CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Kaiwen Yang,Yifan Zhao,Chuyao Wang,Yeke Yu,Xiaoyu Zhang,Jie Liu,Chuan Lu,Luxiang Zou,Xiaohui Wei,Dongmei He
Synovial inflammation and cartilage degeneration are two crucial pathologic features in temporomandibular joint osteoarthritis (TMJ OA). Cartilage repair can be very thorny in inflammatory environment, which is highly associated with the activated macrophages. Thus, simultaneous inflammation suppression and cartilage repair are strongly required. However, the clinically used intra-articular injection agents face the problems of insufficient inflammation suppression, deficient cartilage repair and non-targeted therapy. Hence, we developed the novel dual-targeted lipid nanoparticles (LNPs) loaded with miR-330-3p, an important inflammation inhibitor, and kartogenin (KGN), a pro-chondrogenic small molecular, for synergistic anti-inflammation and cartilage repair of TMJ OA. The folic acid (FA) and collagen II-targeting peptide (WYRGRL) were modified on the surface of LNPs for precise delivery to macrophages or chondrocytes, respectively. The dual-targeted miR-330-3p@FA-LNP and KGN@WYRGRL-LNP both manifested high bioavailability and selectively active cellular uptake. Furthermore, it functioned synergistically to alleviate synovium inflammation and cartilage degeneration via modulating the M1 to M2 repolarization of macrophages and maintaining the homeostasis of chondrocytes, with a low intra-articular injection dose of miR-330-3p@FA-LNP (0.0125 nmol) and KGN@W-LNP (0.025 nmol) in vivo. RNA-seq and further validation demonstrated that miR-330-3p functioned by inhibiting SPARC and KGN functioned by upregulating EPHB4. In summary, this dual-targeted LNPs system provides a promising therapeutic strategy for TMJ OA treatment.
研究领域:
纳米技术
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药理学
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骨科
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炎症
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软骨生物学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
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2023
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IF 14
Xinyue Ge,Hong Wen,Yang Fei,Rui Xue,Zhuo Cheng,Yanan Li,Kaiyong Cai,Liqi Li,Menghuan Li,Zhong Luo
Hydrogels are a class of biocompatible materials with versatile functions that have been increasing explored for the localized treatment of ulcerative colitis (UC), but various mechanical stimuli may cause premature hydrogel breakage and detachment, impeding their further clinical translation. Here we report a multifunctional mechanically-resilient self-healing hydrogel for effective UC treatment, which is synthesized through the host-guest interaction between dopamine/β-cyclodextrin-modified hyaluronic acid (HA-CD-DA) and amantadine-modified carboxymethyl chitosan (CMCS-AD). The excessive β-CD cavities allow the incorporation of dexamethasone (DEX), while the porous hydrogel network potentiates the encapsulation of basic fibroblast growth factor (bFGF) and L-alanyl- l -glutamine (ALG). DA moieties in HA components allow firm adhesion of the hydrogel to the ulcerative lesions after in-situ implantation, while the reversible host-guest interaction between CD and AD could enhance the persistence of hydrogel. The hydrogel demonstrated favorable biocompatibility and could continuously release DEX to induce M1-to-M2 repolarization of mucosal macrophages through inhibiting the toll-like receptor 4 (TLR4)-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) axis. Furthermore, the co-delivered bFGF and ALG facilitates the regeneration of ulcerative mucosa and restore its barrier functions to ameliorate UC symptoms. The mechanically resilient hydrogel offers an integrative approach for UC therapy in the clinics.
研究领域:
药学
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生物医学工程
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材料科学
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炎症生物学
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2024
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IF 10.7
Wanglin Duan,Xianzhen Jin,Yiyang Zhao,Sergio Martin-Saldaña,Shuaijun Li,Lina Qiao,Liang Shao,Bin Zhu,Shibo Hu,Furong Li,Luyao Feng,Yao Ma,Baoji Du,Lining Zhang,Yazhong Bu
Diabetic wounds remain a global challenge due to disordered wound healing led by inflammation, infection, oxidative stress, and delayed proliferation. Therefore, an ideal wound dressing for diabetic wounds not only needs tissue adhesiveness, injectability, and self-healing properties but also needs a full regulation of the microenvironment. In this work, adhesive wound dressings (HA-DA/PRP) with injectability were fabricated by combining platelet rich plasma (PRP) and dopamine-modified-hyaluronic acid (HA-DA). The engineered wound dressings exhibited tissue adhesiveness, rapid self-healing, and shape adaptability, thereby enhancing stability and adaptability to irregular wounds. The in vitro experiments demonstrated that HA-DA/PRP adhesives significantly promoted fibroblast proliferation and migration, attributed to the loaded PRP. The adhesives showed antibacterial properties against both gram-positive and negative bacteria. Moreover, in vitro experiments confirmed that HA-DA/PRP adhesives effectively mitigated oxidative stress and inflammation. Finally, HA-DA/PRP accelerated the healing of diabetic wounds by inhibiting bacterial growth, promoting granulation tissue regeneration, accelerating neovascularization, facilitating collagen deposition, and modulating inflammation through inducing M1 to M2 polarization, in an in vivo model of infected diabetic wounds. Overall, HA-DA/PRP adhesives with the ability to comprehensively regulate the microenvironment in diabetic wounds may provide a novel approach to expedite the diabetic wounds healing in clinic.
研究领域:
生物医学工程
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伤口愈合
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组织工程
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材料科学
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药剂学
✓ 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）