Acta biomaterialia最新文献

{"title":"Disorder-engineered thermoelectric Cu₂Se/SnSe₂ heterojunctions embedded in glycyrrhizic acid hydrogels for pyro-photo-ultrasonic therapy of periodontitis.","authors":"Boyu Zeng, Maoxin Ren, Meng Chen, Qiyao Zheng, Congyang Mao, Yuan Li, Chaofeng Wang, Talante Juma, Xiangmei Liu, Yongping Cao, Yufeng Zheng, Shuilin Wu","doi":"10.1016/j.actbio.2026.09.052","DOIUrl":"10.1016/j.actbio.2026.09.052","url":null,"abstract":"<p><p>Periodontitis treatment is severely hampered by rapid electron-hole recombination and hypoxic microenvironment, which fundamentally limit reactive oxygen species (ROS) yields in conventional photo/sonodynamic therapies. Herein, we propose a disorder-engineered thermoelectric heterojunction strategy that couples pyro-photo-ultrasonic effects to overcome these bottlenecks. Thermoelectric Cu₂Se(CuSe)/SnSe₂ heterojunctions, synthesized by mechanochemical ball milling, introduce dense CuSe nanodomains and interfacial defects that serve simultaneously as phonon-scattering centers (minimizing thermal conductivity of κ_tot = 0.09 W/(m·K)) and non-radiative relaxation channels, enabling efficient photo-to-thermal conversion. A pronounced built-in electric field, arising from the large work function difference between Cu₂Se (7.17 eV) and SnSe₂ (6.52 eV), synergizes with the thermoelectric field induced by photo-ultrasonic thermal gradients, yielding sustained carrier separation (ZT = 0.08 at 450 K) and robust ROS generation under hypoxic conditions. The resultant heterojunction achieves unprecedented antibacterial efficacy (>98.37% against Staphylococcus aureus and >99.54% against Porphyromonas gingivalis) under 808 nm NIR/ultrasound co-activation. Integration of glycyrrhizic acid hydrogel provides a biocompatible matrix (97.8% cell viability, <5% hemolysis) that substantially downregulates TNF-α, reduces osteoclastogenesis significantly, and markedly restores alveolar bone height. This work establishes a \"disorder-engineering for biocatalysis\" strategy, demonstrating that controllable lattice imperfections can be harnessed to drive multi-physical coupling for high-efficacy therapy of infected bone tissues. STATEMENT OF SIGNIFICANCE: Conventional mechanical/antibiotic treatment and prevailing exogenous stimulus-responsive strategies face significant problems in the treatment of periodontitis, mainly in rising bacterial resistance, insufficient deep pathogen elimination and limited antibacterial ability. In this work, we constructed a Cu₂Se(CuSe)/SnSe₂ thermoelectric heterojunction based on disorder-engineering strategy. Under near-infrared and ultrasonic co-stimulation, the synergy between built-in electric field and thermoelectromotive force effectively suppresses carrier recombination, enabling remarkably enhanced ROS generation and bactericidal efficacy under periodontal hypoxic microenvironment. Integrated with glycyrrhizic acid hydrogel, the system achieves favorable biocompatibility, anti-inflammatory activity, and alveolar bone repair capacity, offering a meaningful paradigm for multi-physical field synergistic antibacterial therapy.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Setd2 is associated with strontium-induced bone regeneration\" [Acta Biomaterialia 2017;53:495-505].","authors":"Xiaoshi Jia, Qiaoyun Long, Richard J Miron, Chengcheng Yin, Yan Wei, Yufeng Zhang, Min Wu","doi":"10.1016/j.actbio.2026.09.043","DOIUrl":"https://doi.org/10.1016/j.actbio.2026.09.043","url":null,"abstract":"","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An NIR-triggered self-propelled janus nanomotor-integrated hydrogel with enzymatic cascade reactions and photothermal-enhanced drug release for the treatment of gouty arthritis.","authors":"Lingzi Feng, Yun Li, Cong Ding, Yifan Li, Juntao Jiang, Qiang Zhang, Manqi Yan, Fei Cao, Ting Wu, Yong Hu","doi":"10.1016/j.actbio.2026.10.005","DOIUrl":"10.1016/j.actbio.2026.10.005","url":null,"abstract":"<p><p>Gouty arthritis is characterized by monosodium urate (MSU) crystal deposition, persistent joint inflammation, oxidative stress, and limited drug penetration. Here, we report an injectable hydrogel system embedding asymmetric Janus nanomotors (Col-PLGA@Au-CU) that integrates enzymatic cascade reaction, photothermal propulsion, and on-demand drug release for active gout therapy. The nanomotors consist of colchicine-loaded PLGA cores partially coated with