Philip Lifwergren, Viktoria Schoen, Sajjad Naeimipour, Lalit Khare, Anna Wunder, Hanna Blom, Jose G Martinez, Pierfrancesco Pagella, Anders Fridberger, Johan Junker, Daniel Aili
{"title":"Printing and Rerouting of Elastic and Protease Responsive Shape Memory Hydrogel Filaments.","authors":"Philip Lifwergren, Viktoria Schoen, Sajjad Naeimipour, Lalit Khare, Anna Wunder, Hanna Blom, Jose G Martinez, Pierfrancesco Pagella, Anders Fridberger, Johan Junker, Daniel Aili","doi":"10.1002/adhm.202502262","DOIUrl":"10.1002/adhm.202502262","url":null,"abstract":"<p><p>The fabrication of mechanically robust and reconfigurable hydrogel filaments remains a major challenge in biofabrication of perfusable architectures, dynamic tissue models, and complex 3D cell-laden constructs. Conventional extrusion-based bioprinting techniques generate filaments that are soft and fragile, limiting post-processing, scalability, and functional adaptability. Rerouting of Free-Floating Suspended Hydrogel Filaments (REFRESH) is introduced as a biofabrication strategy that integrates an aqueous two-phase system (ATPS)-compatible elastic extracellular matrix mimicking bioink material with a flexible printing and post-processing approach to overcome these constraints. This method enables the formation of highly elastic hydrogel filaments cross-linked via strain-promoted azide-alkyne cycloaddition (SPAAC) of bicyclo[6.1.0]non-4-yne-functionalized hyaluronan, exhibiting a strain at break exceeding 100%. The printed filaments maintain mechanical integrity during manual handling and post-processing using textile-inspired techniques, such as knotting and braiding, into reconfigurable 3D architectures. A distinct shape memory function enables programmed mechanical actuation and recovery of deformed structures. The hydrogel system supports high cell viability across multiple cell types and enables the fabrication of multicellular constructs with spatially defined organization. By incorporating protease-degradable cross-linkers, REFRESH-generated filaments function as sacrificial templates for perfusable tubular structures. This approach significantly expands the biofabrication design space, offering new possibilities for engineering vascularized tissues and complex hydrogel-based architectures.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2502262"},"PeriodicalIF":10.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332116","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}
Sofia F Melo, Anna Pierrard, Fréderic Lifrange, Marco Caliari, Céline D'Emal, Margaux Debuisson, Haritz Sardon, Philippe Delvenne, Patrizio Lancellotti, Christophe Detrembleur, Christine Jérôme, Cécile Oury
{"title":"Poly(hydroxy-oxazolidone) Thermoplastic Elastomers for Safer, Greener and Customizable Blood-Contacting Medical Devices.","authors":"Sofia F Melo, Anna Pierrard, Fréderic Lifrange, Marco Caliari, Céline D'Emal, Margaux Debuisson, Haritz Sardon, Philippe Delvenne, Patrizio Lancellotti, Christophe Detrembleur, Christine Jérôme, Cécile Oury","doi":"10.1002/adhm.202502670","DOIUrl":"https://doi.org/10.1002/adhm.202502670","url":null,"abstract":"<p><p>Thermoplastic elastomers (TPEs) of the polyurethane (PU)-type have broad applications in healthcare. However, these materials have a number of drawbacks. Their synthesis requires the use of toxic isocyanates. Their hemocompatibility remains insufficient, resulting in high rates of thrombotic complications of most common blood-contacting devices, which further increases the risk of infection. Here, we report the facile, up-scalable preparation of a greener non-isocyanate polyurethane (NIPU) TPE, poly(hydroxy-oxazolidone) (PHOx). We show that PHOx can be processed by multiple relevant manufacturing techniques, i.e., hot pressing, injection-molding, electrospinning, and additive manufacturing. In vitro hemocompatibility tests with human blood demonstrate better performance than a conventional medical grade PU. PHOx triggers less contact phase activation of coagulation, less plasma protein adsorption and less platelet adhesion than PU. The adhesion of Staphylococcus epidermidis is also reduced in the first 2 hours of contact as compared to PU. PHOx is neither hemolytic nor cytotoxic upon indirect or direct contact with endothelial cells or fibroblasts. Additionally, subcutaneous implantation of PHOx in rabbits for one and four weeks confirms in vivo biocompatibility and no material degradation. PHOx is therefore a highly valuable biomaterial and a potential isocyanate-free alternative to conventional PU-based TPEs for manufacturing customizable blood-contacting devices with improved hemocompatibility.