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ADVANCED MATERIALS · 2025 · IF 26.8

Spatiotemporal Delivery of Required Facilitators for Microenvironment Remodeling Propels Neural Regeneration after Spinal Cord Injury

Jialin Liu,Zehao Yao,Zijun Hu,Xindan Zhang,Bowen Gong,Yu Dai,Haiyan Weng,Longyou Xiao,Baobao Zhang,Ting Li,Kaixi Shi,Pengfei Xie,Feng Tian,Limin Rong,Jiajia Xue,Liumin He

Intricate pathological responses and multiple components within the lesion make it challenging to repair spinal cord injury (SCI). A multifunctional hybrid neural restorative conduit is developed, composed of a sandwich-like hydrogel encapsulated within a polycaprolactone (PCL) nanofiber membrane. The sandwich structure consists of a hyaluronic acid-graft-dopamine (HADA)/HGF-(RADA)4-DGDRGDS (HRR) hydrogel loaded with epidermal growth factor (EGF), neurotrophin 3 (NT3), and glial-derived neurotrophic factor (GDNF), flanked by gelatin methacryloyl (GelMA) hydrogels containing catalase at both ends. The hybrid conduit enables the spatiotemporal release of multiple bioactive factors, precisely targeting critical pathological cascades after SCI. This approach reduces oxidative stress, promotes neuronal survival at the lesion borders, facilitates the relay of ascending and descending axons, and enhances signal transmission across the lesion. Restored serotonergic signaling enhances motor neuron excitability, facilitating functional recovery, while reconstitution of bladder reflexes improves urinary control. By orchestrating the reinstatement of multiple essential mechanisms to counteract the pathological progression of the hostile post-SCI microenvironment, this approach provides a strategy for regenerative therapies targeting SCI.

研究领域: 神经生物学 · 组织工程 · 再生医学 · 生物材料学 · 神经创伤学 · 分子神经科学
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BIOMATERIALS · 2017 · IF 8.402

Rapid initiation of guided bone regeneration driven by spatiotemporal delivery of IL-8 and BMP-2 from hierarchical MBG-based scaffold

Dan Lin,Yanjun Chai,Yifan Ma,Bing Duan,Yuan Yuan,Changsheng Liu

Initiation of endogenous repair mechanisms, including key steps of stem cell recruitment and cartilage intermediate formation in endochondral ossification , is vital to regeneration of large bone defects. To biomimetically promote a rapid initiation and ensuing osteogenic stimulation, exogenous chemokine IL-8 and growth factor BMP-2 were orchestrated in a mesoporous bioactive glass (MBG)-based spatiotemporal delivery system, to achieve a rapid release of IL-8 followed by a long-term sustained release of BMP-2. The synergistic effect of IL-8 and BMP-2 on initiation stage of bone healing and underlying mechanism were thoroughly investigated in vitro and in vivo . Intriguingly, apart from its superiority in stem cell recruitment to BMP-2, IL-8 not only endowed a histological “prep-state” of endochondral ossification by up-regulating chondrogenic genes and inducing the formation of extensive cartilage tissues, facilitating rapid bone transformation by BMP-2, but also triggered a cellular “prep-state” with high expression of BMP receptors, enhancing the osteoinductivity of BMP-2. With the spatiotemporal delivery system, orchestrated signal stimuli of IL-8 and BMP-2 induced a rapid initiation including efficient stem cell recruitment and a “chondrogenic/osteogenic balance” at the first stage of endochondral ossification, and the scaffold facilitated sufficient osteoconductivity , together resulting in early extensive bone mineralization and an advanced regeneration throughout the repair of large bone defect. We believe this new idea could provide insights toward designing bone-repairing biomaterials with higher regenerative efficiency.

研究领域: 组织工程 · 再生医学 · 生物材料科学 · 骨科
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Albumin-Based Microneedles for Spatiotemporal Delivery of Temozolomide and Niclosamide to Resistant Glioblastoma

Zhipeng Yang,Haoyuan Li,Biao Yang,Yanjie Liu

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Standard therapy includes maximal surgical resection, radiotherapy, and adjuvant temozolomide (TMZ) administration. However, the rapid development of TMZ resistance and the impermeability of the blood–brain barrier (BBB) significantly hinder the therapeutic efficacy. Herein, we developed spatiotemporally controlled microneedle patches (BMNs) loaded with TMZ and niclosamide (NIC) to overcome GBM resistance. We found that hyaluronic acid (HA) increased the viscosity of bovine serum albumin (BSA) and evidenced that concentrations of BSA/HA exert an impact degradation rates exposure to high-temperature treatment, showing that the higher BSA/HA concentrations result in slower drug release. To optimize drug release rates and ensure synergistic antitumor effects, a 15% BSA/HA solution constituting the bottoms of BMNs was chosen to load TMZ, showing sustained drug release for over 28 days, guaranteeing long-term DNA damage in TMZ-resistant cells (U251-TR). Needle tips made from 10% BSA/HA solution loaded with NIC released the drug within 14 days, enhancing TMZ’s efficacy by inhibiting the activity of O6-methylguanine-DNA methyltransferase (MGMT). BMNs exhibit superior mechanical properties, bypass the BBB, and gradually release the drug into the tumor periphery, thus significantly inhibiting tumor proliferation and expanding median survival in mice. The on-demand delivery of BMNs patches shows a strong translational potential for clinical applications, particularly in synergistic GBM treatment.

CAS / MDL: 9004-61-9 85622-93-1
研究领域: 肿瘤学 · 药学 · 神经科学 · 生物医学工程
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Advanced Science · 2022 ·Vol. 9 ·期 27 ·2202744 · IF 17.521

Glutathione Pulse Therapy: Promote Spatiotemporal Delivery of Reduction-Sensitive Nanoparticles at the “Cellular Level” and Synergize PD-1 Blockade Therapy

Songtao Dong,Yuan Zhang,Xiangnan Guo,Chuang Zhang,Zhaomeng Wang,Jiang Yu,Yubo Liu,Chang Li,Yuting Hu,Bingjun Sun,Mengchi Sun,Haotian Zhang,Defang Ouyang,Zhonggui He,Yongjun Wang

Spatiotemporal delivery of nanoparticles (NPs) at the “cellular level” is critical for nanomedicine, which is expected to deliver as much cytotoxic drug into cancer cells as possible when NPs accumulate in tumors. However, macrophages and cancer-associated fibroblasts (CAFs) that are present within tumors limit the efficiency of spatiotemporal delivery. To overcome this limitation, glutathion pulse therapy is designed to promote reduction-sensitive Larotaxel (LTX) prodrug NPs to escape the phagocytosis of macrophages and penetrate through the stromal barrier established by CAFs in the murine triple negative breast cancer model. This therapy improves the penetration of NPs in tumor tissues as well as the accumulation of LTX in cancer cells, and remodels the immunosuppressive microenvironment to synergize PD-1 blockade therapy. More importantly, a method is established that can directly observe the biodistribution of NPs between different cells in vivo to accurately quantify the target drugs accumulated in these cells, thereby advancing the spatiotemporal delivery research of NPs at the “cellular level.”

研究领域: 纳米医学 · 癌症治疗 · 免疫疗法 · 药物递送系统 · 生物医学工程
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