ACS Biomaterials Science & Engineering最新文献

{"title":"Surface Functionalization of Thermoplastic Polyurethane Scaffolds to Enhance Microparticle Attachment.","authors":"Megan C Welch, Courtney K Rowe, Kelly A Burke","doi":"10.1021/acsbiomaterials.6c01093","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.6c01093","url":null,"abstract":"<p><p>While the use of polymer micro- and nanoparticles for drug delivery has been demonstrated for diverse biomedical applications, not all techniques have allowed for the precise localization of the drug that is needed to support surrounding tissues. Herein, we report a biocompatible thermoplastic polyurethane silk fibroin composite drug delivery platform for localized drug release. The work leverages two distinct materials, combining the biocompatibility of silk fibroin protein particles as a drug carrier with the modularity of a thermoplastic polyurethane scaffold, whose mechanical properties are tuned by composition. Two different particle attachment strategies were investigated; a Michael addition reaction was found to result in a high number of particles attached and a more complete surface coverage than carbodiimide coupling that is often employed with silk-based materials. The attachment of silk fibroin microparticles allows localized delivery of molecules, and the incorporation of poly(tetrahydrofuran) (pTHF) into polyurethane was found to tailor phase separation of the hard and soft segments that, in turn, affects the crystallinity and stiffness of the scaffold. The hard segment crystallinity of unprocessed powders (range: 16.26-35.51%) and slow-cooled films (range: 9.04-37.29%) increased as the pTHF content increased, indicating an increase in phase separation. The Young's modulus of thermoplastic polyurethanes (TPUs) also increased with increasing pTHF, from 9.02 to 14.49 MPa. In vitro cytocompatibility testing with human dermal fibroblasts showed >85% viability and no significant changes in cell growth with respect to composition. This platform demonstrates a promising strategy by combining two distinct materials to provide localized drug delivery with potential application for longer-term biocompatible medical implants.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163593","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":"Copper Peroxide Nanodots Encapsulated in a Metal–Organic Framework as H2O2 Self-Supplying Agents for Enhanced Antibacterial Activity and Wound Healing","authors":"Yulan Zhao,&nbsp;Quan Xu,&nbsp;Shijie Zheng,&nbsp;Yi Liu,&nbsp;Zhiyong Song,&nbsp;Heyou Han","doi":"10.1021/acsbiomaterials.6c00345","DOIUrl":"10.1021/acsbiomaterials.6c00345","url":null,"abstract":"<p>Drug-resistant bacterial infections rank among the most critical public health threats across the globe. The development of novel antibiotics falls considerably behind the rise of bacterial resistance. The advancement of nanotechnology offers novel opportunities to address the challenges posed by drug-resistant bacterial infections. In recent years, copper-based nanomaterials have gained widespread application in chemodynamic therapy (CDT) due to their favorable nanoenzymatic activities. However, their therapeutic efficacy is seriously constrained by the insufficient H₂O₂ supply and overexpressed glutathione (GSH) within the infected wound microenvironment. Therefore, a H₂O₂ self-supplying and GSH-depleting nanosystem (CuO₂@ZIF-8) was rationally constructed by simply encapsulating copper peroxide (CuO₂) within a zeolitic imidazolate framework-8 (ZIF-8). Under the acidic microenvironment of the infection sites, ZIF-8 underwent degradation to liberate Zn²⁺ ions, which exhibited potent antibacterial activity. Meanwhile, after being degraded, ZIF-8 released CuO₂, which in the slightly acidic infected microenvironment decomposed to generate H₂O₂ and Cu²⁺. The released Cu²⁺ then catalyzed the H₂O₂ into highly toxic hydroxyl radicals (·OH), thus achieving a great antibacterial effect between CDT and Zn²⁺. In addition, Cu²⁺ could be reduced to Cu⁺ by the overexpressed GSH, further enhancing the efficacy of CDT. In vitro antibacterial assay showed that due to the antibacterial effect of CDT and Zn²⁺, the antibacterial rate of CuO₂ @ ZIF-8 reached as high as 98.8%, which was significantly superior to that of ZIF-8 or CuO₂ used alone. In vivo assay showed that CuO₂ @ ZIF-8 had good antibacterial effects and excellent wound healing with great in vivo biosafety. In conclusion, the CuO₂ @ ZIF-8 nanoplatform developed in this work has considerable promise for future biomedical applications.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"12 10","pages":"5515–5526"},"PeriodicalIF":6.