{"title":"Regional-Specific Decellularized Meniscus Extracellular Matrix Elastic Nanofiber Aerogels Regulate Meniscal Regeneration and Vascularization.","authors":"Moran Huang, Yangfan Ding, Jize Dong, Guoqi Li, Guojian Fu, Jinhui Pang, Yaying Sun, Shanxing Zhang, Jinglei Wu, Jiwu Chen","doi":"10.1002/adhm.202404626","DOIUrl":"https://doi.org/10.1002/adhm.202404626","url":null,"abstract":"<p><p>The meniscus is a heterogeneous structure with spatial distribution of cells and vessels. Promoting meniscus healing remains challenging, especially in its avascular inner region. The ideal repair mode shall promote meniscus repair while maintaining local avascularity to prevent pathological changes from vascular invasion. Given the natural biochemical components of native meniscus, decellularized meniscus extracellular matrix (dmECM) shows promise for meniscus repair. Compared to homogeneous dmECM, regional-specific dmECM (RS-dmECM) appears to offer greater potential for constructing heterogeneous meniscus structures. Furthermore, there is currently no study on the effects of RS-dmECM on vascularization. Thus, RS-dmECM is prepared and found dmECM-Outer induced stem cells fibrochondrogenic differentiation, while dmECM-Inner induced the chondrogenic differentiation and inhibited angiogenesis through suppressing the peroxisome proliferators-activated receptors signaling pathway. Subsequently, regional-specific poly(lactic acid)/gelatin/dmECM elastic 3D nanofiber aerogels (PG-dmECM) are fabricated to repair meniscal avascular area defects in a rabbit model. The PG-Outer promotes meniscal fibrocartilage regeneration without a significant effect on vascular invasion. In contrast, the PG-Inner achieves meniscal cartilage regeneration and inhibits vascular invasion. Moreover, the compressive stress can reach 117 kPa, comparable to that of the avascular area. This PG-Inner may have the potential to promote meniscal cartilage regeneration and prevent pathological changes within the avascular area.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2404626"},"PeriodicalIF":10.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466510","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}
Xiaochen Xu, Nan Luo, Jing Ru, Hua Zeng, Xiaohao Liu, Shuo Tan, Feng Chen, Bing-Qiang Lu, Xi Chen
{"title":"Metastable Calcium Phosphate Cluster-Involved Mineralization Process Regulated by a Dual Biomolecule System Toward the Application in Dentinal Tubules Occlusion.","authors":"Xiaochen Xu, Nan Luo, Jing Ru, Hua Zeng, Xiaohao Liu, Shuo Tan, Feng Chen, Bing-Qiang Lu, Xi Chen","doi":"10.1002/adhm.202405074","DOIUrl":"https://doi.org/10.1002/adhm.202405074","url":null,"abstract":"<p><p>Dentin hypersensitivity caused by the exposure of dentinal tubules is affecting a significant portion of the population. With promising prospects, the biomimetic mineralization materials used in treating dentin hypersensitivity are expected to possess a metastable characteristic, for which they can easily penetrate the tubules and the surrounding tissues, but then occlude them via a transformation of size and phase immediately. Herein, this study develops a metastable calcium phosphate cluster (MCPC)-involved mineralization process, which is regulated by dual biological macromolecules: bovine serum albumin (BSA) and poly-L-lysine (PLL). BSA functions to stabilize the primary calcium phosphate clusters; PLL further tunes the cluster's evolution (toward larger and crystalline particles) into a metastable fashion, and meanwhile inhibits the local bacteria. Upon treatments, the system generates amorphous MCPC with ultrasmall size (1-2 nm); then they enter the deep dentinal tubules, subsequently aggregate and crystalline into immobile larger particles, which finally seal the exposed dentinal tubules. The effective occlusion of dentinal tubules as well as significant antibacterial performance are confirmed both in vivo and in vitro. This study has devised not only a regulatory approach for the evolution of mineralization-active clusters but also established an efficient method for managing dentin hypersensitivity.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2405074"},"PeriodicalIF":10.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466545","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}
Morgan R Pfaff, Aboubacar Wague, Michael Davies, Anouk R Killaars, Derek Ning, Steven Garcia, Anthony Nguyen, Prashant Nuthalapati, Mengyao Liu, Xuhui Liu, Brian T Feeley, Kevin E Healy
