Biomaterials最新文献

{"title":"A metal-semimetal Zn–Ge alloy with modified biodegradation behavior and enhanced osteogenic activity mediated by eutectic Ge phases-induced microgalvanic cells","authors":"Kai Chen ,&nbsp;Shan Gao ,&nbsp;Xuenan Gu ,&nbsp;Li Zhao ,&nbsp;Yunan Lu ,&nbsp;Jinwu Bai ,&nbsp;Linjun Huang ,&nbsp;Hongtao Yang ,&nbsp;Yu Qin ,&nbsp;Fang Zhou ,&nbsp;Yongcan Huang ,&nbsp;Yang Lv ,&nbsp;Yufeng Zheng","doi":"10.1016/j.biomaterials.2025.123343","DOIUrl":"10.1016/j.biomaterials.2025.123343","url":null,"abstract":"<div><div>Implants with strong osteogenic properties are crucial for effective bone repair in clinical settings. Recently, biodegradable zinc (Zn)-based metals have shown significant potential as orthopedic implants. However, pure Zn is prone to pitting corrosion and exhibits insufficient osteogenic activity in vivo. To enhance the degradation behavior and osteogenic potential of Zn-based implants, this study developed metal-semimetal Zn–Ge alloys with varying Ge content. The addition of Ge significantly promotes the formation of eutectic Ge phases, refines the microstructure, and improves the mechanical properties of the implants. Incorporating ∼3 wt% Ge into the matrix also facilitates enhanced Zn²⁺ release and ensures uniform biodegradation. Besides, the formation of uniformly distributed heteroid Zn–Ge microgalvanic cells provides a balance between osteogenic and bacteriostatic effects. In vivo tests using a femoral condyle defect model demonstrate that Zn–3Ge implants have favorable osteogenic property and excellent biosafety; the enhanced osteogenic activity of the alloy is attributed to intracellular Zn²⁺ activation of the Wnt signaling pathway, which promotes osteoblast differentiation, cell proliferation, survival, as well as extracellular matrix mineralization and osteogenesis. The incorporation of eutectic Ge phases and effective creation of microgalvanic cells offer a promising strategy for optimizing the biological function of Zn-based implants.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123343"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839406","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":"Living therapeutics: Precision diagnosis and therapy with engineered bacteria","authors":"Ruyan Xie ,&nbsp;Duoyang Fan ,&nbsp;Xiang Cheng ,&nbsp;Ying Yin ,&nbsp;Haohan Li ,&nbsp;Seraphine V. Wegner ,&nbsp;Fei Chen ,&nbsp;Wenbin Zeng","doi":"10.1016/j.biomaterials.2025.123342","DOIUrl":"10.1016/j.biomaterials.2025.123342","url":null,"abstract":"<div><div>Bacteria-based therapy has emerged as a promising strategy for cancer treatment, offering the potential for targeted tumor delivery, immune activation, and modulation of the tumor microenvironment. However, the unpredictable behavior, safety concerns, and limited efficacy of wild-type bacteria pose significant challenges to their clinical translation. Recent advancements in synthetic biology and chemical engineering have enabled the development of precisely engineered bacterial platforms with enhanced controllability, targeted delivery, and reduced toxicity. This review summarize the current progress of engineered bacteria in cancer therapy. We first introduce the theoretical underpinnings and key advantages of bacterial therapies in cancer. Subsequently, we delve into the applications of genetic engineering and chemical modification techniques to enhance their therapeutic potential. Finally, we address critical challenges and future prospects, with a focus on improving safety and efficacy. This review aims to stimulate further research and provide valuable insights into the development of engineered bacterial therapies for precision oncology.