Biomaterials最新文献

{"title":"On-demand reprogramming of immunosuppressive microenvironment in tumor tissue via multi-regulation of carcinogenic microRNAs and RNAs dependent photothermal-immunotherapy using engineered gold nanoparticles for malignant tumor treatment","authors":"Li Chen ,&nbsp;Wenjun Tang ,&nbsp;Jie Liu ,&nbsp;Man Zhu ,&nbsp;Wenyun Mu ,&nbsp;Xiaoyu Tang ,&nbsp;Tao Liu ,&nbsp;Zeren Zhu ,&nbsp;Lin Weng ,&nbsp;Yumeng Cheng ,&nbsp;Yanmin Zhang ,&nbsp;Xin Chen","doi":"10.1016/j.biomaterials.2024.122956","DOIUrl":"10.1016/j.biomaterials.2024.122956","url":null,"abstract":"<div><div>The frequent immune escape of tumor cells and fluctuating therapeutic efficiency vary with each individual are two critical issues for immunotherapy against malignant tumor. Herein, we fabricated an intelligent core-shell nanoparticle (SNAs@CCM_R) to significantly inhibit the PD-1/PD-L1 mediated immune escape by on-demand regulation of various oncogenic microRNAs and perform RNAs dependent photothermal-immunotherapy to achieve precise and efficient treatment meeting the individual requirements of specific patients by in situ generation of customized tumor-associated antigens. The SNAs@CCM_R consisted of antisense oligonucleotides grafted gold nanoparticles (SNAs) as core and TLR7 agonist imiquimod (R837) functionalized cancer cell membrane (CCM) as shell, in which the acid-labile Schiff base bond was used to connect the R837 and CCM. During therapy, the acid environment of tumor tissue cleaved the Schiff base to generate free R837 and SNAs@CCM. The SNAs@CCM further entered tumor cells via CCM mediated internalization, and then specifically hybridized with over-expressed miR-130a and miR-21, resulting in effective inhibition of the migration and PD-L1 expression of tumor cells to avoid their immune escape. Meanwhile, the RNAs capture also caused significant aggregation of SNAs, which immediately generated photothermal agents within tumor cells to perform highly selective photothermal therapy under NIR irradiation. These chain processes not only damaged the primary tumor, but also produced plenty of tumor-associated antigens, which matured the surrounding dendritic cells (DCs) and activated anti-tumor T cells along with the released R837, resulting in the enhanced immunotherapy with suppressive immune escape. Both in vivo and in vitro experiments demonstrated that our nanoparticles were able to inhibit primary tumor and its metastasis via multi-regulation of carcinogenic microRNAs and RNAs dependent photothermal-immune activations, which provided a promising strategy to reprogram the immunosuppressive microenvironment in tumor tissue for better malignant tumor therapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122956"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643588","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":"Pulmonary delivery of dual-targeted nanoparticles improves tumor accumulation and cancer cell targeting by restricting macrophage interception in orthotopic lung tumors","authors":"Di Ge ,&nbsp;Siqi Ma ,&nbsp;Tingting Sun ,&nbsp;Yunfei Li ,&nbsp;Jiaxing Wei ,&nbsp;Chenao Wang ,&nbsp;Xiaoyuan Chen ,&nbsp;Yonghong Liao","doi":"10.1016/j.biomaterials.2024.122955","DOIUrl":"10.1016/j.biomaterials.2024.122955","url":null,"abstract":"<div><div>Despite the recognized potential of inhaled nanomedicines to enhance and sustain local drug concentrations for lung cancer treatment, the influence of macrophage uptake on targeted nanoparticle delivery to and within tumors remains unclear. Here, we developed three ligand-coated nanoparticles for pulmonary delivery in lung cancer therapy: phenylboronic acid-modified nanoparticles (PBA-NPs), PBA combined with folic acid (FA-PBA-NPs), and PBA with mannose (MAN-PBA-NPs). <em>In vitro,</em> MAN-PBA-NPs were preferentially internalized by macrophages, whereas FA-PBA-NPs exhibited superior uptake by cancer cells compared to macrophages. Following intratracheal instillation into mice with orthotopic Lewis lung carcinoma tumors, all three nanoparticles showed similar lung retention. However, MAN-PBA-NPs were more prone to interception by lung macrophages, which limited their accumulation in tumor tissues. In contrast, both PBA-NPs and FA-PBA-NPs achieved comparable high tumor accumulation (∼11.3% of the dose). Furthermore, FA-PBA-NPs were internalized by ∼30% of cancer cells, significantly more than the 10–18% seen with PBA-NPs or MAN-PBA-NPs. Additionally, FA-PBA-NPs loaded with icaritin effectively inhibited the Wnt/β-catenin pathway, resulting in superior anti-tumor efficacy through targeted cancer cell delivery. Overall, FA-PBA-NPs demonstrated advantageous competitive uptake kinetics by cancer cells compared to macrophages, enhancing tumor targeting and therapeutic outcomes.