Materials Science & Engineering C-Materials for Biological Applications最新文献

{"title":"Exploring the efficacy and mechanisms of exemestane-loaded nanoparticles in targeted breast cancer therapy","authors":"Meghna Chauhan ,&nbsp;Mohammad Ali Abdullah Almoyad ,&nbsp;Shadma Wahab ,&nbsp;Khang Wen Goh ,&nbsp;Garima Gupta ,&nbsp;Amirhossein Sahebkar ,&nbsp;Prashant Kesharwani","doi":"10.1016/j.bioadv.2025.214519","DOIUrl":"10.1016/j.bioadv.2025.214519","url":null,"abstract":"<div><div>Exemestane (EXE), an irreversible aromatase inhibitor, is a well-established therapeutic agent for the management of estrogen receptor-positive (ER⁺) breast cancer. Despite its proven clinical benefits, its broader therapeutic potential is limited by factors such as poor bioavailability, short plasma half-life, and undesirable off-target effects. Recent advances in nanotechnology have introduced promising strategies to address these limitations. Encapsulating EXE within nanoparticles (NPs) offers a novel platform to improve drug delivery, enhance tumor targeting, and optimize therapeutic efficacy. Various NP systems including lipid-based, polymeric, and inorganic carriers have been investigated for EXE encapsulation and delivery. These nanoformulations confer multiple advantages, such as improved solubility, sustained and controlled release, and selective delivery to malignant cells. The presented review examines the in vitro and in vivo evidence supporting the superior anticancer performance of EXE-loaded NPs, alongside their potential to overcome key challenges in breast cancer therapy. In addition, safety profiles, translational potential, and future perspectives for integrating EXE NPs into precision medicine approaches are discussed, offering insights into their application in combination with conventional treatment regimens for improved breast cancer management.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"179 ","pages":"Article 214519"},"PeriodicalIF":6.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158807","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":"Tantalum-doped β-TCP porous bioceramic scaffolds: In vitro and in vivo evaluation of biodegradation and osteoinductive properties","authors":"Jing Luo ,&nbsp;Zhi Li ,&nbsp;Bowen Zhang ,&nbsp;Bo Cheng ,&nbsp;Jing Yang ,&nbsp;Binbin Li ,&nbsp;Xinyu Wang","doi":"10.1016/j.bioadv.2025.214517","DOIUrl":"10.1016/j.bioadv.2025.214517","url":null,"abstract":"<div><div>The development of biodegradable bone substitutes with balanced mechanical properties, osteogenic activity, and controlled degradation remains a critical challenge in bone tissue engineering. In this study, <em>in situ</em> doping Ta-doped β-tricalcium phosphate(β-TCP) powders were synthesized <em>via</em> a microwave-ultrasound-assisted method, and porous bioceramic scaffolds were prepared from this material. The effects of Ta doping concentration on the scaffolds' physicochemical properties, <em>in vitro</em> and <em>in vivo</em> biological safety and osteogenic properties of the scaffolds were systematically evaluated. The results showed that Ta⁵⁺ incorporation significantly improved structural stability and enhanced compressive strength from 5.65 MPa (pure β-TCP) to 9.84 MPa (2.5 % Ta group), while maintaining high porosity (65.98 %). <em>In vitro</em>, the scaffolds showed excellent cytocompatibility with cell viability exceeding 90 %, and the 2.5 % Ta group exhibited the most substantial promotion of osteogenic differentiation, as evidenced by enhanced ALP activity and calcium deposition. <em>In vivo</em> experiments further confirmed superior bone regenerative performance, with the 2.5 % Ta group achieving a bone volume fraction (BV/TV) of 42.29 % at 12 weeks, significantly higher than the 22.27 % observed in pure β-TCP. These findings underscore the role of Ta in simultaneously improving mechanical integrity, biodegradation kinetics, and osteoinductivity, establishing 2.5 % Ta-doped β-TCP as a highly promising scaffold for clinical bone regeneration applications.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"179 ","pages":"Article 214517"},"PeriodicalIF":6.