Materials Today Bio最新文献

{"title":"Engineering functionally-optimized aptamers against SARS-Cov-2 for blocking spike-ACE2 interaction and aptasensor detection","authors":"Xiangdong Lai ,&nbsp;Weiwei Zhao ,&nbsp;Lihua Jiang ,&nbsp;Jing Li ,&nbsp;Muhammad Faizan Munawer ,&nbsp;Jiejuan Lai ,&nbsp;Jesus Alejandro Martinez Juarez ,&nbsp;Miraj Ud din ,&nbsp;Xiaoyang Zhang ,&nbsp;Zhongquan Song ,&nbsp;Tao Wu ,&nbsp;Yiyue Ge ,&nbsp;Hui Jiang ,&nbsp;Xiaohui Liu ,&nbsp;Xuemei Wang","doi":"10.1016/j.mtbio.2025.102020","DOIUrl":"10.1016/j.mtbio.2025.102020","url":null,"abstract":"<div><div>Both the limited research about structure-function relationship and the ill-defined process of conformational dynamic change greatly impede the development of aptamer engineering transformation and seriously restrict the practical applications of aptamers. In this work, an optimization strategy combining exonuclease III (Exo III) digestion and in silico simulation was presented for the first time for constructing high-affinity and functional aptamers and clarifying the three-dimensional (3D) structure of aptamer-target complexes and the conformational dynamic conversion in the process of aptamer recognizing its target. As a demonstration, the parent aptamer (Apt2) against SARS-CoV-2 spike subunit 1 (S1) was mutated or truncated at the predicted binding sites to produce eight derivatives (Seq1–Seq8). The progeny Seq3 exhibited a higher affinity for S1 and a better blocking effect on S1-angiotensin-converting enzyme 2 (ACE2) interaction compared to Apt2. Subsequently, Seq3 sealed the pores of nickel-doped zeolitic imidazolate framework-8 (NZIF-8) loaded with Rhodanine (Rho) to fabricate the aptasensor (NZIF-8-Rho-Apt) for inactivated virus detection, showing excellent performances in spiked actual samples. Therefore, this post systematic evolution of ligands by exponential enrichment (post-SELEX) is a very effective and general strategy for acquiring functionally-optimized aptamers.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 102020"},"PeriodicalIF":8.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481788","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":"Organoids for tissue repair and regeneration","authors":"Biao Yu ,&nbsp;Dongyang Zhou ,&nbsp;Fuxiao Wang ,&nbsp;Xiao Chen ,&nbsp;Mengmeng Li ,&nbsp;Jiacan Su","doi":"10.1016/j.mtbio.2025.102013","DOIUrl":"10.1016/j.mtbio.2025.102013","url":null,"abstract":"<div><div>Tissue damage and dysfunction are common consequences of various diseases and trauma, severely impacting patients' quality of life. Organoids, three-dimensional cell clusters formed through the self-organization of stem cells, not only recapitulate the developmental processes of native tissues but also exhibit remarkable plasticity and long-term expansion capabilities, demonstrating potential to overcome limitations of conventional therapeutic approaches. Particularly in addressing challenges such as immune rejection and regenerative efficiency, organoid technology has shown distinct advantages. This review summarizes the applications of organoids in tissue repair, including the biological principles and cultivation strategies of organoid culture, as well as their specific applications and preclinical research progress across diverse tissues (e.g., brain, liver, intestine, bone). Additionally, it discusses current challenges in organoid technology, such as large-scale production, heterogeneity control, and clinical translation, while outlining future development directions.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 102013"},"PeriodicalIF":8.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365954","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 biomimetic multimodal nanoplatform combining neutrophil-coated two-dimensional metalloporphyrinic framework nanosheet and exendin-4 to treat obesity-related osteoporosis","authors":"Qifan Yang ,&nbsp;Jing Liu ,&nbsp;Yanwei Liu ,&nbsp;Shun Liu ,&nbsp;Xiaokang Wei ,&nbsp;Yilin Yang ,&nbsp;Weijie Zhang ,&nbsp;Shuqi Zhang ,&nbsp;Maosheng Zhang ,&nbsp;Bin Liu ,&nbsp;Xinyu Wang ,&nbsp;Dong Zhu","doi":"10.1016/j.mtbio.2025.102009","DOIUrl":"10.1016/j.mtbio.2025.102009","url":null,"abstract":"<div><h3>Background</h3><div>Obesity-induced osteoporosis is a prevalent complication among obese individuals. Conventional anti-osteoporosis medications often lack therapeutic specificity and may exacerbate lipid metabolism disorders. Consequently, identifying suitable pharmacological interventions for obesity-induced osteoporosis, elucidating its underlying biological mechanisms, and developing nanodrug delivery systems with enhanced biocompatibility and targeted delivery remain significant challenges.