ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Zhanwei Zhou,Chenzi Li,Minghua Zhang,Qingyan Zhang,Chenggen Qian,David Oupicky,Minjie Sun
Hydrophobic modification on polycations were commonly used to improve the stability and transfection efficiency of polyplexes. However, the improved stability often means undesired release of the encapsulated siRNA, limiting the application of cationic micelles for siRNA delivery. The current strategy of preparing bioresponsive micelles based on the cleavage of sensitive linkages between polycation and hydrophobic part was far from sufficient, owing to the siRNA binding of the separated polycations from micelles leading to the incomplete release of siRNA. In this study, we propose a new strategy by the combination of micelles disassembly and separated polycations charge reversal. FPBA (3-fluoro-4-carboxyphenylboronic acid) grafted PEI 1.8 k (polyethylenimine) as the polycations of PEI-FPBA and dopamine (with diol-containing moiety) conjugated with cholesterol as the hydrophobic part (Chol-Dopa). The PFCDM micelles was assembled by PEI-FPBA and Chol-Dopa, based on the FPBA-Dopa conjugation. The prepared PFCDM showed strong siRNA loading ability and superior stability in the presence of PBS or serum. Besides, the PFCDM exhibited excellent ATP sensibility. The intracellular ATP could effectively trigger the disassembly of micelles and charge reversal of PEI-FPBA, resulting in the burst release of siRNA in the cytosol. With the property of extracellular stability and intracellular instability, PFCDM displayed good performance on in vitro and in vivo luciferase silencing on 4T1 cells. It should also be noted that the assembly of low molecular weight PEI was relatively safe to cells compared with 25 k PEI. To sum up, the ATP-fueled assembly and charge reversible micelles gave examples for polyplexes to achieve better stability and on demand cargo release at the same time and shows potential to be used for in vitro and in vivo siRNA transfection.
研究领域:
纳米技术
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药学
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生物医学工程
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分子生物学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
A li mu Ke re mu,Maimaitiaili Abulikemu,Zhilin Liang,Abudurusuli Abulikemu,Aikebaier Tuxun
Background Given the limitations of traditional therapies, the treatment of infected bone defects (IBD) remains a great challenge. It is urgent to find a novel method that can simultaneously eradicate infection and promote new bone formation. With the increasing application of personalized scaffolds in orthopedics, novel biomaterials with both antibacterial and osteoinductive properties have provided a viable option for IBD treatment. Through the three-dimensional (3D) printing technology, we fabricated a poly(lactic-co-glycolic acid)(PLGA)/nano-hydroxyapatite (n-HA) composite scaffold grafted with the antibiotic vancomycin and loaded with the osteoinductive agent recombinant human bone morphogenic protein-2 (rhBMP-2) via polydopamine (DOPA) chemistry, whose therapeutic effects on IBD were determined.Methods After examining the hydrophilicity, surface chemical composition, mechanical properties, and drug release of the PLGA/n-HA, PLGA/n-HA/VAN, and PLGA/n-HA/VAN+DOPA/rhBMP-2 composite scaffolds, pre-osteoblast MC3T3-E1 cells were seeded onto the scaffold surface to assess the biocompatibility and osteoconductive properties of the scaffolds in vitro. For in vivo experiments, the composite scaffolds contaminated with Staphylococcus aureus were implanted into the defect sites of rabbit radius. After 12 weeks, micro-CT analysis, H&E and Masson staining, immunohistochemistry, and viable bacteria counting were conducted to compare the effects of three composite scaffolds on new bone formation and bone infection.Results The surface modification with DOPA/rhBMP-2 increased the hydrophilicity of PLGA/n-HA scaffolds. Vancomycin and BMP-2 were continuously and regularly eluted from the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds. The PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds promoted MC3T3-E1 cell survival and proliferation and enhanced ALP activity and calcium deposition compared with the PLGA/n-HA and PLGA/n-HA/VAN scaffolds. Additionally, the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds significantly facilitated new bone formation and inhibited bone infection in IBD rabbit models. The rabbits implanted with the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds exhibited normal heart, lung, and kidney histologies and normal serum biochemical indices, suggesting the safety of the scaffolds.Conclusion The 3D-printed PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds exhibited both antibacterial and osteoinductive activities in IBD.
