Biomaterials Advances
·
2025
·
IF 6
Long Yang,Yufei Liu,Yong Yang,Yuhu Zhou,Zihao Zou,Min He,Changlei Yang,Daizhu Yuan,Jieheng Wu,Chuan Ye
Artificial bone substitutes have garnered significant attention within the field of biomaterials, and the use of tissue engineering technology to repair bone defects has emerged as a promising alternative. However, when artificial bone substitutes are implanted in the body, they can induce many adverse cellular and tissue immune responses. In this study, we use coaxial electrospinning technology to fabricate microfiber with controllable diameter, excellent mechanical properties and surface porous structure. Poly(3-hydroxybutyrate- co -4-hydroxybutyrate) (P34HB) and polyethylene glycol (PEG) were used as shell solutions and polyvinyl alcohol (PVA) and bone morphogenetic protein-2 (BMP-2) peptides as core solutions. Compared to PVA/P34HB-PEG (P/P-P) scaffolds, PVA-BMP-2/P34HB-PEG (P-B/P-P) scaffolds polarized more human monocytic leukemia cell line (THP-1 cells) toward alternatively activated macrophages (M2), as demonstrated by increased M2 and decreased classically activated macrophage (M1) phenotypic marker expression in the cells. P-B/P-P microfibers have the potential to regulate the polarization state of macrophages, induce them to differentiate into an M2 phenotype and inhibit the inflammatory response of surrounding tissues. In addition, microfibers with a hollow porous structure facilitate the controlled release of BMP-2 peptides by regulating the fiber diameter, enhancing the differentiation of pre-osteoblastic cell line derived from mouse calvaria (MC3T3-E1) cells in an osteogenic direction and facilitating the repair of bone defects in vivo. This study presents microfibers essential for modulating the osteoimmune microenvironment, facilitating efficient bone regeneration.
研究领域:
生物材料
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组织工程
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免疫调节
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骨再生
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纳米纤维技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Rufeng Jia,Yanyan He,Jia Liang,Lin Duan,Chi Ma,Taoyuan Lu,Wenbo Liu,Shikai Li,Haigang Wu,Huixia Cao,Tianxiao Li,Yingkun He
Magnesium alloy is an excellent material for biodegradable cerebrovascular stents. However, the rapid degradation rate of magnesium alloy will make stent unstable. To improve the biocompatibility of magnesium alloy, in this study, biodegradable sodium alginate and carboxymethyl chitosan (SA/CMCS) was used to coat onto hydrothermally treated the surface of magnesium alloy by a dipping coating method. The results show that the SA/CMCS coating facilitates the growth, proliferation, and migration of endothelial cells and promotes neovascularization. Moreover, the SA/CMCS coating suppresses macrophage activation while promoting their transformation into M2 type macrophages. Overall, the SA/CMCS coating demonstrates positive effects on the safety and biocompatibility of magnesium alloy after implantation, and provide a promising therapy for the treatment of intracranial atherosclerotic stenosis in the future.
研究领域:
材料科学
·
生物医学工程
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生物材料
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Meng Zhang,Yiqing Ye,Zhengyun Chen,Xiaodong Wu,Yue Chen,Pengfei Zhao,Mengdan Zhao,Caihong Zheng
Endometriosis seriously affects 6–10% of reproductive women globally and poses significant clinical challenges. The process of ectopic endometrial cell colonization shares similarities with cancer, and a dysfunctional immune microenvironment, characterized by non-classically polarized macrophages, plays a critical role in the progression of endometriosis. In this study, a targeted nano delivery system (BSA@Mif NPs) was developed using bovine serum albumin (BSA) as the carrier of mifepristone. The BSA@Mif NPs were utilized to selectively target M2 macrophages highly enriched in ectopic endometrial tissue via the SPARC receptor. This targeting strategy increases drug concentration at ectopic lesions while minimizing its distribution to normal tissue, thereby reducing side effects. In vitro studies demonstrated that BSA@Mif NPs not only enhanced the cellular uptake of M2-type macrophages and ectopic endometrial cells but also improved the cytotoxic effect of mifepristone on ectopic endometrial cells. Furthermore, the BSA@Mif NPs effectively induced immunogenic cell death (ICD) in ectopic endometrial cells and repolarized M2-type macrophages toward the M1 phenotype, resulting in a synergistic inhibition of ectopic endometrial cell growth. In vivo experiments revealed that BSA@Mif NPs exhibited significant therapeutic efficacy in endometriosis-bearing mice by increasing drug accumulation in the endometriotic tissues and modulating the immune microenvironment. This targeted biomimetic delivery strategy presents a promising approach for the development of endometriosis-specific therapies based on existing drugs. Statement of Significance Macrophages play an essential role in immune dysfunctional microenvironment promoting the occurrence and progression of endometriosis and can be a crucial target for developing immune microenvironment regulation strategies for the unmet long-term management of endometriosis. The albumin nanoparticles constructed based on SPARC overexpression in macrophages and endometrial cells and albumin biosafety can achieve the targeted therapy of endometriosis by increasing the passive- and active-mediated drug accumulation in ectopic endometrium and remodeling the immune microenvironment based on macrophage regulation. This study has the following implications: i) overcoming the inherent shortcomings of clinical drugs by nanotechnology is an alternative way of developing medication; ii) developing microenvironment modulation strategies based on macrophage regulation for endometriosis management is feasible.