</div></div><div><h3>Methods</h3><div>This study reveals that the pathogenesis of obesity-induced osteoporosis is primarily driven by excessive mitophagy. Notably, Exendin-4 (Ex-4) has been shown to ameliorate mitophagy and mitigate obesity-induced osteoporosis. The nanocomposite DSPE-PEG-ALN (DPA)@Neutrophil membrane (NM)@Cu-TCPP(Zn)/Ex-4 (CTZE), characterized by high biocompatibility and reactive oxygen species (ROS) responsiveness, effectively targets bone tissue, reduces ROS levels, and regulates the release of Cu²⁺, Zn²⁺, Ex-4, and Alendronate (ALN). This composite interferes with B-cell lymphoma-2 (BCL2)- Beclin-1 (BECN1) binding via the tet methylcytosine dioxygenase 2 (TET2)/PTEN-induced putative kinase protein 1 (PINK1)/Parkin (E3 ubiquitin-protein ligase parkin) pathway, thereby promoting osteoblast differentiation and mineralization. The safety and efficacy of this nano-delivery platform were validated in a mouse model of obesity-induced osteoporosis.</div></div><div><h3>Conclusions</h3><div>In summary, our study illustrates that excessive mitophagy plays a crucial role in obesity-induced osteoporosis. Furthermore, DPA@NM@CTZE exhibits significant potential for the precise treatment of obesity-induced osteoporosis, mitigating the side effects of Ex-4, and enhancing the bone microenvironment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 102009"},"PeriodicalIF":8.7,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471603","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":"Pathogenesis guided application of nanozymes in the treatment of inflammatory bowel disease","authors":"Fang Lei ,&nbsp;Qizhen Huang ,&nbsp;Chengfeng Zhang ,&nbsp;Youhui Lin ,&nbsp;Yan Zhang ,&nbsp;Faming Wang","doi":"10.1016/j.mtbio.2025.102008","DOIUrl":"10.1016/j.mtbio.2025.102008","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut that has caused an escalating burden on the global healthcare system in recent years. Researchers have been actively seeking innovative therapeutic strategies to combat this intractable disease. Recent advances in nanozyme technology have opened up new avenues for the development of novel therapeutic strategies for IBD. This review provides a comprehensive overview of the related works in the developments and applications of different nanozymes for IBD therapy. By overviewing the known pathogenesis of IBD and pathogenesis-guided applications of nanozymes in IBD therapy, this review highlights the opportunities for nanozyme-based strategies to address IBD via the underlying mechanisms. This review also examines the current state of nanozyme research in IBD, including the design and application of nanozymes, and discusses the challenges and future directions for this emerging field. In addition, by integrating the understanding of IBD pathogenesis with the development of nanozyme technology, this review aims to stimulate further research to uncover new opportunities for this debilitating disease.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 102008"},"PeriodicalIF":8.7,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338521","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":"Multivalent Co-assembly of LL37-CpG nanoparticles: Enhanced immune response through activating multiple cell internalization pathways","authors":"Yushuang Wei ,&nbsp;Wenwen Li ,&nbsp;Rong Xu ,&nbsp;Cheng Xu ,&nbsp;Xiangyang Li ,&nbsp;Ning Li ,&nbsp;Fengdan Xu ,&nbsp;Kai Yang ,&nbsp;Bing Yuan","doi":"10.1016/j.mtbio.2025.102011","DOIUrl":"10.1016/j.mtbio.2025.102011","url":null,"abstract":"<div><div>Recent studies have demonstrated that the human antimicrobial peptide LL37 