{"title":"Stem Cells from the Apical Papilla-Laden Microgels in Combination with Mandibular Advancement for Adult Condylar Cartilage Development.","authors":"Shengchao Wang, Chichong Chan, Xinyu Shi, Huijuan Wang, Lingxi Du, Xiaolong Yi, Xin Cheng, Liangching Huang, Silong Li, Qi Feng, Xiaodong Cao, Yue Huang","doi":"10.1002/adhm.202502762","DOIUrl":"https://doi.org/10.1002/adhm.202502762","url":null,"abstract":"<p><p>Angle's Class II malocclusion, characterized by mandibular retraction, significantly impacts occlusal function and facial aesthetics. In adults, the limited development potential of the condylar cartilage poses challenges to effective mandibular remodeling. Clinically, mandibular advancement (MA) can promote the development of condylar cartilage in adolescents, but its effect on adult condylar cartilage remains controversial. Herein, MA is achieved via three methods in adult rats to investigate the effect of MA on adult condylar cartilage development. MA could stimulate the growth of adult condylar cartilage. Nevertheless, the rate of condylar cartilage development remains slow, as evidenced by a maximum cartilage thickness increase of 7.7%. To further promote condylar cartilage development, stem cells from the apical papilla (SCAPs)-laden microgels are fabricated via droplet microfluidic technology. Microgels with reduced stiffness and accelerated stress relaxation significantly promote the proliferation and chondrogenic differentiation of SCAPs. Animal experiments have demonstrated that SCAPs-laden microgels combined with MA significantly accelerate the development of condylar cartilage, with a 15% increase in condylar cartilage thickness and upregulated expressions of Col I, Col II, and SOX9 compared to that in the MA group. This study demonstrates that SCAPs-laden microgels in combination with MA can enhance cartilage development, which will advance the adult mandibular remodeling technologies.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02762"},"PeriodicalIF":9.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273213","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}
Sophie K Hill, Min Zeng, Santhosh Kalash Rajendrakumar, Robert Dallmann, Sébastien Perrier
{"title":"Cyclic Peptide-Polymer Conjugate Nanotubes for Delivery of SN-38 in Treatment of Colorectal Cancer Model.","authors":"Sophie K Hill, Min Zeng, Santhosh Kalash Rajendrakumar, Robert Dallmann, Sébastien Perrier","doi":"10.1002/adhm.202502527","DOIUrl":"https://doi.org/10.1002/adhm.202502527","url":null,"abstract":"<p><p>Cyclic peptide-polymer conjugate nanotubes have been shown to be powerful drug delivery vectors, due to their propensity for dynamic self-assembly, high aspect ratio morphology and structural interchangeability. Building upon previous studies that demonstrate the shielding abilities of the polymeric corona of nanotubes to enhance pro-drug bond stabilities and modulate hydrolysis, here the concept of a hydrophobic core building block with multiple drug units to improve drug loading capacity and overall efficiency of the nanotube carriers is utilized. By leveraging the intermolecular features of the drug core to strengthen assembly, it is hypothesized that these nanotubes have the potential as a responsive supramolecular delivery system whereby upon full hydrolysis of the labile drug, these core forming interactions disappear, and nanotubes can fall apart and undergo clearance. Herein, the self-assembly, in vitro efficacy and in vivo pharmacokinetic and anti-tumor pharmacodynamics of these nanotubes in colorectal cancer models, comparing the potent topoisomerase inhibitor SN-38 with its clinically-used parent pro-drug irinotecan, is explored.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02527"},"PeriodicalIF":9.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273204","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}
Lanka Tata Rao, Chandan Kumar Mandal, Fernando Patolsky
