Acta Biomaterialia最新文献

{"title":"Applications and challenges of stage-specific microenvironment-responsive hydrogels for myocardial infarction","authors":"Jiahao Hu,&nbsp;Yue Wang,&nbsp;Boya Yan,&nbsp;Yuling Zhao,&nbsp;Zeqi Chen,&nbsp;Li Yang,&nbsp;Yunbing Wang","doi":"10.1016/j.actbio.2026.09.009","DOIUrl":"10.1016/j.actbio.2026.09.009","url":null,"abstract":"<div><div>Myocardial infarction (MI) progresses through a series of distinct pathological stages, from acute ischemia and reperfusion injury to chronic inflammation, fibrotic proliferation, and ventricular remodeling, each characterized by a unique combination of microenvironmental cues and therapeutic demands. Traditional injectable hydrogels, designed primarily as passive mechanical fillers, largely fail to adapt to these stage-specific needs: their fixed degradation, mechanics, and drug release profiles cannot match the dynamic post-MI milieu. Microenvironment-responsive hydrogels, by sensing signals such as reactive oxygen species (ROS), pH changes, and matrix metalloproteinases (MMPs), offer a means to align hydrogel behavior more closely with pathological progression. While existing reviews have catalogued these systems by their response mechanisms, this review takes a pathology-driven perspective. We first analyze the evolving microenvironmental characteristics and repair requirements across the major phases of MI. Then, rather than organizing the discussion by stimulus type, we examine how hydrogel properties, including responsiveness, mechanical support, electrical conductivity, and degradation, can be rationally combined with appropriate delivery formats (injectable hydrogels, cardiac patches, and composite constructs) and clinical workflows to address phase-specific therapeutic objectives. Finally, we identify bottlenecks that currently prevent these materials from reaching clinical application and outline practical strategies for overcoming them. By linking material design directly to stage-specific pathology, this review aims to offer a more clinically relevant framework for developing next-generation responsive hydrogels for MI repair.</div></div><div><h3>Statement of significance</h3><div>Myocardial infarction (MI) is a leading cause of heart failure. Revascularization improves survival, yet reperfusion injury and remodeling drive long-term mortality. Traditional injectable hydrogels are passive fillers that cannot adapt to the post-infarction microenvironment. Most reviews classify responsive hydrogels by chemical trigger, separating material design from clinical pathology. We take a different view, linking hydrogel design to the four phases of MI healing. For each phase we identify the microenvironmental signals, then show how reactive oxygen species (ROS), pH and matrix metalloproteinase (MMP) responsiveness, mechanics, conductivity, and degradation can be combined for stage-specific therapy. We also examine how injectable hydrogels, epicardial patches, and composite constructs integrate with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) workflows. This pathology-matched framework highlights translational bottlenecks and strategies to bridge materials science and clinical application.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"225 ","pages":"Pages 41-65"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-4-Loaded lipid nanoparticles reprogram adipose tissue immunity and promote adipocyte browning for the treatment of obesity","authors":"Neda Mohaghegh,&nbsp;Narges Zargar Balajam,&nbsp;Nick Kraemer,&nbsp;Talia Marx,&nbsp;Shraddha Sawant,&nbsp;Gargi Y Digholkar,&nbsp;Aliesha O'Raw,&nbsp;Xiling Shen,&nbsp;Heemin Kang,&nbsp;Ryan M Pearson,&nbsp;Alireza Hassani Najafabadi","doi":"10.1016/j.actbio.2026.09.007","DOIUrl":"10.1016/j.actbio.2026.09.007","url":null,"abstract":"<div><div>Obesity represents a global health crisis characterized by chronic adipose tissue (AT) inflammation (metaflammation) driven by pro-inflammatory M1 macrophage (MΦ) polarization, adipocyte hypertrophy, and impaired thermogenic capacity of white adipose tissue (WAT). While interleukin-4 (IL-4) potently induces M2 MΦ polarization, its clinical translation is limited by poor stability, rapid clearance, and off-target effects. Here, we engineered lipid nanoparticles (IL-4/LNP) via simple, robust thin-film hydration and extrusion to enable sustained IL-4 delivery to MΦs in inflamed AT. <em>In vitro</em>, IL-4/LNP achieved &gt;70% encapsulation efficiency, a uniform ∼150 nm size, and superior M1 to M2 MΦ reprogramming compared with free IL-4, as evidenced by CD206 upregulation, reduced CD80/CD40 expression, and attenuated TNF-α/IL-6 secretion in LPS-stimulated MΦ. In adipocyte-mimicking cells (3T3-L1)-MΦ co-cultures representing white and brown adipose tissue (BAT), paracrine signaling from IL-4/LNP-polarized M2 MΦs drove a profound reduction in lipid droplets (LDs) and beiging, with decreased Feret diameter and integrated optical density. Using a high-fat diet-induced obese mouse model, localized inguinal/visceral AT injections blunted weight gain by ∼10%, induced multilocular beige-like adipocytes across depots, upregulated thermogenic genes (<em>UCP1</em> and <em>PGC1α</em>), downregulated inflammatory markers (<em>IL-6</em>), and improved hepatic steatosis without systemic toxicity. These findings establish IL-4/LNP as a safe, multifunctional platform that links MΦ immunomodulation and adipose browning in obesity therapy.