{"title":"Viscoelastic HyA Hydrogel Promotes Recovery of Muscle Quality and Vascularization in a Murine Model of Delayed Rotator Cuff Repair.","authors":"Morgan R Pfaff, Aboubacar Wague, Michael Davies, Anouk R Killaars, Derek Ning, Steven Garcia, Anthony Nguyen, Prashant Nuthalapati, Mengyao Liu, Xuhui Liu, Brian T Feeley, Kevin E Healy","doi":"10.1002/adhm.202403962","DOIUrl":"https://doi.org/10.1002/adhm.202403962","url":null,"abstract":"<p><p>Rotator cuff tears are common musculotendinous injuries with a high risk of permanent functional disability. Following surgical repair, sub-optimal patient outcomes are directly correlated with poor muscle quality; namely, injury site fatty infiltration, fibrosis, and muscle atrophy. Muscle resident fibro-adipogenic progenitor cells (FAPs) have been identified as key regulators of post-injury skeletal muscle regeneration and repair by maintaining a pro-myogenic environment. In this work, human FAPs (hFAPs) were encapsulated into hyaluronic acid (HyA)-based hydrogels functionalized with bsp-RGD(15) cell adhesion peptide, heparin, and a matrix metalloproteinase (MMP)-cleavable crosslinker. Hydrogel-encapsulated hFAPs increased expression of the pro-myogenic marker UCP1 and production of the anti-inflammatory cytokine IL-10 while downregulating the expression of the fibrotic marker αSMA over time. A murine model of unilateral rotator cuff transection, denervation, and delayed repair was treated with the HyA hydrogel or PBS and compared to a contralateral, non-injured control limb. Muscle histology 6 weeks post-repair revealed that the hydrogel reduced fibrosis, FI, and muscle atrophy while supporting vascularization of the injured tissue region. Collectively, these results suggest that the HyA hydrogel alone can promote muscle regeneration in a clinically relevant delayed repair model of rotator cuff tear, which is hypothesized due to controlled FAP differentiation into pro-myogenic lineages.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403962"},"PeriodicalIF":10.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466580","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":"Tetrodotoxin Delivery Pen Safely Uses Potent Natural Neurotoxin to Manage Severe Cutaneous Pain.","authors":"Yuhao Cai, Qi Li, Ajay K Banga, Ursula Wesselmann, Chao Zhao","doi":"10.1002/adhm.202401549","DOIUrl":"https://doi.org/10.1002/adhm.202401549","url":null,"abstract":"<p><p>Clinically available therapies often inadequately address severe chronic cutaneous pain due to short anesthetic duration, insufficient intensity, or side effects. This study introduces a pen device delivering tetrodotoxin (TTX), a potent neurotoxin targeting nerve voltage-gated sodium channels, as a safe and effective topical anesthetic to treat severe chronic cutaneous pain. Chemical permeation enhancers, such as sodium dodecyl sulfate (SDS) and limonene (LIM), are incorporated to enhance TTX skin permeability. The device ensures precise TTX dosing down to the nanogram level, essential to avoid TTX overdose. In rats, the pen device treatment produces TTX-dose-dependent anesthetic effectiveness. An administration of 900 ng of TTX with SDS and LIM to the rat back skin produces a 393.25% increase (measurement limit) in the nociceptive skin pressure threshold, and the hypoalgesia lasts for 11.25 h, outperforming bupivacaine (28 µg), of which are 25.24% and under 1 h. Moreover, the pen device provides on-demand therapy for multiple treatments, consistently achieving prolonged anesthesia over ten sessions (1 treatment per day) without noted toxicity. Furthermore, a single topical administration of 16 µg of TTX exhibits no TTX-related toxicity in rats. The TTX delivery pen paves the way for clinical trials, offering a promising solution for severe cutaneous pain.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2401549"},"PeriodicalIF":10.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466548","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}
Grace N Bechtel, Gabriella P Sugerman, Tatum Eades, Zuzanna Malinowska, Adam M Bush, Hamidreza Saber, Sapun H Parekh, Manuel K Rausch
{"title":"Mechano-Lysis in Whole Blood Clots: On How Mechanics Affect Clot Lysis, and How Lysis Affects Clot Mechanics.","authors":"Grace N Bechtel, Gabriella P Sugerman, Tatum Eades, Zuzanna Malinowska, Adam M Bush, Hamidreza Saber, Sapun H Parekh, Manuel K Rausch","doi":"10.1002/adhm.202403389","DOIUrl":"https://doi.org/10.1002/adhm.202403389","url":null,"abstract":"<p><p>Thromboembolic diseases are a significant cause of mortality and are clinically treated enzymatically with tissue plasminogen activator (tPA). Interestingly, prior studies in fibrin fibers and fibrin gels have demonstrated that thrombolysis may be mechanically sensitive. This study aims to expand mechano-lytic studies to whole blood clots. Furthermore, this study investigates not only how mechanics impacts lysis but also how lysis impacts