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2502670"},"PeriodicalIF":10.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323918","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":"Enhanced Xanthium-Inspired ZnO for Precision Antibacterial Therapy and Regeneration of Infected Wounds.","authors":"Jiaojiao Zhu, Tiao Wen, Yunxiao Ma, Qingya Zeng, Yilan Lin, Yutian Liu, Shanshan Chen, Qiang Wang, Wenhu Zhou","doi":"10.1002/adhm.202501009","DOIUrl":"https://doi.org/10.1002/adhm.202501009","url":null,"abstract":"<p><p>Bacterial infections significantly hinder wound healing. Despite the widespread use of antibiotics, their limited efficacy and the growing issue of drug resistance necessitate the development of new antibacterial agents with enhanced therapeutic effects and wound healing properties. We developed DNA-templated nano zinc oxide (ZnO) as an effective antibacterial wound treatment. Through systematic studies, we found both DNA nucleobases and phosphate backbone contribute to ZnO formation and stabilization. Using C20 DNA (20-base oligonucleotide) as the optimal stabilizer, we created uniformly sized ZnO nanoparticles. Subsequent interfacial modification with 15% hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) yielded H-ZnO with enhanced colloidal stability, photocatalytic activity, and bacterial adhesion. These modifications significantly increased the antibacterial properties of H-ZnO compared to ZnO, while also regulating Zn<sup>2+</sup> release. The sustained release of Zn<sup>2+</sup> not only enhanced the biosafety of the nanoparticles but also promoted wound healing. As a result, H-ZnO effectively promoted wound healing with reduced fibrotic response of both ordinary and bacterial-infected wounds without noticeable toxicity. The H-ZnO gel formulation demonstrated superior antibacterial activity and wound healing promotion, making it a promising candidate for clinical application in treating infected wounds.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501009"},"PeriodicalIF":10.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323914","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}
Yong How Tan, Cynthia A Alcazar-Daleo, Jonah G Holbrook, Krista M Habing, Owen J Lally, Joshua C Vanderpool, Theo Seah, Renee Liu, Rashaad Ahsan, Leanna Li, Karina H Nakayama
{"title":"Shear-Induced Patterning of Decellularized Skeletal Muscle Extracellular Matrix for Enhanced Myogenesis.","authors":"Yong How Tan, Cynthia A Alcazar-Daleo, Jonah G Holbrook, Krista M Habing, Owen J Lally, Joshua C Vanderpool, Theo Seah, Renee Liu, Rashaad Ahsan, Leanna Li, Karina H Nakayama","doi":"10.1002/adhm.202501357","DOIUrl":"https://doi.org/10.1002/adhm.202501357","url":null,"abstract":"<p><p>Severe skeletal muscle injuries often result in permanent functional deficits, posing a major clinical challenge; biomaterials that support cellular activity and provide instructive microenvironmental cues offer a promising strategy to enhance regeneration. To address this challenge, a novel engineering strategy is introduced to fabricate and pattern decellularized extracellular matrix (dECM) scaffolds with tunable biophysical properties. By leveraging pH-driven fibrillogenesis, combined with shear-based extrusion, controlled fibril assembly within skeletal muscle dECM, with precise topographical patterning of scaffold nanoarchitecture is demonstrated. This dual-modulation produces patterned scaffolds with compositionally mimetic ECM that direct myogenic cell alignment, influence cell phenotype, and facilitate scaffold remodeling. In a preclinical mouse model of volumetric muscle loss, these engineered dECM scaffolds promote the formation of new myofibers and enhance muscle regeneration, largely through the facilitation of scaffold and tissue remodeling for better integration. This work highlights the versatility of ECM-derived materials tailored to mimic the native composition of skeletal muscle, while also imparting new biophysical features that optimize myogenesis. By supporting tissue remodeling and functional integration, fibrillar patterned dECM represents a robust platform for advancing musculoskeletal regenerative therapies following traumatic injuries.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501357"},"PeriodicalIF":10.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323919","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}
