Ioannis A. Tsigkos, Penelope M. Tsimbouri, Manuel Salmeron-Sanchez, Matthew J. Dalby
{"title":"Sustained growth factor release driven cellular therapy indicates enhanced potential for regeneration upon mechanical injury","authors":"Ioannis A. Tsigkos, Penelope M. Tsimbouri, Manuel Salmeron-Sanchez, Matthew J. Dalby","doi":"10.1016/j.bioadv.2025.214389","DOIUrl":"10.1016/j.bioadv.2025.214389","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) are characterised by excellent plasticity and clonogenic potential, thus rendering them great candidates for the development of cellular therapies against damaged tissues where regeneration is needed. Nevertheless, their multipotency becomes significantly affected upon removal from their natural niches, signifying the need for developing efficient methods that will preserve their regenerative and immunomodulatory capacity. It is crucial to protect these properties beyond traditional modelling, ensuring scalability to large numbers, which will optimise their potential for use in cellular therapies. In this study, a combination of strategies was implemented to maximise the preservation of MSC multipotent phenotype, such as their growth as spheroids and their incorporation into non-bioactive polyethylene glycol (PEG)-hydrogels. Importantly, we further propose that the use of a novel continuous growth factor (GF) release technology in a crystal form can be locally administered inside the MSC spheroids. This establishes an intimate, responsive connection between the crystals and the cells, where the cell-induced degradation stimuli are proportional to the corresponding release of GFs that they receive. We report that the gradual release of NGF-β acts superiorly compared to the conventional soluble form while conferring important benefits on spheroids, such as cytoprotection from stress as well as higher persistence of multipotent markers. Subsequently, the enhanced retention translates to a more responsive phenotype upon mechanical injury, initiation of migration and upregulation in expression of markers that facilitate cytoskeletal rearrangement and homing to damaged tissues.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214389"},"PeriodicalIF":5.5,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480417","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":"Silver nanoparticles: Forging a new frontline in lung cancer therapy","authors":"Samar Raies , Urushi Rehman , Ayesha Siddiqua , Shadma Wahab , Garima Gupta , Khang Wen Goh , Prashant Kesharwani","doi":"10.1016/j.bioadv.2025.214395","DOIUrl":"10.1016/j.bioadv.2025.214395","url":null,"abstract":"<div><div>Lung cancer remains the leading cause of cancer-related mortality worldwide, accounting for 18 % of all cancer deaths. The limitations of conventional therapies, such as chemotherapy, are exacerbated by multidrug resistance (MDR) and systemic toxicity, underscoring the urgent need for innovative treatment strategies. Nanotechnology, particularly silver nanoparticles (AgNPs), shows potential in overcoming MDR by modulating key transporters and associated pathways, providing a promising approach for site-specific drug delivery with reduced adverse effects. AgNPs exhibit significant cytotoxic and apoptotic effects in lung cancer cell lines through mechanisms involving gene regulation, reactive oxygen species (ROS) production, and mitochondrial depolarization. Biosynthesized AgNPs, particularly those derived from plant extracts, demonstrate enhanced biocompatibility and reduced toxicity. Their anticancer potential has been validated in both in vitro and in vivo models, showing dose-dependent reductions in cell viability, cell cycle arrest, and apoptosis induction. Furthermore, AgNPs can modulate the tumor microenvironment and inhibit angiogenesis, paving the way for targeted lung cancer therapies. Advances such as functionalized AgNPs and their integration into photodynamic therapy further enhance their therapeutic potential. However, challenges related to off-target toxicity and clinical translation remain. Continued research is essential to fully harness AgNPs' potential, bridging the gap between treatment efficacy and safety in lung cancer therapy.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214395"},"PeriodicalIF":5.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480510","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}