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107099","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":"Smart responsive injectable hydrogel loaded with icariin inhibits ferroptosis and promotes nucleus pulposus repair in intervertebral disc degeneration","authors":"Zhidong Lin ,&nbsp;Luoqi Mai ,&nbsp;Huitong Luo ,&nbsp;Zetao Wang ,&nbsp;Yongpeng Lin ,&nbsp;HongShen Wang ,&nbsp;Shaohua Chen ,&nbsp;Guoyi Su ,&nbsp;Xulin Hu ,&nbsp;Bolai Chen ,&nbsp;Xiaodong Cao","doi":"10.1016/j.bioadv.2025.214513","DOIUrl":"10.1016/j.bioadv.2025.214513","url":null,"abstract":"<div><div>Intervertebral disc degeneration (IVDD) is a leading cause of lower back pain, characterized by the ferroptosis of nucleus pulposus cells (NPCs) and imbalance in reactive oxygen species (ROS) metabolism. Icariin (ICA), an active compound from traditional Chinese medicine, scavenges ROS and inhibits ferroptosis, but its poor water solubility and low bioavailability limit clinical use. A dual-crosslinked hydrogel (HP@ICA) is developed to address these challenges. Cyclodextrin is integrated into polyvinyl alcohol to enhance ICA loading via hydrophobic interactions. Methacrylic acid and phenylboronic acid are incorporated into hyaluronic acid, enabling dynamic bonding with polyvinyl alcohol. Ultraviolet crosslinking creates a secondary crosslinked hydrogel with pH and ROS responsiveness, self-healing properties, and improved ICA solubility, increasing its water solubility tenfold. Enhanced solubility boosts ICA's free radical scavenging capacity by 103 %, suppressing ferroptosis and promoting NP cell regeneration, as demonstrated by reduced iron ion concentrations, lower malondialdehyde levels, and restored glutathione peroxidase 4 activity. Ferroptosis inhibition facilitates type II collagen production in NP cells. Mechanistic studies reveal activation of the Nrf2-GPX4 pathway as key to regeneration. These findings suggest a promising regenerative therapeutic approach for IVDD.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"179 ","pages":"Article 214513"},"PeriodicalIF":6.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107062","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":"Multimodal topical gel combining 2-hydroxyflavanone, gabapentin, and ketamine alleviates diabetic vulvodynia and allodynia with concurrent tissue regeneration in streptozocin-induced rat models","authors":"Gowhar Ali ,&nbsp;Fatima Ayyaz ,&nbsp;Pordil Khan ,&nbsp;Mushtaq Ahmad Mir ,&nbsp;Jibran Qayyum ,&nbsp;Nazar-Ul- Islam ,&nbsp;Nasreena Bashir ,&nbsp;Muhammad Ayaz","doi":"10.1016/j.bioadv.2025.214509","DOIUrl":"10.1016/j.bioadv.2025.214509","url":null,"abstract":"<div><div>Neuropathic pain arises from damage or illness affecting either central or peripheral or both somatosensory systems. Vulvodynia, a chronic neuropathic pain disorder in women, remains largely neglected despite its significant impact. This study was aimed to evaluate safety and efficacy of a multimodal analgesic gel (MMG-10 %) in relieving diabetic neuropathic pain; specifically vulvodynia and allodynia in female rats. We have formulated a highly promising flavonoid, 2’-Hydroxyflavanone (2-HF) with gabapentin and ketamine. Streptozotocin-induced Diabetes Mellitus (DM) was used as a painful neuropathic model. Static and dynamic vulvodynia and allodynia were assessed using parameters including Flinching Response Threshold (FRT), Paw Withdrawal Threshold (PWT), Flinching Response Latency (FRL) and Paw withdrawal Latency (PWL) by applying the stimuli of Von Frey Filaments to the vulvar region and hind mid-planter regions of paws. A uniform quantity for five consecutive days post 29 days of MMG-10 % and control gel (1.0 mg/cm²) was applied three times daily (TDS) on vulvar area for vulvodynia and mid-plantar paws for allodynia studies. Safety with respect to sensorimotor functions was assessed via Rota rod and Balance beam tests. We conducted the vulvar histological tissue study to evaluate diabetes-induced structural damage and assess the therapeutic potential of a multimodal gel in tissue regeneration. Treatment with tested MMG 10 % resulted in a significant increase in FRT, PWT, FRL and PWL respectively (***<em>p</em> &lt; 0.001, ** <em>p</em> &lt; 0.01, <em>p</em> &gt; 0.05) compared to the STZ treated group. Falling latency time was not affected in all treated groups exhibiting sensorimotor safety. The multimodal gel demonstrated significant regenerative efficacy by reducing atrophy, desquamation, and hyperkeratosis, effectively restoring vulvar tissue integrity in diabetic animals. Our MMG-10 %) could be potentially an effective therapeutic remedy for the relief against diabetes-induced vulvodynia and allodynia.