International Journal of Biological Macromolecules最新文献

{"title":"Pullulan-mediated dynamic interfacial regulation for antifreezing conductive hydrogels with high toughness and low hysteresis.","authors":"Bingyao Wang, Jianing Li, Hongyao Ding, Xu Yang, Changpeng Wang, Hui Li","doi":"10.1016/j.ijbiomac.2026.154890","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154890","url":null,"abstract":"<p><p>Developing conductive hydrogels with both mechanical integrity and electrical functionality at subzero temperatures remains challenging. This is mainly due to the intrinsic trade-off between energy dissipation and structural stability. In this work, we report a multi-component conductive hydrogel based on poly(sodium acrylate-co-N-(2-hydroxyethyl)acrylamide), pullulan, glycerol, and liquid metal, in which the interplay between weak interfacial interactions and a dynamic polymer network is rationally regulated. The incorporation of pullulan modulates interfacial interactions in the hydrogel network and contributes to low hysteresis during cyclic deformation. Meanwhile, the copolymer network enables efficient stress transfer through chain entanglement, while dynamic interactions provide controlled energy dissipation under deformation, leading to a desirable balance between elasticity and toughness. Glycerol further enhances the anti-freezing capability by forming hydrogen bonds with water, thereby ensuring ionic mobility and mechanical compliance at low temperatures. As a result, the hydrogel exhibits high stretchability, outstanding toughness, low hysteresis, and high conductivity. Demonstrations of strain sensing for human motion monitoring confirm its potential in wearable electronics. This work offers a promising strategy for designing hydrogels with tailored mechanical and electrical properties for flexible electronics.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154890"},"PeriodicalIF":8.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-functional hydrogel capable of scavenging reactive oxygen species and regulating macrophage polarization for repairing MRSA-infected wounds.","authors":"Hang Shi, Xiaohuan Lu, Xuan Hou, Qin Bai, Xin Zhang, Xiaozhong Wang, Xiaolin Li","doi":"10.1016/j.ijbiomac.2026.154872","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154872","url":null,"abstract":"<p><p>The healing of infected wounds presents a remarkable clinical challenge owing to bacterial infection-induced oxidative stress and persistent inflammation. To address these issues, a multifunctional hydrogel was prepared by means of Schiff base crosslinking between oxidized konjac glucomannan (OKGM) and sericin, followed by the incorporation of polydopamine nanoparticles (PDA NPs). The OKGM/Sericin-PDA NPs (KSP) hydrogel exhibited excellent antioxidant capacity, facilitating macrophage polarization to the M2 phenotype. Transcriptomic analysis revealed that the KSP hydrogel exerted immunomodulatory effect by activation of the PI3K/AKT signaling pathway. Furthermore, the KSP hydrogel exhibited photothermal properties, thereby demonstrating potent antibacterial efficacy against both Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). Significantly, in a murine model of full-thickness wounds infected with MRSA, the hydrogel combined with near-infrared irradiation demonstrated remarkable antibacterial activity and anti-inflammation, contributing to accelerating wounds healing by reducing bacterial load and regulating the wound immune microenvironment. In summary, these results indicate that the KSP hydrogel serves as a promising multifunctional dressing, offering an effective clinical approach for repairing and regenerating full-thickness infected wounds.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154872"},"PeriodicalIF":8.