</div></div><div><h3>Statement of significance</h3><div>This study establishes IL-4–loaded lipid nanoparticles (IL-4/LNPs) as a nanomedicine platform that targets the immunometabolic roots of obesity by reprogramming adipose tissue macrophages and promoting white fat browning. IL-4/LNPs are produced by a simple, scalable thin-film hydration–extrusion method, yielding ∼150 nm particles with ∼73% encapsulation, suitable for local adipose delivery. <em>In vitro</em>, the NPs outperform free IL-4 by enhancing M2 polarization, driving paracrine adipocyte remodeling, and reducing lipid burden in 3T3-L1 co-cultures. In high-fat diet–obese mice, depot-specific IL-4/LNP injections limit weight gain, induce adipocyte beiging, improve hepatic steatosis, and reduce systemic inflammation without detectable toxicity, supporting IL-4/LNPs as a translatable cytokine nanotherapy for metaflammatory obesity.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"225 ","pages":"Pages 632-644"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioengineered skeletal muscle construct using a cell-seeded decellularized diaphragm muscle scaffolding system for pelvic muscle regeneration","authors":"Michael Won S Kim,&nbsp;Hyeongjin Lee,&nbsp;Erika Billman,&nbsp;Ickhee Kim,&nbsp;Young Min Ju,&nbsp;Anthony Atala,&nbsp;James J. Yoo,&nbsp;Ji Hyun Kim","doi":"10.1016/j.actbio.2026.09.040","DOIUrl":"10.1016/j.actbio.2026.09.040","url":null,"abstract":"<div><div>Pelvic floor muscle injury often leads to dysfunction of the entire pelvic urogenital system, negatively impacting the patient’s quality of life. Current treatment options include autologous muscle transfer and biomaterial-based meshes and slings; however, adequately restoring muscle function remains a significant challenge. With advances in skeletal muscle tissue engineering, bioengineered skeletal muscle constructs have emerged as promising therapeutic solutions for treating various types of muscle injuries. Recently, these strategies have been expanded to address injuries involving pelvic musculature. In this study, we developed a bioengineered skeletal muscle construct by seeding human muscle progenitor cells (hMPCs) onto a decellularized skeletal muscle scaffold to regenerate damaged pelvic muscle tissues. Allogeneic decellularized diaphragm muscle tissue was employed as a biological scaffold due to its structural and mechanical similarities to native pelvic muscle tissues. We demonstrated that the decellularized diaphragm retained aligned skeletal muscle matrix microstructures and preserved mechanical properties. hMPCs seeded on the decellularized scaffold remained viable and differentiated into aligned muscle fibers. The feasibility of the bioengineered muscle construct was investigated in a rat model of extensive pelvic muscle injury. Our in vivo results demonstrated that the implanted construct supported the formation of new skeletal muscle tissue with vascular and neural integration and improved recovery of muscle weight and function. To our knowledge, this is the first approach using decellularized diaphragm muscle tissue matrices as a biologic scaffold for pelvic muscle repair. With further advances, this approach may offer an alternative strategy for repairing pelvic muscle injuries.</div></div><div><h3>Statement of significance</h3><div>Pelvic floor muscle injury significantly impairs quality of life, yet current mesh- and sling-based treatments are limited by poor structural and biological integration. Here, we developed a bioengineered skeletal muscle construct using human muscle progenitor cells seeded onto a decellularized diaphragm scaffold, given its biomimetic architecture and mechanical properties that closely resemble native pelvic floor muscle. In a rat model of pelvic floor injury, this construct promoted muscle regeneration, vascularization, and neural integration while improving muscle mass and function. To our knowledge, this is the first use of decellularized diaphragm tissue for pelvic muscle reconstruction. This approach may provide a promising strategy for supporting structural and functional muscle repair.