Acta biomaterialia最新文献

{"title":"The crescent cross-section and dichotomous chitin structure make the proboscis of butterflies and moths a hydraulic spring.","authors":"Taiyo Yoshioka, Tatiana Stepanova, Artis Brasovs, Vincent Y Blouin, Charles E Beard, Peter H Adler, Konstantin G Kornev","doi":"10.1016/j.actbio.2025.09.034","DOIUrl":"10.1016/j.actbio.2025.09.034","url":null,"abstract":"<p><p>The proboscis of butterflies and moths is made of two C-shaped tubular strands, each with a crescent cross-section. Together, they form a food canal for fluid uptake. Each strand is sealed at the free end and blood is pumped in at the head. The accepted scenario for proboscis uncoiling assumes that intrinsic muscles deform the proboscis walls like fingers pressing a bicycle tire, decreasing the cross-sectional area and displacing blood that pushes the external walls outward, as does the air in the tire. This scenario requires the external walls of the strands to be softer than the food canal walls. We tensile-tested the proboscis of Manduca sexta hawk moths and discovered that the food canal walls are softer than the external walls, contradicting the accepted scenario. We hypothesize that the proboscis works as a hydraulic spring, requiring no muscular action to uncoil. The model supports this hypothesis: the pump pressurizes the blood, which pushes on the food canal walls, buckling them inward. The crescent edges along which the strands are connected are free to move loosening the coil and unrolling the proboscis. Using X-ray scattering and assuming the same cuticle matrix for both walls of the crescent strands, we showed that the difference in cuticular stiffnesses is achieved through a unidirectional ordering of α-chitin nanofibrils aligned mutually orthogonal in the food canal and external walls of the proboscis, making it a transversely anisotropic tubular composite and preventing buckling. This arrangement opens new engineering opportunities for multifunctional fiber-based hydraulic springs in micromachines. STATEMENT OF SIGNIFICANCE: Our discovery replaces the conventional textbook scenario of proboscis uncoiling in the manner of a tape measure triggered by muscles and blood. We emphasize the importance of the crescent-shaped cross-section, enabling the uncoiling of the proboscis by low blood pressure and recoiling by the deformed crescent bows. Small- and wide-angle synchrotron X-ray scattering revealed the dichotomous chitin nanocrystal orientation of the proboscis cuticle. Nanocrystals differentially reinforce the internal and external walls of the proboscis that experience different mechanical stresses. This hydraulic spring mechanism in proboscises can be used to engineer microfluidic devices that require coiling-uncoiling.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182488","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":"Micropore-forming photocurable tissue adhesive promotes cell infiltration for wound healing.","authors":"Akihiro Nishiguchi, Miho Ohta, Debabrata Palai, Hana Yasue, Pritha Sarkar, Hiyori Komatsu, Tetsushi Taguchi","doi":"10.1016/j.actbio.2025.09.033","DOIUrl":"10.1016/j.actbio.2025.09.033","url":null,"abstract":"<p><p>Tissue adhesives suffer from a trade-off relationship between tissue adhesion strength for long-term wound closure and degradation rate for tissue regeneration, which results in the suppression of postoperative wound healing. Here, we report the development of micropore-forming tissue adhesives with an enhanced cell infiltration capacity for tissue regeneration. By leveraging the phase-separation behavior of gelatin modified with hydrogen-bonding moieties, bicontinuous and micropore-forming photocrosslinked hydrogels were developed. The photocrosslinked hydrogels are injectable and enzymatically degradable, showing high tissue adhesive strength against tissues of the collagen membrane, heart, stomach, and large intestine. Moreover, the microporous structure of the hydrogels could enhance fibroblast infiltration through the micropores. These hydrogels could also induce hair follicle regeneration and wound healing in skin incision wound models. This tissue adhesive has enormous potential for promoting wound healing and preventing postoperative complications. STATEMENT OF SIGNIFICANCE: Our study furthers the development of tissue adhesives to overcome a trade-off relationship between tissue adhesion strength for long-term wound closure and degradation rate for tissue regeneration. Micropore-forming tissue adhesives with an enhanced cell infiltration capacity was developed which can be used for tissue regeneration. By leveraging the phase-separation behavior of gelatin modified with hydrogen-bonding moieties, bicontinuous and micropore-forming photocrosslinked hydrogels were developed. The photocrosslinked hydrogels with micropores are injectable and enzymatically degradable, showing high tissue adhesive strength and cell infiltration. This tissue adhesive has enormous potential for promoting wound healing and preventing postoperative complications.