Jong Seob Choi, Hye-Bin Park, Su Han Lee, Byunggik Kim, Jihoon Lee, Sang-Keun Sung, Chia-Yi Su, JuKyung Lee, Seongjun Jang, Yongjin Lee, Jung Hyun Lee, Hyung Jin Kim, Deok-Ho Kim
{"title":"High-Throughput 96-Well Nanogroove-Enhanced Electrical Impedance Biosensor for Real-Time Label-Free Cancer Drug Screening.","authors":"Jong Seob Choi, Hye-Bin Park, Su Han Lee, Byunggik Kim, Jihoon Lee, Sang-Keun Sung, Chia-Yi Su, JuKyung Lee, Seongjun Jang, Yongjin Lee, Jung Hyun Lee, Hyung Jin Kim, Deok-Ho Kim","doi":"10.1002/adhm.202402057","DOIUrl":"https://doi.org/10.1002/adhm.202402057","url":null,"abstract":"<p><p>This study advances bioelectronic platforms and cellular behavior analysis by enhancing the precision and scalability of nanopatterned membranes integrated with electrode arrays for real-time, high-throughput monitoring. By employing self-assembled monolayers (SAMs) and optimizing imprinting parameters, uniform large-area nanopatterns are successfully fabricated, overcoming challenges such as the \"rabbit ears\" effect and inconsistent pattern fidelity. The nanopatterned substrates, integrated within 96-well plates with electrode arrays, enable real-time impedance spectroscopy, providing a dynamic assessment of cellular behavior under chemotherapeutic drug exposure. The developed NanoIEA platform facilitates comprehensive investigations into cellular growth and drug interactions. RNA sequencing of MCF-7 cells cultured on nanopatterned substrates reveals significant differential gene expression, suggesting that traditional flat-surface cultures may induce artificial gene regulation, potentially biasing drug screening results. Patterned cell cultures that mimic physiological conditions yield more accurate and predictive outcomes for anticancer drug screening. This research underscores the critical role of nanopatterning in recapitulating in vivo-like gene expression and highlights the profound impact of microenvironmental cues on cellular behavior. By integrating advanced nanofabrication with precise real-time monitoring, this approach addresses technical limitations in bioelectronic sensing while providing deeper insights into dynamic cellular responses, reinforcing the importance of substrate design in tissue engineering and drug development.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2402057"},"PeriodicalIF":10.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323915","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}
Ludivine Delon, Mathias Busek, Pedro Duarte Menezes, Nikolaj Gadegaard, Justyna Stokowiec, Alexey Golovin, Yuliia Boichuk, Thomas Combriat, Aleksandra Aizenshtadt, Stefan Krauss
{"title":"Placental Syncytium-on-Chip (PSoC)-Comparison of Forskolin or Mechanical Induced-Syncytialization.","authors":"Ludivine Delon, Mathias Busek, Pedro Duarte Menezes, Nikolaj Gadegaard, Justyna Stokowiec, Alexey Golovin, Yuliia Boichuk, Thomas Combriat, Aleksandra Aizenshtadt, Stefan Krauss","doi":"10.1002/adhm.202404462","DOIUrl":"https://doi.org/10.1002/adhm.202404462","url":null,"abstract":"<p><p>The placenta is a key embryonic structure that separates maternal and fetal blood systems. The barrier function of the human placenta is performed by villous trophoblasts, i.e. undifferentiated cytotrophoblasts and differentiated syncytiotrophoblats, whose maturation and function are influenced by wall shear stress (WSS) from the maternal blood circulation. Most in vitro placenta models rely on cyclic adenosine monophosphate inducer forskolin (FSK) to establish a placental syncytium. Here a trophoblastic BeWo cell line is used to systematically compare the effect of FSK treatment in static culture with WSS stimulation in a pumpless, recirculating organ-on-chip. It is shown that BeWo cells undergo a similar differentiation under WSS exposure to FSK treatment. A WSS of 0.1 dyn cm<sup>-2</sup> leads to cell fusion, polarization, barrier functions, human chorionic gonadotropin (β-hCG) secretion, and increased expression of key transporters. Moreover, WSS induces favorable changes in the levels of FMS-like tyrosine kinase-1 (FLT-1) and Placental Growth Factor (PlGF) suggesting the development of a physiologically relevant placental syncytium-on-chip (PSoC) without the need for FSK. The platform is further expanded to a syncytiotrophoblast/endothelial co-culture showing physiological vascular functions under WSS. The forskolin-free PSoC presented here represents the first pumpless recirculating and scalable platform for physiological placental studies and drug testing.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2404462"},"PeriodicalIF":10.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323917","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}