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123342"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844662","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 ROS-Responsive nanoparticle for nuclear gene delivery and autophagy restoration in Parkinson's disease therapy","authors":"Limin Zhai ,&nbsp;Yifei Gao ,&nbsp;Hao Yang ,&nbsp;Haoyuan Wang ,&nbsp;Beining Liao ,&nbsp;Yuxue Cheng ,&nbsp;Chao Liu ,&nbsp;Jingfeng Che ,&nbsp;Kunwen Xia ,&nbsp;Lingkun Zhang ,&nbsp;Yanqing Guan","doi":"10.1016/j.biomaterials.2025.123345","DOIUrl":"10.1016/j.biomaterials.2025.123345","url":null,"abstract":"<div><div>Parkinson's disease (PD) is characterized by the pathological aggregation of α-synuclein (α-syn) and neuroinflammation. Current gene therapies face challenges in nuclear delivery and resolving pre-existing α-syn aggregates. Here, we developed glucose-and trehalose-functionalized carbonized polymer dots (GT-PCDs) loaded with plasmid DNA (pDNA) for targeted gene delivery and autophagy restoration. The GT-PCDs@pDNA nanoparticles exhibit reactive oxygen species (ROS)-responsive behavior, enabling efficient nuclear entry under oxidative stress conditions. Both in vitro and in vivo studies demonstrated that GT-PCDs@pDNA effectively silenced <em>SNCA</em> gene expression, reduced α-syn aggregates, and restored autophagic flux by promoting transcription factor EB (TFEB) nuclear translocation. Moreover, GT-PCDs@pDNA enhanced blood-brain barrier (BBB) permeability via glucose transporter 1 (Glut-1)-mediated transcytosis, significantly improving motor deficits and reducing neuroinflammation in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. This multifunctional nanocarrier system offers a promising strategy for combined gene therapy and autophagy modulation in neurodegenerative diseases.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123345"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839407","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":"Albumin nanocomplex of BCL-2/xL inhibitor reduced platelet toxicity and improved anticancer efficacy in myeloproliferative neoplasm and lymphoma","authors":"Hongxiang Hu ,&nbsp;Chengyi Li ,&nbsp;Yudong Song ,&nbsp;Jizhao Xie ,&nbsp;Qiuxia Li ,&nbsp;Fang Ke ,&nbsp;Bo Wen ,&nbsp;Shaomeng Wang ,&nbsp;Wei Gao ,&nbsp;Duxin Sun","doi":"10.1016/j.biomaterials.2025.123347","DOIUrl":"10.1016/j.biomaterials.2025.123347","url":null,"abstract":"<div><div>The clinical application of BCL-2/xL inhibitors for cancer treatment is limited by the on-target thrombocytopenia. Although APG-1252 was designed to mitigate this issue, platelet toxicity at higher doses in clinical trials restricts dose escalation for greater efficacy. We have developed albumin nanocomplexes of APG-1252 (Nano-1252) to reduce platelet toxicity while improving drug efficacy through enhancing drug delivery to lymphoid organs. Nano-1252 forms stable nanoparticles due to the strong binding affinity between APG-1252 and albumin, reducing the platelet toxicity threshold by fourfold by limiting premature drug release and conversion to its active forms in circulation. Furthermore, Nano-1252 exhibited preferential accumulation in lymphoid organs, leading to enhanced anticancer efficacy in Mantle Cell Lymphoma (MCL) and Myeloproliferative Neoplasms (MPNs) mouse models. Our study not only develops a potential formulation to overcome the current translational barrier of APG-1252 but also reveals novel properties of the well-established albumin nanoformulation, thereby expanding its clinical applications.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"322 ","pages":"Article 123347"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881555","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":"Smooth muscle extracellular matrix modified small intestinal submucosa conduits promote peripheral nerve repair","authors":"Ya-Xing Li ,&nbsp;Long-Mei Zhao ,&nbsp;Xiu-Zhen Zhang ,&nbsp;Xi-Kun Ma ,&nbsp;Jing-Qi Liang ,&nbsp;Ting-Jiang Gan ,&nbsp;Heng Gong ,&nbsp;Yan-Lin Jiang ,&nbsp;Ye Wu ,&nbsp;Yu-Ting Song ,&nbsp;Yi Zhang ,&nbsp;Yue Li ,&nbsp;Xiao-Ting Chen ,&nbsp;Cong-Hui Xu ,&nbsp;Xiang-Yu Ouyang ,&nbsp;Jesse Li-Ling ,&nbsp;Hui Zhang ,&nbsp;Hui-Qi Xie","doi":"10.1016/j.biomaterials.2025.123346","DOIUrl":"10.1016/j.biomaterials.2025.123346","url":null,"abstract":"<div><div>Challenges still exist to develop an ideal cell-free nerve guidance conduit (NGC) providing a favorable microenvironment for rapid and successful nerve regeneration. Proteomic analysis revealed that extracellular matrix (ECM) derived from smooth muscle cells (SMCs) was abundant in nerve-related active