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182527","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":"Reactive oxygen species-responsive sulfated polysaccharide-based nanogels for ischemic stroke: A precision therapy through pathological microenvironment modulation.","authors":"Dingfu Wang, Dan Li, Xiaolin Liu, Shixin Wang, Yile Fan, Ling Lu, Chuanbin Shen, Chunxia Li","doi":"10.1016/j.actbio.2025.09.031","DOIUrl":"10.1016/j.actbio.2025.09.031","url":null,"abstract":"<p><p>Thrombolytic therapy for cardiovascular and cerebrovascular diseases is significantly limited by the short half-life, inadequate targeting specificity, and hemorrhagic complications of conventional therapeutic agents. To overcome these challenges, we developed a dual-functional nanogel (PGS-SP@UK) that integrates P-selectin-mediated thrombus targeting with ROS-responsive drug release. Taking advantage of the P-selectin targeting capability of polyguluronate sulfate (PGS), we synthesized the sulfated polysaccharide with selenocystamine and pinacol phenylboronate (PBAP) to construct an amphiphilic copolymer capable of encapsulating urokinase (UK). Notably, this nanogel exhibited H₂O₂-triggered UK release (85.79 %) while maintaining great stability under physiological conditions. In vitro studies confirmed its neuroprotective effects through modulation of the ferroptosis signaling pathway in an OGD/R-induced model. In vivo studies revealed efficient blood-brain barrier penetration and thrombus-specific accumulation, achieving 84.3 % recovery in cerebral infarct area through synergistic thrombolysis and oxidative stress mitigation. Our study presents an innovative drug delivery system with significant potential for clinical ischemic stroke treatment. STATEMENT OF SIGNIFICANCE: Conventional thrombolytic agents suffer from poor targeting specificity and severe bleeding complications, limiting their clinical efficacy in ischemic stroke treatment. We designed a dual-functional nanogel (PGS-SP@UK) that uniquely integrates P-selectin-mediated active targeting with ROS-responsive drug release mechanisms. This innovative design represents a system to combine polyguluronate sulfate-based thrombus recognition with oxidative stress-triggered urokinase liberation. Our nanogel achieves unprecedented selectivity through dual targeting: bioactive targeting via P-selectin binding and microenvironmental responsiveness to pathological ROS levels. In vivo validation demonstrated exceptional therapeutic outcomes with 84.3 % cerebral infarct recovery while eliminating systemic hemorrhagic risks. This breakthrough establishes a new therapeutic paradigm that transcends current limitations through synergistic thrombolysis and neuroprotection, offering transformative potential for precision medicine in thrombotic disorders.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180822","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":"A photodriven nano-extinguisher alleviates acute bacterial infections via toll-like receptor 4-regulated immune response.","authors":"Jie Li, Ji- Yu Che, Hong- Yu Wang, Rui-Yao Wang, Si-Yuan Huang, Zhong-Ming Wu, Xin-Ge Zhang","doi":"10.1016/j.actbio.2025.09.032","DOIUrl":"10.1016/j.actbio.2025.09.032","url":null,"abstract":"<p><p>Pattern recognition receptors on immune cells play essential roles in detecting pathogen-associated molecular patterns and initiating downstream immune defense cascades. Toll-like receptor-4, a key member of the PRR family, regulates macrophage-mediated innate immune responses; however, its dysregulation due to excessive activation often exacerbates inflammatory processes. Herein, we report a Toll-like receptor-4-targeted nano-extinguisher designed to combat acute pneumonia caused by multidrug-resistant Pseudomonas aeruginosa infection. This innovative nanoplatform integrates bacterial capture ligands, a photothermal agent, and a Toll-like receptor-4 signaling inhibitor. Upon near-infrared light irradiation, the nano-extinguisher generates localized hyperthermia, leading to bacterial death through disruption of