Kim, Bruno Rigo, Hodam Kim, Jaeho Lee, Yun Hyeok Choi, Robert Herbert, Deok Hee Lee, Woon-Hong Yeo
{"title":"Non-Surgical, In-Stent Membrane Bioelectronics for Long-Term Intracranial Pressure Monitoring (Adv. Healthcare Mater. 13/2025)","authors":"Jimin Lee, Allison Bateman, Mi Hyeon Kim, Bruno Rigo, Hodam Kim, Jaeho Lee, Yun Hyeok Choi, Robert Herbert, Deok Hee Lee, Woon-Hong Yeo","doi":"10.1002/adhm.202570077","DOIUrl":"https://doi.org/10.1002/adhm.202570077","url":null,"abstract":"<p><b>Intracranial Pressure Monitoring</b></p><p>This cover image shows the in-stent intracranial pressure sensor's journey from the antecubital vein to the dural venous sinus, highlighting its minimally invasive approach. These advancements pave the way for broader clinical applications, minimizing complications and improving patient outcomes in neurocritical care. More details can be found in article 2404680 by Deok Hee Lee, Woon-Hong Yeo, and co-workers.\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 13","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adhm.202570077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074411","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}
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 (Adv. Healthcare Mater. 13/2025)","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.202570079","DOIUrl":"https://doi.org/10.1002/adhm.202570079","url":null,"abstract":"<p><b>AI-Assisted Bioprinting of Personalized Grafts</b></p><p>In article 2402727, Dean Ho, Gopu Sriram and co-workers present a 3D bioprinting technique coupled with AI-based optimization and polysaccharide/fibrinogen-based bioinks to fabricate personalized gingival tissue constructs. This innovative method targets to repair mucogingival defects associated with periodontal disease and dental implants, with promising potential for broader applications in the biofabrication of personalized soft tissue grafts.\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 13","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adhm.202570079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074673","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":"Integrated Iontronic FMG-sEMG Sensing for Decoding Muscle Activation Mechanisms and Force Assessment.","authors":"Peikai Zou, Junhan Wang, Xian Zhao, Xigong Zhang, Kehan Hua, Yejun Zha, Ruya Li, Yubo Fan","doi":"10.1002/adhm.202500843","DOIUrl":"https://doi.org/10.1002/adhm.202500843","url":null,"abstract":"<p><p>Muscle activity generates both physiological electrical and mechanical signals, the monitoring of which is crucial in rehabilitation and sports medicine, underpinning effective diagnosis, treatment, and rehabilitation processes. Advances in flexible electronics enable force myography (FMG) and surface electromyography (sEMG) signals for muscle activation monitoring, but the multi-sensor integration and physiological mechanisms underlying FMG signals remain poorly studied, limiting the accuracy of muscle function assessments and underutilizes the high sensitivity of the flexible sensors. This study introduces a novel thin-film iontronic force-electromyography (iFEMG) sensor, integrating a high-sensitivity iontronic pressure sensor and sEMG electrodes for high-fidelity muscle physiological signal acquisition. Based on ultrasound imaging and statistical analysis, the relationship between muscle force, muscle geometric features, and FMG signals is established, providing evidence for elucidating the physiological mechanisms of FMG signals. Based on these findings, an effective and highly adaptable method is proposed for precise muscle force prediction. The iFEMG system is successfully applied to assess motor nerve and muscle function in patients, demonstrating its clinical utility. This system holds significant potential for broader applications, such as rehabilitation training and early diagnosis of musculoskeletal disorders, paving the way for advanced personalized healthcare solutions.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500843"},"PeriodicalIF":10.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075197","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":"Fabrication of a Lipopolysaccharide-Targeting Peptide-Based Colloid for Alleviating Carbapenem-Resistant Enterobacteriaceae-Induced Cutaneous Infection.","authors":"Ping Zeng, Xinyi Ding, Chenyu Liu, Sheng Chen, Kin-Fai Chan, Sharon Shui Yee Leung","doi":"10.1002/adhm.202500659","DOIUrl":"https://doi.org/10.1002/adhm.202500659","url":null,"abstract":"<p><p>Carbapenem-resistant Enterobacteriaceae (CRE) becomes a growing threat to human health. Many clinical isolates have shown strong resistance to commonly used antibacterial agents. Inspired by cationic amphiphiles with tandem-repeat sequence, two novel peptides termed IW (IWRRIWRRIWRRIWRR-NH<sub>2</sub>) and WI (WIRRWIRRWIRRWIRR-NH<sub>2</sub>) are designed, synthesized, and investigated in this study. Both exhibited favorable antibacterial activity against \"superbugs\" at micromole level, surpassing conventional antibiotics, like meropenem and imipenem. Adopting the analytic strategies of molecular dynamics simulation in combination with experimental verification, lipopolysaccharide (LPS) is proposed as a potential target for IW with a calculated dissociation constant of 886 ± 879 nM. Though deadly to infamous bacteria, IW demonstrated negligible toxicity to Galleria mellonella (GM) larvae at 500 mg kg<sup>-1</sup>. For better administration, IW was formulated with a commercial pharmaceutical excipient poloxamer 407 (P407) to fabricate an antibacterial colloid. This material was verified to effectively reduce the bacterial burden of Escherichia coli-infected skin in a mouse model by ≈1.5 log compared with the P407-treated group. Overall, this work expanded the potential arsenal against carbapenem-resistant strains by introducing a new engineered molecule delivered using a cheap, concise formulation strategy accordingly.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500659"},"PeriodicalIF":10.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075195","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}
