{"title":"Recent Advances in Dual-Function Janus Membranes for Guided Periodontal and Bone Regeneration.","authors":"Ying Li, Yeying Lin, Tianhua Xiao, Wen Liu, Chengyun Ning, Guoxin Tan, Lei Zhou","doi":"10.1002/adhm.202502888","DOIUrl":"https://doi.org/10.1002/adhm.202502888","url":null,"abstract":"<p><p>Guided Tissue Regeneration (GTR) and Guided Bone Regeneration (GBR) are essential surgical techniques in periodontal therapy, employing barrier membranes to prevent soft tissue infiltration and create a conducive environment for bone regeneration. However, the regenerative performance of conventional barrier membranes remains limited due to poor interface management and insufficient biological functionality. Recent developments have introduced the concept of Janus membranes-structures with asymmetric, dual-function surfaces-offering promising solutions to these challenges. While various reviews have addressed barrier membranes for periodontal and bone regeneration, comprehensive reviews specifically focusing on multifunctional Janus membranes are still limited. This review highlights recent advances in Janus membrane design for GTR and GBR applications. It first outlines key structural configurations, followed by an in-depth analysis of fabrication techniques and functional strategies, including osteogenesis promotion, antibacterial activity, and immunomodulation. By summarizing current progress and challenges, this review offers valuable insights into next-generation biomaterial development for periodontal regeneration. Looking forward, Janus membranes represent a compelling avenue for enhancing clinical outcomes in GTR and GBR procedures.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2502888"},"PeriodicalIF":10.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648036","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}
Hongjuan Weng, Monize Caiado Decarli, Lei He, Wen Chen, Sabine van Rijt, Katrien V Bernaerts, Lorenzo Moroni
{"title":"Mechanical Reinforced and Self-healing Hydrogels: Bioprinted Biomimetic Methacrylated Collagen Peptide-Xanthan Gum Constructs for Ligament Regeneration.","authors":"Hongjuan Weng, Monize Caiado Decarli, Lei He, Wen Chen, Sabine van Rijt, Katrien V Bernaerts, Lorenzo Moroni","doi":"10.1002/adhm.202502341","DOIUrl":"https://doi.org/10.1002/adhm.202502341","url":null,"abstract":"<p><p>Collagen peptide (COP) is water soluble, bioactive, and tends to be a promising alternative to collagen for tissue regeneration. However, its low viscosity and lack of readily polymerizable groups hinder its bioprinting and limit its wide applications in tissue engineering. In this study, methacrylated collagen peptide-xanthan gum (COPMA-XG) bioinks with interpenetrating networks are developed for bioprinting stable constructs, followed by stem cell differentiation. First, self-healing COPMA hydrogels are developed with rapid UV-curing and tunable mechanical properties. To increase the printability and the mechanical properties of COPMA, XG is mixed to create a set of COPMA-XG bioinks. COPMA-XG hydrogels show self-healing properties, optimal printability, and stable morphology in the medium. The bioprinted human bone marrow mesenchymal stem cells (hMSCs) laden COPMA-XG constructs are biocompatible and bioactive, with increased production of extracellular matrix, collagen type I, and scleraxis over 28 days. Overall, bioprinted COPMA-XG constructs are versatile matrices to support hMSCs proliferation and differentiation with potential for ligament tissue engineering.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2502341"},"PeriodicalIF":10.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641302","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}
Jaemyung Shin, Nima Tabatabaei Rezaei, Subin Choi, Zhangkang Li, Deok-Ho Kim, Keekyoung Kim
