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ACS Applied Materials & Interfaces · 2021 · IF 9.229

pH-Triggered Copper-Free Click Reaction-Mediated Micelle Aggregation for Enhanced Tumor Retention and Elevated Immuno–Chemotherapy against Melanoma

Miao Deng,Rong Guo,Shuya Zang,Jingdong Rao,Mengmeng Li,Xian Tang,Chunyu Xia,Man Li,Zhirong Zhang,Qin He

Natural killer (NK) cell-based immunotherapy presents a promising antitumor strategy and holds potential for combination with chemotherapy. However, the suppressed NK cell activity and poor tumor retention of therapeutics hinder the efficacy. To activate NK cell-based immuno–chemotherapy and enhance the tumor retention, we proposed a pH-responsive self-aggregated nanoparticle for the codelivery of chemotherapeutic doxorubicin (DOX) and the transforming growth factor-β (TGF-β)/Smad3 signaling pathway inhibitor SIS3. Polycaprolactone-poly(ethylene glycol) (PCL-PEG2000) micelles modified with dibenzylcyclooctyne (DBCO) or azido (N3) and coated with acid-cleavable PEG5000 were established. This nanoplatform, namely, M-DN@DOX/SIS3, could remain well dispersed in the neutral systemic circulation, while quickly respond to the acidic tumor microenvironment and intracellular lysosomes, triggering copper-free click reaction-mediated aggregation, leading to the increased tumor accumulation and reduced cellular efflux. In addition, the combination of DOX with SIS3 facilitated by the aggregation strategy resulted in potent inhibition of melanoma tumor growth and significantly increased NK cells, NK cell cytokines, and antitumor T cells in the tumor. Taken together, our study offered a new concept of applying copper-free click chemistry to achieve nanoparticle aggregation and enhance tumor retention, as well as a promising new combined tumor treatment approach of chemotherapy and immunotherapy.

研究领域: 癌症研究 · 纳米技术 · 免疫疗法 · 化疗 · 药学
✓ 已验证 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2022 · IF 10.383

3D Printed Integrated Bionic Oxygenated Scaffold for Bone Regeneration

Yihan Wang,Changnan Xie,Zhiming Zhang,Haining Liu,Haixia Xu,Ziyue Peng,Chun Liu,Jianjun Li,Chengqiang Wang,Tao Xu,Lixin Zhu

The repair of large bone defects remains a challenging problem in bone tissue engineering. Ischemia and hypoxia in the bone defect area make it difficult for seed cells to survive and differentiate, which fail to perform effective tissue regeneration. Current oxygen-producing materials frequently encounter problems such as a rapid degradation rate, insufficient mechanical properties, difficult molding, and cumbersome fabrication. Here, a novel three-dimensional (3D) printed integrated bionic oxygenated scaffold was fabricated with gelatin-CaO2 microspheres, polycaprolactone (PCL), and nanohydroxyapatite (nHA) using low-temperature molding 3D printing technology. The scaffold had outstanding mechanical properties with bionic hierarchical porous structures. In vitro reports showed that the scaffold exhibited excellent cytocompatibility and could release O2 sustainably for more than 2 weeks, which significantly enhanced the survival, growth, and osteogenic differentiation of bone marrow mesenchymal stem cells under hypoxia. In vivo experiments revealed that the scaffold facilitated efficient bone repair after it was transplanted into a rabbit calvarial defect model. This result may be due to the scaffolds reducing hypoxia-inducible factor-1α accumulation, improving the expression of osteogenic regulatory transcription factors, and accelerating osteogenesis. In summary, the integrated bionic PCL/nHA/CaO2 scaffold had excellent capabilities in sustainable O2 release and bone regeneration, which provided a promising clinical strategy for bone defect repair.