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954549","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":"Biomimetic Mineralized Capsules for Haematococcus pluvialis Clustering and Functional Regulation","authors":"Peihan Kang,&nbsp;Yunyang Zhang,&nbsp;Xiangdong Kong,&nbsp;Ruibo Zhao","doi":"10.1021/acsbiomaterials.6c00751","DOIUrl":"10.1021/acsbiomaterials.6c00751","url":null,"abstract":"<p>Astaxanthin is a high-value ketocarotenoid with potent antioxidant activity and wide applications in nutraceutical, cosmetic, and aquaculture industries. The green microalga <em>Haematococcus pluvialis</em> represents the most promising natural source; however, its efficient production requires precise control of growth and stress conditions, while free cells remain susceptible to environmental and mechanical stress. Hydrogel encapsulation offers a protective microenvironment, yet conventional alginate systems are limited by poor mechanical stability and uncontrolled swelling. Here, we report calcium alginate-based biomimetic mineralized core-shell capsules for the encapsulation, cultivation, and high-light-induced astaxanthin production of <em>H. pluvialis</em>. Capsules were fabricated by ionic crosslinking of alginate containing KH₂PO₄ with a CMC/CaCl₂ precursor solution, enabling in situ calcium phosphate formation within the capsule shell. Comprehensive characterization confirmed successful mineralization, reduced swelling, enhanced inorganic content, and improved mechanical strength. Encapsulated cells exhibited sustained growth and metabolic activity under moderate light without cytotoxic effects. Upon high-light exposure, both free and encapsulated cells showed a characteristic transition from green to red, accompanied by a significant increase in astaxanthin content. Notably, astaxanthin accumulation was comparable to that of controls. This study establishes a scalable encapsulation strategy that enhances structural stability without compromising biological function, offering potential for industrial microalgal cultivation and astaxanthin production.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"12 10","pages":"5380–5389"},"PeriodicalIF":6.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056576","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":"Microstructural Anisotropy in Bone-Mimetic Silk Constructs Promotes Self-Mineralization.","authors":"Anyelo R Diaz, Yunteng Cao, Liliana Liverani, Aldo R Boccaccini, Benedetto Marelli, Chiara E Ghezzi","doi":"10.1021/acsbiomaterials.6c00931","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.6c00931","url":null,"abstract":"<p><p>Understanding how organic matrix architecture regulates biomineralization remains a central challenge in mineralized tissue regeneration. Emerging evidence highlights the importance of coupled phenomena, including nanoconfinement, ionic and pH regulation, and hierarchical structural remodeling, in directing mineral formation. Silk fibroin (SF) is a versatile structural protein widely used in biomaterials due to its tunable mechanics, scalable processing into micro- and nanoscale constructs, controllable biodegradation, and ability to support cell infiltration and tissue integration, including in bone. However, despite its favorable biological properties, SF exhibits limited intrinsic self-mineralization in physiological fluids, restricting its mechanical reinforcement and osteogenic potential. In this study, we engineered SF scaffolds with controlled microstructure and anisotropy and incorporated bioactive inorganic phases, nano-hydroxyapatite (HA) or 45S5 bioactive glass (BG) to promote self-directed mineralization. Scaffolds were evaluated in simulated body fluid under static and dynamic conditions to assess mineral formation and distribution. Isotropic architectures supported more uniform, volumetric mineral integration, whereas anisotropic scaffolds promoted preferential surface mineral deposition. Incorporation of HA or BG significantly enhanced mineralization, leading to the formation of carbonate-substituted hydroxyapatite (CHA). These compositional and structural effects translated into marked improvements in compressive mechanical properties. Collectively, these findings demonstrate that synergistic control over scaffold architecture and bioactive cargo can direct in situ mineralization, enabling the design of silk-based constructs with enhanced mechanical performance and potential for bone regeneration.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163303","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":"Bioenergetic and Meniscus-Inspired Anisotropic Hydrogel Scaffolds Loaded with Synovial Mesenchymal Stem Cells for Enhanced Meniscus Tear Repair.","authors":"Yixi Li, Lei Liu, Dan Zhou, Saijiao Lan, Lingtian Lu, Zijie Zhang, Lei Zhao, Jian Zhu, Xiang Zhang, Wenping Pan, Fang Wang, Hongmei Liu, Decheng Wu","doi":"10.1021/acsbiomaterials.6c00999","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.6c00999","url":null,"abstract":"<p><p>Meniscal tears have limited spontaneous healing due to poor vascularization and intrinsic repair capacity, often leading to post-traumatic osteoarthritis. Current clinical treatments fail to restore native meniscal structure and function, necessitating advanced regenerative strategies. Tissue-engineered scaffolds offer promise, yet conventional designs lack the anisotropic architecture and cannot mitigate the oxidative injury microenvironment. Herein, we developed a meniscus-inspired anisotropic hydrogel scaffold incorporating succinate for bioenergetic regulation and loaded with synovial mesenchymal stem cells (SMSCs) for repair of red-red and red-white transitional zones. The anisotropic structure was fabricated via freeze-casting to mimic native meniscal alignment, while succinate modification enabled bioenergetic regulation by reducing intracellular ROS levels, preserving mitochondrial homeostasis, and maintaining cellular energy status, thereby enhancing SMSC proliferation and migration. The scaffold improved SMSC behavior in vitro and promoted fibrocartilage-like meniscal repair while attenuating cartilage degeneration in a rabbit tear model. This bioenergetic, biomimetic scaffold integrates structural anisotropy, stem cell therapy, and metabolic regulation, representing a promising strategy for fibrocartilage-like meniscal repair and attenuation of secondary articular cartilage degeneration.