Russell E Thompson, Maddison I Segal, Stephanie Sipics, Nicola G Judge, Alexia Bensoussan, Bavand Keshavarz, Matthew L Becker
{"title":"Injectable, Solvent Free Strontium Carbonate Poly(Allyl Glycidyl Ether Succinate) Composite Networks for Vertebral Augmentation.","authors":"Russell E Thompson, Maddison I Segal, Stephanie Sipics, Nicola G Judge, Alexia Bensoussan, Bavand Keshavarz, Matthew L Becker","doi":"10.1002/adhm.202501633","DOIUrl":"https://doi.org/10.1002/adhm.202501633","url":null,"abstract":"<p><p>Vertebral body compression fractures are a major cause of chronic back pain, particularly in older adults. Augmentation is currently performed by injecting a poly(methyl methacrylate) (PMMA) slurry of polymer, monomer, and initiator mixed with barium sulfate (BaSO<sub>4</sub>) into the vertebrae, which then polymerizes in vivo. Herein, a solvent-free polymer system using poly(allyl glycidyl ether succinate) (PAGES) is developed for vertebral augmentation. PAGES crosslinks in situ through thiol-ene click chemistry with a cure time at 37 °C ranging from 17 to 53 min based on degree of polymerization and crosslinker concentration. The addition of SrCO<sub>3</sub> increased the ultimate compressive strength (σ<sub>max</sub>) of the PAGES composite to 4.4 ± 0.4 MPa. Furthermore, SrCO<sub>3</sub> increases osteoblast proliferation and differentiation of mesenchymal stem cells seeded onto the surface of PAGES composite. Finally, the compressive strength of fractured vertebrae is increased in an ex vivo surrogate rabbit model when filled with injected PAGES composite, demonstrating its potential as a bone augmentation material.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501633"},"PeriodicalIF":10.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323916","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":"Tumor Microenvironment-responsive Nanocatalyst for Targeted Chemodynamic Cancer Therapy.","authors":"Jun Ma, Jingjing Qiu, Shiren Wang","doi":"10.1002/adhm.202501746","DOIUrl":"https://doi.org/10.1002/adhm.202501746","url":null,"abstract":"<p><p>To address the challenges of insufficient hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) levels, rapid Fe<sup>3+</sup> precipitation, and a slow Fenton reaction cycle, tumor-activated, self-accelerating CDT nanocatalysts are synthesized, comprising poly (lactic-co-glycolic acid) (PLGA)-encapsulated Ca-Fe peroxide clusters and polyarginine (R). Nanocatalysts are camouflaged with cancer cell membranes (CCM) to enhance tumor targeting. Additionally, polyarginine tailored the PLGA responsiveness to low H<sub>2</sub>O<sub>2</sub> levels (50-100 µm). H<sub>2</sub>O<sub>2</sub> triggered the degradation of PLGA, releasing CaFe clusters to produce Fe<sup>3+</sup>/Fe<sup>2+</sup> and additional H<sub>2</sub>O<sub>2</sub>, sustaining the Fenton reaction. Simultaneously, polyarginine releases nitric oxide (NO) in the presence of H<sub>2</sub>O<sub>2</sub>, facilitating Fe<sup>3+</sup> reduction to Fe<sup>2+</sup> and amplifying •OH generation. In vitro cellular studies demonstrate significantly improved homotypic tumor targeting (6.5-fold increase) and deep spheroid penetration (>120 µm), resulting in improved tumor permeability and elevated •OH generation. Additionally, the nanoparticles exhibit dose-dependent cytotoxicity, and polyarginine notably enhanced the cytotoxicity of CCM-PLGA-CaFe NPs, reducing the IC50 value from 216.9 to 43.38 µg mL<sup>-1</sup>. Apoptosis/necrosis assay reveals that the elevated •OH generation by CCM-PLGA-CaFe-R NPs preferentially induced necrosis, effectively inhibiting tumor cell proliferation by 76.3% ± 8.4% over a 7-day treatment. Consequently, this TME-responsive, self-accelerating CDT platform demonstrates enhanced therapeutic efficacy through improved tumor targeting, sustained Fenton reaction, and amplified radical generation.