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DOI
PubMed
高影响因子
SKIN RESEARCH AND TECHNOLOGY
·
2023
·Vol. 29
·期 11
·e13465
·
IF 2.2
Xi-Liang Zang,Fei Gao,Zhao Zhang,Lin-Hua Shen,Yue-Hai Pan
Objective We aimed to develop an electroactive antibacterial material for the treatment of skin wound diseases. Method To this aim, we modified chitosan (CS), a biocompatible polymer, by coupling it with graphene (rGO) and an antimicrobial polypeptide DOPA-PonG1. The material's effect on skin injury healing was studied in combination with external electrical stimulation (EEM). The structure, surface composition, and hydrophilicity of the modified CS materials were evaluated using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and contact angle measurements. We studied NIH3T3 cells cultured with modified materials and subjected to EEM to assess viability, adhesion, and tissue repair-related gene expression. Results SEM data demonstrated that rGO was distributed uniformly on the surface of the CS material, increasing surface roughness, and antimicrobial peptides had minimal impact on surface morphology. FTIR confirmed the uniform distribution of rGO and antibacterial peptides on the material surface. Both rGO and DOPA-PonG1 enhanced the hydrophilicity of CS materials, with rGO also improving tensile strength. The dual modification of CS with rGO and DOPA-PonG1 synergistically increased antibacterial efficacy. Cellular events and gene expression relevant to tissue repair process were enhanced by these modifications. Furthermore, EEM accelerated epidermal regeneration more than the material alone. In a rat skin wound model, DOPA-PonG1@CS/rGO dressing combined with electrical stimulation exhibited accelerated healing of skin defect. Conclusion Overall, our results demonstrate that CS materials modified with rGO and DOPA-PonG1 have increased hydrophilicity, antibacterial characteristics, and tissue regeneration capacities. This modified material in conjunction with EEM hold promise for the clinical management for dermal wounds.
研究领域:
生物医学工程
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材料科学
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组织工程
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伤口愈合
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Ningning Lei,Xu Peng,Mengyue Hu,Chang Wan,Xixun Yu
Acellular porcine aorta (APA) is an excellent candidate for an implanted scaffold but needs to be modified with appropriate cross-linking agent to increase its mechanical property and storage time in vitro as well as to give itself some bioactivities and eliminate its antigenicity for acting as a novel esophageal prosthesis. In this paper, a polysaccharide crosslinker (oxidized chitosan, OCS) was prepared by oxidizing chitosan using NaIO 4 and further used to fix APA to prepare a novel esophageal prosthesis (scaffold). And then the surface modification with dopamine (DOPA) and strontium-doped calcium polyphosphate (SCPP) were performed one after another to prepare DOPA/OCS-APA and SCPP-DOPA/OCS-APA to improve the biocompatibility and inhibit inflammation of the scaffolds. The results showed that the OCS with a feeding ratio of 1.5:1.0 and a reaction time of 24 h had a suitable molecular weight and oxidation degree, almost no cytotoxicity and good cross-linking effect. Compared with glutaraldehyde (GA) and genipin (GP), OCS-fixed APA could provide a more suitable microenvironment for cell proliferation. The vital cross-linking characteristics and cytocompatibility of SCPP-DOPA/OCS-APA were evaluated. Results suggested that SCPP-DOPA/OCS-APA exhibited suitable mechanical properties, excellent resistance to enzymatic degradation/acid degradation, suitable hydrophilicity, and the ability to promote the proliferation of Human normal esophageal epithelial cells (HEECs) and inhibit inflammation in vitro. In vivo tests also confirmed that SCPP-DOPA/OCS-APA could diminish the immunological response to samples and had a positive impact on bioactivity and anti-inflammatory. In conclusion, SCPP-DOPA/OCS-APA could act as an effective, bioactive artificial esophageal scaffold and be expected to be used for clinical in the future.