proteins and significantly enriched signaling pathways involved in nerve regeneration. However, whether NGCs based on SMCs-derived ECM modification strategy promote nerve regeneration remains unclear. In the study, we investigated the neuroregenerative effect of SMCs-derived ECM and developed a novel NGC (MyoNerve) by coating small intestinal submucosa (SIS) with SMCs-derived ECM. The SMCs-ECM was rich in neurotrophic factors, which endowed MyoNerve with remarkable neuroregenerative capabilities by promoting the expression of genes implicated in aspects of neuronal maintenance and activating signaling pathways involved in nerve regeneration. <em>In vitro</em>, MyoNerve exhibited excellent bioactivity for accelerating angiogenesis, regulating macrophages polarization, promoting the proliferation, migration and elongation of Schwann cells, enhancing differentiation of PC12 cells, and inducing the neurite outgrowth of dorsal root ganglia. In the model of rat sciatic nerve 10 mm defect, MyoNerve showed great potential for functional nerve regeneration by promoting angiogenesis, proliferation and migration of Schwann cells and neuron, axonal regeneration, remyelination, and neurological functional recovery.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123346"},"PeriodicalIF":12.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848502","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":"Bioengineered metastatic cancer nanovaccine with a TLR7/8 agonist for needle-free intranasal immunization","authors":"Jae Min Jung ,&nbsp;Min Sang Lee ,&nbsp;Young Kyu Seo ,&nbsp;Jung Eun Lee ,&nbsp;Su Yeon Lim ,&nbsp;Dahwun Kim ,&nbsp;Siyan Lyu ,&nbsp;Chaeeun Park ,&nbsp;Byung Deok Kim ,&nbsp;Ju Hwa Shin ,&nbsp;Ji Hyun Lee ,&nbsp;Pin Liu ,&nbsp;Junku Jung ,&nbsp;João Conde ,&nbsp;Thavasyappan Thambi ,&nbsp;Ji Hoon Jeong ,&nbsp;Doo Sung Lee","doi":"10.1016/j.biomaterials.2025.123331","DOIUrl":"10.1016/j.biomaterials.2025.123331","url":null,"abstract":"<div><div>Recent outbreaks and the global spread of infectious diseases increased the need for the development of mucosal vaccines because of their ability to induce both an antigen-specific humoral and cellular immune response. Vaccines are commonly administered via a systemic route which is ineffective at inducing mucosal immunity. Therefore, developing mucosal vaccines is necessary to prevent and treat diseases that could not only elicit mucosal immune responses but also facilitate mass vaccination via a needle-free approach. Despite the benefits of mucosal vaccines, inducing mucosal immunity remains difficult due to the low antigen stability at mucosal sites. Herein, we developed a co-delivery platform using a polymeric nanoparticle carrier to upregulate the immune responses by improving the antigen's stability. Through hydrophobic and ionic interactions, the cationic polymeric nanoparticle composed of secondary bile acid conjugated polyethyleneimine (DA3) can load both TLR7/8 agonist resiquimod (R848) and anionic ovalbumin (OVA) antigen. The DA3/R848/OVA nanovaccine based co-delivery system can boost immune responses through binding affinity with dendritic cells (DCs). The results showed that DA3/R848/OVA could activate DCs better than OVA or OVA + R848. Furthermore, the nanovaccine demonstrated a strong therapeutic effect by significantly suppressing tumor growth in a B16-OVA melanoma model. Additionally, prophylactic immunization with the nanovaccine effectively induced immunological memory, leading to sustained tumor suppression upon challenge. Intranasal delivery of DA3/R848/OVA upregulates the antitumor effect in the metastatic lung tumor foci and the survival rates. These results suggest that intranasal immunization using the DA3/R848/OVA nanovaccine can promote needle-free vaccination.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123331"},"PeriodicalIF":12.