{"title":"Photocrosslinkable Kidney Decellularized Extracellular Matrix-Based Bioink for 3D Bioprinting.","authors":"Jaemyung Shin, Nima Tabatabaei Rezaei, Subin Choi, Zhangkang Li, Deok-Ho Kim, Keekyoung Kim","doi":"10.1002/adhm.202501616","DOIUrl":"https://doi.org/10.1002/adhm.202501616","url":null,"abstract":"<p><p>Three-dimensional bioprinting has emerged as a promising strategy in tissue engineering, enabling the fabrication of biomimetic tissue constructs for regenerative medicine, disease modeling, and drug screening. A key challenge in this field is the development of organ-specific bioinks capable of recapitulating native microenvironments to support cell viability, proliferation, and tissue-specific maturation. In this study, a novel photocrosslinkable bioink derived from methacrylated decellularized porcine kidney extracellular matrix (KdMA) is reported. The decellularization process effectively removed cellular components while preserving key extracellular matrix constituents. The resulting KdMA bioink exhibited favorable rheological properties, including tunable stiffness and rapid photocuring kinetics, making it compatible with both digital light processing-based stereolithography and extrusion-based bioprinting platforms. Encapsulated human embryonic kidney cells maintained high viability and formed multicellular spheroids, demonstrating the bioink's cytocompatibility and structural support. Additionally, the KdMA bioink enabled stable multilayer bioprinting with preserved structural integrity and tunable mechanical properties. These results underscore the utility of KdMA as a kidney-specific bioink and its promise as a versatile platform for advancing renal tissue engineering and organoid maturation.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501616"},"PeriodicalIF":10.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641303","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}
Chenyu Wang, Ailifeire Fulati, Kenta Kimura, Xianglan Li, Joseph J. Richardson, Mitsuru Naito, Kanjiro Miyata, Takanori Ichiki, Hirotaka Ejima
{"title":"Encapsulation of Small Extracellular Vesicles into Selectively Disassemblable Shells of PEGylated Metal-Phenolic Networks (Adv. Healthcare Mater. 18/2025)","authors":"Chenyu Wang, Ailifeire Fulati, Kenta Kimura, Xianglan Li, Joseph J. Richardson, Mitsuru Naito, Kanjiro Miyata, Takanori Ichiki, Hirotaka Ejima","doi":"10.1002/adhm.202570109","DOIUrl":"https://doi.org/10.1002/adhm.202570109","url":null,"abstract":"<p><b>Small Extracellular Vesicles</b></p><p>In article 2405188, Hirotaka Ejima and co-workers introduce a selectively disassemblable surface modification approach for small extracellular vesicles (sEVs) utilizing metal-phenolic networks that post-modified with polyethylene glycol. Such nanocoating significantly enhances the storage stability of sEVs and allows selectively triggered disassembly of encapsulated shells for the retrieval of intact and functional sEVs, thereby facilitating efficient storage, transport and subsequent promising biomedical applications.\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 18","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adhm.202570109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635340","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":"Triple-Tailored Analgesic Hydrogel System Targeting ADAM17 in Orofacial Inflammatory Pain.","authors":"Yingyu Yi, Yuxuan Wu, Yanghong Xu, Zhengjie Han, Yuzhuo Wang, Jianwen Gong, Yubin Hu, Xinzhao Mai, Weizhe Sheng, Junting Li, Yujie Chen, Zhi Yang, Yaqin Zhu","doi":"10.1002/adhm.202501440","DOIUrl":"https://doi.org/10.1002/adhm.202501440","url":null,"abstract":"<p><p>Orofacial inflammatory pain (OFP) is challenging to manage due to its high incidence, complex anatomy, and multifactorial etiology. To address this, a three-step customized therapeutic system is proposed for prolonged pain relief and efficient local drug delivery. First, ADAM17 is identified as a novel therapeutic target for OFP, and find a small-molecule inhibitor, TAPI-1, which can effectively suppress ADAM17 activity. Subsequently, guided by the presence of an amine group on TAPI-1, an optimized hydrogel matrix is synthesized via Schiff-base bonding to enable stable encapsulation. The hydrogel, composed of hyaluronic acid derivatives carrying aldehyde (HAALD) and aminated gelatin (AGel), forms a scaffold that slows drug release. Second, for clinical application in orofacial tissue, unmodified hyaluronic acid (HA) and gelatin are incorporated to optimize the hydrogel's rheological properties for practicable injection. Third, to further prolong drug release, customized hollow mesoporous silica nanoparticles are added to trap a portion of TAPI-1, matching the drug's molecular diameter. This triple-tailored sustained-release hydrogel (HHGA hydrogel) maintains effective drug levels for 7 days, aligning with the pain phase and obviously relieving pain in mice. This \"drug-device\" innovation exemplifies the potential of personalized medicine in pain management and targeted therapies in translational medicine.