plays a critical role in immune regulation under both normal physiological conditions and during disease progression, as evidenced by its elevated levels observed in various chronic inflammatory diseases. A deeper understanding of its mechanism is essential for elucidating associated physiological and pathological processes, as well as for designing effective immune adjuvants and clinical therapeutics. In this study, we report that LL37 facilitates the assembly of unmethylated CpG dinucleotides (CpG ODNs), a clinically relevant immune adjuvant, into non-crystalline nanoparticles (NPs) with controlled size and zeta potential in a charge ratio-dependent manner. These assembled NPs enter cells via receptor-mediated macropinocytosis, coupled with LL37-mediated membrane penetration, thereby significantly enhancing cellular uptake of CpG compared to CpG alone, which enters cells through clathrin-mediated endocytosis. Consequently, the enhanced internalization of LL37-CpG NPs markedly boosts TNF-α production (&gt;3.5-fold) in macrophages through interactions with lysosomal TLR9. This immunostimulatory mechanism offers an alternative perspective on how LL37 modulates nucleic acid assembly and activates immune cells, providing guidance for the application of peptide-CpG ODN complexes in vaccine adjuvants and immune modulation for disease treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 102011"},"PeriodicalIF":8.7,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365953","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":"Resveratrol-loaded engineered microcapsules with dual antimicrobial and ROS-scavenging for programmed wound healing","authors":"Anning Wang ,&nbsp;Xiang Lin ,&nbsp;Xirui Wang ,&nbsp;Haiqiong Yang ,&nbsp;Chengkai He ,&nbsp;Yaru Su ,&nbsp;Yueqiong Yang ,&nbsp;Jingyuan Zhang ,&nbsp;Changkai Sun ,&nbsp;Xiaoya Ding ,&nbsp;Yinghua Zhu","doi":"10.1016/j.mtbio.2025.102007","DOIUrl":"10.1016/j.mtbio.2025.102007","url":null,"abstract":"<div><div>Hydrogel microparticles have been proved effective for the skin wound repair. Attempts in this area focus on how to enrich the structures and encapsulate bioactive substances to achieve the spatially controllable release for accelerated wound healing. Here, we propose a novel core-shell microcapsule delivery system with the spatial encapsulation and release of resveratrol (RSV) and chitosan (CS) to treat infected wounds. Such microcapsules (ALG-CS) were generated through microfluidic electrospray technology, with the inner core encapsulating RSV and outer layer covered with the imine bond-crosslinked CS hydrogel. The designed CS hydrogel coating can improve the stability of microcapsules and further prevent the premature leakage of RSV. The gradually degraded CS hydrogel layer in acidic environment accompanied with the subsequent release RSV contributed to the enhanced antibacterial properties of the microcapsules. In addition, the released RSV exhibited outstanding antioxidant capacities to protect cells from oxidative stress <em>in vitro</em>. Thus, by applying the obtained RSV-loaded ALG-CS microcapsules onto the <em>S. aureus</em>-infected wound beds, we have demonstrated that such microcapsules showed significant accelerated wound healing effects with alleviated oxidative stress, eliminated bacterial infection, down-regulated inflammatory response, and promoted collagen deposition and angiogenesis. These indicated that the microcapsule delivery systems are valuable for bacteria-infected wound therapy.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 102007"},"PeriodicalIF":8.