[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-detail-40369-en":3,"doc-seo-40369-105":29,"detail-sidebar-cat-0-en-105":91},{"code":4,"msg":5,"data":6},0,"success",{"doc_id":7,"user_id":8,"nickname":9,"user_avatar":10,"doc_module":4,"category_id":11,"category_name":12,"doc_title":13,"doc_description":14,"doc_content":15,"file_id":16,"file_url":17,"file_type":18,"file_size":19,"view_count":20,"is_deleted":4,"is_public":20,"is_downloadable":20,"audit_status":20,"page_count":21,"language":22,"language_code":23,"site_id":24,"html_lang":23,"table_of_contents":25,"faqs":26,"seo_title":13,"seo_description":14,"update_tm":27,"read_time":28},40369,8796095462418,"Noah","https://ap-avatar.wpscdn.com/avatar/80000253c1241d02b47?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778826106357471780",7,"Healthcare","Injectable Silk Fibroin-Based Hydrogels with Ultrafast In Situ Gelation via an Unfolding-Aggregating Strategy for Osteoarthritis Treatment","Intra-articular hydrogel nanodrug delivery for osteoarthritis faces limitations from fabrication complexity and slow, unreliable gelation kinetics that reduce retention and therapeutic bioavailability. An injectable silk fibroin hydrogel is designed using a surfactant-induced unfolding–aggregating assembly to serve as a dual-drug carrier. Benzyldodecyldimethylammonium bromide triggers unfolding, exposes hydrophobic segments, and drives β-sheet nucleation/aggregation, enabling gelation in 4 s. The system loads core–shell methotrexate/chondroitin sulfate nanodrugs, modulating M1/M2 macrophage repolarization and shielding chondrocytes from inflammation. Rat OA models show suppressed disease progression and enhanced cartilage repair, supporting clinical potential.","[pubs.acs.org/Biomac](pubs.acs.org/Biomac)  Article   \nInjectable Silk Fibroin-Based Hydrogels with Ultrafast In Situ Gelation via an Unfolding-Aggregating Strategy for Osteoarthritis Treatment  \nYujun Wu,‡ Lingyu Qiu,‡ Xiatong Ou, Jingjing Tao, Min Zheng, Yan Huang, and Shumeng Bai*  \n Cite This: Biomacromolecules 2025, 26, 7447−7469  \nRead Online  \nACCESS  \n Metrics & More  \n Article Recommendations  \n*sı   \nSupporting Information  \nABSTRACT: Intra-articular injection of hydrogel-based nanodrug delivery systems is receiving considerable attention for the treatment of osteoarthritis (OA). Nevertheless, its therapeutic efficacy and reliability are severely hindered by fabrication proceduresand gelation kinetics, which subsequently exert significant influence on the retention efficiency and bioavailability of therapeutic nanodrugs within the articular cavity. In this study, the utilization of a surfactant-induced unfolding-aggregating assembly strategy is proposed to develop an injectable silk fibroin (SF)-based hydrogel as a dual-drug delivery system for OA treatment, fulfilling the demands of an easy fabrication process, ultrafast in situ gelation, and effective therapeutic outcomes. Under the induction of benzyldodecyldimethylammonium bromide (BDAB), SF molecules initially undergo unfolding from the native state to expose hydrophobic chain segments and then initiate the nucleation and aggregation of β-sheet structures, obviously reducing the energy barrier to achieve in situ gelation within 4 s. Furthermore, the BDAB-induced ultrafast in situ gelation technique is exploited to load core−shell nanodrugs consisting of methotrexate and chondroitin sulfate, thereby modulating M1/M2 macrophage repolarization and protecting chondrocytes from inflammatory invasion. In vivo rat OA models demonstrate that this injectable hydrogel system significantly suppresses the pathological progression of OA and promotes cartilage repair, supporting its potential clinical applications in the treatment of cartilage-related diseases.  \n1. INTRODUCTION 1β), tumor necrosis factor-α (TNF-α) and matrix metal-  \nDownloaded via CHULALONGKORN UNIV on July 3, 2026 at 10:20:51 (UTC) . See [https://pubs.acs.org/sharingguidelines](https://pubs.acs.org/sharingguidelines) for options on how to legitimately share published articles.  \nOsteoarthritis (OA) is a chronic joint disease characterized by progressive synovial inflammation and cartilage matrix degeneration that affects more than 50% of people over the age of 60 years worldwide, leading to joint dysfunction and a dramatic decline in the quality of life. 1−3 Although the exact mechanism of OA onset is not yet fully understood, various pathological changes, such as synovial inflammation, cartilage degeneration, osteophyte formation, and bone lesion, have been proven to play a crucial role in the progression of the disease.4−7 The inflammatory microenvironment of OA caused by synovial macrophage infiltration is one of the key factors leading to cartilage deterioration.8−10 In the human OAsynovium, macrophages primarily polarize into a proinflammatory M1 phenotype and secrete various inflammatory cytokines and matrix metalloproteinases, including interleukin-1β (IL-  \nloproteinase-13 (MMP-13), to accelerate the apoptosis and catabolic processes of articular chondrocytes. During the OA progression, a vicious cycle occurs between inflammatory M1 macrophage activation and cartilage degeneration.11 Thus, providing timely intervention and treatment to prevent its progression in the early stages of OA remains a formidable challenge.  \n\n| Received: May 31, 2025\u003Cbr>Revised: September 27, 2025\u003Cbr>Accepted: September 29, 2025\u003Cbr>Published: October 3, 2025 |  |\n| --- | --- |\n\n© 2025 American Chemical Society  \n7447  \n[https://doi.org/10.1021/acs.biomac.5c01002](https://doi.org/10.1021/acs.biomac.5c01002)  \nBiomacromolecules 2025, 26, 7447−7469  \nFigure 1. Design of the SF/BDAB/CM hydrogel as a nanodrug delivery system f","cbCaic9BXpNujm9y","https://ap.wps.com/l/cbCaic9BXpNujm9y","pdf",7340938,1,23,"English","en",105,"# Abstract\n# Introduction\n# Article Information","[{\"question\":\"Why is hydrogel nanodrug delivery challenging for osteoarthritis treatment?\",\"answer\":\"Therapeutic efficacy and reliability are limited by fabrication procedures and gelation kinetics, which affect retention efficiency and the bioavailability of nanodrugs in the joint cavity.\"},{\"question\":\"How does the BDAB-induced unfolding–aggregating strategy enable ultrafast in situ gelation?\",\"answer\":\"Under BDAB induction, silk fibroin molecules unfold to expose hydrophobic segments, then nucleate and aggregate β-sheet structures, reducing the energy barrier and achieving gelation within 4 seconds.\"},{\"question\":\"What drugs are loaded, and what therapeutic outcomes are targeted?\",\"answer\":\"The hydrogel loads core–shell nanodrugs composed of methotrexate and chondroitin sulfate, aiming to modulate M1/M2 macrophage repolarization and protect chondrocytes from inflammatory 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