研究领域:
妇科学
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药学
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纳米技术
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Meng Yang,Bingyi Wang,Ying Yin,Xiaoyue Ma,Lin Tang,Yu Zhang,Qin Fan,Tieying Yin,Yazhou Wang
Glioblastoma (GBM) is a malignant brain tumor with a poor prognosis that is highly heterogeneous and invasive. One of the most major challenges of GBM treatment in the clinic is the blood-brain barrier (BBB). Additionally, the tumor microenvironment (TME) is highly enriched with immunosuppressed M2-like tumor-associated macrophages (M2 TAMs) and glioblastoma stem cells (GSCs), which promoted the malignancy of GBM through the PTN-PTPRZ1 signaling axis. Here, we developed a self-assembled dual-targeted hybrid micelle (DT-GM1) as a nanocarrier to deliver the chemotherapeutic agent doxorubicin (DOX). We demonstrated that this DT-GM1/DOX can cross the BBB using in vitro and in vivo GBM models, and that M2pep and PTPRZ1 antibodies allow it to precisely target the tumor microenvironment where M2 TAMs and GSCs are enriched, increasing intracellular drug accumulation via multiple internalization pathways. Additionally, simultaneous elimination of M2 TAMs and GSCs blocked the PTN-PTPRZ1 signaling axis, resulting in less M2 TAM infiltration and increased polarization to the M1 phenotype, reshaping the immune microenvironment. Overall, we have established a nanocarrier that can penetrate the BBB and target the TME while also synergizing with GBM chemotherapeutic agents, providing a promising new strategy for GBM treatment.
研究领域:
肿瘤学
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神经科学
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药学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
Cancer Nanotechnology
·
2023
·Vol. 14
·期 1
·1-21
·
IF 5.7
Wang Hongsheng,Jin Xinmeng,Gao Yinghua,He Xin,Xu Yiming,Mu Haoran,Jiang Yafei,Wang Zhuoying,Yu Chen,Zhang Tao,Hua Yingqi,Cai Zhengdong,Xu Jing,Ma Xiaojun,Sun Wei
Background Tumor angiogenesis, immunosuppression, and progression are all closely correlated with the tumor microenvironment (TME). Immune evasion is supported by both M2 phenotype tumor-associated macrophages (TAMs) and vascular aberrations in the TME. TME reprogramming is a promising therapeutic approach for treating tumors. Anti-angiogenesis has the power to control the polarization of macrophages, prevent progression, and increase drug penetration. Additionally, polyamine blocking therapy can increase CD8 + T cell infiltration and decrease immunosuppressive cells. These results led to developing a potential therapeutic regimen that targets TAMs and angiogenesis to reprogram the osteosarcoma TME. Results For the targeted biomimetic co-delivery of regorafenib and alpha-difluoromethylornithine via the mannose receptor, which is overexpressed in both TAMs and osteosarcoma cells, mannosylated poly(lactide-co-glycolide)-polyethylene glycol nanoparticles (Man-NPs) were synthesized. The superior physiological properties and intratumoral accumulation of the Man-NPs efficiently promoted TAMs polarization and inhibited angiogenesis. Macrophage repolarization further activated immune cells, which contributed to remodeling the TME. Conclusion Overall, these findings suggested that using Man-NPs as an immunotherapeutic approach to treat osteosarcoma may be promising. Graphical Abstract
研究领域:
肿瘤学
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药学
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免疫治疗
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Pengtong Li,Chenxi Huang,Yijie He,Xinyu Lei,Xiaoyan Shen,Jialin Xu,Yunfei Mo,Xiuhong Sun,Ling Zheng,Yuqing Niu