研究领域:
生物医学工程
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组织工程
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生物材料科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 20
·15403
·
IF 5.6
Li Chen,Meng Tian,Jing Yang,Zhenxu Wu
Polymer microspheres have recently shown outstanding potential for bone tissue engineering due to their large specific surface area, good porosity, injectable property, good biocompatibility, and biodegradability. Their good load-release function and surface modifiability make them useful as a carrier of drugs or growth factors for the repair of bone defects in irregularly injured or complex microenvironments, such as skull defects. In this study, berberine (BBR)-encapsulated poly(lactic-co-glycolic acid) (PLGA)/hydroxyapatite (HA) microspheres were fabricated using electrified liquid jets and a phase-separation technique, followed by modification with the 3,4-hydroxyphenalyalanine-containing recombinant insulin-like growth–factor-1 (DOPA-IGF-1). Both the BBR and the IGF-1 exhibited sustained release from the IGF-1@PLGA/HA-BBR microspheres, and the composite microspheres exhibited good biocompatibility. The results of the alkaline phosphatase (ALP) activity assays showed that the BBR and IGF-1 in the composite microspheres synergistically promoted the osteogenic differentiation of MC3T3-E1 cells. Furthermore, it was confirmed that immobilized IGF-1 enhances the mRNA expression of an osteogenic-related extracellular matrix and that BBR accelerates the mRNA expression of IGF-1-mediated osteogenic differentiation and cell mineralization. Further cellular studies demonstrate that IGF-1 could further synergistically activate the IGF-1R/PI3K/AKT/mTOR pathway using BBR, thereby enhancing IGF-1-mediated osteogenesis. Rat calvarial defect repair experiments show that IGF-1@PLGA/HA-BBR microspheres can effectively promote the complete bony connection required to cover the defect site and enhance bone defect repair. These findings suggest that IGF-1@PLGA/HA-BBR composite microspheres show a great potential for bone regeneration.Keywords:polymer microspheres;berberine (BBR);IGF-1;bone regeneration;osteogenic differentiation
研究领域:
生物医学工程
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组织工程
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骨再生
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药学
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DOI
PubMed
高影响因子
AQUACULTURE
·
2024
·
IF 3.9
Kunyin Jiang,Hong Yu,Lingfeng Kong,Shikai Liu,Shaojun Du,Qi Li
The visually appealing shell colours and intricate patterns of shellfish not only attract consumers but also enhance their economic value. Understanding the inheritance pattern of shell colour and the molecular mechanism of pigmentation is highly important for enhancing breeding efficiency. This study involved the identification of a tyrosine hydroxylase gene ( CgTH ) and the investigation of its function in the metabolism of tyrosine and pigmentation in Pacific oysters. CgTH contains a conserved Biopterin_H domain that consists of a binding site for iron atoms and a binding site for tetrahydrobiopterin (BH4). Quantitative PCR (qPCR) and immunofluorescence analysis revealed that the expression of CgTH was higher in the mantle of black shell oysters in comparison to the white strain. The in vitro and in vivo experiments confirmed that Cg TH is involved in tyrosine metabolism through the catalysis of the conversion of L-tyrosine to L-DOPA. In order to examine its functions in melanin synthesis in oysters, 3-Iodo-L-tyrosine (3-IT) treatment, RNA interference (RNAi), and L-DOPA treatment assays were conducted. The results of our study showed that 3-IT effectively inhibited Cg TH activity, leading to a suppression of tyrosine metabolism. Knockdown of Cg TH hindered the cAMP-CREM-MITF axis and decreased pigmentation. On the other hand, L-DOPA stimulated melanin production through cAMP signaling and counteracted the inhibitory effects of 3-IT on the metabolism of tyrosine. These data indicated that there may be a feedback loop involving Cg TH and the cAMP-CREM-MITF axis that regulates tyrosine metabolism and melanogenesis in Pacific oysters. This study enhances our understanding of the molecular mechanism that governs oyster pigmentation and offers a possible molecular indicator for the targeted breeding of particular strains of Pacific oysters ( Crassostrea gigas ).