gold nanoshells and functionalized with uricase (UOx) and catalase (CAT), which are encapsulated in a chitosan-based hydrogel for intra-articular retention. Under near-infrared (NIR) irradiation, the gold nanoshells generate localized heat, which accelerates the release of the nanomotors from the hydrogel. The elevated temperature also enhances the UOx/CAT cascade reaction, resulting in increased oxygen generation and enhanced active motion of the nanomotors. Meanwhile, the photothermal effect accelerates the release of colchicine from the hydrogel. The enzymatic cascade not only depletes uric acid but also decomposes H₂O₂ into O₂ and H₂O, relieving oxidative stress and hypoxia. In vitro, the NIR-triggered nanomotors exhibited significantly enhanced cellular uptake, ROS scavenging, HIF-1α suppression, and M2 macrophage polarization. In a murine MSU-induced gout model, intra-articular injection of Col-PLGA@Au-CU@CS hydrogel followed by NIR irradiation effectively reduced joint swelling, restored gait patterns, decreased synovial inflammation, protected cartilage integrity, and downregulated TNF-α and IL-6 expression, without systemic toxicity. This enzyme-powered, photothermal-activatable Janus nanomotor hydrogel represents a controlled-release platform that combines enhanced active transport, microenvironment modulation, and triggered drug delivery, offering a promising strategy for precision therapy of gouty arthritis. STATEMENT OF SIGNIFICANCE: This study presents a novel injectable Janus nanomotor-integrated hydrogel (Col-PLGA@Au-CU@CS) for the treatment of gouty arthritis. By combining an enzymatic cascade (uricase and catalase) with a photothermal gold nanoshell, the system achieves simultaneous uric acid depletion, hydrogen peroxide decomposition, and NIR-triggered self-propulsion. The asymmetric nanomotors overcome poor drug penetration into avascular cartilage, while the hydrogel ensures intra-articular retention. Under NIR irradiation, enhanced directional motion, on-demand colchicine release, and reactive oxygen species scavenging lead to marked suppression of synovial inflammation, M2 macrophage polarization, and cartilage protection in a murine gout model. This work establishes an enzyme-powered, photothermal-activatable platform that integrates active tissue penetration, microenvironment modulation, and triggered drug delivery, offering a promising precision therapy strategy for gouty arthritis and potentially other inflammatory joint diseases.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contractile and hemodynamic modulation of skeletal muscle viscoelasticity quantified in vivo by ultrasound time-harmonic elastography.","authors":"Tom Meyer, Eduard Kurz, Stefan Klemmer Chandía, Pascal Engl, Giacomo Valli, Yanglei Wu, Klaus Jenderka, Thomas Bartels, René Schwesig, Jing Guo, Ingolf Sack, Hossein S Aghamiry","doi":"10.1016/j.actbio.2026.10.006","DOIUrl":"10.1016/j.actbio.2026.10.006","url":null,"abstract":"<p><p>Skeletal muscle is a living, perfused soft tissue whose viscoelastic behavior is shaped by both voluntary contraction and hemodynamic state. However, the independent and superimposed contributions of contractile loading and blood flow restriction (BFR) have not been quantified simultaneously in real time. Twenty-six healthy adults underwent multi-frequency ultrasound time-harmonic elastography (THE, 60-80 Hz) of the vastus lateralis under six conditions: rest, 15% and 30% maximal voluntary contraction (MVC) before BFR, passive BFR after 4 min of cuff inflation, and 15% and 30% MVC shortly after cuff release. Shear wave speed (SWS), reflecting elasticity, and penetration rate (PR), reflecting inverse viscous damping, were extracted using the k-MDEV inversion algorithm. BFR significantly elevated SWS at all three contraction levels relative to the corresponding pre-BFR measurements (Holm-corrected p ≤ 0.011; dz = 0.54-2.13). PR decreased during resting BFR (dz = 1.34, p < 0.001) and at 15% MVC after cuff release (dz = 0.94, p < 0.001), but not at 30% MVC (dz = 0.21, p = 0.294). BFR-related changes reduced the SWS-force slope by 15% and the PR-force slope by 40%. Men exhibited a greater BFR-induced increase in resting SWS than women. These findings show that THE can distinguish contractile and hemodynamic contributions to skeletal muscle viscoelasticity and provide complementary information on elastic and dissipative tissue