The earliest tissue-engineered vascular grafts (TEVGs) applied clinically are biodegradable scaffolds laden with bone marrow mononuclear cells (BMCs). However, the inability to control BMCs fate after transplantation severely restricts their clinical use. To overcome this limitation, we developed a regenerative TEVG and investigated its role in modulating the immune microenvironment at arterial defects sites to enhance tissue regeneration. This TEVG was fabricated from a degradable elastomeric nanofiber scaffold combined with rBMCs, which had been induced to differentiate into regenerative M2 macrophages through in vitro culture. The resulting M2-derived extracellular matrix (ECM) dynamically modulated scaffold elasticity to match the biomechanical environment of the implantation site. When implanted into a rat abdominal aortic (rAA) defect model, the TEVGs, serving as interpositional artery grafts, could maintain the patency of abdominal artery blood circulation in rats and gradually transform into mature abdominal arteries within 12 months. However, the implanted rBMCs migrated away shortly after implantation. Instead, the scaffolds were initially repopulated by rat monocytes and subsequently gradually replaced by rat endothelial cells (ECs) and smooth muscle cells (SMCs). Further research revealed that the implanted M2 macrophages secrete IL-10 and IL-4, activating CD4 + T cells and initiating the Th2 pathway. IL-4 derived from Th2 cells sustained the M2 macrophages phenotype, forming a positive feedback loop that boosted the regenerative microenvironment-key to restoring arterial function. These findings suggest that integrating BMCs into vascular grafts and regulating the extracellular microenvironment may offers a practical and efficient strategy for treating damaged and diseased arteries. Statement of Significance The earliest clinically applied tissue-engineered vascular grafts (TEVGs) are biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs), but the uncontrolled fate of BMCs after transplantation restricts their clinical use. This study developed a regenerative TEVG combining a degradable elastic nanofiber scaffold with in vitro -induced M2 macrophages. In a rat model, the TEVG maintained arterial patency and transformed into mature arteries within 12 months by activating an M2/Th2 immune positive feedback loop, offering a new strategy for arterial injury treatment.
研究领域:
生物医学工程
·
组织工程
·
免疫学
·
再生医学
·
血管生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Yongyuan Kang,Xiaoqing Liu,Jie Wang,Pai Peng,Min Liang,Qiaoxuan Wang,Weiwei Zheng,Shifen Li,Changyou Gao
The processes of skin wound healing and scar formation are complex, often involving hypoxia and inflammation, which create a pathological microenvironment that impedes normal healing. Improving wound oxygenation and reducing inflammation are crucial for accelerating healing and reducing scarring. Traditional dressings like sponges, gauze, and hydrogels struggle to balance moisture retention, breathability, and exudate absorption. To address these challenges, rod-shaped microgel scaffolds with larger surface areas and interconnected porous structures are explored to enhance gas transport, promoting wound oxygenation and moisture retention, thus accelerating healing and reducing scarring. Nanoparticles (NPs) are used to mediate the formation of microgels-assembled scaffold and to load catalase (CAT) for enhanced bioactivity. In vitro experiments showed that this material alleviated oxidative stress and reduced the activity of hypoxia-inducible factor-1α (HIF-1α), nuclear factor kappa B (NF-κB), and the downstream transforming growth factor-β1 (TGF-β)/Smad pathway in fibroblasts. The incorporation of CAT showed a significant promotion of M2-phenotype macrophage polarization. In vivo studies on rat and rabbit wounds demonstrated that the microgel scaffolds significantly improved exudate absorption and breathability, maintaining a moist and oxygenated environment. These scaffolds reduced tissue hypoxia, accelerated wound healing, and decreased hypertrophic scar formation in vivo. This innovative method leveraged the unique properties of microgels to effectively enhance skin tissue regeneration.