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Djcoronin controls the AP axis polarity through Wnt signaling pathway during planarian regeneration.","authors":"Cui Ge, Shengchao Zhang, Ruohan Lin, Duan Lin, Hongyu Cui, Wenjuan Xue, Yuan Yu, Fulin Chen","doi":"10.1016/j.ijbiomac.2026.154871","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154871","url":null,"abstract":"<p><p>Planarians have whole body regeneration ability and are model animals for the study of regeneration and development. Coronin is an actin binding protein involved in a variety of cellular processes. However, the precise role of coronins in tissue regeneration remains unclear. In this study, we found that Djcoronin exhibited a concentration gradient expression pattern throughout the worm and was highly expressed in the newly formed tail region after amputation. We used RNA interference to knockdown Djcoronin and found that loss of Djcoronin function affected tail regeneration, characterized by nervous system defects and a two-headed phenotype, while having no significant effect on head regeneration. Importantly, knockdown of Djcoronin downregulated the expression of β-catenin and posterior Wnt genes, accompanied with the reversal of the head-tail polarity. Moreover, treatment with Wnt agonist 1 significantly alleviated the regeneration and polarity defects caused by Djcoronin knockdown. In conclusion, our study suggests that Djcoronin is an important regulator of polarity maintenance that contributes to AP polarity regulation via the Wnt/β-catenin signaling pathway.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154871"},"PeriodicalIF":8.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Open or closed? Structural characterization of plasma-derived and recombinant human plasminogen across multiple resolution scales.","authors":"Linda Kasiarova, Naina Verma, Matyas Pinkas, Tomas Henek, Tomas Klumpler, Marie Chovancikova, Helena Reutova, Petr Kasparek, Martina Hlozankova, Jiri Damborsky, Jiri Novacek, Lenka Hernychova, Martin Marek","doi":"10.1016/j.ijbiomac.2026.154885","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154885","url":null,"abstract":"<p><p>Plasminogen (Plg), the zymogen of the fibrinolytic protease plasmin, is a multidomain, conformationally rich protein that plays a crucial role in targeted thrombolysis for stroke and heart attack treatments. Yet, the conformational state that affects binding to Plg activators and fibrinolytic activity is rarely validated, contributing to poor reproducibility and failures in drug development. Here, we establish a structural biology workflow to characterize human Plg suspended in an aqueous solution, preserving it in a near-native state and eliminating the need for crystal growth. Two variants, cleavage-resistant Plg-RV (R561A) and catalytically inactive Plg-CAT (S741A), were expressed in mammalian cells. Both variants showed comparable global secondary structure and thermal stability (Tm ≈ 60.6 °C) and were resistant to staphylokinase-mediated activation, in contrast to commercial plasma-derived Plg. Small-angle X-ray scattering revealed substantial conformational heterogeneity, and hydrogen‑deuterium exchange mass spectrometry mapped SAK-associated local structural changes. The recombinantly-produced Plg variants adopted a closed conformation, exhibiting a good fit to the closed structure determined by X-ray diffraction. Conversely, the plasma-derived Plg populated an extended, open-like state. Cryo-EM analysis of the Plg-RV variant yielded a 4.4 Å resolution map, and a rigid-body-fitted model revealed the closed-state architecture. Our findings demonstrate that rigorous structural validation of Plg is essential for future functional studies and rational development of next-generation thrombolytic agents.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154885"},"PeriodicalIF":8.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural-functional modulation and macromolecular interactions in buckwheat protein films induced by heat, rutin, and transglutaminase.","authors":"Viola A N Nicholas-Okpara, Ian Israelsen, Kristen Matak, Jacek Jaczynski, Ayesha Sarker","doi":"10.1016/j.ijbiomac.2026.154952","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154952","url":null,"abstract":"<p><p>Thermal energy processing, enzymatic crosslinking by transglutaminase, and polyphenol-rutin interaction modulated the buckwheat protein (BWP) macromolecular structure and functional properties. In this study, film formation as a model system was investigated to evaluate structure-function relationships. Isoelectric-precipitated BWP was used for film production and conditioned at 50% relative humidity (RH) at 25 °C. Standard methods were used to evaluate water vapor permeability (WVP) and mechanical, microstructural, physical, and physicochemical properties. Formation of hydrophobic barriers