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134017","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":"Tailoring the Wound Microenvironment: Programmable Hydrogel Fibers for Adaptive Tissue Repair.","authors":"Yibin Huang, Jun Zhu, Yize Zhang, Xiaoli Li, Bin Chu, Boning Li","doi":"10.1021/acsbiomaterials.6c00899","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.6c00899","url":null,"abstract":"<p><p>Wound healing and tissue reconstruction following a skin defect, particularly the restoration of full skin function and appearance, remain a major clinical challenge. Traditional hydrogel dressings face limitations in mechanical strength, poor permeability, and a lack of multifunctionality, making them inadequate for meeting the dynamic demands of the wound healing process. Fibrous hydrogels offer a compelling alternative by combining the high-water content and biocompatibility of hydrogels with the anisotropic structure and design flexibility of fibers, allowing them to closely mimic native tissue architecture. In this review, we introduce a three-tier framework based on structural, functional, and responsive programmability to systematically classify and evaluate programmable hydrogel fibers for wound healing. Recent advances in structural design strategies, functionalization approaches, and biomedical applications are summarized. Notably, this review uniquely integrates structural design, functional strategies, and translational potential within a unified programmability framework, while critically examining current limitations and challenges in clinical translation. Despite these obstacles, hydrogel fibers hold considerable promise for personalized tissue engineering and functional regeneration.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134009","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":"Cell-Laden 3D-Bioprinted Artificial Skin Grafts for Tissue Engineering Wound Healing.","authors":"Xiaofeng Wang, Zhichao Ye, Jiang Chen, Zichun Gu, Weiqiang Tan, Jianing Yan","doi":"10.1021/acsbiomaterials.6c01007","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.6c01007","url":null,"abstract":"<p><p>In recent years, with the rapid advancement of tissue engineering and regenerative medicine, cell-laden 3D bioprinting has emerged as a key driving force in the construction of functional artificial skin grafts. By precisely controlling the three-dimensional spatial distribution of cells, biomaterials, and growth factors, this technology can replicate the complex hierarchical structure and physiological functions of native skin. This review aims to provide a comprehensive overview of the key research advances recently achieved in the field of cell-laden 3D bioprinting of artificial skin. In this review, we summarize the physiological architecture of native skin, the selection and enhancement of common bioinks, strategies to improve cellular responses during printing, analysis of 3D bioprinting technologies and fabrication approaches, and the opportunities and challenges of clinical translation, aiming to provide optimized insights for the preparation of cell-laden 3D bioprinted artificial skin grafts. It systematically examines the biomimetic structural principles of engineered skin, innovative bioink formulations and their cytocompatibility, the evolution of 3D bioprinting technologies and improvements in resolution, breakthroughs in skin tissue functionalization including vascularization, innervation, appendage and pigmentation regeneration, the opportunities and challenges facing clinical translation and future perspectives.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149133959","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":"Nanozymes in Upper Respiratory Tract Infections: Catalytic Mechanisms, Current Evidence, and Emerging Theranostic Strategies.","authors":"Jingjing Huang, Zhuyu Han, Yang Liu, Jiechao Yang, Jiafu Liu, Yiwen Tao, Fangyong Zhu, Zelda Ziyi Zhao","doi":"10.1021/acsbiomaterials.6c01534","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.6c01534","url":null,"abstract":"<p><p>Objective: This review evaluates nanozymes as catalytic biomaterials for upper respiratory tract infection (URTI)-related diagnosis, therapy, and prevention, with particular attention to differences in the maturity of evidence across these applications. The anatomically adjacent middle ear is also considered as a relevant model of biofilm-associated infection and barrier-limited local delivery. Methods: We reviewed studies involving respiratory pathogens, sinonasal disease, pharyngitis, intranasal vaccination, and otitis media. Evidence from other disease models was included only when it addressed a specific materials problem relevant to the upper airway, such as catalytic regulation, biofilm disruption, mucus transport, or local retention. Results: Diagnostic applications currently have the strongest evidence base, particularly for catalytic signal amplification in respiratory pathogen assays. In contrast, therapeutic evidence remains sparse and predominantly preclinical, with direct treatment studies in URTIs especially limited. Preventive applications are less extensively studied and are represented mainly by proof-of-concept intranasal influenza vaccination. Across these applications, performance depends on catalytic activity in protein- and mucus-rich media, biofilm penetration, control of pro-oxidant and antioxidant effects, and delivery to the intended anatomical site. Evidence from other anatomical sites provides useful design principles but should not be interpreted as evidence of efficacy in URTIs. Conclusion: Nanozymes should currently be regarded as engineerable catalytic biomaterials rather than clinically established anti-infective platforms for URTIs. Translation will require reproducible activity in airway-relevant environments, effective site-specific delivery, appropriate safety margins, and validation in disease-relevant models.