研究领域:
生物医学工程
·
组织工程
·
伤口愈合
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Shuangjun Li,Ruyue Shi,Yankun Liu,Mingcong Niu,Zhicun Liu,Zhongjuan Wang,Jiwang Gao,Hongda Cai,Zhuyu Zhou,Shengnan Li,Xiuhua Zhao
Immune cells infiltrating tumors play a pivotal role in tumor progression regulation; however, their functionality is frequently suppressed by the acidic conditions of the tumor microenvironment (TME). Targeting and reversing tumor acidity holds significant potential for enhancing the efficacy of immunotherapy. Here, we present a proof-of-concept study on tumor acidity-reversal therapy mediated by bacterial cellulose-targeted micelles to promote M2 macrophage repolarization to M1 macrophages and restore the anti-tumor function of T cells. Our strategy utilizes a bacterial cellulose (BC) composite modified with folic acid (FA) and chrysin (BY), loaded with lactic acid-neutralizing chemotherapeutic vincristine (VCR) and lactate dehydrogenase inhibitor GNE-140, to self-assemble into tumor-targeted nanoparticles. Post-treatment, FA-BC-BY@VCR@GNE-140 demonstrated notable efficacy in reversing tumor acidity, inducing tumor cell death, mitigating immunosuppression, and stimulating host adaptive immunity. This approach represents an innovative strategy for synergizing chemotherapy and immunotherapy to combat tumor progression.
研究领域:
肿瘤免疫学
·
纳米医学
·
药物递送
·
肿瘤微环境
·
免疫治疗
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2023
·
IF 5.3
Li Liu,Rong Zhang,Chang Chen,Changbo Xia,Guangda Yao,Xiaogang He,Baomei Xia
It has been reported that Banxia-houpo decoction (BXHPD) serves as the anti-depressant treatment for a mild and severe depressive disease with limited side effects. The present study was performed to evaluate the protective effect of BXHPD on chronic unpredicted mild stress (CUMS)-induced depression and explore its effect on TrkA/Akt-mediated microglia polarization. The CUMS procedure was carried out, and the mice were intragastrically treated with BXHPD once daily. The selective TrkA inhibitor GW441756 was applied to further investigate the role of TrkA in BXHPD-mediated microglia polarization. The behaviour test including open field test (OFT), sucrose preference test (SPT), novelty-suppressed feeding test (NSFT), tail suspension test (TST) and forced swim test (FST) was performed. The concentrations of pro-inflammatory cytokines IL-6, TNF-α, IL-1β, IL-12 and anti-inflammatory cytokines IL-4, IL-10 were determined using Enzyme-linked immunosorbent assay. The population of Iba1+ cells and the length of microglia processes were observed under the fluorescence microscope. The mRNA expressions of Arg1, Ym1 and Fizzl1 were measured by PCR. The protein expressions of TrkA, p-Tyr490-TrkA, p-Ser473-Akt, p-Ser473-Akt1, p-Ser474-Akt2, p-CREB and Jmjd3 were detected by western blot. Our results showed that BXHPD attenuated CUMS-induced depressive-like behaviour, promoted anti-inflammatory cytokines, inhibited pro-inflammatory cytokines, suppressed microglia activation, promoted M2 phenotype-specific indices and upregulated the expressions of TrkA, p-Tyr490-TrkA, p-Ser473-Akt, p-Ser473-Akt1, p-Ser474-Akt2, p-CREB and Jmjd3. The above beneficial effect of BXHPD can be blocked by TrkA inhibitor GW441756. This work demonstrated that BXHPD exerted an anti-depressant effect by promoting M2 phenotype microglia polarization via TrkA/Akt pathway.