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848720","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":"NIR-II AIEgen with high photothermal efficiency for mild PTT: Optimized natural killer cell spatial distribution for boosted immune response","authors":"Yan Feng ,&nbsp;Junjun Ni ,&nbsp;Huilin Xie ,&nbsp;Na Zhu ,&nbsp;Wenjing Liu ,&nbsp;Liang Guo ,&nbsp;Jianquan Zhang ,&nbsp;Jia Di ,&nbsp;Shuixiang He ,&nbsp;Hao Hu ,&nbsp;Hui Xing ,&nbsp;Feng Xu ,&nbsp;Guorui Jin ,&nbsp;Ben Zhong Tang ,&nbsp;Xiaoran Yin","doi":"10.1016/j.biomaterials.2025.123340","DOIUrl":"10.1016/j.biomaterials.2025.123340","url":null,"abstract":"<div><div>Organic photothermal agents (PTAs) with high photothermal conversion efficiency (PCE) and biocompatibility are ideal for mild photothermal therapy (PTT), which can selectively eliminate tumor cells and elicit an active immune response. However, the challenge lies in developing PTAs with high PCE, and the impact of PTT-induced temperature gradients on the cytolytic potential of natural killer (NK) cells against tumor cells has yet been investigated. Herein a novel NIR-II aggregation-induced emission (AIE) molecule named C12T-BBT is proposed by conjugating an electron donor TPA with a strong electron acceptor BBT, using a long alkyl chain (C12) substituted thiophene as <em>π</em>-bridge. By doing this, C12T-BBT has a relative planar structure to ensure a high extinction coefficient, while the long alkyl chain restricts the <em>π-π</em> interaction and provides more room for molecular motion in excited state. Together, these design strategies assure C12T-BBT with a high PCE of 84.7 %. In vivo experiments exhibit favorable NIR-II imaging and tumor elimination using water-soluble cRGD@C12T-BBT nanoparticles. The application of mild PTT results in an effective induction of NK cell response in terms of shortening its distance with tumor cells from 25.6 μm to 10.6 μm, characterized using a machine-learning based spatial analysis, thereby enhancing the efficacy of cancer therapy. Therefore, this work provides evidence for a novel combined anti-tumor strategy of aligning mild PTT and NK cell immunotherapy by illustrating crucial optimization of NK-tumor intercellular proximity in mild PTT.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123340"},"PeriodicalIF":12.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848563","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":"Aminated fullerene for comprehensive dry eye therapy: Promoting epithelial-barrier reconstruction and nerve regeneration by suppressing oxidation and inflammation","authors":"Ying Lyu ,&nbsp;Qichuan Yin ,&nbsp;Xiaodan Liao ,&nbsp;Youxuan Xie ,&nbsp;Hao Yang ,&nbsp;Yilei Cui ,&nbsp;Yuqi Han ,&nbsp;Ke Yao ,&nbsp;Chunru Wang ,&nbsp;Xingchao Shentu","doi":"10.1016/j.biomaterials.2025.123329","DOIUrl":"10.1016/j.biomaterials.2025.123329","url":null,"abstract":"<div><div>Dry eye disease (DED) affects up to 50 % of the global population, leading to serious discomforts that affect patients’ quality of life. In the multifactorial etiology of DED, oxidative stress is at the core, initiating a sequence of inflammatory responses and surface damage via a vicious cycle. However, current therapies merely have a narrow focus on inflammation. In this study, we developed a novel antioxidative eye drop, ethylenediamine (EDA)-modified C₇₀ fullerene derivatives (abbreviated as FN-EDA), to break this vicious cycle. FN-EDA was successfully synthesized by modifying C₇₀ fullerene with multiple ethylenediamine (EDA) groups, resulting in enhanced water solubility and a positive charge. This modification significantly improved ocular surface retention time, cellular uptake, and lysosomal escape <em>in vitro</em>. Therapeutically, FN-EDA significantly alleviated dry eye disease (DED) in a mouse model. It reduced corneal epithelial damage by 3.8-fold compared to 0.05 % cyclosporine A (CsA) and restored tear secretion to approximately 65 % of the normal level. Mechanistically, both <em>in vivo</em> and <em>in vitro</em> results demonstrate that FN-EDA is endowed with superior biological activity in effectively scavenging excessive oxidative stress, down-regulating proinflammatory cytokines expression, and promoting epithelial barrier reconstruction, even recovering corneal innervation. Thus, our findings open an avenue to make this multi-functional eye drop a promising candidate for DED.