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338520","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":"Ruthenium-quercetin coordinated nanotherapeutics with macrophage polarization regulation to rapidly promote bacterial-infected wound healing","authors":"Zhongxiong Fan ,&nbsp;Guoyu Xia ,&nbsp;Fukai Zhu ,&nbsp;Nan Yang ,&nbsp;Aixia Ma ,&nbsp;Yanrong Shi ,&nbsp;Ziwen Jiang ,&nbsp;Xianhui Zhou ,&nbsp;Zhenqing Hou","doi":"10.1016/j.mtbio.2025.101983","DOIUrl":"10.1016/j.mtbio.2025.101983","url":null,"abstract":"<div><div>The hypoxic and inflammatory microenvironment induced by bacterial invasion of wound tissue severely hinders the healing process. In recent years, photothermal therapy (PTT) based on metal–polyphenol coordination networks has garnered considerable attention due to its potent antibacterial effects, biofilm-disrupting capabilities, and intrinsic enzyme-like activities. In this study, a metal–polyphenol coordinated nanotherapeutic system was constructed via synergistic coordination-driven self-assembly between the transition metal ruthenium and quercetin (referred to as QRs). These QRs demonstrated excellent photothermal conversion efficiency and antibacterial performance, while also catalyzing the decomposition of hydrogen peroxide into oxygen under inflammatory conditions. In an <em>in vitro</em> LPS-stimulated hypoxic macrophage model, treatment with QRs significantly reduced intracellular reactive oxygen species (ROS) levels and alleviated hypoxia, thereby downregulating hypoxia-inducible factor-1α (HIF-1α) expression and promoting macrophage polarization from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype. In a murine bacterial wound infection model, QRs effectively suppressed the expression of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), while enhancing endothelial cell proliferation and increasing the proportion of M2 macrophages at the wound site. These changes collectively facilitated the timely transition of the wound into the remodeling phase and maximized the regenerative potential of endogenous immune cells. Overall, this work highlights the potential of ruthenium-based materials for photothermal antibacterial therapy and proposes a promising strategy to remodel the wound microenvironment for enhanced tissue repair.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 101983"},"PeriodicalIF":8.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335850","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":"Thermosensitive polygalacturonic acid glycoprotein hydrogel encapsulating bionic shikonin nanoparticles for the treatment of psoriasis","authors":"Biaobiao Wang ,&nbsp;Huan Shi ,&nbsp;Yunmei Li ,&nbsp;Huilin Ma ,&nbsp;Shuang Gao ,&nbsp;Xiaolan Zhang ,&nbsp;He Tian ,&nbsp;Xifan Mei ,&nbsp;Chao Wu","doi":"10.1016/j.mtbio.2025.102003","DOIUrl":"10.1016/j.mtbio.2025.102003","url":null,"abstract":"<div><div>Psoriasis is histopathologically characterized by hyperproliferation of keratinocytes, loss of the granular layer, and elongation and thickening of the rete ridges in the epidermis. The thickening of the stratum corneum in psoriatic skin poses a significant barrier to effective drug delivery, as many therapeutic agents with poor solubility, limited release, and side effects struggle to penetrate the skin and achieve prolonged retention, thereby limiting their therapeutic efficacy. To address these challenges, we developed a non-invasive transdermal delivery system. In this system, biomimetic shikonin nanoparticles (CNC) were modified with citric acid and combined with a deep eutectic solvent (DES) composed of L-lysine (L-Lys) and citric acid (CA), forming a CCNCD complex that significantly enhanced the transdermal permeability of CNC. The CCNCD complex was then loaded into a thermosensitive composite hydrogel composed of polygalacturonic acid (PGA)-grafted bovine serum albumin (BSA) and the thermosensitive material F-127 (FPB-CCNCD). This hydrogel exhibited sol-gel transition at body temperature, enabling uniform application on psoriatic skin and prolonging the retention time of CCNCD. The FPB-CCNCD system demonstrated high drug loading capacity, uniform particle size distribution, sustained release, excellent adhesion, enhanced skin retention and penetration in psoriatic-like lesions, and effective targeting of keratinocytes. In vitro experiments revealed that CCNC exhibited strong targeting ability, promoted keratinocyte apoptosis, and reduced the expression of inflammatory cytokines (TNF-α, IL-1β, and IL-6). In an imiquimod-induced psoriatic mouse model, FPB-CCNCD significantly alleviated psoriatic symptoms and reduced the expression of inflammatory factors. Therefore, FPB-CCNCD holds great promise for providing new clinical treatment strategies for psoriasis.