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"179 ","pages":"Article 214509"},"PeriodicalIF":6.0,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082152","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":"Modeling glioblastoma in 3D hydrogels enables investigation of Zika virus targeting and immune modulation in oncolytic virotherapy","authors":"Hui Ling Ma ,&nbsp;Larissa Suellen Amorim Garcia ,&nbsp;Renata Ishiba ,&nbsp;Larissa Camargo Dametto ,&nbsp;Káthia Aurea da Silva Moraes ,&nbsp;Raiane Oliveira Ferreira ,&nbsp;Oswaldo Keith Okamoto ,&nbsp;Mayana Zatz","doi":"10.1016/j.bioadv.2025.214492","DOIUrl":"10.1016/j.bioadv.2025.214492","url":null,"abstract":"<div><div>Glioblastoma (GBM) is a highly aggressive brain tumor with limited therapeutic options. Zika virus (ZIKV) has emerged as a potential oncolytic agent due to its selective tropism for tumor cells. To investigate how the extracellular matrix (ECM) modulates ZIKV oncolytic efficacy, we developed a three-dimensional (3D) GBM model using photocrosslinked Gelatin methacryloyl (GelMA) hydrogel supplemented with fibronectin. This platform recapitulates the biomechanical and structural features of solid tumors, enabling analysis of ZIKV–cell–ECM interactions. ZIKV efficiently penetrated the 3D hydrogel, replicated within GBM cells, and induced pronounced cytotoxicity. In comparison to 2D cultures, cells in stiff 3D scaffolds exhibited elevated expression of Nestin, GFAP, ABCC1, COL1A1, and COL5A1. Notably, ZIKV infection elicited stronger and more complex immune responses in 3D cultures, with increased pro-inflammatory cytokines and interferon signaling. While 2D monolayers enriched TNF/NF-κB pathways, 3D cultures preferentially activated T cell–related, chemotactic, and JAK–STAT pathways, highlighting the critical influence of spatial context on innate and adaptive immune activation. These results establish the 3D GelMA-based GBM model as a robust preclinical platform and underscore ZIKV's potential as a multifaceted oncolytic virotherapy capable of both direct tumor lysis and immune modulation.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"179 ","pages":"Article 214492"},"PeriodicalIF":6.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145061161","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":"Metformin nanoparticles mitigate cerebral ischemia reperfusion injury by improving mitochondrial dysfunction and inhibiting NLRP3 activation","authors":"Lin Deng ,&nbsp;Ting Cai ,&nbsp;Jiayu Li ,&nbsp;Yinfei Song ,&nbsp;Sheng Guo ,&nbsp;Tao Tao","doi":"10.1016/j.bioadv.2025.214507","DOIUrl":"10.1016/j.bioadv.2025.214507","url":null,"abstract":"<div><h3>Background</h3><div>Cerebral ischemia reperfusion injury (CIRI) is a serious condition that lacks highly effective treatment methods. After CIRI, microglia in the cortex of mice show high expression of CD44, which offers a potential target for the development of targeted drug-delivery systems to treat ischemic brain injury.</div></div><div><h3>Objective</h3><div>This study aimed to design a targeted drug-delivery system for ischemic brain injury, and explore the underlying molecular mechanisms on CIRI.</div></div><div><h3>Methodology</h3><div>Hyaluronic acid-PEG-DSPE@metformin (HA@MET) nanoparticles were designed to specifically target the CD44 receptor on microglia. HA@MET was used to intervene in a CIRI mouse model, and then the infarct size and neurological scores were measured. Moreover, experiments on the expression of autophagy-related proteins (Beclin-1, Atg5, Sirt3), the production of reactive oxygen species (ROS), the activation of the NLRP3 inflammasome and the release of associated inflammatory factors (Caspase-1, IL-6, IL-1β) were performed.