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122955"},"PeriodicalIF":12.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637985","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":"Visible light-induced simultaneous bioactive amorphous calcium phosphate mineralization and in situ crosslinking of coacervate-based injectable underwater adhesive hydrogels for enhanced bone regeneration","authors":"Jinyoung Yun ,&nbsp;Hyun Tack Woo ,&nbsp;Sangmin Lee ,&nbsp;Hyung Joon Cha","doi":"10.1016/j.biomaterials.2024.122948","DOIUrl":"10.1016/j.biomaterials.2024.122948","url":null,"abstract":"<div><div>The field of bone tissue engineering is vital due to increasing bone disorders and limitations of traditional grafts. Injectable hydrogels offer minimally invasive solutions but often lack mechanical integrity and biological functionality, including osteoinductive capacity and structural stability under physiological conditions. To address these issues, we propose a coacervate-based injectable adhesive hydrogel that utilizes the dual functionality of <em>in situ</em> photocrosslinking and osteoinductive amorphous calcium phosphate formation, both of which are activated simultaneously by visible light irradiation. The developed hydrogel formulation integrated a photoreactive agent with calcium ions and phosphonodiol in a matrix of tyramine-conjugated alginate and RGD peptide-fused bioengineered mussel adhesive protein, promoting rapid setting, robust underwater adhesion, and bioactive mineral deposition. The hydrogel also exhibited superior mechanical properties, including enhanced underwater tissue adhesive strength and compressive resistance. <em>In vivo</em> evaluation using a rat femoral tunnel defect model confirmed the efficacy of the developed adhesive hydrogel in facilitating easy application to irregularly shaped defects through injection, rapid bone regeneration without the addition of bone grafts, and integration within the defect sites. This injectable adhesive hydrogel system holds significant potential for advancing bone tissue engineering, providing a versatile, efficient, and biologically favorable alternative to conventional bone repair methodologies.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122948"},"PeriodicalIF":12.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613396","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":"Emerging COX-2 inhibitors-based nanotherapeutics for cancer diagnosis and treatment","authors":"Ruiping Huang ,&nbsp;Jiang Yu ,&nbsp;Baoyue Zhang ,&nbsp;Xin Li ,&nbsp;Hongzhuo Liu ,&nbsp;Yongjun Wang","doi":"10.1016/j.biomaterials.2024.122954","DOIUrl":"10.1016/j.biomaterials.2024.122954","url":null,"abstract":"<div><div>Increasing evidence has showed that tumorigenesis is closely linked to inflammation, regulated by multiple signaling pathways. Among these, the cyclooxygenase-2/prostaglandin E₂ (COX-2/PGE₂) axis plays a crucial role in the progression of both inflammation and cancer. Inhibiting the activity of COX-2 can reduce PGE₂ secretion, thereby suppressing tumor growth. Therefore, COX-2 inhibitors are considered potential therapeutic agents for cancers. However, their clinical applications are greatly hindered by poor physicochemical properties and serious adverse effects. Fortunately, the advent of nanotechnology offers solutions to these limitations, enhancing drug delivery efficiency and mitigating adverse effects. Given the considerable progress in this area, it is timely to review emerging COX-2 inhibitors-based nanotherapeutics for cancer diagnosis and therapy. In this review, we first outline the various antineoplastic mechanisms of COX-2 inhibitors, then comprehensively summarize COX-2 inhibitors-based nanotherapeutics for cancer monotherapy, combination therapy, and diagnosis. Finally, we highlight and discuss future perspectives and challenges in the development of COX-2 inhibitors-based nanomedicine.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122954"},"PeriodicalIF":12.