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"225 ","pages":"Pages 337-348"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A concave corneal stromal scaffold based on multi-crosslinked GelMA hydrogel for delaying keratoconus progression and improving corneal morphology","authors":"Wenfang Liu,&nbsp;Zhuhao Tan,&nbsp;Sulei Lv,&nbsp;Wentai Guo,&nbsp;Qi Zhao,&nbsp;Baolei Huang,&nbsp;Yiping Liu,&nbsp;Yingni Xu,&nbsp;Wenjing Song,&nbsp;Li Ren","doi":"10.1016/j.actbio.2026.09.042","DOIUrl":"10.1016/j.actbio.2026.09.042","url":null,"abstract":"<div><div>Keratoconus (KC), a progressive corneal ectasia characterized by central thinning, elevated curvature, and compromised biomechanical integrity, presents considerable therapeutic challenges. Existing clinical interventions exhibit limited efficacy in delaying disease progression or restoring native corneal structure. We report a concave corneal stromal scaffold (CCSS) featuring a unique concave structure, fabricated based on multi-crosslinked gelatin methacryloyl and β-cyclodextrin aldehyde hydrogels and specifically designed for intrastromal implantation. <em>In vitro</em> characterization confirmed that the optimized gelatin methacryloyl-based hydrogel possesses high optical transparency (&gt;90%), suitable mechanical properties, and favorable cytocompatibility. Based on finite element model analysis of stress disparities between normal cornea and KC, a concave scaffold was fabricated to prevent KC progression. <em>In vivo</em> rabbit models of KC resulted in increased central corneal thickness in the Sc region (scaffold center), while a specially designed incremental topology in the peripheral Sp region (scaffold periphery) contributed to significant reduction in corneal curvature. The CCSS also promoted epithelial remodeling and substantially improved biomechanical properties, exhibiting notable restorative capacity. Importantly, animal studies experimentally validated finite element model predictions that the concave topology of the CCSS effectively redistributes stress, attenuating central stress concentration and reducing apical displacement. Moreover, the scaffold demonstrated sustained structural integrity over extended periods, thereby delaying KC progression and potentially diminishing the necessity for corneal transplantation. The design principles of the CCSS may inform future therapeutic strategies for stromal corneal disorders.</div></div><div><h3>Statement of significance</h3><div>Keratoconus (KC) as a progressive corneal ectasia characterized by structural disintegration and biomechanical weakening, for which current clinical interventions often fail to halt disease progression without biomechanical mismatch. While biomaterial-based strategies offer promise, conventional flat scaffolds cannot replicate the native stress distribution of the cornea. Here, we report a concave corneal stromal scaffold (CCSS)fabricated from a multi-crosslinked GelMA hydrogel. By synergizing material reinforcement with topological design, the CCSS actively redistributes intraocular stress from the thinned apex to the peripheral stroma, a mechanism predicted by finite element modeling and validated <em>in vivo</em>. Our findings provide a transformative paradigm for treating stromal corneal disorders by integrating structural restoration with biomechanical normalization, potentially reducing the reliance on corneal transplantation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"225 ","pages":"Pages 364-382"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","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,&nbsp;Qiaoyun Long,&nbsp;Richard J. Miron,&nbsp;Chengcheng Yin,&nbsp;Yan Wei,&nbsp;Yufeng Zhang,&nbsp;Min Wu","doi":"10.1016/j.actbio.2026.09.043","DOIUrl":"10.1016/j.actbio.2026.09.043","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"225 ","pages":"Pages 911-912"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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,&nbsp;Yun Li,&nbsp;Cong Ding,&nbsp;Yifan Li,&nbsp;Juntao Jiang,&nbsp;Qiang Zhang,&nbsp;Manqi Yan,&nbsp;Fei Cao,&nbsp;Ting Wu,&nbsp;Yong Hu","doi":"10.1016/j.actbio.2026.10.005","DOIUrl":"10.1016/j.actbio.2026.10.005","url":null,"abstract":"&lt;div&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;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.&lt;/di","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"225 ","pages":"Pages 755-771"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","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,&nbsp;Ruoxuan Zhao,&nbsp;Shuangyue Li,&nbsp;Qing Fang,&nbsp;Ao Liu,&nbsp;Yanan Di","doi":"10.1016/j.actbio.2026.10.004","DOIUrl":"10.1016/j.actbio.2026.10.004","url":null,"abstract":"<div><div>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 <em>Mytilus coruscus</em> under contrasting high- and low-concentration FeCl₃ conditions (Fe1 and Fe2). The foot exhibited regional specialization. Plaque glands were concentrated distally, several <em>Mfp</em> transcripts were enriched in distal layers, <em>PTMP</em> transcript abundance was highest proximally, and <em>preCOL-P</em> showed its highest basal abundance in the middle region. Fe2 elicited a broad <em>preCOL-P</em> 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.