membrane integrity. Moreover, the thermal-triggered release of the Toll-like receptor-4 signaling inhibitor enables dual immunomodulation by simultaneously regulating macrophage polarization and scavenging reactive oxygen species. The nano-extinguisher significantly alleviated the pathological progression of infection-induced acute pneumonia in our experiments. By combining photothermal antibacterial activity with spatiotemporal immunomodulation, this nanoengineered system offers a promising translational strategy for the treatment of acute bacterial infections and concurrent mitigation of Toll-like receptor-4-mediated immunopathology. STATEMENT OF SIGNIFICANCE: TLR4, which is crucial for initiating innate immunity via pathogen detection, often exacerbates inflammation when hyperactivated. We developed TLR-4-targeted nano-extinguishers to combat multidrug-resistant Pseudomonas aeruginosa-induced pneumonia. This system integrates bacterial capturing, photothermal therapy, and TLR-4 inhibition. Photo-driven localized hyperthermia disrupts bacterial membranes while thermally releasing the inhibitor, thereby achieving simultaneous macrophage polarization modulation and reactive oxygen species scavenging, effectively mitigating infection-induced pneumonia. By integrating precision photothermal sterilization with spatiotemporal immunoregulation, our nanoengineered strategy addresses both bacterial eradication and TLR-4-mediated immunopathology, offering translational potential for the treatment of acute infections.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180784","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":"Broad-spectrum antibacterial peptidopolysaccharides for targeted therapy of a drug-resistant bacterial liver abscess.","authors":"Luofeng Yu, Jingjie Chen, Pandi Peng, Rui Ding, Kun Wang, Cuiping Yan, Mengjie Sun, Zhaoqing Du, Cyrille Boyer, Peng Li","doi":"10.1016/j.actbio.2025.09.030","DOIUrl":"10.1016/j.actbio.2025.09.030","url":null,"abstract":"<p><p>Liver abscesses, which are caused primarily by bacteria, represent a significant clinical challenge. Current therapeutic approaches rely heavily on antibiotics, and their efficacy is constrained by the poor drug delivery efficiency and the escalating resistance of bacteria. This study explores a hepatotropic pullulan-based peptidopolysaccharide engineered for liver targeting and broad-spectrum antibacterial activity. With an optimized balance between antibacterial activity and hemocompatibility, copolymer PP11 demonstrated remarkable antibacterial efficacy against all kinds of ESKAPE pathogens, including several important multi-drug resistance (MDR) strains, e.g., vancomycin-resistant Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, tetracycline-resistant and extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E. coli). Mechanistic studies demonstrated that PP11 is capable of aggregating on bacterial cell membranes and then disrupting membrane integrity. Unlike conventional antibiotics, PP11 showed low susceptibility to induce bacterial resistance owing to this membrane-damaging mechanism. Furthermore, PP11 exhibited pronounced hepatotropic targeting properties both ex vivo and in vivo. The therapeutic efficacy of PP11 was verified in a murine liver abscess model induced by ESBL-E. coli, where it evinced potent bacterial elimination with a log reduction above 3 (> 99.9 % killing) and inflammation-suppressing effects characterized by IL-6 and IL-1β cytokines down-regulation. A four-week animal biosafety study validated that PP11 was non-toxic to major organs (heart, liver, spleen, lungs, and kidneys), particularly unaffected hepatic and renal functions. These results highlight the potential of pullulan-based peptidopolysaccharides as a promising hepatotropic targeting platform, establishing a pioneering exploration for customized antibacterial therapy of hepatic infections. STATEMENT OF SIGNIFICANCE: Liver abscesses pose a pressing clinical concern, especially in the face of rising antibiotic resistance and poor drug delivery efficiency to hepatic tissues. This study introduces a pullulan-based peptidopolysaccharide, PP11, that uniquely combines potent broad-spectrum antibacterial activity (including efficacy against multidrug-resistant (MDR) ESKAPE pathogens) with targeted liver delivery. Unlike conventional antibiotics, PP11 directly disrupts bacterial membranes, minimizing the risk of resistance development. Its selective hepatotropic targeting, demonstrated therapeutic effectiveness in a murine liver abscess model, and favorable safety profile position PP11 as a promising and innovative platform for precision antibacterial therapy in hepatic infections.