behavior in vivo. STATEMENT OF SIGNIFICANCE: Skeletal muscle is a living, perfused soft tissue whose mechanical behavior reflects the interaction of contractile structures, extracellular matrix, and fluid-containing compartments. Most elastography studies focus primarily on contraction-related stiffness changes. Here, we show that blood flow restriction modifies both shear wave speed and penetration rate even without voluntary contraction, and that these hemodynamic effects remain detectable during the early post-release phase. The distinct responses of the two parameters indicate complementary sensitivity to elastic and dissipative tissue behavior. These findings establish ultrasound time-harmonic elastography as a non-invasive approach for probing coupled contractile and fluid-mediated contributions to skeletal muscle viscoelasticity in vivo.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Fiber density-driven mechanotransduction reconstructs collagen heterogeneity in the annulus fibrosus\".","authors":"Chunwang Yang, Kaishan Ye","doi":"10.1016/j.actbio.2026.10.001","DOIUrl":"10.1016/j.actbio.2026.10.001","url":null,"abstract":"","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Volumetric imaging of Young's modulus and nonlinear elasticity on the micro-scale.","authors":"Kai L Metzner, Rowan W Sanderson, Jiansha Wu, Rhys Jones, Juliana Hamzah, Qi Fang, Brendan F Kennedy","doi":"10.1016/j.actbio.2026.10.007","DOIUrl":"10.1016/j.actbio.2026.10.007","url":null,"abstract":"<p><p>Compression optical coherence elastography (OCE) provides micro-scale imaging of tissue and biomaterial mechanical properties in three dimensions (3-D), showing promise in a range of biomedical applications. Despite substantial progress, most 3-D OCE techniques do not account for the nonlinear elastic response of tissue, resulting in deformation-dependent variations in estimated Young's modulus within an image that reduce reliability and confound comparison both within and between samples. In this work, we overcome these limitations by explicitly accounting for sample deformation and present the first 3-D images of the nonlinear elastic response of tissue, parameterized into Young's modulus and a nonlinear parameter, a capability not previously achieved in OCE or any other elastography modality. To achieve this, we introduce a volumetric, sparsely sampled, phase-based stretch estimation protocol to quantify finite sample deformation and estimate the nonlinear elastic response from between five and nine volumes. We also use an integrated stress sensing layer to minimize temporally varying friction. We validate these new capabilities on phantoms, demonstrating volumetric estimation of the nonlinear elastic response, with mean errors <20 %, compared to >50 % without the integrated layer. Finally, we apply this technique to ex vivo mouse liver, imaging Young's modulus and the nonlinear parameter in healthy and diseased tissue. This method enables more accurate and reliable mechanical characterization of tissue with potential applications in many areas, including tissue engineering, mechanobiology, and disease diagnostics. STATEMENT OF SIGNIFICANCE: Compression optical coherence elastography (OCE) provides micro-scale imaging of tissue mechanical properties in three dimensions (3-D). However, most 3-D OCE techniques do not account for the nonlinear elastic response of tissue, leading to errors in the reported elasticity. In this work, we overcome these limitations and present a technique to volumetrically image the nonlinear elastic response of tissue, a capability not previously achieved in elastography. By parameterizing the nonlinear elastic response into Young's modulus and a nonlinear parameter, our method enables more accurate mechanical characterization and additional contrast for differentiating tissue microstructure. These results establish a foundation for volumetric imaging of nonlinear tissue elasticity using OCE in a range of biomedical applications, including tissue engineering, mechanobiology, and disease diagnostics.