through matrix reorganization, enzymatic crosslinking, and protein-phenolic interactions reduced WVP by 1.09%-43.92% and increased tensile strength (TS) (p < 0.05) in the treated films. The heated group showed the strongest effect on TS (57.88% increase, 7.23 MPa). The treated films' lightness (L*) and yellowness (b*) were improved, while thermal treatment notably reduced opacity. The 1% TGase film showed the highest time-dependent moisture-sorption uptake. The rutin and TGase BWP films' antioxidant potentials were enhanced by an increase of 9.17%-15.34% Trolox antioxidant equivalents. The ninhydrin assay indicated an optimum crosslinking at 1% TGase, with a reduction at higher concentrations indicating saturation. Structural integrity and compactness improved progressively in the heated, rutin, and TGase-treated BWP film. The 2% rutin and 1% TGase films showed the most cohesive and homogeneous matrices, correlating with reduced WVP and enhanced TS. FTIR analysis showed that heat, rutin, and TGase treatments altered hydrogen bonding and protein conformation, enhancing molecular stability and improving the biofunctional, mechanical, and barrier properties of BWP films for sustainable food packaging.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154952"},"PeriodicalIF":8.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gal-3 N-terminal prolines within residues 69 to 117 regulate CRD glycan binding, phase separation and Gal-3-mediated cellular function.","authors":"Zhen He, Xiaomeng Wang, Dongmei Wang, Guihua Tai, Kevin H Mayo, Yanchao Zhang, Zihan Zhao","doi":"10.1016/j.ijbiomac.2026.154867","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154867","url":null,"abstract":"<p><p>Galectin-3 (Gal-3), the only chimeric galectin, is a central driver and potential biomarker for cancer progression, fibrotic disorders, and heart failure. As a key proinflammatory factor, Gal-3 aggravates various disease states by promoting immune cell activation, cytokine storm amplification, and cell migration. Previously, we reported on the structural and functional role of prolines within Gal-3 NT residues 1-68. Here, we report on how the 14 NT prolines within the 69-117 segment affect Gal-3 structure and function. Circular dichroism (CD) and fluorescence spectroscopies showed that none of these proline-to-alanine substitutions altered overall Gal-3 conformation, whereas some of them did modulate glycoprotein-induced phase separation and ligand binding (lactose (Lac), LacNAc, (LacNAc)₃), as well as Gal-3-mediated cell function, i.e., cell activation, hemagglutination, and endocytosis. Three of these prolines were found to be the most crucial to Gal-3-mediated activities, with P86A and P113A attenuating glycan-binding, glycoprotein-induced phase separation, and cellular function and P117A enhancing these processes. Correlation analysis of all prolines within the Gal-3 NT revealed that prolines within the 1-68 segment primarily modulate cellular function via glycan binding, whereas prolines within the 69-117 segment modulate glycan-induced phase separation and cellular function. Overall, our findings reveal distinct functional roles for specific Gal-3 NT prolines, provide mechanistic insight into Gal-3 structure-function relationships, and identify potential NT prolines as targets for ameliorating various Gal-3-related pathological disorders.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154867"},"PeriodicalIF":8.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-function relationships of branched and linear β-1,3-glucan/DNA complexes in Dectin-1 recognition and nucleic acid delivery.","authors":"Kazuki Sumiya, Takuya Matsunaga, Rui Tada, Yoshiyuki Adachi, Kazuo Sakurai","doi":"10.1016/j.ijbiomac.2026.154958","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154958","url":null,"abstract":"<p><p>β-1,3-glucans (BGs) are promising biomaterials for targeted nucleic acid delivery because they can form stable complexes with single-stranded homopolynucleotides and interact with the C-type lectin receptor Dectin-1. However, the influence of structural differences among BGs on complex formation and receptor recognition remains poorly understood. Therefore, in this study, we compared complex formation behavior, structural characteristics, and CpG-ODN delivery efficiency between a β-1,6-branched