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152320","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":"Corneal stiffness mapping that accounts for anisotropic properties of corneal tissue.","authors":"Yuanwan Lou, Chenyan Wang, Yabo Ye, Shuiyang Shen, Fangjun Bao, Junjie Wang, Ahmed Elsheikh","doi":"10.1016/j.actbio.2025.09.028","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.09.028","url":null,"abstract":"<p><p>This study introduces Stress-Strain Index (ASSI) maps that quantify and visualize corneal stiffness while accounting for anisotropy driven by collagen fibril orientation. Our earlier efforts to produce SSI maps assume isotropy and overlook directional stiffness variations critical to accurate modelling and diagnosis. By integrating fibril distribution data with finite element modelling, ASSI maps were developed for both healthy and keratoconic corneas. Clinical case studies demonstrated the maps' ability to capture age-related changes, surgical impacts, and disease progression. ASSI maps enhance understanding of corneal biomechanics and provide a foundation for more precise, personalized interventions in ophthalmology. This innovation may support improved diagnostic sensitivity, optimized treatment planning, and more equitable care through accessible, in-vivo biomechanical mapping technologies. STATEMENT OF SIGNIFICANCE: •This study introduces a stiffness mapping technique that accounts for the anisotropic properties of corneal tissue and directly incorporates the influence of collagen fibril distribution on biomechanical behavior. •By integrating numerical modeling, microstructural characterization, and clinical data, the proposed method enables estimation of biomechanical changes following corneal surgery, and supports monitoring of keratoconus progression. •The technique offers a versatile platform for interdisciplinary research at the intersection of biomechanics and clinical ophthalmology, highlighting the role of engineering in advancing personalized medicine.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115354","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 engineering-reinforced hypoxia-preconditioned exosome-integrated hydrogel delays intervertebral disc degeneration via the PPARγ-autophagy axis.","authors":"Guantong Sun, Mingzhi Liu, Qingyu Yao, Julong Lu, Mengxuan Wang, Hongtao Ge, Wentao Liu, Chuanli Zhou","doi":"10.1016/j.actbio.2025.09.027","DOIUrl":"10.1016/j.actbio.2025.09.027","url":null,"abstract":"<p><p>The local delivery of exosomes (Exo) through hydrogels is considered an effective method for treating intervertebral disc degeneration (IVDD). Based on the limitations of the hypoxic microenvironment in intervertebral disc (IVD), this study adopted a series of engineering methods to enhance the therapeutic efficacy of Exo and achieve sustained release effects. Specifically, by applying hypoxic preconditioning (HP), we strengthened the ability of Exo to induce extracellular matrix (ECM) synthesis and anti-apoptotic effects in nucleus pulposus cells and annulus fibrosus cells within inflammatory microenvironments, while simultaneously encapsulating them in a collagen methacrylate (COMA) hydrogel to mimic the native physiological state of IVD and achieve optimal therapeutic outcomes. HP-Exo-loaded COMA regulate ECM degradation and apoptosis through autophagy. Additionally, this study introduced si-peroxisome proliferator-activated receptor γ (PPARγ) into HP-Exo, whereby the engineered Exo within the hydrogel induced ECM regeneration and suppressed apoptosis via PPARγ-autophagy axis. Injecting HP-Exo@COMA into annulus fibrosus defects in IVDD rat models significantly promoted ​​structural-functional IVD repair​​, demonstrating the synergistic regeneration of both nucleus pulposus tissue and annulus fibrosus architecture. This strategy may provide a therapeutic approach to restore ​​postoperative IVD. STATEMENT OF SIGNIFICANCE: : A collagen methacrylate (COMA) hydrogel loaded with hypoxic preconditioning exosomes (HP-Exo) was developed for intervertebral disc (IVD) repair after discectomy. This hydrogel enabled the sustained release of HP-Exo while providing mechanical support. HP-Exo@COMA promotes coordinated regeneration of the nucleus pulposus and annulus fibrosus by activating the PPARγ-autophagy axis, thereby inducing extracellular matrix regeneration and inhibiting apoptosis. This study presents a novel therapeutic strategy for postoperative IVD repair.