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Letter to Editor \"Comment on \"Fiber density-driven mechanotransduction reconstructs collagen heterogeneity in the annulus fibrosus\"\".","authors":"Mingyang Qian, Yongqiang Xiao, Wei Jiang, Yucai Li, Lin Du, Zhibao Chen, Xiaojian Ye, Youfu Wang, Yujie Chen, Jiangming Yu","doi":"10.1016/j.actbio.2026.10.002","DOIUrl":"10.1016/j.actbio.2026.10.002","url":null,"abstract":"","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compromised elastin network load transfer in aging human aorta.","authors":"Yeganeh Taheri, Anastasia Gkousioudi, Yanhang Zhang","doi":"10.1016/j.actbio.2026.09.054","DOIUrl":"10.1016/j.actbio.2026.09.054","url":null,"abstract":"<p><p>Elastic fibers are essential for passive arterial load bearing and must withstand billions of loading cycles throughout life. Although arterial stiffening is a hallmark of cardiovascular aging, how elastin mechanical function evolves with aging in humans remains poorly understood. This study investigated age-dependent changes in the mechanical properties and microstructure of purified human aortic elastin networks. Purified elastin networks were obtained from human thoracic aortas (17 in total; 9 males, 8 females; ages 26-92 years). Uniaxial tensile testing was performed, and tangent modulus at 1.1 stretch was calculated from Cauchy stress-stretch responses. Elastin microstructure was examined using multiphoton microscopy, histology, and scanning electron microscopy (SEM), combined with quantitative image analysis. Elastin tangent modulus decreases significantly with aging in male subjects (p < 0.05). Multiphoton imaging revealed progressive reduction in fiber straightness with age (p < 0.05 in males), with young elastin networks characterized by straight, continuous fibers that primarily reoriented under load, whereas older networks exhibited increased waviness, fragmentation, and loss of load-bearing fibers. Histological analysis further demonstrated a significant age-related reduction in lamellar length in males (p < 0.05), indicating increased network discontinuity. SEM further demonstrated pronounced ultrastructural deterioration in older male samples, with elastic fibers appearing fragmented and frayed compared to the continuous and organized fibers in younger males. These microstructural alterations were consistent with diminished mechanical engagement of elastin fibers under tensile loading in the older male samples. In contrast, female samples did not exhibit consistent age-dependent deterioration in either mechanical or microstructural metrics. STATEMENT OF SIGNIFICANCE: This study provides direct experimental evidence linking age-related microstructural degradation of isolated human elastin networks to impaired mechanical function. Using purified elastin from naturally aged human thoracic aortas, we demonstrate that aging in males is associated with increased elastin fragmentation, fiber waviness, reduced lamellar continuity, and diminished mechanical stiffness, whereas female elastin networks exhibit relative structural and functional preservation. These findings identify deterioration of elastin network integrity as a potential mechanobiological contributor to arterial aging and stiffening. By integrating biomechanics with multiscale imaging of aged human tissues, this work advances understanding of elastin's role in vascular biomechanics and suggests potential sex-specific differences in elastin aging.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A calcination-based method for the indirect determination of octacalcium phosphate phase purity.","authors":"Nicola Döbelin, Ryo Hamai, Kaori Tsuchiya, Osamu Suzuki","doi":"10.1016/j.actbio.2026.10.008","DOIUrl":"10.1016/j.actbio.2026.10.008","url":null,"abstract":"<p><p>Octacalcium phosphate (OCP) is a precursor of bone mineral, but its phase purity is difficult to quantify because of strong peak overlap with biomimetic hydroxyapatite (HAp) in X-ray diffraction (XRD). Here, we present an indirect quantification approach based on the bulk molar Ca/P ratio after controlled calcination. Upon thermal treatment, OCP, HAp, and amorphous calcium phosphate decompose into a binary mixture of β-calcium pyrophosphate (β-CPP) and β-tricalcium phosphate (β-TCP), which can be reliably quantified by XRD. From their relative amounts, the bulk Ca/P ratio and an equivalent OCP phase content can be calculated. Because phosphate evaporation during calcination alters the β-CPP/β-TCP equilibrium and biases the derived Ca/P ratio, we demonstrate that stabilizing the furnace atmosphere is essential for reproducible results. Saturating the atmosphere with sacrificial monetite effectively suppresses phosphate loss and preserves the original