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643587","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 precision intelligent nanomissile for inhibiting tumor metastasis, boosting energy deprivation and immunotherapy","authors":"Shan Gao ,&nbsp;Meng Liu ,&nbsp;Yu Zhang ,&nbsp;Zhijing He ,&nbsp;Yingying Li ,&nbsp;Jianbo Ji ,&nbsp;Lei Ye ,&nbsp;Xiaoye Yang ,&nbsp;Guangxi Zhai","doi":"10.1016/j.biomaterials.2024.122953","DOIUrl":"10.1016/j.biomaterials.2024.122953","url":null,"abstract":"<div><div>The epithelial-mesenchymal transition (EMT), tumor stroma and local metabolic alterations cooperate to establish a unique tumor microenvironment (TME) that fosters tumor progression and metastasis. To tackle this challenge, a precision intelligent nanomissile named HA@AT-Pd has been designed for dual-pronged cancer-associated fibroblast (CAF) transformation and tumor cell elimination. It is observed that HA@AT-Pd inhibits the production of cancer stem cells (CSCs) by blocking the TGF-β/Smad signaling pathway-mediated EMT and reversing activated CAFs to quiescence. Notably, HA@AT-Pd induces energy depletion in breast cancer cells through simultaneously suppressing cellular oxidative phosphorylation and glycolysis. The inhibition of glycolysis results in reduced lactic acid production, thereby converting an immunosuppressive TME into an immune-activating environment. Furthermore, the photothermal effect generated by HA@AT-Pd evokes immunogenic cell death, which can further enhance the anti-tumor immune response. Overall, this multifunctional combination strategy unveils potential therapeutic avenues to inhibit tumor progression and metastasis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122953"},"PeriodicalIF":12.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613386","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":"Aggregation-induced emission-based phototheranostics to combat bacterial infection at wound sites: A review","authors":"Zhurun Fang ,&nbsp;Shixuan Zhang ,&nbsp;Wentao Wang ,&nbsp;Yan Xu ,&nbsp;Mengmeng Lu ,&nbsp;Yuxin Qian ,&nbsp;Xiyan Xiao ,&nbsp;Yuanyuan Li ,&nbsp;Ben Zhong Tang ,&nbsp;Ming Zhang","doi":"10.1016/j.biomaterials.2024.122950","DOIUrl":"10.1016/j.biomaterials.2024.122950","url":null,"abstract":"<div><div>The healing of chronic wounds infected by bacteria has attracted increasing global concerns. In the past decades, antibiotics have certainly brought hope to cure bacteria-infected chronic wounds. However, the misuse of antibiotics leads to the emergence of numerous multidrug-resistant bacteria, which aggravate the health threat to clinical patients. To address these increasing challenges, scientists are committed to creating novel non-antibiotic strategies to kill bacteria and promote bacteria-infected chronic wound healing. Fortunately, with the quick development of nanotechnology, the representatives of phototherapy, such as photothermal therapy (PTT) and photodynamic therapy (PDT), exhibit promising possibilities in promoting bacteria-infected wound healing. Well-known, photothermal agents and photosensitizers largely determine the effects of PTT and PDT. A common problem for these molecules is the aggregation-induced quenching effect, which highly limits their further applicability in biomedical and clinical fields. Fortunately, the occurrence of aggregation-induced emission luminogens (AIEgens) efficiently overcomes the photobleaching and exhibit advantages, such as strongly aggregated emission, superior photostability, aggregation-enhanced reactive oxygen species (ROS), and heat generation, which makes great sense to the development of PTT and PDT. This article reviews various studies conducted on novel AIEgen-based materials that can mediate potent PDT, PTT, and a combination of PDT and PTT to promote bacteria-infected chronic wound healing.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122950"},"PeriodicalIF":12.