BG, schizophyllan (SPG), and a linear β-1,3-glucan, curdlan (CUR). The model DNAs were a 40-mer poly(deoxyadenosine) single-stranded DNA (dA40), and CpG-ODN conjugated to the 5' end of dA40. Although both BGs formed stable complexes with dA40, their supramolecular structures differed, reflecting structural differences between branched and linear glucans. Both complexes retained Dectin-1 recognition; however, their binding ability differed between the SPG/dA40 and CUR/dA40 complexes. Cellular assays demonstrated efficient internalization in Dectin-1-expressing cells, and both BG/CpG complexes induced significantly more potent immune responses than naked CpG-ODNs. Despite their different binding abilities toward Dectin-1, both complexes induced similar levels of IL-6 and TNF-α, showing that stronger receptor recognition does not necessarily lead to greater immunostimulatory activity. These findings demonstrate that BG structural properties control complex formation and receptor interactions, providing mechanistic insights into the rational design of polysaccharide-based nucleic acid delivery systems.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154958"},"PeriodicalIF":8.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upcycling of cardoon root biomass into polyhydroxyalkanoate nanocarriers for docetaxel delivery.","authors":"Simona Varriale, Pierluigi Gabriele Di Matteo, Ovidio Catanzano, Michele Guida, Pasquale d'Anna, Ivelina Ivaylova Dzhambazova, Elisabetta Borselleca, Giovanni Dal Poggetto, Maria Laura Alfieri, Fabiana Quaglia, Claudia Conte, Cinzia Pezzella","doi":"10.1016/j.ijbiomac.2026.154887","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154887","url":null,"abstract":"<p><p>Lignocellulosic residues represent a promising low-cost feedstock for the sustainable production of polyhydroxyalkanoates (PHAs), although their integration into high-value biomedical applications remains limited. This work reports an integrated approach for the valorization of cardoon root biomass into poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and its subsequent application as a nanocarrier for docetaxel delivery. Cardoon roots were subjected to cascade fractionation followed by deep eutectic solvent (DES)-based pretreatment to enhance lignin removal while preserving the carbohydrate fraction. Among the tested conditions, a choline chloride/lactic acid system (1:4 mol/mol, 140 °C, 3 h) provided the best balance between delignification (≈ 70%) and cellulose retention (≈ 95%), enabling efficient enzymatic saccharification and glucose release (up to 12.8 g L^-1). The resulting hydrolysate was directly used as a carbon source for PHBHHx production in an engineered Escherichia coli strain, yielding polymers with high molecular weight (up to 2.1 × 10⁵ g mol^-1) and a high hydroxyhexanoate content (∼ 37 mol%), suitable for nanoparticle formulation. PHBHHx nanoparticles were prepared via nanoprecipitation and exhibited controlled size (∼ 220-250 nm), narrow size distribution, and high docetaxel encapsulation efficiency (> 85%). The nanocarriers showed sustained drug release (∼ 45% over 35 days) and good colloidal stability, while in vitro studies on 4 T1 and 3 T3 cells demonstrated time-dependent cell uptake, an enhanced early cytotoxicity compared to free drug and absence of intrinsic toxicity of the unloaded system. Overall, this work demonstrates an integrated cascade for the valorization of aged cardoon-root, from tailored fractionation to PHBHHx formulation into functional drug-delivery material.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":"384 Pt 2","pages":"154887"},"PeriodicalIF":8.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eumelanin-loaded ZnO@Ag/kombucha-derived bacterial cellulose gauze as a multifunctional bioactive dressing for antimicrobial and pro-healing applications.","authors":"Ghada E Dawwam, Mona T Al-Shemy, Aly Al-Sayed, Chiara Botta, Riccardo Donnini, Antonella Caterina Boccia","doi":"10.1016/j.ijbiomac.2026.154956","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154956","url":null,"abstract":"<p><p>Developing sustainable wound dressings that combine antimicrobial activity, antioxidant activity, cytocompatibility, and adequate mechanical performance remains challenging. To address this, an eco-friendly multifunctional