</div></div><div><h3>Results</h3><div>In the CIRI mouse model, HA@MET treatment led to a significant reduction in infarct size and an improvement in neurological scores, indicating a strong therapeutic effect on ischemic brain injury. Mechanistically, HA@MET inhibited the expression of key autophagy proteins Beclin-1 and Atg5, while increasing the expression of Sirt3 protein. This action alleviated excessive mitochondrial autophagy and promoted the clearance of damaged mitochondria. After entering microglia, HA@MET released metformin, which decreased ROS production and inhibited the activation of the NLRP3 inflammasome, resulting in reduced concentrations of inflammatory factors (Caspase-1, IL-6, IL-1β) and alleviating the inflammatory responses associated with CIRI.</div></div><div><h3>Conclusions</h3><div>This study provides new perspectives and potential therapeutic targets for the treatment of ischemic brain injury. HA@MET, as a targeted drug-delivery system, shows promise in treating CIRI through multiple mechanisms, including regulating mitochondrial autophagy and inhibiting inflammation.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"179 ","pages":"Article 214507"},"PeriodicalIF":6.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082147","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 and optimization of a multifunctional cellulose-based hydrogel for enhanced crosslinking and tunability","authors":"Behina Sadat Tabatabaei Hosseini ,&nbsp;Nima Tabatabaei Rezaei ,&nbsp;Fereshteh Oustadi ,&nbsp;Maryam Badv ,&nbsp;Vincent Gabriel ,&nbsp;Keekyoung Kim ,&nbsp;Jinguang Hu","doi":"10.1016/j.bioadv.2025.214490","DOIUrl":"10.1016/j.bioadv.2025.214490","url":null,"abstract":"<div><div>Donor site wounds arise from the extraction of healthy skin for grafting to treat extensive skin loss from burns, ulcers, or trauma. These wounds often face challenges such as elevated pain, infection, and slow healing. Current treatments, like Xeroform gauze dressings, are inadequate in managing moisture and pain effectively. This study introduces a novel photocrosslinkable hydrogel dressing designed to address these issues. Using methacrylated cellulose and chitosan derivatives, we created an interpenetrating polymer network that crosslinks rapidly within 1 min. With a methacrylation degree of around 30 %, the hydrogel's mechanical properties, swelling ratio, and rheological characteristics were optimized by adjusting the cellulose concentration. The optimal hydrogel demonstrated excellent hemocompatibility and no toxicity towards 3T3 fibroblast cells. Compared to a commercial dressing (Jelonet), it exhibited better antimicrobial properties without containing any antimicrobial agents and demonstrated remarkable antifouling properties against <em>E. coli</em>, preventing biofilm formation. This advanced hydrogel offers enhanced moisture control and potential for pain management, providing a promising solution for improved donor site wound care.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"179 ","pages":"Article 214490"},"PeriodicalIF":6.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151825","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":"Adipose-precise delivery of microwave-derived soybean lecithin-polypyrrole nano-pufferfish-shaped nanoparticle for localized NIR-photothermal therapy in managing obesity","authors":"Chih-Kuang Chen ,&nbsp;Shen-Han Wu ,&nbsp;Hsien-Tsung Lu ,&nbsp;Hieu Trung Nguyen ,&nbsp;Pin-Yen Lin ,&nbsp;Wen-Yu Pan ,&nbsp;Ke-Hung Tsui ,&nbsp;Andrew E.-Y. Chuang","doi":"10.1016/j.bioadv.2025.214508","DOIUrl":"10.1016/j.bioadv.2025.214508","url":null,"abstract":"<div><div>Obesity is a major global health issue, and current treatments targeting appetite suppression or fat absorption often have limited effectiveness and adverse side effects. Localized therapies with minimal systemic toxicity are needed to address obesity's underlying causes.</div><div>We developed a photothermal therapy using intraperitoneally (IP) administered microwave-derived soybean lecithin-polypyrrole nanoparticles with a nano-pufferfish shape, responsive to near-infrared (NIR) light. This therapy directly targets adipose tissue to induce apoptosis, providing localized treatment with minimized side effects.</div><div>Compared to untreated or NIR-only control groups, this method changed adipocyte metabolic activity. It also increased the expression of biomarkers, indicating activation of stress pathways that contribute to anti-obesity effects.