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123329"},"PeriodicalIF":12.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858782","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":"Multifunctional albumin-based hydrogel/microglia composites enhancing the therapeutic potential of neonatal microglia in complex spinal cord injuries and sealing dural rupture","authors":"Shang Li ,&nbsp;Yijian Guo ,&nbsp;Xiaoyu Zhou ,&nbsp;Can Li ,&nbsp;Yatian Hong ,&nbsp;Mingxin Li ,&nbsp;Qingchen Zhang ,&nbsp;Bin Ning ,&nbsp;Yanyan Jiang","doi":"10.1016/j.biomaterials.2025.123327","DOIUrl":"10.1016/j.biomaterials.2025.123327","url":null,"abstract":"<div><div>Treatment for spinal cord injuries (SCIs) remains largely ineffective, with scar formation and neural degeneration being major barriers to functional recovery. Neonatal microglia have shown potential in reducing scar formation and promoting axonal regrowth. However, cell viability and retention at the injury site are often suboptimal. The hostile post-SCI inflammatory microenvironment leads to poor cell survival and the dural damage that is frequently associated with SCIs results in cell loss. To address these challenges, we have developed an albumin-based hydrogel. This hydrogel creates a favorable microenvironment for the encapsulated cells, mimicking the extracellular matrix and enhancing the viability of the transplanted cells. <em>In vivo</em> studies demonstrate its efficacy in preventing scar formation, promoting axonal regeneration, and sealing the dura. Importantly, this hydrogel leverages albumin, a natural polymer in the body, and is synthesized through a simple process, making it highly feasible for clinical translation. In summary, this albumin hydrogel is a valuable delivery vehicle that enhances the therapeutic potential of neonatal microglia in treating SCIs, particularly those involving dural rupture.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123327"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817797","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":"Orally-deliverable liposome-microgel complexes dynamically remodel intestinal environment to enhance probiotic ulcerative colitis therapy via TLR4 inhibition and tryptophan metabolic crosstalk","authors":"Yuanyuan Fu ,&nbsp;Ting Wang ,&nbsp;Xinyue Ge ,&nbsp;Hong Wen ,&nbsp;Yang Fei ,&nbsp;Menghuan Li ,&nbsp;Zhong Luo","doi":"10.1016/j.biomaterials.2025.123339","DOIUrl":"10.1016/j.biomaterials.2025.123339","url":null,"abstract":"<div><div>Probiotics emerges as a promising option for ulcerative colitis (UC) treatment, but its application remains challenging due to insufficient colon-targeted delivery efficiency and survival against the inflammation-associated intestinal oxidative stress. To address these issues, here we report a supramolecular liposome-microgel complex (SLMC) incorporated with Bacillus subtilis spores (BSSs) and dexamethasone (DEX) for orally-deliverable probiotic UC therapy. Specifically, BSSs and cholesterols were conjugated with gelatin via diselenide ligation to prepare microgels, followed by supramolecular complexation with UC-targeted DEX-loaded liposome via microfluidic engineering. The orally-administered SLMC efficiently accumulated in UC-affected colonic sites to release BSSs and DEX. DEX elicited rapid anti-inflammatory effect to reduce ROS generation, which cooperated with the ROS consumption by spore germination and diselenide cleavage to orchestrate an anaerobic intestinal microenvironment, thus promoting Bacillus subtilis colonization to restore gut homeostasis and initiate anti-inflammatory microbiota-macrophage metabolic crosstalk. Indeed, in vivo analysis showed that the SLMC treatment markedly inhibited pro-inflammatory TLR4-NF-κB signaling activities in mucosal macrophages through localized DEX delivery and boosting tryptophan metabolite production, leading to robust and durable UC abolishment. This study offers a practical approach for improving UC treatment in the clinic.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123339"},"PeriodicalIF":12.8,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830309","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}