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501746"},"PeriodicalIF":10.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315638","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":"Hydrogen Bond-Driven Conductive Thermosensitive Hydrogel for Advancing Endoscopic Electrosurgery.","authors":"Zhenning Di, Ying Xiang, Yinya Pan, Yingying Shao, Xiang Fan, Yang Hua, Guifang Xu, Zhongze Gu, Xin Zhou","doi":"10.1002/adhm.202501495","DOIUrl":"https://doi.org/10.1002/adhm.202501495","url":null,"abstract":"<p><p>Endoscopic electrosurgery faces critical challenges in achieving safe tissue dissection, particularly in procedures like endoscopic submucosal dissection (ESD). Current submucosal injection agents (e.g., normal saline) suffer from rapid diffusion requiring frequent reinjections that disrupt procedural continuity, while their poor electrical conductivity causes uneven current distribution and localized heat accumulation, increasing risks of tissue carbonization and iatrogenic perforation. Here a hydrogen bond-driven conductive thermosensitive hydrogel, poly(3,4-ethylenedioxythiophene):polystyrene sulfonate/Pluronic F127 (PEDOT:PSS/F127), is presented that overcomes these dual limitations through molecular engineering. The hydrogel integrates temperature-triggered gelation with enhanced mechanical strength (G' = 13.11 ± 0.22 kPa) via hydrogen bonding between F127's ether-oxygen and PEDOT:PSS's sulfonic groups. This synergy enables sustained mucosal elevation (> 60 min) while its embedded conductive phase optimizes electrosurgical current conduction. In vitro, ESD shows an 8.7 and 3 °C temperature reduction compared to saline and F127 controls, respectively. In vivo, PEDOT:PSS/F127 reduces tissue burns and bleeding, improving surgical safety. By addressing both mechanical instability and electrical limitations of conventional submucosal agents, this platform sets new standards for precision electrosurgery and demonstrates promising potential for a range of energy-based interventions.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501495"},"PeriodicalIF":10.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315617","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}
M A Kristine Tolentino, Eric Y Du, Giulia Silvani, Elvis Pandzic, Kristopher A Kilian, J Justin Gooding
{"title":"Decoding Hydrogel Porosity: Advancing the Structural Analysis of Hydrogels for Biomedical Applications.","authors":"M A Kristine Tolentino, Eric Y Du, Giulia Silvani, Elvis Pandzic, Kristopher A Kilian, J Justin Gooding","doi":"10.1002/adhm.202500658","DOIUrl":"https://doi.org/10.1002/adhm.202500658","url":null,"abstract":"<p><p>Hydrogels are essential biomaterials for biomedical applications, valued for their tunable properties and biocompatibility. A key feature influencing their function is porosity, which governs transport properties. Cryogenic scanning electron microscopy (cryo-SEM) is widely used to directly characterize porosity, but may introduce structural artifacts. Accurately characterizing the porosity of a hydrogel in its native state remains a challenge. Here, we characterized the hydrogel porosity in its native state using particle tracking assay and compared the results with cryo-SEM in polyethylene glycol (PEG) hydrogels. Both methods revealed the presence of micropores in PEG, likely arising from defects during polymerization. The equilibrium swelling assay showed nanoscale mesh sizes between polymer chains, distinct from the micron-scale pores. To overcome conventional limitations, we developed a novel three-dimensional (3D) pore reconstruction approach by leveraging the convex hull algorithm. The method enabled measurement of pore volume, surface area, sphericity, and size distribution. We found that cryo-SEM underestimates pore diameters due to the two-dimensional (2D) depiction, but after the 2D-to-3D conversion, remarkably similar pore dimensions are obtained. By advancing porosity analysis, this work provides insights for tailoring hydrogels to optimize interactions with cells, biomolecules, and therapeutic agents, opening avenues in drug delivery, tissue engineering, and other biomedical applications.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2500658"},"PeriodicalIF":10.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315616","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}