dressing was fabricated by integrating a kombucha-derived bacterial cellulose/ZnO@Ag (KBC/ZnO@Ag) nanohybrid and eumelanin derived from Hermetia illucens puparia within a hydroxypropyl methylcellulose (HPMC) matrix. The structural, chemical, morphological, thermal, optical, and elemental properties of the prepared materials were evaluated using XRD, FTIR, SEM-EDX, TGA/DTG, photoluminescence, and atomic absorption spectroscopy. Among the tested formulations, the eumelanin-containing KBC/ZnO@Ag formulation (S4-EuMe) exhibited broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria and Candida albicans, with inhibition zones of up to 47 mm. Eumelanin incorporation further enhanced antioxidant activity, reducing the DPPH radical-scavenging IC₅₀ from 26 μg mL^-1 for KBC/ZnO@Ag (S4) to 14 μg mL^-1 for S4-EuMe. The selected formulation also showed a concentration-dependent effect on HFB4 fibroblast viability, with an IC₅₀ of 177.45 ± 1.35 μg mL^-1, and enhanced in vitro scratch closure to 72.72% after 48 h compared with 60.73% for the untreated control. Mechanically, S4-treated gauze showed reduced tensile strength and stiffness relative to the neat substrate, whereas eumelanin incorporation in S4-EuMe increased tensile strength, stiffness, and Young's modulus. In the corresponding freeze-dried scaffold, eumelanin also enhanced resistance to repeated compression, increasing the mean compressive stress over 15 loading-unloading cycles from 8.15 ± 0.52 to 13.16 ± 1.23 kPa. Overall, S4-EuMe integrates complementary antimicrobial and antioxidant activities, cytocompatibility, fibroblast-associated effects, and favorable mechanical properties, supporting its potential as a sustainable bioactive wound-dressing material for further investigation.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154956"},"PeriodicalIF":8.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoring joint homeostasis: In vitro and in vivo efficacy of a sodium hyaluronate-lipoate-formate therapy for osteoarthritis.","authors":"F Salamanna, L Cavazza, L Martini, L Stucchi, S Pagani, F Nucera, G Giavaresi","doi":"10.1016/j.ijbiomac.2026.154891","DOIUrl":"https://doi.org/10.1016/j.ijbiomac.2026.154891","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a multifactorial joint disorder characterized by inflammation, cartilage homeostasis disruption, and extracellular matrix degradation. Although hyaluronic acid (HA) viscosupplementation is widely used, available formulations mainly provide symptomatic relief without targeting underlying inflammatory and catabolic processes. Here, two innovative HA derivatives covalently functionalized with lipoic acid and formate (SHLF0.5% and SHLF1%) were developed to enhance viscoelastic properties and modulate the oxidative joint microenvironment. Biological performance was evaluated in human chondrocyte-synoviocyte co-cultures under healthy and OA conditions by assessing cell viability and markers of cartilage metabolism, extracellular matrix turnover, and inflammation. The most promising formulation, SHLF0.5%, was further investigated in vivo in a rat destabilization of the medial meniscus (DMM) model, evaluating pain-related behaviour, cartilage integrity, synovial morphology, and extracellular matrix features. In vitro, SHLF0.5% supported cell viability and modulated markers associated with cartilage homeostasis and matrix turnover (increased expression of PRG4 and TIMP1, and decreased expression of MMP1, MMP3, MMP13, ADAMTS-5, IL6, and PTGS2). SHLF1% also showed a favourable biological profile, supporting the functional potential of the SHLF platform. In vivo, SHLF0.5% improved pain-related outcomes and preserved cartilage structure, with lower OARSI scores, maintained proteoglycan content and Type II collagen/aggrecan expression, and preserved synovial features compared with NaCl and a clinically used HA formulation. Overall, SHLF0.5% showed favourable biological performance and preservation of joint tissue integrity, supporting its potential as a next-generation viscosupplement combining enhanced viscoelastic properties with features resembling physiological synovial fluid.</p>","PeriodicalId":333,"journal":{"name":"International Journal of Biological Macromolecules","volume":" ","pages":"154891"},"PeriodicalIF":8.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}