mechanics. Therefore, clots made from whole human blood are exposed to tPA while the clots are either stretched or unstretched. After, the resulting degree of clot lysis is measured by weighing the clots and by measuring the concentration of D-dimer in the surrounding bath. Additionally, each clot's mechanical properties are measured. This study finds that mechanical stretch accelerates loss in clot weight but does not impact the lysis rate as measured by D-dimer. Moreover, lysis not only removes clot volume but also reduces the remaining clot's stiffness and toughness. In summary, tPA-induced lysis of whole clot appears mechanically insensitive, but stretch reduces clot weight. Furthermore, results show that thrombolysis weakens clot. This suggests that thrombolysis may increase the risk of secondary embolizations but may also ease clot removal during thrombectomy, for example.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403389"},"PeriodicalIF":10.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466474","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}
Alex Hartley, Philip Michael Williams, Alvaro Mata
{"title":"A Comparison of the Mechanical Properties of ECM Components and Synthetic Self-Assembling Peptides.","authors":"Alex Hartley, Philip Michael Williams, Alvaro Mata","doi":"10.1002/adhm.202402385","DOIUrl":"https://doi.org/10.1002/adhm.202402385","url":null,"abstract":"<p><p>The field of tissue engineering is increasingly moving away from a one-size-fits-all approach of simple synthetic homogeneous gels, and embracing more tailored designs to optimize cell function and differentiation for the organ of interest. Extracellular matrix (ECM) proteins are still the optimal route for controlling cell function, while a field of great promise is that of synthetic self-assembling peptides (SSAPs), which are fully biocompatible, biodegradable, and offer both the hierarchical structure and dynamic properties displayed by protein networks found in natural tissue. However, the mechanical properties of neither group have been comprehensively reviewed. In this review, rheological data and the Young's modulus of the most prevalent proteins involved in the ECM (collagen I, elastin, and fibronectin) are collated for the first time, and compared against the most widely researched SSAPs: peptide amphiphiles (PAs), β-sheets, β-hairpin peptides, and Fmoc-based gels (with a focus on PA-E3, RADA16, MAX1, and FmocFF, respectively).</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402385"},"PeriodicalIF":10.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456501","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 Assisted Melittin-Chondroitin Sulfate Administration for the Transdermal Therapy of Rheumatoid Arthritis.","authors":"Lili Jin, Zhenhui Wang, Cheng Peng, Miao He, Feng Wang, Hongyan He, Changsheng Liu","doi":"10.1002/adhm.202400543","DOIUrl":"https://doi.org/10.1002/adhm.202400543","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA), a persistent and debilitating chronic disease characterize by joint damage and deformity, significantly impairs the life quality of patients and presents challenges for conventional drug administration due to organ damage and unsatisfactory therapeutic outcomes. To address these challenges, this study introduces an innovative hydrogel cryo-microneedle patch (CMNP)-mediated local administration system, primarily composed of chondroitin sulfate (CS), to deliver the potent anti-inflammatory drug melittin (MEL). This innovative approach not only circumvents organ impairment but also enhances patient compliance. The acute toxicity of MEL is effectively mitigated by electrostatic binding with CS molecules, forming MC complexes that induce apoptosis in fibroblast-like synoviocytes (FLS). The MC-loaded CMNPs (MC@CCMNPs) exhibit remarkable therapeutic capacity with a notably meliorated joint damage and suppressed arthritis severity in the RA rat model. Therefore, MC@CCMNPs emerge as a promising anti-inflammatory and safe therapy for RA treatment, as well as for other inflammation related chronic diseases.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2400543"},"PeriodicalIF":10.