研究领域: 组织工程 · 生物医学工程 · 再生医学 · 材料科学
✓ 已验证 DOI PubMed 高影响因子
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Biofabrication · 2024 · IF 8.2

Biofabrication of biomimetic undulating microtopography at the dermal-epidermal junction and its effects on the growth and differentiation of epidermal cells

Chuang Gao,Chunxiang Lu,Huazhen Liu,Yi Zhang,Hao Qiao,Aoxiang Jin,Qiqi Dai,Yuanyuan Liu

The undulating microtopography located at the junction of the dermis and epidermis of the native skin is called rete ridges (RRs), which plays an important role in enhancing keratinocyte function, improving skin structure and stability, and providing three-dimensional (3D) microenvironment for skin cells. Despite some progress in recent years, most currently designed and manufactured tissue-engineered skin models still cannot replicate the RRs, resulting in a lack of biological signals in the manufactured skin models. In this study, a composite manufacturing method including electrospinning, 3D printing, and functional coating was developed to produce the epidermal models with RRs. Polycaprolactone (PCL) nanofibers were firstly electrospun to mimic the extracellular matrix environment and be responsible for cell attachment. PCL microfibers were then printed onto top of the PCL nanofibers layer by 3D printing to quickly prepare undulating microtopography and finally the entire structures were dip-coated with gelatin hydrogel to form a functional coating layer. The morphology, chemical composition, and structural properties of the fabricated models were studied. The results proved that the multi-process composite fabricated models were suitable for skin tissue engineering. Live and dead staining, cell counting kit-8 (CCK-8) as well as histology (haematoxylin and eosin (HE) methodology) and immunofluorescence (primary and secondary antibodies combination assay) were used to investigate the viability, metabolic activity, and differentiation of skin cells for in vitro culturing. In vitro results showed that each model had high cell viability, good proliferation, and the expression of differentiation marker. It was worth noting that the sizes of the RRs affected the cell growth status of the epidermal models. In addition, the unique undulation characteristics of the epidermal-dermal junction can be reproduced in the developed epidermal models. Overall, these in vitro human epidermal models can provide valuable reference for skin transplantation, screening and safety evaluation of drugs and cosmetics.

研究领域: 生物医学工程 · 组织工程 · 材料科学 · 细胞生物学 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2021 · IF 4.539

Biodegradable polyurethane based clay composite and their anti-biofouling properties

Abid Ali,Yue Xiao,Lina Song,Jiankun Hu,Qingqing Rao,Muhammad Shoaib,Bilal Ul Amin,Xiaoli Zhan,Qinghua Zhang

The colonization of tiny marine organisms on ship's hull which are connected directly from seawater , is a costly issue. Biofouling contributes to enhanced hydrodynamic drag, which leads to higher consumption of fuel and greenhouse gas emissions . Therefore, the environment-friendly solution is very necessary for anti-biofouling activity. For this purpose, we have synthesized biodegradable polyurethane (CL-PU) composed of ε-CL and 4,4′-methylenebis(cyclohexyl isocyanate) (H 12 MDI) and 1,4 butanediol (1,4 BD). The synthesized CL-PU was further modified with 4, 5-dicholoro-2-octyl-isothiazolone (DCOIT) and clay by mixing of the solution to make composites. Our study showed that CL-PU/DCOIT/clay composite degraded in the artificial seawater (ASW), enzymatic solution and seawater (through laboratory test) due to the contents of clay. Because the existence of clay reduced the size of the spherulite of polycaprolactone (PCL) in the composite, therefore remarkably improved the crystallinity as determined via the polarizing optical microscope (POM) and differential scanning calorimetry (DSC). The composite acted as carrier of antifoulant (DCOIT) and controlled their release rate. The anti-bacterial and anti-diatom experiments exhibited that the composite with DCOIT contents were effective in preventing the accretion of Escherichia coli ( E.coli) (region inhibition 14 mm) and marine diatom Navicula incerta (82.5% reduction). The degradable CL-PU/DCOIT/clay composite will have tremendous durability and excellent anti-fouling activity for marine biofouling owning to sustainability and tunability without being toxic to aquatic biota.

研究领域: 材料科学 · 海洋生物学 · 环境科学 · 化学工程
✓ 已验证 DOI 高影响因子
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