</div></div><div><h3>Statement of significance</h3><div>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 <em>Mytilus coruscus</em>, 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.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"225 ","pages":"Pages 452-465"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local administration of exendin-4 ameliorates wear-particle-induced periprosthetic osteolysis by rebalancing bone remodeling","authors":"Boyan Ma,&nbsp;Zhi Peng,&nbsp;Yixiao Pan,&nbsp;Zixiang Yi,&nbsp;Weiping Su","doi":"10.1016/j.actbio.2026.09.014","DOIUrl":"10.1016/j.actbio.2026.09.014","url":null,"abstract":"<div><div>Periprosthetic osteolysis and aseptic loosening are the leading causes of total joint arthroplasty failure. Wear debris triggers chronic sterile inflammation, driving excessive osteoclast activation and insufficient osteoblastic bone formation. Drug-target Mendelian randomization showed that genetically predicted higher systemic expression of glucagon-like peptide-1 receptor (GLP-1R) is causally associated with a reduced risk of clinical revision arthroplasty. Histological analysis confirmed GLP-1R expression within osteolytic bone tissues. Whether local activation of GLP-1R could counter particle-induced osteolysis, however, remained untested. To address this, we evaluated the therapeutic potential of the GLP-1R agonist, Exendin-4, across animal models and <em>in vitro</em> assays. In a murine model of ultra-high-molecular-weight polyethylene (UHMWPE)-induced calvarial osteolysis, local Exendin-4 administration significantly mitigated bone resorption, suppressed osteoclastogenesis, and stimulated periprosthetic bone formation. Mechanistically, Exendin-4 shifted macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, reducing osteolytic cytokines such as IL-6 and TNF-α; <em>In vitro</em>, it also acted directly on osteoclast precursors to suppress RANKL-driven osteoclastogenesis and rescued the osteogenic differentiation of bone marrow mesenchymal stem cells. These findings demonstrate that targeting GLP-1R signaling effectively restores the uncoupled bone homeostatic axis, offering a promising translational strategy for treating periprosthetic osteolysis.</div></div><div><h3>Statement of significance</h3><div>Periprosthetic osteolysis (PPO) caused by wear debris is a major cause of joint replacement failure. While traditional treatments focus only on slowing down bone loss, strategies that can both stop bone destruction and promote bone healing are critically needed. In this study, we combined human genetic evidence with animal models to show that targeting the local GLP-1 receptor via Exendin-4 effectively treats PPO. Locally delivering Exendin-4 successfully switches pro-inflammatory M1 macrophages to an anti-inflammatory M2 phenotype and directly rescues the multi-stage bone formation process of stem cells under wear-particle stress, without causing systemic toxicity. This study provides a practical, biosafe strategy for reusing clinical metabolic drugs to balance bone remodeling and extend implant survival.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"225 ","pages":"Pages 664-677"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal mapping of cranial sutures guides application of an MMP13-inhibiting hydrogel patch to restore asymmetric mineralization and prevent craniosynostosis","authors":"Hongxu Meng,&nbsp;Xinyi Wang,&nbsp;Boxuan Wu,&nbsp;Yingqi Jiang,&nbsp;Yuning Dong,&nbsp;Tianyi Zhang,&nbsp;Bingqian Chen,&nbsp;Hanzhang Li,&nbsp;Taozehan Chen,&nbsp;Wenyue Li,&nbsp;Xiaozhao Wang,&nbsp;Xin Lan,&nbsp;Tianrui Zhao,&nbsp;Huan Hu,&nbsp;Wenwen Huang,&nbsp;Núria Gavara,&nbsp;Hongwei Ouyang,&nbsp;Yuan Yuan","doi":"10.1016/j.actbio.2026.09.041","DOIUrl":"10.1016/j.actbio.2026.09.041","url":null,"abstract":"<div><div>Craniosynostosis, resulting from the premature fusion of one or more cranial sutures, often requires invasive surgery for treatment. Currently, the spatiotemporal regulation of calvarial ossification during suture development is largely focused on cellular and molecular patterns. Using physicochemical imaging and nanomechanical mapping, we identified a unidirectional osteoperiosteal interface characterized by calcium phosphate deposition gradient during early postnatal calvarial development. Lineage tracing and dynamic bone formation assays revealed that <em>Mmp13</em>-positive osteoprogenitors, derived from <em>Erg-</em>expressing suture mesenchyme, establish this osteoperiosteal interface and drive asymmetric calvarial osteogenesis in mice. In the <em>Twist1^+/–</em> craniosynostosis model, mineralization patterns initially resembled those of wild-type mice; however, misregulation of the