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501440"},"PeriodicalIF":10.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648037","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":"Dual-Functional Nanoparticles to Reverse Osteoblast Senescence and Enhance Calcium Supplementation for Alleviating Senile Osteoporosis.","authors":"Caini Yu, Yanling Peng, Tong Yu, Jia Ke, Qi Jiang, Peirong Li, Renxiang Yuan, Tingting Meng, Fuqiang Hu, Jianwei Wang, Hong Yuan","doi":"10.1002/adhm.202501164","DOIUrl":"https://doi.org/10.1002/adhm.202501164","url":null,"abstract":"<p><p>Senile osteoporosis (SOP) primarily arises from an imbalance between bone formation and bone resorption. The tightly regulated coupling between osteoblasts and osteoclasts limits the therapeutic efficacy of conventional anti-resorptive agents and anabolic agents. Anti-aging therapy offers a potential strategy to modify the senescent phenotype of bone-associated cells, restore cellular function, and re-establish homeostasis between bone resorption and formation. Calcium-based nanoparticles can effectively deliver therapeutic agents to target sites while simultaneously supplying exogenous calcium. Moreover, restored osteoblast function enhances the cellular capacity to process supplemented exogenous calcium ions, ultimately increasing bone density and further alleviating osteoporosis. In this context, a dual-functional calcium carbonate nanoparticle is engineered. This nanoparticle facilitates the complexation of nicotinamide mononucleotide, enabling targeted delivery to osteoblasts, reversing osteoblast senescence, and restoring their osteogenic function. Simultaneously, through calcium supplementation, the nanoparticle promotes osteoblast differentiation and mineralization. In vitro and in vivo studies have demonstrated the promising therapeutic efficacy of this nanoparticle in treating SOP, providing critical insights for the future development of integrated anti-senescence therapies and calcium supplementation strategies.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501164"},"PeriodicalIF":10.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635799","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}
Min Hao, Yidan Chen, Stavros Thomopoulos, Younan Xia
{"title":"Biomimetic Scaffolds with Dual Gradients of Biological Effectors for Tendon-to-Bone Repair.","authors":"Min Hao, Yidan Chen, Stavros Thomopoulos, Younan Xia","doi":"10.1002/adhm.202503171","DOIUrl":"https://doi.org/10.1002/adhm.202503171","url":null,"abstract":"<p><p>Due to the complexspatial gradients in composition and structure at the native tendon-to-bone attachment, it remains a clinical challenge to repair rotator cuff tears. Herein, we describe a biomimetic scaffold with dual gradients in osteogenic and tendon enthesis effectors to regulate the graded differentiation of stem cells for tendon-to-bone repair. Funnel-shaped microchannels prompted stem cells to rapidly infiltrate into the scaffold to experience the dual gradients in biological effectors along the walls of each microchannel. The graded distributions of two different effectors-hydroxyapatite nanorods and hedgehog agonist-worked synergistically to promote the differentiation of stem cells into osteoblasts, chondrocytes, and tenocytes, reproducing the cell phenotypes present in the natural tendon enthesis. The new scaffold offers a versatile platform to address key requirements for successful repair/regeneration of the tendon-to-bone attachment while also presenting an innovative strategy for the repair of connective tissue interfaces in general.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2503171"},"PeriodicalIF":10.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635797","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}