composition. By varying dwell time between 2 and 24 h at two temperatures, we delimit the processing window within which the derived phase content is independent of the treatment conditions. At 1000°C, this approach yields stable and reproducible OCP phase contents with negligible compositional drift over dwell times up to 24 h. The method is simple to implement and provides a robust tool for assessing OCP phase purity in both research and quality control settings. STATEMENT OF SIGNIFICANCE: Octacalcium phosphate (OCP) is an important precursor of bone mineral, yet its phase purity is difficult to quantify due to strong X-ray diffraction peak overlap with biomimetic hydroxyapatite. In this study, we present a simple and reproducible indirect method to assess OCP phase purity based on the bulk Ca/P ratio after controlled calcination and quantitative phase analysis of the resulting high-temperature phases. We demonstrate that phosphate evaporation during calcination can significantly bias the calculated Ca/P ratio and show that stabilizing the furnace atmosphere using sacrificial monetite effectively suppresses this effect. At 1000°C, the method yields stable and reproducible OCP phase purity values over extended dwell times, making it suitable for both research and quality control applications.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatially differentiated byssus-related responses of the mussel foot to iron stimulation inform bioinspired adhesive fabrication.","authors":"Shuimei Li, Ruoxuan Zhao, Shuangyue Li, Qing Fang, Ao Liu, Yanan Di","doi":"10.1016/j.actbio.2026.10.004","DOIUrl":"https://doi.org/10.1016/j.actbio.2026.10.004","url":null,"abstract":"<p><p>Marine mussels fabricate durable underwater adhesives through coordinated precursor production, secretion, and metal-mediated assembly, yet the organization of these events within the foot remains poorly understood. In this study, anatomical, transcriptional, histochemical, and PBS-extractable protein analyses were integrated to characterize the foot of Mytilus coruscus under contrasting high- and low-concentration FeCl₃ conditions (Fe1 and Fe2). The foot exhibited regional specialization. Plaque glands were concentrated distally, several Mfp transcripts were enriched in distal layers, PTMP transcript abundance was highest proximally, and preCOL-P showed its highest basal abundance in the middle region. Fe2 elicited a broad preCOL-P response across most regions and a localized increase in nitroblue tetrazolium-glycinate-positive area in the middle foot, whereas Fe1 was associated with distinct regional changes in collagen distribution and PBS-extractable band profiles. Foot tissues and collected secreted fractions also showed non-equivalent banding patterns, demonstrating that the secreted material did not simply mirror the tissue-extractable pool. Together, the divergence among transcriptional, histochemical, and protein-extractability patterns supports a working model in which early precursor-related processes are spatially separated yet functionally coordinated along the foot prior to final byssal assembly. These findings suggest testable design principles for bioinspired underwater adhesives based on spatial precursor management and controlled activation, while providing a framework for future studies to determine how early regional processing is translated into mature byssus composition and performance. STATEMENT OF SIGNIFICANCE: Marine mussel adhesion is well characterized at the level of mature byssal chemistry, but the spatial organization of precursor processing within the foot remains unclear. Using the non-model marine mussel Mytilus coruscus, this study integrates regional anatomy, targeted transcription, histochemistry, and PBS-extractable protein profiling to identify organ-scale spatial differentiation of early byssus-related processing. The middle foot emerges as a candidate zone for precursor conditioning and protein-state reorganization, while contrasting FeCl₃ conditions reveal region-dependent responses shaped by physicochemical context and tissue organization. Beyond providing a spatial framework for byssal processing in a non-model biomaterials system, these findings suggest testable principles for precursor compartmentalization and controlled activation, and provide a basis for future validation in mature byssus.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}