{"title":"Body Biofluids for Minimally-Invasive Diagnostics: Insights, Challenges, Emerging Technologies, and Clinical Potential.","authors":"Lanka Tata Rao, Chandan Kumar Mandal, Fernando Patolsky","doi":"10.1002/adhm.202503096","DOIUrl":"https://doi.org/10.1002/adhm.202503096","url":null,"abstract":"<p><p>Recent advances in diagnostics have accelerated the development of miniaturized wearable technologies for the continuous monitoring of diseases. This paradigm is shifting healthcare away from invasive, centralized blood tests toward decentralized monitoring, using alternative body biofluids. Biofluids such as sweat, saliva, urine, and interstitial fluid (ISF) emerged as promising candidates in this context, due to their accessibility and potential ability to reflect physiological states. This review examines recent progress in non- and minimally-invasive diagnostics, with focus on sweat and ISF as potentially suitable biofluids. For biofluids to achieve clinical utility, they must contain quantifiable and disease-specific biomarker levels, supported by standardized collection and analysis protocols. However, sweat presents inherent limitations for diagnostics, such as intra- and interpersonal variability, biomarker concentration fluctuations, etc., and thus only suitable for non-clinical applications. In contrast, ISF, a robust plasma-like biofluid potentially fulfills all requirements posed by clinical applications, being readily accessed by minimally-invasive microneedle-based platforms. These developing platforms may advance this field by eliminating the need for biofluid extraction, enabling continuous sensing in clinical diagnostics. Future integration of these platforms with AI/ML-driven algorithms may lead to powerful technologies for real-time, predictive personalized diagnostics. These technological innovations establish a strong foundation for next-generation diagnostics and transformative healthcare solutions.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03096"},"PeriodicalIF":9.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273264","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":"Hierarchical Integration of MOF-Based Nanoplatforms with Electrospun Nanofiber Scaffolds for Spatiotemporally Sustained Diabetic Wound Healing.","authors":"Qizhen Wang, Jia Xu, YueHao Xu, Xiangyan Chen, Xintao Gao, Junyao Li, Qishan Xu, Fusheng Liu, Yantao Li","doi":"10.1002/adhm.202503699","DOIUrl":"https://doi.org/10.1002/adhm.202503699","url":null,"abstract":"<p><p>Currently, diabetic wound dressings continue to exhibit various limitations, hindering their ability to effectively respond to the dynamic and complex microenvironment of diabetic wounds. Particularly, significant challenges remain in developing multifunctional dressings capable of effective multicomponent integration and precise, controlled release of each component. Herein, the novel electrospun nanofiber composite membranes (NCMs) are developed that hierarchically incorporate zeolitic imidazolate framework (ZIF)-based nanoplatforms for spatiotemporally controlled and continuous release of multiple bioactive components, enabling the effective regulation of key factors involved in diabetic wound healing. Specifically, platelet-derived growth factor-BB (PDGF-BB)-loaded ZIF-8 (PZ) nanoparticles (NPs) are embedded within poly(ε-caprolactone)/gelatin (PCL/GT) nanofibers, while ZIF-67 NPs are in situ grown on the nanofiber surface, yielding multifunctional ZIF-67/PZ/PCL/GT (ZPZPG) NCMs. The hierarchical structures facilitate a staged pH-responsive release, wherein initially released Co<sup>2+</sup> from ZIF-67 NPs rapidly exerts antibacterial effects and promotes early angiogenesis, followed by the prolonged release of Zn<sup>2+</sup> and PDGF-BB from embedded ZIF-8 NPs, further enhancing antimicrobial activity, neovascularization, fibroblast proliferation, and tissue regeneration. Both in vitro and in vivo studies demonstrate effective infection control, improved vascularization, and accelerated wound healing, underscoring the potential of hierarchical metal-organic framework (MOF)-integrated NCMs as an attractive way to overcome current limitations in diabetic wound therapy.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03699"},"PeriodicalIF":9.