Lin Yang , Wanfu Zhong , Jincan Chen , Ruyi Huang , Wenzhen Liu , Tao Dai , Jieming Xie , Ping Hu , Bowen Li , Zhuo Chen
{"title":"Fibrin-targeted photosensitizer aggregates significantly enhance the delivery of chemotherapeutic drugs to tumor vasculature","authors":"Lin Yang , Wanfu Zhong , Jincan Chen , Ruyi Huang , Wenzhen Liu , Tao Dai , Jieming Xie , Ping Hu , Bowen Li , Zhuo Chen","doi":"10.1016/j.bioadv.2025.214393","DOIUrl":"10.1016/j.bioadv.2025.214393","url":null,"abstract":"<div><div>Current drug carriers, while effective in mitigating therapeutic side effects, frequently elicit non-drug-related adverse reactions, including hepatorenal toxicity, oxidative stress and allergic responses. To address these issues and enhance drug efficacy, we propose a “drug-carrying-drug” strategy that integrates photodynamic therapy (PDT) with chemotherapy for potential tumor eradication. Traditional photosensitizers often confront a paradoxical dilemma between aggregation-induced photodynamic deactivation and dispersion-mediated premature photobleaching. To overcome these limitations, we developed PPCNM, a multifunctional micellar carrier. PPCNM is constructed by PEGylating pyropheophorbide-α (PPA), a porphyrin-based photosensitizer, and conjugating it with the tumor-targeting pentapeptide CREKA. Before entering tumor cells, PPCNM remains aggregated to prevent photobleaching. Upon internalization, it disassembles to activate PDT and stably delivers doxorubicin (DOX). DOX@PPCNM not only mitigates photobleaching and phototoxicity caused by premature PDT activation but also alleviates adverse effects associated with chemotherapeutic monotherapy. The fibrin- specific CREKA peptide, which targets tumor vasculature, improves the precise delivery of photosensitizers and chemotherapeutics to tumor tissues. Overall, this study presents a promising strategy for developing a dual-drug targeted delivery system combining PDT with other therapies.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214393"},"PeriodicalIF":5.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144364460","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}
Remant KC , Mohammad Nasrullah , Gurkirat Sandhu , Cezary Kucharski , Afsaneh Lavasanifar , Hasan Uludag
{"title":"Cationic lipopolymer based siRNA delivery for experimental lung cancer treatment","authors":"Remant KC , Mohammad Nasrullah , Gurkirat Sandhu , Cezary Kucharski , Afsaneh Lavasanifar , Hasan Uludag","doi":"10.1016/j.bioadv.2025.214394","DOIUrl":"10.1016/j.bioadv.2025.214394","url":null,"abstract":"<div><div>Conventional therapeutic approaches often struggle to address “undruggable” or intracellular targets, limiting their effectiveness in treating critical diseases. RNA interference (RNAi), particularly through the delivery of short interfering RNAs (siRNAs), has emerged as a promising alternative. In this study, we evaluated the potential of a series of cationic lipopolymers, including ALL-Fect, Leu-Fect, and Prime-Fect, for delivering siRNAs targeting CDC20, Survivin, and STAT5 in lung cancer cell models. These polymers exhibited strong siRNA binding (BC50: 0.17 ± 0.04 to 1.67 ± 0.31) and dissociation (DC50: 57.9 to 13.6 U/mL) properties, forming nanoparticles with ζ-potential of −15 to +23 mV, and particles sizes of 150 to 400 nm suitable for efficient cellular uptake, achieving over 75 % FAM-positive cell populations in lung cancer cells. Remarkably, these complexes demonstrated significant cell killing effects with specific siRNAs even at a low siRNA concentration (20 nM), with maximal effects observed at a polymer/siRNA ratio of 5:1 ratio and 40 nM siRNA concentration, resulting in over 75 % cell killing. The performance of lipid nanoparticles (LNPs) for the delivery of the specific siRNAs was minimal compared to the lipopolymeric carriers under similar conditions. These findings underscore the potential of lipopolymers as safe and effective non-viral vectors for siRNA-based lung cancer therapeutics.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214394"},"PeriodicalIF":5.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144364459","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}