研究领域:
药理学
·
神经科学
·
精神病学
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Renwen Wan,Zhiheng Lin,Mowen Xu,Wei Luo,Hengjie Jia,Zhufeng Hu,Zhengyuan Fang,Junming Sun,Yisheng Chen,Shiyi Chen,Zhiwen Luo,Lei Yi,Zhijie Zhao
Diabetic wound healing is a significant complication of diabetes mellitus, characterized by prolonged healing times, heightened infection risks, and potential amputations, necessitating innovative therapeutic approaches. This study aims to evaluate the efficacy of a novel injectable hydrogel, AP@HA-Si InjGel, which combines hyaluronic acid, silanol, and bioactive compounds to promote wound healing in diabetic patients. Utilizing a combination of in vitro assays, diabetic mouse models, and advanced techniques such as single-cell RNA sequencing, we demonstrated that AP@HA-Si InjGel significantly accelerates wound closure, enhances collagen deposition, and modulates macrophage polarization towards a pro-healing M2 phenotype while suppressing the inflammatory M1 phenotype. The hydrogel exhibited excellent biocompatibility with over 90 % cell viability and significant antioxidant properties, reducing reactive oxygen species accumulation. Histological analysis confirmed that AP@HA-Si InjGel promoted neovascularization and improved extracellular matrix remodeling, thereby enhancing tissue regeneration. Furthermore, single-cell RNA sequencing revealed distinct macrophage subtypes, with an increased proportion of M2 macrophages and a favorable differentiation trajectory towards enhanced wound healing. Overall, these findings highlight the therapeutic potential of AP@HA-Si InjGel as a comprehensive strategy for diabetic wound management, warranting further exploration in clinical settings to address the growing challenge of impaired wound healing in diabetic patients.
研究领域:
生物医学工程
·
伤口愈合
·
免疫调节
·
糖尿病并发症
·
生物材料
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xiaowei Liu,Ningning Diao,Shiqing Song,Wenxin Wang,Min Cao,Weili Yang,Chunjing Guo,Daquan Chen
During the pathogenesis of rheumatoid arthritis, inflammatory cells usually infiltrate synovial tissues, notably, M1-type macrophages, whose redox imbalance leads to the degradation of joint structures and deterioration of function. Natural active products play a vital role in immune modulation and antioxidants. In this study, we constructed a ROS-responsive nanoparticle called FTL@SIN, which consists of fucoidan (Fuc) and luteolin (Lut) connected by a ROS-responsive bond, Thioketal (TK), and encapsulated with an anti-rheumatic drug, Sinomenine (SIN), for synergistic anti-inflammatory effects. The FTL@SIN is then dispersed in high molecular weight Fuc-fabricated dissolvable microneedles (FTL@SIN MNs) for local administration. Therapy of FTL@SIN MNs afforded a significant decrease in macrophage inflammation while decreasing key pro-inflammatory cytokines and repolarizing M1 type to M2 type, thereby ameliorating synovial inflammation, and promoting cartilage repair. Additionally, our investigations have revealed that Fucoidan (Fuc) demonstrates synergistic effects, exhibiting superior mechanical strength and enhanced physical stability when compared to microneedles formulated solely with hyaluronic acid. This study combines nanomedicine with traditional Chinese medicine, a novel drug delivery strategy that presents a promising avenue for therapeutic intervention in rheumatoid arthritis.
研究领域:
药学
·
纳米技术
·
免疫学
·
风湿病学
·
药物递送系统
·
传统中药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 39
·16571-16588
·
IF 7.79
Yu Zhang,Yifeng Yang,Jinsheng Shi,Lili Wang
Weak acidity (6.5–6.9) and limited H2O2 level in the tumor microenvironment (TME) usually impact the therapeutic effect of chemodynamic therapy (CDT) for cancer. A Specific TME promotes the formation of an immunosuppressive microenvironment and results in high rate of recurrence and metastasis of cancer. Fe3O4@ZIF-8/GOx@MnO2 multi-layer core shell nanostructure was constructed as a hybrid nanozyme. After magnetic targeting of the tumor site, the outermost MnO2 shell catalyzed H2O2 in TME to produce O2 and was broken due to the reaction with glutathione. Due to the acid response, the ZIF-8 layer would crack and release glucose oxidase (GOx) and Fe3O4. The generated O2 was utilized by GOx in starvation therapy to consume glucose and produce H2O2 and gluconic acid. The Fenton reaction efficiency of Fe(II) was improved by the increased H2O2 concentration and the enhanced acidity in TME. At the same time, the intrinsic photothermal effect of Fe3O4 upon 808 nm laser irradiation promoted the activity of MnO2 and GOx as oxidase, and Fe(II) as catalase-like, and ablated the primary tumor. Moreover, the hybrid nanozyme can facilitate the transformation of M2-type macrophages to M1-type, and strong systemic antitumor immune effect was induced. A synergy of multiple therapeutic modes including starvation therapy, CDT, photothermal therapy (PTT), and immunotherapy can be realized in the hybrid nanozyme for tumor therapy.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
材料科学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）