Cheng Yao, Heqi Wang, Jingxia Han, Kai Yang, Tingting Lin, Jing Jin, Caibin Zhu, Huijuan Liu
{"title":"Zn-Based Multi-Active Framework Nanoparticles TSA-CAN-Zn Inhibit Skin Glycation via Dual Blockade of HMGB1/RAGE and AGEs/RAGE Pathways.","authors":"Cheng Yao, Heqi Wang, Jingxia Han, Kai Yang, Tingting Lin, Jing Jin, Caibin Zhu, Huijuan Liu","doi":"10.1002/adhm.202500664","DOIUrl":"https://doi.org/10.1002/adhm.202500664","url":null,"abstract":"<p><p>Receptor for advanced glycation end products (RAGE) plays an important role in skin glycation damage. High-mobility group 1B protein (HMGB1) and advanced glycation end products (AGEs) are key RAGE ligands. Simultaneous inhibition of HMGB1/RAGE and AGEs/RAGE pathways maybe an effective strategy to alleviate glycation induced skin damage. In this work, Theasinensin A (TSA) is identified as the active molecule inhibiting HMGB1-RAGE interaction through molecular docking. To simultaneously suppress HMGB1/RAGE and AGEs/RAGE pathways, Zn-based multi-active framework nanoparticles TSA-CAN-Zn are designed, which contain TSA and the active molecule L-carnosine (CAN) that inhibits AGEs production. In vitro studies demonstrated that TSA-CAN-Zn have radical scavenging activity and AGEs formation inhibition activity. TSA-CAN-Zn can not only inhibit ROS accumulation, cell apoptosis, and inflammatory factors production induced by glycation in HaCaT cells but also enhanced the lysosomal degradation of AGEs. TSA-CAN-Zn also mitigated the damage caused by glycation in mouse skin glycation model. Single-cell RNA sequencing results revealed the impact of TSA-CAN-Zn on different cell types of skin tissue, especially the basal cells of the epidermal layer and inflammation-related macrophages. And pathway analysis revealed that TSA-CAN-Zn mainly influences the downstream pathways of RAGE. Collectively, TSA-CAN-Zn is a promising therapeutic candidate for ameliorating glycation-induced skin damage.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500664"},"PeriodicalIF":10.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075133","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":"Microneedle-Enabled Breakthroughs in Nucleic Acid Therapeutics.","authors":"Pengfei Wu, Tian Zhang, Deyao Zhao, Yingqiu Xie, Dong Huang, Zhihong Li, Yuanyu Huang","doi":"10.1002/adhm.202501015","DOIUrl":"https://doi.org/10.1002/adhm.202501015","url":null,"abstract":"<p><p>Nucleic acid therapy demonstrates great potential in cancer treatment, infectious disease prevention, and vaccine development due to its advantages, such as rapid production, long-lasting effects, and high target specificity. Although nucleic acid therapy is considered ideal for the development of novel therapeutic strategies, its clinical application still faces numerous challenges, including the lack of efficient delivery systems, insufficient drug formulation stability, and the limitations imposed by the skin barrier on drug dosage delivery. Microneedles, as an innovative transdermal drug delivery technology, can penetrate the stratum corneum and directly access the skin's microcirculation, enabling the efficient delivery of genes and drugs. This technology offers several advantages, such as ease of operation, minimally invasive and painless application, and high safety. Combining microneedle technology with nucleic acid therapy fully leverages the strengths of both approaches, significantly enhancing therapeutic efficacy and bioavailability while maximizing treatment potential. This review explores the application prospects and advantages of combining microneedle delivery systems with nucleic acid therapy.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501015"},"PeriodicalIF":10.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075201","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":"Dynamic Mechanical Stimulation of Thermoresponsive Nanofibers for Activation of Fibroblasts in Skin Repair.","authors":"Xuran Guo, Ying Gao, Jiajia Yu, Sha Qiu, Xiaoli Wang, Shasha Wang, Chunling Zhang, Bingcheng Yi, Yinghua Gao","doi":"10.1002/adhm.202500277","DOIUrl":"https://doi.org/10.1002/adhm.202500277","url":null,"abstract":"<p><p>Substrate stiffness regulates fibroblast phenotype through focal adhesion-mediated mechanotransduction pathways to facilitate tissue repair and regeneration. To analyze the effects of dynamic mechanical stimulation of substrates on cell behavior and skin wound healing, collagen-like hydrogel nanofibers are fabricated using coaxial electrospinning of gelatin methacryloyl (GelMA) and poly-L-lactic acid (PLLA). These nanofibers are then grafted with thermoresponsive poly(N-vinylcaprolactam) (PNVCL) via dehydration condensation reaction, providing temperature-dependent mechanical signals. The incorporation of PLLA significantly enhanced the mechanical properties of the GelMA hydrogel nanofibers, while the subsequent grafting of PNVCL effectively reduced the swelling ratio and porosity. Upon exposure to temperatures above the lowest critical solution temperature (LCST), PNVCL molecules underwent a phase transition and self-contraction, improving mechanical properties by forming robust hydrogen bonds with GelMA and expelling water molecules from the polymer matrix. This dynamic mechanical stimulation further promoted cytoskeletal remodeling of mouse skin fibroblasts (MSFs) without significantly affecting cell proliferation and migration. Additionally, it stimulated the differentiation of fibroblasts into myofibroblasts, thereby enhancing extracellular matrix secretion and skin regeneration in vivo. Overall, the engineering of thermoresponsive hydrogel nanofibers with dynamic mechanical stimulation introduces a novel design paradigm in functional tissue engineering, enabling precise regulation of cellular behaviors for effective skin wound healing.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500277"},"PeriodicalIF":10.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955820","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}