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 102003"},"PeriodicalIF":8.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335851","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":"Schottky barrier in pea-like Au@Bi2S3 nanoreactor enabling efficient photodynamic therapy of hepatocellular carcinoma","authors":"Liangsong Tao ,&nbsp;Rongrong Gu ,&nbsp;Junfa Yang ,&nbsp;Jiewei Wang ,&nbsp;Tiling Wu ,&nbsp;Xianyue Rao ,&nbsp;Hao Wang ,&nbsp;Cheng Qian ,&nbsp;Jian Liu ,&nbsp;Sheng Ye ,&nbsp;Tao Xu","doi":"10.1016/j.mtbio.2025.102001","DOIUrl":"10.1016/j.mtbio.2025.102001","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC), a leading cause of tumor-related mortality globally, demands innovative therapeutic strategies to overcome limitations of conventional treatments. Photodynamic therapy (PDT), reliant on reactive oxygen species (ROS) generation, has emerged as a promising therapeutic strategy for neoplastic diseases. But it is constrained by inefficient charge separation in traditional photosensitizers. Here, we engineered a pea-like Au@Bi₂S₃ nanoreactors by anchoring gold nanoparticles onto Bi₂S₃ surfaces to establish a Schottky junction with interfacial Au-S covalent bonds, which suppresses electron-hole recombination and amplifies ROS production. Under light irradiation, Au@Bi₂S₃ exhibited remarkable inhibitory efficacy against HepG-2 cells, producing twice the ROS yield of Bi₂S₃. Transcriptomic analysis via RNA sequencing identified activation of the Hippo/Yap signaling pathway, which orchestrated endoplasmic reticulum stress and autophagic flux in malignant cells, ultimately driving apoptotic elimination of HepG-2 populations. These findings delineate a mechanistic paradigm wherein Schottky junction engineering potentiates ROS-mediated cytotoxicity, thereby advancing precise photodynamic interventions for HCC management.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 102001"},"PeriodicalIF":8.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481790","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":"Dissolvable microneedle-assisted transdermal administration of diacerein nanoparticles achieved satisfactory therapeutic effects in tendon-bone insertion repair by reducing oxidative stress and inflammation","authors":"Jie Sun ,&nbsp;Qing Zhong Chen ,&nbsp;Ai Zi Hong ,&nbsp;Fei Ju,&nbsp;Hao Liang Wang,&nbsp;Bo Zhang,&nbsp;Wang Liu,&nbsp;Yu Cheng Sun,&nbsp;Jun Tan,&nbsp;Qian Qian Yang,&nbsp;You Lang Zhou","doi":"10.1016/j.mtbio.2025.101999","DOIUrl":"10.1016/j.mtbio.2025.101999","url":null,"abstract":"<div><div>Tendon-bone insertion injuries are frequently encountered in sports medicine clinics, with the healing process posing a significant challenge within this field. When it comes to non-surgical interventions for such injuries, the use of local drug injections may carry the risk of damaging peripheral nerves and blood vessels. In this study, a simple dissolvable microneedle (DMN) patch loaded with diacerein (Dia) nanoparticles (DMN/PLGA@Dia) is established to achieve a constant delivery of Dia for enhancing tendon-bone healing. <em>In vitro</em> experiments demonstrate that Dia alleviates oxidative stress, reduces apoptosis, and prevents senescence in tendon cells, while also polarizing macrophages to the M2 phenotype. In a rat model of Achilles tendon-bone insertion injury, the application of DMN/PLGA@Dia enhances the regeneration of the tendon-bone insertion by reducing reactive oxygen species (ROS) levels and shifting macrophage polarization from M1 to M2. Additionally, DMN/PLGA@Dia improves functional recovery, as evidenced by biomechanical and gait analyses. These findings suggest that DMN/PLGA@Dia is capable of promoting tendon-bone insertion repair by alleviating oxidative stress and regulating the immune microenvironment strategies. Simple DMN/PLGA@Dia may be an effective and safe nanomedicine delivery system for tendon-bone insertion repair.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"33 ","pages":"Article 101999"},"PeriodicalIF":8.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338518","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}