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134046","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":"Ferrocene-Cystamine Conjugate Encapsulated Hyaluronic Acid Nanomicelles with Sequential pH/GSH Responsiveness for Synergistic Chemodynamic-Immunotherapy.","authors":"Zheng Cheng, Yibo Huo, Chunyu Qu, Xu Zhu, Rui Yan, Zhiqiang Wang, Xiaodan Wu, Hui Zhang, Yingxue Jin","doi":"10.1021/acsbiomaterials.6c01030","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.6c01030","url":null,"abstract":"<p><p>Metastasis and postoperative recurrence of malignant tumors remain critical obstacles that undermine clinical therapeutic efficacy. Traditional chemodynamic therapy (CDT) is plagued by three inherent, hard-to-resolve drawbacks: abundant intratumoral glutathione (GSH) quenches reactive oxygen species; robust systemic antitumor immunity fails to be activated; and unbound iron catalysts initiate off-target Fenton cascades within healthy tissues, inducing systemic oxidative injury and toxic side effects. To address these critical barriers, we rationally designed a bifunctional ferrocene-cystamine conjugate (FD) and encapsulated this payload within amphiphilic hyaluronic acid-cinnamaldehyde (HA-CA) Schiff-base nanomicelles, thereby fabricating a nanoplatform designed to target HA receptors (presumably CD44) with sequential pH/GSH responsiveness. The resultant HA-CA@FD nanomicelles attain a high FD loading efficiency of 36 ± 2% and display excellent colloidal stability under physiological environments. Once exposed to the acidic, reductive tumor microenvironment, the nanocarrier undergoes structural dissociation to liberate loaded FD. The released FD depletes intracellular GSH through two cooperative redox routes-disulfide bond cleavage and reversible Fe2+/Fe3+ cycling-while simultaneously generating massive cytotoxic hydroxyl radicals (·OH) to elicit potent immunogenic cell death. In vitro biological characterizations validate that the nanomedicine raises the proportion of mature dendritic cells to 66.7% and elevates the percentage of anti-tumor M1-type macrophages from 3.9 to 48.2%. In vivo assays using bilateral 4T1 tumor-bearing mice reveal that intratumoral injection of HA-CA@FD diminishes primary tumor weight by 67% and abscopal contralateral tumor weight by 52%. This therapeutic regimen substantially augments intratumoral infiltration of CD4+/CD8+ effector T cells and diminishes immunosuppressive regulatory T cell (Treg) populations, accompanied by elevated memory T-cell signatures that suggest potential for establishing durable antitumor immune responses. This modular, biocompatible biopolymer nanosystem surmounts the core limitations of classic CDT agents, furnishing a straightforward, translation-ready nanoengineering paradigm for precision combinatorial chemo-dynamic-immunotherapy against solid tumors.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126109","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":"Evidence of a Calcium-Chelating Protein Involved in Silkworm Silk Fiber Spinning.","authors":"Benjamin J Allardyce, Stuart M Linton, Dilendra Wijesekara, Martin Zaki, Chris Holland, Heena Faulder, Rangam Rajkhowa","doi":"10.1021/acsbiomaterials.6c01458","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.6c01458","url":null,"abstract":"<p><p>Silk cocoons consist primarily of fibroin and sericin but also contain hundreds of uncharacterized proteins with unknown biological function. This study characterizes a silk extract produced using a recently developed extraction method that preserves native protein structure and composition, revealing proteins that are likely lost or overlooked using conventional extraction approaches. As expected, it extracted the primary fibroin and sericin proteins, but unexpectedly, the extract was dominated by sericin 3 and an 18.4 kDa protein with unknown function. We propose two possible functions: firstly, that it facilitates sericin 3 expression or secretion and secondly, that it acts as a \"calcium chelator\", acting as a molecular trigger for fiber formation. In addition, analysis of the theoretical fractional charges of the primary silk proteins predicts that sericin 3 and fibrohexamerin (P25) transitions from negatively charged to neutral charge at the pH in the anterior silk gland, suggesting a previously unrecognized mechanism for regulating protein interactions during spinning. Together, these findings point towards an explanation for how silkworms can store silk proteins at high concentrations in the gland without aggregation then selectively destabilize the mixture on demand during fiber spinning. This understanding could have significant implications for the development of regenerated silk feedstocks for artificial silk spinning.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100977","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}