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613389","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":"Engineered VNP20009 expressing IL-15&15Rα augments anti-tumor immunity for bladder cancer treatment","authors":"Bo Liu ,&nbsp;Kaiwei Wang ,&nbsp;Qiaofeng Li ,&nbsp;Zhisheng Xiao ,&nbsp;Zihao Chen ,&nbsp;Yuting Zhang ,&nbsp;Yuzhe Wu ,&nbsp;Yuchun Xu ,&nbsp;Yumin Wu ,&nbsp;Zhuang Liu","doi":"10.1016/j.biomaterials.2024.122951","DOIUrl":"10.1016/j.biomaterials.2024.122951","url":null,"abstract":"<div><div>Surgical resection combined with intravesical instillation of chemotherapeutics or Bacillus Calmette-Guerin (BCG) to remove residual cancer cells is the gold standard for the clinical treatment of patients with bladder cancer. In a recent clinical trial, a new super-agonist complex of IL-15 - N803, has shown promising results when used in combination with BCG to treat patients with bladder cancer who do not respond to BCG. Herein, we used temperature-controlled pBV220 plasmid encoding Interleukin-15 and its receptor alpha subunit (IL-15&amp;15Rα) to transform VNP20009, an attenuated salmonella typhimurium strain, obtaining engineered bacteria named 15&amp;15Rα@VNP. After induction at 42 °C, 15&amp;15Rα@VNP can secrete functional IL-15&amp;15Rα stably. It was found that intravesical instillation of thermally activated 15&amp;15Rα@VNP could inhibit the growth of bladder tumors if used alone. Moreover, the sequential intravesical instillation of epirubicin (EPI), a first-line bladder cancer drug, followed by thermally activated 15&amp;15Rα@VNP, could achieve further improved therapeutic responses, without causing significant side effects. Therefore, this study shows that 15&amp;15Rα@VNP can be effectively used in the treatment of bladder cancer and can be used as a complementary therapy to chemotherapy agents, promising for potential clinical translation in bladder cancer treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122951"},"PeriodicalIF":12.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613392","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":"Transplantation of peripheral nerve tissueoid based on a decellularized optic nerve scaffold to restore rat hindlimb sensory and movement functions","authors":"Zhao-Wei Zhu ,&nbsp;Ge Li ,&nbsp;Guang-Geng Wu ,&nbsp;Yu-Jing Zhang ,&nbsp;Yu-Rong Bai ,&nbsp;Bi-Qin Lai ,&nbsp;Ying Ding ,&nbsp;Xiang Zeng ,&nbsp;Yuan-Huan Ma ,&nbsp;Shu Liu ,&nbsp;Rui Wang ,&nbsp;Jing-Hua Liang ,&nbsp;Yang-Bin Xu ,&nbsp;Bo He ,&nbsp;Yuan-Shan Zeng","doi":"10.1016/j.biomaterials.2024.122949","DOIUrl":"10.1016/j.biomaterials.2024.122949","url":null,"abstract":"<div><div>Peripheral nerve injury (PNI) involving the loss of sensory and movement functions is challenging to repair. Although the gold standard of PNI repair is still the use of autologous nerve grafts, the destruction of the donor side is inevitable. In the present study, peripheral nerve tissueoids (PNTs) composed of a Schwann cell (SC)-based neurotrophin-3 (NT-3) delivery system and a decellularized optic nerve (DON) with naturally oriented channels were engineered to investigate the mechanism of PNTs in nerve regeneration. Proteomic analysis and mRNA sequencing revealed that PNTs have the advantage of promoting nerve regeneration by the three mechanisms of chemotaxis, adhesion and intrinsic mobilisation. The results demonstrated that a local NT-3-enriched pool was constructed by laminin γ3 (LAMC3) in PNTs, creating a niche for the colonization of TrkC-positive SCs, attraction of axons to the defect/graft area, and remyelination. In addition, LAMC3 in PNTs can rapidly promote axon adhesion through integrin aVβ6 and can precisely guide long projecting axons to target tissues. Furthermore, the interactions among the NT-3/TrkC, LAMC3/integrin aVβ6 and the scaffold synergistically activate the PI3K-AKT signalling pathway in damaged neurons, further stimulating the intrinsic regenerative drive within the neurons to ultimately achieve the rapid reinnervation and the improvement of sensory and movement functions in the hindlimb.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122949"},"PeriodicalIF":12.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613394","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":"A 3D-printed microdevice encapsulates vascularized islets composed of iPSC-derived β-like cells and microvascular fragments for type 1 diabetes treatment","authors":"Shuang Chen,&nbsp;Wenshuang Wang,&nbsp;Lanlin Shen,&nbsp;Haofan Liu,&nbsp;Jing Luo,&nbsp;Yushuang Ren,&nbsp;Susu Cui,&nbsp;Yixin Ye,&nbsp;Gang Shi,&nbsp;Fuyi Cheng,&nbsp;Xiaolan Su,&nbsp;Lei Dai,&nbsp;Maling Gou,&nbsp;Hongxin Deng","doi":"10.1016/j.biomaterials.2024.122947","DOIUrl":"10.1016/j.biomaterials.2024.122947","url":null,"abstract":"<div><div>Transplantation of insulin-secreting cells provides a promising method for re-establishing the