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456461","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":"Continuous High-Throughput Plasma Separation for Blood Biomarker Sensing Using a Hydrodynamic Microfluidic Device.","authors":"Hesam Abouali, Fatemeh Keyvani, Seied Ali Hosseini, Sanjana Srikant, Mahla Poudineh","doi":"10.1002/adhm.202404193","DOIUrl":"https://doi.org/10.1002/adhm.202404193","url":null,"abstract":"<p><p>Continuous, cost-effective, high-throughput with admissible yield and purity of blood plasma separation is widely needed for biomarker detection in the clinic. The existing gold standard technique (centrifugation) and microfluidic technologies fall short of meeting these criteria. In this study, a microfluidic device design is demonstrated based on passive hydrodynamic principles to achieve admissible yield and purity plasma samples. Through computational and experimental assessments, it is shown that side channels with varying lengths are required to improve the plasma extraction rate. The optimized side channels in this device design use the formed cell-free layer regions in the expanded areas to extract plasma consistently and efficiently. These Hydrodynamic Continuous, High-Throughput Plasma Separator (HCHPS) microfluidic devices achieve a purity in the range of 47% to 64% with whole blood and maintaining a yield of 10% to 18%, with half hemolysis compared to gold standard centrifugation. These devices also separate the plasma from diluted blood with a purity in the range of 62% to 97% with a similar yield range. Additionally, whole human blood spiked with lactate was processed through the HCHPS device, and the separated plasma is collected and analyzed using two biosensing approaches, a bead-based fluorescence, and an electrochemical aptamer biosensing, confirming the quality of plasma for downstream biomarker detection.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2404193"},"PeriodicalIF":10.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456456","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}
Yanping Xie, Yunfei Zhu, Ya Wen, Siqi Hu, Ju Jiao, Yue Wu, Lijun Jiang, Bruno Viana, Ka-Leung Wong, Jing Wang, Rui Zou
{"title":"EBNA1 Targeted Ultra-Small Near-Infrared Persistent Luminescent Nano-Inhibitor for Theranostics of EBV-Associated Cancer.","authors":"Yanping Xie, Yunfei Zhu, Ya Wen, Siqi Hu, Ju Jiao, Yue Wu, Lijun Jiang, Bruno Viana, Ka-Leung Wong, Jing Wang, Rui Zou","doi":"10.1002/adhm.202500007","DOIUrl":"https://doi.org/10.1002/adhm.202500007","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) is a well-recognized oncogenic virus that promotes several lymphoid and epithelial cancers. The Epstein-Barr nuclear antigen 1 (EBNA1), which is known to be expressed in all EBV-positive cancers, plays a vital role in viral genome replication and maintenance and is therefore emerged as an attractive target for clinical intervention. Several EBNA1 inhibitors have shown potency in the growth inhibition of EBV-positive cancers, yet low bioavailability and in vivo unmonitored nature hamper their further implementation. Here a novel EBNA1 nano-inhibitor based on EBNA1-specific peptide inhibitor (P4) functionalized ZnGa<sub>2</sub>O<sub>4</sub>:Cr<sup>3+</sup> ultra-small near-infrared persistent luminescent (NIR-PL) nanoparticles (ZGOC-P4) is developed. Owing to the specific binding to EBNA1, ZGOC-P4 nano-inhibitor can quickly achieve nuclear internalization in EBV-positive nasopharyngeal carcinoma (NPC) cells (C666-1) and selectively inhibit their growth. In sharp contrast, ZGOC-P4 nano-inhibitor shows no inhibition effect on EBV-negative NPC cells (HK-1). Moreover, the results indicate that the well-designed nano-inhibitor enables efficient tumor-targeting accumulation in NPC xenograft model under the monitoring of autofluorescence interference-free NIR-PL imaging in vivo and suppresses EBV-associated tumor growth with an inhibition rate of 61.6%. This work highlights the potency of ZGOC-P4 on NPC treatment and may provide new sight into future research on EBV-associated diseases.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500007"},"PeriodicalIF":10.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456459","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":"Enhancement of Bone Tissue Regeneration with Multi-Functional Nanoparticles by Coordination of Immune, Osteogenic, and Angiogenic Responses (Adv. Healthcare Mater. 5/2025)","authors":"Hyewoo Jeong, Hayeon Byun, Jinkyu Lee, Yujin Han, Seung Jae Huh, Heungsoo Shin","doi":"10.1002/adhm.202570031","DOIUrl":"https://doi.org/10.1002/adhm.202570031","url":null,"abstract":"<p><b>Multifunctional Nanoparticles</b></p><p>The cover image of article 2400232 by Heungsoo Shin and co-workers shows the regeneration of bone tissue via multifunctional tannic acid-magnesium nanoparticles (TMgPs). The nanoparticles enhance osteogenic differentiation and angiogenesis while modulating the immune system, resulting in a mature, vascularized bone recovery.\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 5","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adhm.202570031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431258","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}