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249087","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 Human Kidney Tubuloid Model of Repeated Cisplatin-Induced Cellular Senescence and Fibrosis for Drug Screening.","authors":"Yuki Nakao, Makiko Mori, Yuta Sekiguchi, Iori Morita, Ryota Shindoh, Shintaro Mandai, Tamami Fujiki, Hiroaki Kikuchi, Fumiaki Ando, Koichiro Susa, Takayasu Mori, Ayumi Suzuki, Yuji Nashimoto, Hirokazu Kaji, Yuma Waseda, Soichiro Yoshida, Yasuhisa Fujii, Eisei Sohara, Shinichi Uchida, Kensuke Miyake, Yutaro Mori","doi":"10.1002/adhm.202501795","DOIUrl":"https://doi.org/10.1002/adhm.202501795","url":null,"abstract":"<p><p>In advancing pathophysiological models to assess renal drug responses, kidney organoids derived from human pluripotent stem cells mark notable progress. However, replicating aging- and senescence-related pathologies remains a challenge. In this study, an alternative model is introduced using \"tubuloids\"-epithelial-like structures generated from primary human renal proximal tubular epithelial cells (hRPTECs) isolated from resected human kidneys. Bulk RNA-seq deconvolution confirmed that tubuloids are highly differentiated and predominantly composed of proximal tubule-like cells. Exposure to cisplatin increased γH2AX, Kidney Injury Molecule-1, and Cleaved Caspase-3, markers for DNA damage response, epithelial damage, and apoptosis, respectively. Repeated cisplatin administration resulted in the upregulation of senescence markers and secretion of inflammatory cytokines, consistent with a senescence-associated secretory phenotype (SASP). Supernatants from cisplatin-treated tubuloids triggered myofibroblast activation, suggesting early fibrotic changes. A hRPTEC-derived tubuloid model of cisplatin-induced kidney injury is successfully developed that mimics senescence, SASP, and fibrosis-hallmarks of chronic kidney disease. This model offers a promising human-relevant platform for studying renal epithelial responses and drug screening.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e01795"},"PeriodicalIF":9.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256929","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}
Ke Ning, Yuanyuan Xie, Xiaoyan Yang, Yirong Chen, Wen Sun, Jinhua Chen, Jingtao Zhu, Yan Li, Yingshuai Liu, Ling Yu
{"title":"Pump-Free Unidirectional Vertical Centrifugal Microfluidic Platform for Dynamic 3D Tumor Cluster Culture and Functional Drug Screening.","authors":"Ke Ning, Yuanyuan Xie, Xiaoyan Yang, Yirong Chen, Wen Sun, Jinhua Chen, Jingtao Zhu, Yan Li, Yingshuai Liu, Ling Yu","doi":"10.1002/adhm.202504241","DOIUrl":"https://doi.org/10.1002/adhm.202504241","url":null,"abstract":"<p><p>Recapitulating the dynamic microenvironment is essential for advanced 3D cell culture and reliable drug testing, yet conventional static platforms lack physiologically relevant fluid dynamics. Here, a pump-free vertical dual-circulation centrifugal microfluidic platform is presented, enabling unidirectional medium flow and efficient nutrient exchange for hydrogel-based 3D cultures. By combining centrifugal and gravitational forces, this integrated system achieves stable long-term circulation and establishes tunable concentration gradients, supporting sustained tumor clusters growth under dynamic conditions. Compared with static systems, the platform significantly enhances tumor spheroid expansion, promotes complex morphological remodeling, and facilitates fusion events. Functional drug perfusion studies demonstrate improved doxorubicin distribution and reduced local drug accumulation. This new type of vertical centrifugal microfluidic platform provides a versatile solution for dynamic tissue culture and drug screening, advancing the capabilities of in vitro disease modeling and personalized medicine.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e04241"},"PeriodicalIF":9.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249089","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":"Precisely Targeting Cardiac Remodeling Nanomachine for Restarting Healthy Heartbeat.","authors":"Weixin Wang, Rui Gao, Lin Zhang, Yu Dong, Yongsheng Du, Qian Dai, Baolong Liu, Chunyan Fang, Chuanle Wang, Hao Sun, Fei Tong, Wei Huang","doi":"10.1002/adhm.202503478","DOIUrl":"https://doi.org/10.1002/adhm.202503478","url":null,"abstract":"<p><p>Atrial fibrillation (AF) is a common arrhythmia that can cause serious symptoms and affect the quality of life of patients. Therefore, the treatment of AF has always faced challenges in the medical field. Here, Zn@Mg@MSNs@PEG nanosphere-based nanomachines with a unique composite structure in which Zn and Mg are deposited on the surface of mesoporous silica nanoparticle (MSNs) nanospheres, followed by polyethylene glycol (PEG) modification, display excellent acid-responsive properties due to their unique ion sputtering structure. The nanomaterials show autonomous mobility in PBS with acid input, without the use of energetic toxic fuels. This active release of Zn<sup>2+</sup>/Mg<sup>2+</sup>/H<sub>2</sub> improves the intracellular Ca<sup>2+</sup>/Na<sup>+</sup>/K<sup>+</sup>/Cl<sup>-</sup> ratio via nanomachines. The intracellular Ca<sup>2+</sup>/Na<sup>+</sup>/K<sup>+</sup>/Cl<sup>-</sup> gradients are the key to AF electrophysiology. Electrophysiology amelioration combined with oxidative stress and inflammatory mediator inhibition is found to mediate AF following Zn@Mg@MSNs@PEG nanomachine invasion. The designed star arrow-separated nanomachine system, activated by acidic conditions to enhance mobility and enable the targeted release of Zn<sup>2</sup>⁺, Mg<sup>2</sup>⁺, and H<sub>2</sub>, effectively inhibits cardiac remodeling associated with AF by precisely targeting both structural and electrical abnormalities, achieving therapeutic effects without causing additional damage.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03478"},"PeriodicalIF":9.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249091","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":"Precision Photothermal Therapy at Mild Temperature: NIR-II Imaging-Guided, H2O2-Responsive Stealth Nanobomb (Adv. Healthcare Mater. 26/2025)","authors":"Gongcheng Ma, Qihang Ding, Yue Wang, Zhiwei Zhang, Yuding Zhang, Hui Shi, Lintao Cai, Ping Gong, Pengfei Zhang, Zhen Cheng, Jong Seung Kim","doi":"10.1002/adhm.70239","DOIUrl":"https://doi.org/10.1002/adhm.70239","url":null,"abstract":"<p><b>Precision Photothermal Therapy</b></p><p>This work introduces a novel Stealth NanoBomb (SNB) for precision photothermal therapy at mild temperatures (<45°C), designed to enhance cancer treatment efficacy. The SNB, composed of small-molecule NIR-II AIEgens and CO carrier polymers, selectively releases CO in response to H<sub>2</sub>O<sub>2</sub> in the tumor microenvironment, effectively inhibiting heat shock proteins and improving therapeutic outcomes. More details can be found in the Research Article by Ping Gong, Pengfei Zhang, Zhen Cheng, Jong Seung Kim, and co-workers (DOI: 10.1002/adhm.202402767).\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 26","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adhm.70239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243071","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":"Natural Sweetener Stevioside-Based Dissolving Microneedles Solubilize Minoxidil for the Treatment of Androgenic Alopecia.","authors":"Junying Zhang, Tianyu Shao, Hailiang Li, Luying Zhu, Lamyaa Albakr, Nial J Wheate, Lifeng Kang, Chungyong Wu","doi":"10.1002/adhm.202503575","DOIUrl":"https://doi.org/10.1002/adhm.202503575","url":null,"abstract":"<p><p>Androgenetic alopecia (AGA) is a prevalent form of non-scarring hair loss. Standard treatments, which include minoxidil (MXD) tincture and foam, face challenges due to MXD's water insolubility and poor skin permeability. The result is extended treatment duration and reduced therapeutic effectiveness. This study utilized stevioside (STV), a natural sweetener derived from the Stevia plant, as a novel solubilizing excipient and microneedle (MN) material. A solid dispersion of STV with insoluble drugs is developed and molded into an MN patch. STV significantly increased MXD's solubility to 47 mg mL<sup>-1</sup> in water, ≈18 fold higher than the control. STV solubilizes MXD by forming micelles in aqueous solution with a critical micelle concentration of 15 mg mL<sup>-1</sup>. In vitro skin permeation studies showed cumulative drug release of 85% and 18% skin retention for the MN patch, which indicated excellent drug absorption into the skin. Animal studies demonstrated that the MN patch significantly promoted hair growth. There is a significant increase in hair follicle transition to the growth phase, which resulted in 67.5% coverage of the treatment area by day 35. Collectively, the results highlight the potential of the STV MN delivery system for the treatment of AGA.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03575"},"PeriodicalIF":9.6,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243297","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}