研究领域:
海洋生物学
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分子生物学
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遗传学
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水产养殖
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DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2014
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IF 4.787
Yanping Li,Yangyang Zhou,Bowen Qi,Tao Gong,Xun Sun,Yao Fu,Zhirong Zhang
Parkinson’s disease (PD) has become one of the most deadly diseases due to a lack of effective treatment. Herein, N-3,4-bis(pivaloyloxy)dopamine-3-(dimethylamino)propanamide (PDDP), a brain-specific derivative of dopamine, was designed and synthesized, which consists of a brain targeted ligand, N,N-dimethyl amino group, and two dipivaloyloxy groups for lipophilic modification. PDDP was investigated both in vitro and in vivo by comparing with L-DOPA and another derivative (BPD) without N,N-dimethyl amino group. PDDP showed a more pronounced accumulation in mouse brain microvascular endothelial cells (bEnd.3) than BPD via an active transport process. The increased cellular uptake of PDDP was proven to be mediated by putative pyrilamine cationic transporters. Following intravenous administration, the concentration of PDDP in the brain was 269.28-fold and 6.41-fold higher than that of L-DOPA and BPD at 5 min, respectively. Additionally, PDDP effectively attenuated the striatum lesion caused by 6-hydroxydopamine (6-OHDA) in rats. More importantly, PDDP presented antioxidant and antiapoptotic effects on 6-OHDA-induced toxicity in human neuroblastoma cells (SH-SY5Y). Thus, N,N-dimethyl amino group-based PDDP represents an effective and safe treatment for PD.
研究领域:
神经科学
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药理学
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药物递送系统
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Shengjie Liang,Xin Gao,Xinyang Li,Chenmin Yao,Cui Huang
Intrafibrillar mineralization plays an important role in dentin repair. Current research on intrafibrillar mineralization primarily focuses on the precise positioning of mineral precursors within collagen and the reduction of mineralization time. Inspired by the multifunctionality of noncollagenous proteins (NCPs), we developed a dual-analogue system, 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) followed by 3-(3,4-dihydroxyphenyl)-l-alanine (l-DOPA)-stabilized amorphous calcium phosphate (M + LA), which integrated a nucleation inhibitor l-DOPA and inducer 10-MDP. In this study, we investigated the impact of a preinfiltration strategy using the M + LA system on intrafibrillar mineralization. l-DOPA with a concentration of 250 μg mL–1, acting as a mussel-inspired nucleation inhibitor, was demonstrated to stabilize amorphous calcium phosphate (ACP) precursors within 2 h at 37 °C, with the formed precursors termed “LACP” (l-DOPA-stabilized amorphous calcium phosphate). Numerous LACP precursors were immobilized within collagen via the M + LA system, referred to as “preinfiltration.” The M + LA system exhibited no significant cytotoxicity, as evidenced by the biocompatibility evaluation through a modified trans-dentin disk model. Notably, the M + LA preinfiltration strategy significantly reduced intrafibrillar mineralization time to 3 h, superior to that of bare collagen and MDP-modified collagen. Furthermore, the resulting mineralized M + LA-modified collagen achieved functional mechanical properties. Moreover, 10-MDP-Ca nanolayering was generated via a bottom-up approach during the preinfiltration process. This study introduces a preinfiltration strategy for promoting intrafibrillar mineralization, which provides a reference for understanding the mechanism of intrafibrillar mineralization and shows promising clinical application prospects for dentin repair.