PAK1/MMP13/BMP7 signaling cascade at the dura side triggered bilateral mineralization within the coronal suture, ultimately leading to bone fusion. Importantly, early localized inhibition of MMP13 overactivation, achieved by applying CL-82198 (a small-molecule MMP13 inhibitor) in a thin 20% gelatin methacryloyl (GelMA) hydrogel-based \"Suture Patch\", preserved coronal suture patency in <em>Twist1</em> mutants via a minimally invasive surgical procedure. Our work identifies a unilateral osteoperiosteal interface that is critical for coronal suture patency, reveals the regulatory role of non-cellular components in calvarial development, and proposes a minimally invasive strategy to preserve asymmetric osteogenesis in cranial sutures for the treatment of craniosynostosis.</div></div><div><h3>Statement of significance</h3><div>Craniosynostosis is a premature skull suture fusion that currently requires invasive surgery. We discover a unidirectional mineralization gradient driven by <em>Mmp13⁺</em> osteoprogenitors. In a craniosynostosis model, this asymmetric process becomes bilateral and pathological. Leveraging this insight, we engineer a 200-μm hydrogel “Suture Patch” that delivers a small-molecule MMP13 inhibitor locally. A single application in newborn mice preserves suture patency in 80% of treated animals, corrects skull deformity, and restores progenitor pools—without additional surgery. Our work integrates advanced materials characterization, single-cell biology, and translational bioengineering to provide both a fundamental revision of suture development and a practical, minimally invasive biomaterial therapy for the debilitating pediatric disorder.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"225 ","pages":"Pages 349-363"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Soft, curved and transparent fish scale biocornea for anterior lamellar keratoplasty","authors":"Yue Yin,&nbsp;Ran Wei,&nbsp;Linyu Long,&nbsp;Yifan Hao,&nbsp;Zhinuo Li,&nbsp;Daihua Fu,&nbsp;Fanju Zhang,&nbsp;Ke Ma,&nbsp;Li Yang,&nbsp;Yunbing Wang","doi":"10.1016/j.actbio.2026.09.039","DOIUrl":"10.1016/j.actbio.2026.09.039","url":null,"abstract":"<div><div>Due to structural and compositional similarities with human corneas, decellularized fish scale scaffolds have emerged as potential substitutes for donor corneas. However, to date, their effective use in anterior lamellar keratoplasty has rarely been reported, as their rigid texture and poor conformity to the curved corneal bed can cause graft–host mismatch and sustained mechanical irritation. To overcome these limitations, this study introduced a softening strategy to convert rigid decellularized fish scales into soft and curved matrices. A subsequent mild crosslinking treatment stabilized the softened structure and yielded fish scale biocorneas (FSBCs). The softening process was associated with partial weakening of noncovalent interactions within the extracellular matrix. This strategy simultaneously improved mechanical compliance, curvature conformity and optical transparency while preserving the ordered collagen framework. The resulting FSBCs exhibited compressive elastic modulus and light transmittance comparable to those of human corneas. Moreover, FSBCs demonstrated suitable nutrient permeability, supported corneal cell adhesion and proliferation and displayed improved tissue biocompatibility in subcutaneous implantation. In a three-month rabbit anterior lamellar keratoplasty model, FSBCs showed good conformity to the corneal bed and favorable graft–host integration, facilitated complete epithelialization and restored stromal thickness to near-normal levels. Overall, this study addresses the mechanical and morphological limitations of conventional fish scale scaffolds, offering a promising option for lamellar corneal transplantation.</div></div><div><h3>Statement of significance</h3><div>Corneal transplantation is the gold standard for treating irreversible corneal blindness, but its use is limited by donor shortage. Fish scales exhibit compositional and structural similarities to the human corneas, but conventional decellularized fish scale scaffolds are mechanically rigid and morphologically mismatched with the curved corneal bed, which limits their application in anterior lamellar keratoplasty. This study presents a simple softening-and-shaping strategy to convert fish scales into soft and curved biocorneas. The resulting biocorneas showed cornea-like mechanical and optical properties and supported corneal repair in a rabbit model. This study provides a promising option for anterior lamellar keratoplasty and may also offer a useful reference for regulating the structure and mechanical properties of other collagen-based biomaterials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"225 ","pages":"Pages 317-336"},"PeriodicalIF":10.4,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}