</div><div>This localized, adipose-targeted photothermal therapy significantly improves metabolism while minimizing systemic toxicity. It holds promise for long-term, self-administered obesity management, offering an effective, low-risk alternative to conventional treatments.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"179 ","pages":"Article 214508"},"PeriodicalIF":6.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158806","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":"Injectable self-healing hydrogel loaded PLGA nanoparticles for long-term osteoarthritis therapy","authors":"Hongxia Fan ,&nbsp;Jiansong Zhao ,&nbsp;Zhencheng Gao ,&nbsp;Yinling Mu ,&nbsp;Xiaoman Zhang ,&nbsp;Wanbing Pan ,&nbsp;Sishu Li ,&nbsp;Haibing He ,&nbsp;Jingxin Gou ,&nbsp;Xing Tang ,&nbsp;Tian Yin ,&nbsp;Yu Zhang","doi":"10.1016/j.bioadv.2025.214506","DOIUrl":"10.1016/j.bioadv.2025.214506","url":null,"abstract":"<div><div>This study focuses on an injectable hydrogel for osteoarthritis (OA) therapy. We developed a reactive oxygen species (ROS)/pH-responsive self-healing hydrogel loaded with icariin-PLGA nanoparticles (ICA NPs-HG), demonstrating &gt;30-day joint retention, synergistic ROS scavenging via ICA-borate bond interactions, and dual anti-inflammatory and antioxidative therapeutic effects in vivo. This system, based on a borate/diol cross-linked network, addresses the challenge of hydrogel damage under mechanical force and offers significant potential for OA treatment.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"179 ","pages":"Article 214506"},"PeriodicalIF":6.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158808","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":"3D-printed conductive hydrogel scaffolds for bone regeneration: Electromechanical coupling, neurovascular integration, and immunomodulatory strategies","authors":"Yumiao Liu,&nbsp;Longhui Li,&nbsp;Xiaoyu Zhan,&nbsp;Susu Hong,&nbsp;Shaopeng Chang,&nbsp;Gan Huang,&nbsp;Shu-Ting Pan,&nbsp;Y. Liu,&nbsp;L. Li,&nbsp;X. Zhan,&nbsp;S. Hong,&nbsp;S. Chang,&nbsp;G. Huang,&nbsp;S. Pan","doi":"10.1016/j.bioadv.2025.214497","DOIUrl":"10.1016/j.bioadv.2025.214497","url":null,"abstract":"<div><div>Bone defect repair remains a formidable clinical challenge due to the limitations of traditional grafts and scaffolds, such as insufficient mechanical compatibility, minimal bioactivity, and poor biomimicry of bone's complex architecture. Emerging 3D-printed conductive hydrogel scaffolds offer a promising solution by combining the electroactive functionality of conductive materials with the cell-friendly, extracellular matrix-like properties of hydrogels. When fabricated into specific architectures via advanced 3D printing techniques, these composite scaffolds provide active biochemical and biophysical cues that enhance tissue regeneration. They can promote osteogenesis by activating key signaling pathways such as integrin–FAK–ERK and Piezo1/2-mediated calcium influx that upregulates osteogenic transcription factors. Simultaneously, they support neurogenesis and angiogenesis: the scaffold's conductivity and micro-topography guide neural differentiation and axon growth for nerve repair, while electrical stimulation and embedded conductive networks trigger the release of angiogenic factors to foster vascular network formation. These scaffolds also modulate the immune response, for example by polarizing macrophages toward a pro-regenerative M2 phenotype, thereby creating a more favorable healing microenvironment. As a result, 3D-printed conductive hydrogels can orchestrate bone regeneration in concert with vascularization and innervation, transcending the single-functionality of conventional scaffolds. Remaining challenges include ensuring long-term biocompatibility, achieving high-resolution microfabrication without compromising bioactivity, and optimizing electrical stimulation parameters for maximal regenerative benefit. Ongoing research is focused on developing bio-safe conductive composites, refining 3D printing methods, and employing dynamic stimulation strategies to address these challenges and accelerate the translation of conductive hydrogel scaffolds into clinical use.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"179 ","pages":"Article 214497"},"PeriodicalIF":6.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145061163","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}