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103175","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":"Fibronectin composition and transglutaminase 2 cross-linking cooperatively regulate ovarian cancer cell adhesion in ECM-mimetic constructs.","authors":"Ning Yang, Ali Abbaspour, James M Considine, Stephanie M McGregor, Erin G Brooks, Alexandra Naba, Kristyn S Masters, Pamela K Kreeger","doi":"10.1016/j.actbio.2025.09.025","DOIUrl":"10.1016/j.actbio.2025.09.025","url":null,"abstract":"<p><p>The extracellular matrix (ECM) plays a crucial role in tumor progression. Here, we analyzed collagen I and cellular fibronectin (cFN) in normal omentum and metastatic omentum from high-grade serous ovarian cancer (HGSOC). The levels of both proteins were significantly elevated and collagen I fibers were significantly thicker in HGSOC metastases. Moreover, the ECM cross-linking enzyme transglutaminase 2 (TG2) was increased in omental metastases, where it is enzymatically active in the extracellular environment. This information was used to develop ECM constructs recapitulating these key changes, alone and in combination, to investigate their impact on HGSOC cell adhesion. To our knowledge, this is the first report using TG2 as a cross-linking agent to generate constructs from multiple ECM components. Low levels of HGSOC cell adhesion were observed on colIagen-only (coll) gels, while inclusion of cFN or plasma fibronection (pFN) increased cell adhesion. TG2-mediated cross-linking of colI/cFN hydrogels promoted HGSOC cell adhesion, while cross-linking of coll/pFN had no effect. Cell adhesion was dependent on ligand identity and fiber diameter. When fiber thickness was held constant, the inclusion of cFN led to greater HGSOC cell adhesion relative to pFN or coll, due to interactions of β1 integrins with the EDA and RGD domains of cFN. Meanwhile, when gel composition was held constant, HGSOC cell adhesion increased as fiber thickness was increased through modifications to gelation temperature. Combined, our results demonstrate how ECM changes associated with omental metastasis can support tumor progression and provide insights into methods to tailor biomaterials to support cell adhesion. STATEMENT OF SIGNIFICANCE: The ECM is dysregulated in solid tumors, with altered protein levels and physical organization. We modeled changes in collagen I, fibronectin, and transglutaminase 2 (TG2) observed in the omentum, the most common metastatic site of advanced ovarian cancer. While prior studies have examined ECM combinations through PEG-peptide gels or blends of native ECM, we report here the first use of TG2 to cross-link multiple ECM components and generate a fibrillar material. TG2 cross-linking increased fiber thickness, which supported increased tumor cell adhesion, with differential effects observed for cellular vs. plasma fibronectin. These results support the important role of the physical structure of the ECM in directing cellular behaviors and provide a new method of biomimicry to achieve this end.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103114","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":"Direct insights into synthesis, protein integrity, and blood microrheology of albumin microbubbles.","authors":"Tatiana M Estifeeva, Denis A Borozdenko, Arina V Papugaeva, Galina L Kalinichenko, Irina P Vlasova, Leonid I Gudzerov, Timur Aliev, Nikita A Krotkov, Alexey V Boltenko, Anna O Orlova, Anna M Nechaeva, Yaroslav O Mezhuev, Irina M Le-Deygen, Dmitry A Bunin, Vladislav S Petrovskii, Gennady B Khomutov, Matvei K Maksimov, Andrei E Lugovtsov, Alexander V Priezzhev, Igor I Potemkin, Dmitry A Gorin, Yulia G Gorbunova, Ekaterina V Skorb, Sviatlana A Ulasevich, Roman A Barmin, Polina G Rudakovskaya","doi":"10.1016/j.actbio.2025.09.026","DOIUrl":"10.1016/j.actbio.2025.09.026","url":null,"abstract":"<p><p>Albumin microbubbles (MB) were among the first ultrasound (US) contrast agents used clinically. However, they are believed to contain denatured protein motifs, which compromise their stability, hence, limit their diagnostic and therapeutic utility. This study investigates the protein integrity, cavitation dynamics during US-assisted synthesis, and blood microrheology of albumin MB to better understand and improve their performance. Using bovine serum albumin as the shell material, we found that complexation with either a small molecule or macromolecular additive increased MB yield and enhanced acoustic stability. Spectroscopic analysis showed that MB shell formation favors protein structures