Lavinia Raimondi , Viviana Costa , Gianluca Zappini , Marzio Piccinini , Simone Dario Scilabra , Margot Lo Pinto , Angela De Luca , Daniele Bellavia , Angelo Toscano , Alice Bondi , Gianluca Giavaresi
{"title":"Mesenchymal stem cell secretome discovery in response to a brushite-coated titanium alloy: highlighted a specific signature of factors involved in bone healing","authors":"Lavinia Raimondi , Viviana Costa , Gianluca Zappini , Marzio Piccinini , Simone Dario Scilabra , Margot Lo Pinto , Angela De Luca , Daniele Bellavia , Angelo Toscano , Alice Bondi , Gianluca Giavaresi","doi":"10.1016/j.bioadv.2025.214391","DOIUrl":"10.1016/j.bioadv.2025.214391","url":null,"abstract":"<div><div>Increased use of titanium (Ti) and its alloys in implant manufacture is due to their biocompatibility and mechanical properties. However, their biological inertness must be considered. Surface modifications are essential for accelerating osteointegration and bone healing. Herein, calcium phosphate (brushite, CaHPO<sub>4</sub>.2H<sub>2</sub>O) was deposited on an additive-manufactured Ti6Al4V alloy substrate by electrochemical deposition technique. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy confirmed the presence of brushite on the Ti6Al4V substrate. Scanning electron microscopy (SEM) and cross-section micrograph observations confirmed the homogeneity of the coating's coverage, composed of microcrystals approximately 1–3 μm thick and 10 μm long. EDXS analysis revealed pure brushite stoichiometric values, and tensile adhesion tests demonstrated good adhesion to the substrate. The coating demonstrated a rapid dissolution in MES (pH 5.5) and HEPES (pH 7.4) buffer solutions. Human mesenchymal stem cells (hMSCs) cultured with brushite-coated Ti alloy in osteogenic medium showed normal proliferation and increased biomineralization with SP7 mRNA upregulation. To explore how Brushite improved bone healing, we performed liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics analysis of hMSCs secretome from co-cultures with Ti alloys, for 7 and 14 days. Brushite promoted secretion of osteogenic and bone matrix factors. Factors involved in blood clotting (e.g. FII, FV, FX), mitochondrial biogenesis, energy metabolism (e.g. mitochondrial ATP synthase), lipid metabolism (e.g. apolipoproteins) and cellular stress response (e.g. heat shock proteins) were enriched. Increased specific chromatin-related proteins suggest chromatin's role in enhancing bone regeneration. Secretome profiling showed the unique role of brushite Ti alloys in bone regeneration, encouraging further study.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214391"},"PeriodicalIF":5.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144364462","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":"Multifunctional lignin-gum Arabic nanocomposites: Green nanoarchitectonics via ultrasonic-assisted laccase catalysis for antimicrobial, antioxidant, and antidiabetic therapies","authors":"Babbiker Mohammed Taher Gorish , Waha Ismail Yahia Abdelmula , Dang Wenqian , Daochen Zhu","doi":"10.1016/j.bioadv.2025.214390","DOIUrl":"10.1016/j.bioadv.2025.214390","url":null,"abstract":"<div><div>Nanotechnology leveraging natural materials offers sustainable and cost-effective solutions for therapeutic advancements. Lignin and gum Arabic (GA), as biocompatible natural polymers, possess significant bioactive properties; however, their synergistic potential in nanocomposite form remains underexplored. This study synthesized and characterized Lignin-GA nanocomposites (LGA-NPs) through ultrasonic-assisted laccase catalysis, a green synthesis method. The resulting nanocomposites exhibited an average size of 67 ± 18.9 nm and a zeta potential of −32 ± 0.3 mV. Structural analysis via XRD, FTIR, and XPS confirmed the introduction of new functional groups and enhanced oxygen functionalities driven by enzymatic oxidative coupling and ultrasonic treatments. LGA-NPs demonstrated potent antimicrobial activity, with MIC values of 156 μg/mL for <em>S. aureus</em> and <em>C. albicans</em> and 312 μg/mL for <em>E. coli</em>, significantly outperforming lignin, GA, and lignin nanoparticles. Mechanistic studies revealed that LGA-NPs interact with microbial