autonomous blood glucose control ability of type 1 diabetes (T1D) patients, but the low survival of the transplanted cells hinder the therapeutic efficacy. In this study, we 3D-printed an encapsulation system containing β-like cells and microvascular fragments (MVF), to create a retrivable microdevice with vascularized islets in vivo for T1D therapy. The functional β-like cells were differentiated from the urine epithelial cell-derived induced pluripotent stem cells (UiPSCs). Single-cell RNA sequencing provided an integrative study and macroscopic developmental analyses of the entire process of differentiation, which revealed the developmental trajectory of differentiation in vitro follows the developmental pattern of embryonic pancreas in vivo. The MVF were isolated from the epididymal fat pad. The microdevice with a groove structure were rapidly fabricated by the digital light processing (DLP)-3D printing technology. The β-like cells and MVF were uniformly distributed in the device. After subcutaneous transplantation into C57BL/6 mice, the microdevice have less collagen accumulation and low immune cell infiltration. Moreover, the microdevice encapsulated vascularized islets reduced hyperglycemia in 33 % of the treated mice for up to 100 days without immunosuppressants, and the humanized C-peptide was also detected in the serum of the mice. In summary, we described the microdevice-protected vascularized islets for long-term treatment of T1D, with high safety and potential clinical transformative value, and may therefore provide a translatable solution to advance the research progress of β cell replacement therapy for T1D.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122947"},"PeriodicalIF":12.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637983","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":"UC-MSCs based on biomimetic microniche exert excellent regulatory effects on acute brain inflammation through advantageous properties","authors":"Bichun Zhao ,&nbsp;Chao Wang ,&nbsp;Manqiang Sun ,&nbsp;Xiaocao Ma ,&nbsp;Quan Zeng ,&nbsp;Jiafei Xi ,&nbsp;Junnian Zhou ,&nbsp;Xuetao Pei ,&nbsp;Yali Jia ,&nbsp;Wen Yue","doi":"10.1016/j.biomaterials.2024.122945","DOIUrl":"10.1016/j.biomaterials.2024.122945","url":null,"abstract":"<div><div>Neuroinflammation triggered by activated microglia leads to neuronal damage and, to a certain extent, neurodegeneration. Human umbilical cord mesenchymal stem cells (UC-MSCs) have good immunomodulatory and neuroprotective effects as well as therapeutic potential for neuroinflammation-related diseases. However, the complex microenvironment created by neuroinflammation poses a challenge to transplanted UC-MSCs. The emerging biomimetic microniche (BN)-based culture technology provides new opportunities to optimize the preparation of UC-MSCs; but the fundamental changes in the characteristics of UC-MSCs based on BN remain unclear, and more reliable preclinical data are needed to support their ability to regulate inflammation. Here, we systematically studied the cellular properties and inflammation regulatory capacity of UC-MSCs in conventional static planar culture (SP-UCMSCs) and suspension culture based on BN (BN-UCMSCs). <em>In vitro</em>, compared with SP-UCMSCs, BN-UCMSCs not only maintained the fundamental characteristics of MSCs, but also significantly enhanced cell proliferation, adhesion, and migration capabilities, etc; notably, the paracrine function and anti-inflammatory capacity of BN-UCMSCs were also enhanced. We further established a murine model of acute brain inflammation and demonstrated that the expression level of pro-inflammatory cytokines in hippocampal and cortical tissues of the BN-UCMSCs group was significantly decreased compared with that in the SP-UCMSCs group. Subsequent transcriptomic analysis of hippocampal and cortical tissues revealed that BN-UCMSCs had the advantage of significantly reducing the expression of pro-inflammatory cytokines through the TLR4-Myd88-NF-κB axis, which was further validated at the gene and protein levels. Taken together, these data strongly indicated that BN-UCMSCs exerts excellent regulatory effects on acute brain inflammation through advantageous properties.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122945"},"PeriodicalIF":12.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613395","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}