close to the native state, while more severely altered fractions remain excluded from the shell. High-speed imaging and cavitation activity profiling revealed that additive-containing solutions suppressed cavitation activity while promoting the formation of sub-50 µm MB precursors under synthesis-mimicking conditions, leading to higher MB concentrations. Blood microrheology tests confirmed that albumin-copolymer MB had minimal impact on red blood cell deformability, aggregation, and critical shear stress, while in vivo cardiac US imaging showed their strong echogenicity lasting over 5 min post-injection. Together, these findings highlight how fine-tuning MB shell composition ‒ combined with structural and functional evaluation ‒ advances the understanding needed to improve albumin MB application potential. STATEMENT OF SIGNIFICANCE: This work provides integrated analysis of albumin-coated microbubbles, correlating protein structural integrity, synthesis dynamics, and blood microrheology. By combining spectroscopy, high-speed imaging, and rheological profiling, we demonstrate that rational additive selection enables microbubble formulations with enhanced acoustic stability, supported by in vivo cardiac ultrasound imaging. Notably, we show that microbubble formation favors albumin molecules retaining structures close to the native state, challenging the prevailing assumption that albumin shells are irreversibly denatured during synthesis. These findings provide a basis for designing structurally stable protein-coated microbubbles for effective ultrasound use.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103151","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":"Interface before bulk: Mechanism-informed strategy for preventing postoperative adhesion based on polymer implants.","authors":"Zhen Zheng, Shengli Gao, Jingwen Liu, Yong Zhang","doi":"10.1016/j.actbio.2025.09.021","DOIUrl":"10.1016/j.actbio.2025.09.021","url":null,"abstract":"<p><p>Postoperative adhesions (POAs) are a pervasive and serious complication following surgery, representing a major clinical challenge across multiple specialties. Drawing upon a comprehensive review of recent literature, this article systematically re-examines the prevention mechanisms of POAs with a specific focus on anti-adhesion implants (AAIs). Through analyzing diverse biological, chemical, and physical studies at the tissue interface, we propose a conceptual framework that emphasizes the dominant role of the AAI-tissue interface in the initiation and progression of adhesions. Unlike conventional bulk-focused designs, this interface-driven approach targets early adhesion events for enhanced efficacy. In this framework, the interface properties of AAIs, such as anti-fouling, anti-inflammatory, and anti-fibrotic effects, are recognized as the primary determinants of anti-adhesion efficacy, while bulk properties, including mechanical strength, degradation kinetics, and compliance, serve as essential supportive factors to maintain and reinforce interface functionality. Additionally, we highlight recent advancements in polymer-based AAIs, including mechanistically informed surface modifications and bulk material optimizations, which collectively aim to enhance both interface performance and structural durability. This structured discussion not only synthesizes current findings but also establishes a guiding principle: that effective adhesion prevention should prioritize interface-driven design strategies, complemented by tailored bulk material engineering. STATEMENT OF SIGNIFICANCE: We present an \"interface-before-bulk\" design strategy that rethinks how polymer-based anti-adhesion implants (AAIs) are engineered to prevent post-surgery tissue adhesions, a pervasive surgical complication. Unlike conventional approaches that focus on an implant's bulk properties or passive barrier function, this approach emphasizes the implant-tissue interface as the critical determinant of success. By framing adhesion formation as a stepwise interface-driven process, we pinpoint key stages for intervention and highlight surface modifications (anti-fouling, anti-inflammatory, anti-fibrotic) that proactively disrupt adhesion pathways. This interface-first perspective, supported by appropriate bulk material properties, offers a new framework for designing AAIs with improved clinical efficacy, guiding a shift from passive barrier designs to proactive interface engineering.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093266","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}