surfaces, disrupting membranes, inhibiting respiratory chains, generating ROS, and reducing ATP and metabolic activity, ultimately impairing microbial growth. Antioxidant evaluations showed superior radical scavenging activity (IC50 at 50 μg/mL), while α-amylase inhibition assays confirmed antidiabetic potential (IC50 of 75.0 μg/mL). Hemolysis tests demonstrated biocompatibility, with hemolysis rates below 5 %, reflecting safety for biomedical applications. The incorporation of GA into lignin not only improved bioactivity but also enhanced safety, emphasizing the synergistic effects of composite formation. These nanocomposites present a novel, sustainable, and economically viable therapeutic platform, addressing complex conditions like diabetic septic foot that demand effective glycemic control, robust antimicrobial action, and potent antioxidant capabilities.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214390"},"PeriodicalIF":5.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321188","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}
Wenjie Liu , Qing Wang , Hao Liu , Suqin He , Hongxiang Wang , Chengwei Xu , Bingyang Zhao , Chaofan Jin , Na Li , Siwang Hu
{"title":"Multifunctional bioactive metal phenolic networks (MPN) with copper ion retardation and dual-peptides for enhanced osteointegration","authors":"Wenjie Liu , Qing Wang , Hao Liu , Suqin He , Hongxiang Wang , Chengwei Xu , Bingyang Zhao , Chaofan Jin , Na Li , Siwang Hu","doi":"10.1016/j.bioadv.2025.214388","DOIUrl":"10.1016/j.bioadv.2025.214388","url":null,"abstract":"<div><div>Titanium rods are widely used as orthopedic implants, but their biologically inert surface limits their effectiveness in bone healing. To enhance osseointegration, implants need to be multifunctional, capable of modulating cellular behaviors such as early adhesion, migration, angiogenesis, and bone formation. In this study, copper ion-doped phenolic networks (P/Cu MPNs) were developed as a platform for grafting bioactive peptides (OGP and RGD), terminally coupled with K6 (hexameric lysine), to create a multifunctional bioactive coating (RGD/OGP@P/Cu) aimed at improving osteointegration. The properties of RGD/OGP@P/Cu, including hydrophilicity, chemical composition, morphology, roughness, and mechanical characteristics, were thoroughly characterized using techniques such as XPS, AFM, and SEM. The peptide coating effectively modulates the release of copper ions, and the synergistic effects of copper ions and bioactive peptides promoted cell adhesion, migration, osteogenesis, and angiogenesis in vitro. Furthermore, in a rat bone defect model, RGD/OGP@P/Cu demonstrated promising potential for bone regeneration and osseointegration. This synergistic strategy between peptide and controlled release of metal ions has great potential for application in promoting implant osseointegration in complex biological environments.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214388"},"PeriodicalIF":5.5,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321187","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}
Ilijana Kovrlija, Ksenia Menshikh, Hugo Abreu, Andrea Cochis, Lia Rimondini, Olivier Marsan, Christian Rey, Christèle Combes, Janis Locs, Dagnija Loca
{"title":"Corrigendum to \"Challenging applicability of ISO 10993-5 for calcium phosphate biomaterials evaluation: Towards more accurate in vitro cytotoxicity assessment\" [Biomater. Adv. 160 (2024) 213866].","authors":"Ilijana Kovrlija, Ksenia Menshikh, Hugo Abreu, Andrea Cochis, Lia Rimondini, Olivier Marsan, Christian Rey, Christèle Combes, Janis Locs, Dagnija Loca","doi":"10.1016/j.bioadv.2025.214386","DOIUrl":"https://doi.org/10.1016/j.bioadv.2025.214386","url":null,"abstract":"","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":" ","pages":"214386"},"PeriodicalIF":5.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295351","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}
Jianfeng Yang , Wenjing Li , Pei Ma , Pan Wang , Tianyu Yao , Yu Mi