研究领域:
生物材料
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牙科材料
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组织工程
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矿化
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生物矿化
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材料科学
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仿生材料
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产品关联
DOI
PubMed
高影响因子
Journal of Cleaner Production
·
2025
·
IF 10
Tong Xu,Xiaopei Ding,Chengcai Li,Haoyang Cheng,Guojin Liu,Hailin Zhu,Yuhai Guo,Xueliang Jiang,Jiuming Li
Accelerated industrial expansion has led to significant wastewater pollution, with effluent containing the toxic heavy metal Cr(VI) posing severe threats to ecosystems and human health. The combination of metal-organic frameworks (MOFs) and membrane separation techniques offers promising solutions for pollutant removal. This study developed a polytetrafluoroethylene (PTFE)-based composite membrane for effective Cr(VI) removal from aqueous solutions. This membrane was prepared through the in-situ synthesis of zinc-zirconium bimetallic MOFs on a PTFE membrane that had been modified with L-DOPA/PEI. The composite membrane demonstrated optimal Cr(VI) adsorption at a Zr:Zn molar ratio of 1:4, under conditions of 45 °C and pH = 2, with a maximum adsorption capacity of 335.1 mg/g. The adsorption process of Cr(VI) onto the composite membrane adhered to both the pseudo-second-order kinetic model and the Freundlich adsorption isotherm. Thermodynamic analyses confirmed a spontaneous, endothermic process. The composite membrane, with its excellent adsorption capacity, filtration performance, and recyclability, stands out as a highly effective material for the removal of Cr(VI) from aqueous solutions. Furthermore, it addresses the issues of aggregation, difficulty in separation, and the recycling challenges associated with powder-like MOFs, demonstrating significant potential for practical applications.
研究领域:
环境科学
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材料工程
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水处理
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纳米技术
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化学工程
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Jian-Jiang Lu,Qi Shen,Xiao-Ying Li,Fei-Yun Sun,Jun-Bo Yi,Wen-Yi Dong,Wei-Jia Yan,Hong Du,Jia-Le Mu
Undesired long start-up time and unstable denitrification performance are major bottlenecks for engineering application of methane-based membrane biofilm reactors (MBfRs). In this study, two surface-manipulated membranes by respectively coating dopamine (DOPA) and grafting methoxy-poly(ethyleneglycol)-amine (mPEG-NH 2 ) onto the base polypropylene (PP) membrane were prepared, and for the first employed to aerobic methane oxidation coupled to denitrification (AME-D) process in MBfRs for quick biofilm formation and improving denitrification performance. The experiments demonstrated that the modified membranes, especially for PP/DOPA/mPEGNH 2 membrane, accelerated biofilm formation, and then shorten above 31% start-up time compared to the base PP membrane. Meanwhile, the biofilm detachment resistances also improved in the MBfRs employing the modified membrane. Extended Deraguin-Landau-Verwery-Oxerbeek (XDLVO) theory analysis indicated these benefits mainly attribute to enhanced interfacial interaction energy, which is significant to microbial initial attachment onto membrane surface. 16S rRNA gene analysis demonstrated the modified membrane also preferentially increased the abundances of key microorganisms at initial stage. These findings revealed the importance of quick biofilm formation and robust detachment resistance by involving surface-manipulated membranes onto maintaining MBfRs efficiency and stability.
研究领域:
环境工程
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微生物学
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生物技术
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DOI
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 12
·期 1
·2201594
·
IF 11.092
Yan Hu,Yuanbo Jia,Siwei Wang,Yufei Ma,Guoyou Huang,Tan Ding,Dayun Feng,Guy M. Genin,Zhao Wei,Feng Xu
Brain lesions can arise from traumatic brain injury, infection, and craniotomy. Although injectable hydrogels show promise for promoting healing of lesions and health of surrounding tissue, enabling cellular ingrowth and restoring neural tissue continue to be challenging. It is hypothesized that these challenges arise in part from the mismatch of composition, stiffness, and viscoelasticity between the hydrogel and the brain parenchyma, and this hypothesis is tested by developing and evaluating a self-healing hydrogel that not only mimics the composition, but also the stiffness and viscoelasticity of native brain parenchyma. The hydrogel is crosslinked by dynamic boronate ester bonds between phenylboronic acid grafted hyaluronic acid (HA-PBA) and dopamine grafted gelatin (Gel-Dopa). This HA-PBA/Gel-Dopa hydrogel could be injected into a lesion cavity in a shear-thinning manner with rapid hemostasis, high tissue adhesion, and efficient self-healing. In an in vivo mouse model of brain lesions, the multi-functional injectable hydrogel is found to support neural cell infiltration, decrease astrogliosis and glial scars, and close the lesions. The results suggest a role for extracellular matrix-mimicking viscoelasticity in brain lesion healing, and motivate additional experimentation in larger animals as the technology progresses toward potential application in humans.
研究领域:
神经科学
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材料科学
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生物材料
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组织工程
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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）