Sudipta Panja, Lubaba A Zaman, Chen Zhang, Milankumar Patel, Santhi Gorantla, Prasanta K Dash, Howard E Gendelman
{"title":"Lymphoid and CXCR4 Cell Targeted Lipid Nanoparticles Facilitate HIV-1 Proviral DNA Excision.","authors":"Sudipta Panja, Lubaba A Zaman, Chen Zhang, Milankumar Patel, Santhi Gorantla, Prasanta K Dash, Howard E Gendelman","doi":"10.1002/adhm.202501190","DOIUrl":"https://doi.org/10.1002/adhm.202501190","url":null,"abstract":"<p><p>Advancements in antiretroviral therapy (ART) enable those living with the human immunodeficiency virus type one (HIV-1) to lead longer, healthier lives free from disease comorbidities. However, lifelong ART poses challenges. These include social stigma, medication costs, drug accessibility, mental health, and drug-related toxicities. Moreover, ART does not eliminate latent HIV-1 DNA. Viral persistence in tissue and cell reservoirs results in viral rebound after ART interruption. New strategies are required to achieve a functional HIV-1 cure. To excise latent HIV-1, C-X-C motif chemokine receptor 4 (CXCR4) ligand-decorated lymphoid tissue-targeting lipid nanoparticles (LNPs) for CRISPR-Cas9/gRNA delivery are developed. These LNPs enhance mRNA translation and demonstrate CXCR4-mediated improved uptake to eliminate HIV-1 DNA in infected CD4+ T cells. LNPs also facilitate targeted drug delivery, achieving HIV-1 DNA excision in ART-treated, infected humanized mice. This study emphasizes the potential of tissue and cell-targeted LNPs for effective HIV-1 DNA excision.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501190"},"PeriodicalIF":10.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625046","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}
Haoyang Du, Wanze Tong, Bo Peng, Wei Gao, Yiting Wang, Hao Wang, Jiaxin Liu, Yining Liu, Bin Sun, Jian Ma, Manjie Zhang
{"title":"Mesoporous Nanoplatform That Efficiently Delivers DOX as an H<sub>2</sub>O<sub>2</sub> Generator to Trigger Mutual Amplification of Cuproptosis and Chemodynamic Therapy.","authors":"Haoyang Du, Wanze Tong, Bo Peng, Wei Gao, Yiting Wang, Hao Wang, Jiaxin Liu, Yining Liu, Bin Sun, Jian Ma, Manjie Zhang","doi":"10.1002/adhm.202500933","DOIUrl":"https://doi.org/10.1002/adhm.202500933","url":null,"abstract":"<p><p>H<sub>2</sub>O<sub>2</sub> in the tumor microenvironment (TME) is a critical mediator for both cuproptosis and chemodynamic therapy (CDT). Enhancing H<sub>2</sub>O<sub>2</sub> levels is thus a promising strategy to optimize the efficacy of these therapeutic approaches. Here, utilizing the H<sub>2</sub>O<sub>2</sub> generation capacity of doxorubicin (DOX), polyacrylic acid (PAA)/CuMnSe nanospheres (NSs) are designed for efficient delivery of DOX to the TME, promoting cuproptosis and CDT simultaneously. The NSs exhibit high DOX-loading capacity (0.97 mg DOX/mg NSs) and pH-responsiveness. The cations (Cu<sup>2+</sup>/Cu<sup>+</sup> or Mn<sup>4+</sup>/Mn<sup>2+</sup>) endow the NSs with cuproptosis and CDT activity, respectively, while CuMnSe acts as a photothermal agent, rendering the NSs near-infrared (NIR)-responsive. Controlled release of DOX in the TME rapidly elevates H<sub>2</sub>O<sub>2</sub> to accelerate two coupled redox reactions underpinning cuproptosis and CDT. Specifically, in cuproptosis, Cu<sup>2+</sup> is reduced by GSH to Cu<sup>+</sup>, which is re-oxidized to Cu<sup>2+</sup> by H<sub>2</sub>O<sub>2</sub> via a Fenton-like reaction. This accelerates the transformation of the oxidation state of copper ions, maximizing the dihydrolipoamide S-acetyltransferase(DLAT)-aggregation induced cuproptosis effects, while GSH is greatly depleted to sensitize the CDT effect. The efficacy of the NSs is evaluated both in vitro and in vivo, demonstrating overall superior anti-tumor efficacy originating from the mutually amplified cuproptosis/CDT effects and the chemotherapy effects of DOX.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500933"},"PeriodicalIF":10.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625047","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}