{"title":"Multifunctional protein-polysaccharide hydrogel with antimicrobial and angiogenic properties to promote infected wound healing","authors":"Jianfeng Yang , Wenjing Li , Pei Ma , Pan Wang , Tianyu Yao , Yu Mi","doi":"10.1016/j.bioadv.2025.214387","DOIUrl":"10.1016/j.bioadv.2025.214387","url":null,"abstract":"<div><div>Bacterial infections, slow angiogenesis, and wound irregularities continue to present great clinical challenges in infected wound repair. While recent years have seen increasing interest in advanced composite hydrogels with antibacterial, angiogenic, and wound-healing properties, traditional dynamic hydrogels remain limited by inadequate mechanical strength despite their adaptability to irregular wounds. Here, we used double-bonded functionalized recombinant collagen (CFGMA), sulfhydrylated hyaluronic acid (HA-SH), silver ions (Ag<sup>+</sup>), and VEGF peptide (V-pep), which formed a composite hydrogel that could accommodate irregular wounds as well as have excellent mechanical properties. The CFGMA/HA-SH/Ag<sup>+</sup>/V-pep hydrogel not only exhibits excellent antibacterial properties, but also has good anti-inflammatory, pro-proliferative and angiogenic effects. <em>In vitro</em> study results indicated that the CFGMA/HA-SH/Ag<sup>+</sup>/V-pep hydrogel promoted the polarization of macrophages from M1 to M2 type, enhanced the proliferation of L929 and HUVECs, and facilitated the angiogenesis of HUVECs. <em>In vivo</em> experiments indicated that CFGMA/HA-SH/Ag<sup>+</sup>/V-pep hydrogel effectively killed bacteria, accelerated blood vessel regeneration, and promoted the repair of infected wounds at day 12. Moreover, CFGMA/HA-SH/Ag<sup>+</sup>/V-pep hydrogel promoted the regeneration of granulation tissue and collagen deposition at the wound site. The prepared hydrogel was antimicrobial, anti-inflammatory, pro-proliferative, promoted vascular regeneration and accelerated wound repair, which could be an effective treatment for infected wounds.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214387"},"PeriodicalIF":5.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298552","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}
Wenhao Liu , Zhihua Liu , Hao Chen , Jianyang Shan , Xiang Li , Xiaoqian Hu , Haomin Cui , Yaling Yu , Gen Wen
{"title":"Time-adaptable alterations of the extracellular matrix during chondrocyte dedifferentiation","authors":"Wenhao Liu , Zhihua Liu , Hao Chen , Jianyang Shan , Xiang Li , Xiaoqian Hu , Haomin Cui , Yaling Yu , Gen Wen","doi":"10.1016/j.bioadv.2025.214383","DOIUrl":"10.1016/j.bioadv.2025.214383","url":null,"abstract":"<div><div>Cartilage damage as a universal health problem, remains a significant cause for the development of osteoarthritis, affecting more than one million people worldwide. Poor intrinsic capacity for healing and available therapeutic strategies have severely restricted the cartilage repair post damage. Decellularized extracellular matrix (ECM) provides new thinking for the treatment of cartilage defect. However, chondrocytes dedifferentiation brings uncertainty to the researches and applications of chondrocyte-derived decellularized matrix. In this study, we demonstrated the nuclear deformation during chondrocyte dedifferentiation process, consummating the time-lapse theory atlas of chondrocyte dedifferentiation. We manufactured decellularized chondrocyte sheets (dCS) derived from different stages of dedifferentiated chondrocytes, and performed multimodal assays to characterize the mechanical, physiochemical, and proteomic properties of the dCS. Collagen II peaked at the dCS derived from plastic passage 2 chondrocytes, and decreased at the late dCS. Collagen I increased under temporal correlation. The randomness of collagen fiber direction decreased under temporal correlation, positively correlated with the ultimate tensile strength. Compared with the late dCS, the early dCS promoted cell migration, proliferation, and chondrogenic differentiation. The supplement of Fmod upregulated the biological regulatory activity of the late dCS on the chondrocyte dedifferentiation process. Overall, this study lays a foundation to improve the theory atlas of chondrocyte dedifferentiation, provides insights into cartilage repair and lay a basis for the development of new materials for cartilage repair.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"177 ","pages":"Article 214383"},"PeriodicalIF":5.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298551","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}