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The work develops an in situ moldable fluidic biomimetic niche (GelSSO/PDA@SDF) as a chronotaxic signal amplifier to restore autonomous cranial regeneration. The hydrogel releases nanoparticles for early SDF-1/CXCR4 recruitment, AKT-dependent angiogenesis, and M1 macrophage suppression, followed by SSO-driven osteogenic niche activation and diabetic vascularized bone repair.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/reinstating-niche-failure-in-diabetic-cranial-defects-via-chronotaxic-signal-amplifying-fluidic-biomimetic-hydrogel/439448/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/reinstating-niche-failure-in-diabetic-cranial-defects-via-chronotaxic-signal-amplifying-fluidic-biomimetic-hydrogel/439448.png","ImageObject",300,407,{"name":92,"@type":93},"Fahsai","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What problem does this study address in diabetic cranial injuries?","Question",{"text":113,"@type":114},"Diabetes-related chronic inflammation depletes and hypoactivates stem cell niches, leading to niche failure and impaired regeneration after cranial defects.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does GelSSO/PDA@SDF function as a chronotaxic signal amplifier?",{"text":118,"@type":114},"It provides sequential signal phases by sustainably releasing PDA@SDF nanoparticles first for recruitment and vascular activation, then degrading to enable prolonged SSO release that drives osteogenic niche formation.",{"name":120,"@type":111,"acceptedAnswer":121},"Which biological pathways are highlighted for early vascular and later bone regeneration?",{"text":122,"@type":114},"Early phase recruitment is mediated by SDF-1/CXCR4 and angiogenesis proceeds via AKT-dependent mechanisms, while the secondary osteogenic phase involves MAPK/ERK-induced osteogenesis.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},439448,1790713996,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":14,"preview_urls":147},549768702563,"https://ap-avatar.wpscdn.com/avatar/8000c4aa63b76e948b?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786536092046926083","RESEARCH ARTICLE  \n[www.advancedscience.com](www.advancedscience.com)  \nReinstating Niche Failure in Diabetic Cranial Defects via Chronotaxic Signal-Amplifying Fluidic Biomimetic Hydrogel  \nYingji Mao, Yu Chen, Runlin Fan, Pengzhen Zhuang, Hongbo Zhang,* and Pinghui Zhou*  \nCranial stem cell niches (SCNs) are intrinsically scarce  \nand hypoactive, and, exacerbated by chronic inflammation in diabetes, lead to niche failure and regenerative deficit after injury. Herein, an in situ moldable fluidic biomimetic niche (GelSSO/PDA@SDF) is developed as a chronotaxic signal amplifier to enhance SCN abundance and activity, aiming to restore autonomous regeneration. This biomimetic niche integrates PDA@SDF nanoparticles and a GelSSO hydrogel precursor, synthesized via dopamine self-polymerization/protein coupling and sequential methacrylation/sequencespecific oligodeoxynucleotide (SSO) grafting, respectively. Photocrosslinked GelSSO/PDA@SDF can preferentially and sustainably release PDA@SDF nanoparticles to trigger early-phase signal amplification, characterized by SDF- 1􀀂/CXCR4-mediated recruitment of endothelial and mesenchymal progenitors, vascular niche activation driving AKT-dependent angiogenesis, and suppressed M1 macrophage dominance. Progressive hydrogel degradation initiates the secondary signal amplification phase, in which prolonged SSO release creates a transcriptionally active osteogenic niche for MAPK/ERK-induced osteogenesis. In vivo, the in situ structured GelSSO/PDA@SDF conformed to defect geometry, promoting the early establishment of an immunologically favorable, progenitor-enriched niche through local immunomodulation and endogenous cell homing, followed by successive activation  \nof vascular and osteogenic niches, ultimately achieving diabetic cranial vascularized bone regeneration. Thus, this chronotaxic signal-amplifying biomimetic niche offers a versatile strategy for restoring autonomous regeneration in the diabetic cranium and other poorly regenerative tissues.  \n1. Introduction  \nStem cell niches (SCNs) are specialized microenvironments that integrate multidimensional signals to preserve stemness, direct differentiation, and coordinate repair, thereby determining the regenerability of tissues. [1–3] This capacity varies hierarchically across tissues and anatomy owing to the spatial heterogeneity of SCNs. From atissue perspective, the skin and liver harbor numerous, broadly distributed, and highly injury-responsive SCNs that enable rapid restoration of structure and function. In contrast, the myocardium and central nervous system, characterized by SCN scarcity and hypoactivity, are poorly regenerative, leading to functionally limited scarring. [4,5] Anatomically, marrow-rich endosteal and periosteal SCNs in the femur support structural and mechanical healing, while the cranium, lacking such supportive SCNs, struggles to bridge defects. [6,7] Beyond these baseline constraints, pathological conditions such as diabetes further deplete SCN abundance and activity via chronic inflammation, exacerbating the regenerative deficit, especially in tissues where SCNs are already scarce. [8,9] Thus, enhancing SCN abundance and activity in intrinsically and pathologically disadvantaged  \nY. Mao, R. Fan, P. Zhou  \nDepartment of Orthopedics  \nAnhui Province Key Laboratory of Tissue Transplantation The First Affiliated Hospital of Bengbu Medical University Bengbu 233004, China  \nE-mail: [phzhou@bbmu.edu.cn](phzhou@bbmu.edu.cn)  \nThe ORCID identification number(s) for the author(s) of this article  \ncan be found under [https://doi.org/10.1002/advs.202516398](https://doi.org/10.1002/advs.202516398)[ ](https://doi.org/10.1002/advs.202516398)© 2025 The Author(s). Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \nDOI: 10.1002/advs.202516398  \nY. Mao  ","cbCaim1d1kVGT9xT","https://ap.wps.com/l/cbCaim1d1kVGT9xT","pdf",8594669,18,"English","# Introduction\n## Stem cell niches in health and disease\n## Biomimetic niche strategies\n# Conclusion","[{\"question\":\"What problem does this study address in diabetic cranial injuries?\",\"answer\":\"Diabetes-related chronic inflammation depletes and hypoactivates stem cell niches, leading to niche failure and impaired regeneration after cranial defects.\"},{\"question\":\"How does GelSSO/PDA@SDF function as a chronotaxic signal amplifier?\",\"answer\":\"It provides sequential signal phases by sustainably releasing PDA@SDF nanoparticles first for recruitment and vascular activation, then degrading to enable prolonged SSO release that drives osteogenic niche formation.\"},{\"question\":\"Which biological pathways are highlighted for early vascular and later bone regeneration?\",\"answer\":\"Early phase recruitment is mediated by SDF-1/CXCR4 and angiogenesis proceeds via AKT-dependent mechanisms, while the secondary osteogenic phase involves MAPK/ERK-induced osteogenesis.\"}]","Reinstating Niche Failure in Diabetic Cranial Defects via Chronotaxic Signal-Amplifying Fluidic Biomimetic Hydrogel | PDF",1790688740,45,[148,152],{"page_no":8,"url":149,"width":150,"height":151},"https://res-academy.cache.wpscdn.com/upload/kdocshare/2026-11-08/f95a265710f43a052b03baab165f9f7c.webp",983,1291,{"page_no":14,"url":153,"width":154,"height":155},"https://res-academy.cache.wpscdn.com/upload/kdocshare/2026-11-08/ccc645208f77c327ac481627cb8b0794.webp",982,1290]