Regenerative Biomaterials
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2022
·
IF 5.763
Li Jing,Yan Shunshun,Han Weiju,Dong Zixuan,Li Junliang,Wu Qi,Fu Xiaoling
Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) can deliver a variety of bioactive factors to create a favorable local microenvironment, thereby holding huge potential in chronic wound repair. However, free sEVs administrated intravenously or locally are usually cleared rapidly, resulting in an insufficient duration of the efficacy. Thus, strategies that enable optimized retention and release profiles of sEVs at wound sites are desirable. Herein, we fabricated novel functional phosphoethanolamine phospholipid-grafted poly-l-lactic acid micro/nanofibers (DSPE-PLLA) to carry and retain sEVs from rat adipose MSCs, enabling the slow local release of sEVs. Our results showed that sEVs@DSPE-PLLA promoted the proliferation, migration and gene expression (Col I, Col III, TGF-β, α-SMA, HIF-1α) of fibroblasts. It also promoted keratinocyte proliferation. In addition, sEVs@DSPE-PLLA helped polarize macrophages toward the M2 phenotype by increasing the expression of anti-inflammatory genes (Arginase 1, CD 206, IL-10) and inhibiting the expression of pro-inflammatory genes (IL-1β, TNF-α). Further in vivo study in diabetic rat models showed that sEVs@DSPE-PLLA improved the wound-healing process by alleviating the inflammatory responses, stimulating cell proliferation, collagen deposition and angiogenesis. These results highlight the potential of using DSPE-grafted scaffolds for extracellular vesicle immobilization and suggest sEVs@DSPE-PLLA micro/nanofibers as promising functional wound dressings for diabetic wounds.
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高影响因子
Regenerative Biomaterials
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2022
·
IF 5.763
Li Zhongcheng,Ren Qian,Han Sili,Ding Longjiang,Qin Xi,Hu Die,He Ting,Tian Tian,Lu Ziqian,Zhang Linglin
Recently, a de novo synthetic calcium-responsive self-assembly β-sheet peptide ID8 (Ile-Asp-Ile-Asp-Ile-Asp-Ile-Asp) has been developed to serve as the template inducing hydroxyapatite nucleation. The aim of this study was to evaluate the effect of ID8 on intrafibrillar mineralization of collagen making full use of its self-assembly ability. The mineralization experiments were carried out in vitro on both bare Type I collagen and fully demineralized dentin samples. The calcium-responsive self-assembly of ID8 was revealed by circular dichroism spectrum, 8-anilino-1-naphthalenesulfonic acid ammonium salt hydrate assay, attenuated total reflection Fourier transform infrared spectrum (ATR-FTIR) and transmission electron microscope (TEM). Polyacrylic acid (450 kDa) with a concentration of 100 μg ml−1 was selected as the nucleation inhibitor based on the determination of turbidimetry and TEM with selected area electron diffraction (TEM-SAED). The results showed that collagen intrafibrillar mineralization was significantly promoted with the pretreatment of self-assembly ID8 detected by TEM-SAED, SEM, X-ray diffraction and ATR-FTIR. The pretreatment of collagen utilizing self-assembly ID8 not only enhanced intermolecular hydrogen bonding but also contributed to calcium retention inside collagen and significantly increased the hydrophilicity of collagen. These results indicated that peptides with self-assembly properties like ID8 are expected to be potential tools for biomimetic mineralization of collagen.
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Regenerative Biomaterials
·
2022
·
IF 5.763
Huang Jinzhou,Zhai Dong,Xue Jianmin,Li Tian,Ren Dudi,Wu Chengtie
For the research of biomaterials in bone tissue engineering, it is still a challenge to fabricate bioceramics that overcome brittleness while maintaining the great biological performance. Here, inspired by the toughness of natural materials with hierarchical laminated structure, we presented a directional assembly-sintering approach to fabricate laminated MXene/calcium silicate-based (L-M/CS) bioceramics. Benefiting from the orderly laminated structure, the L-M/CS bioceramics exhibited significantly enhanced toughness (2.23 MPa·m1/2) and high flexural strength (145 MPa), which were close to the mechanical properties of cortical bone. Furthermore, the L-M/CS bioceramics possessed more suitable degradability than traditional CaSiO3 bioceramics due to the newly formed CaTiSiO5 after sintering. Moreover, the L-M/CS bioceramics showed good biocompatibility and could stimulate the expression of osteogenesis-related genes. The mechanism of promoting osteogenic differentiation had been shown to be related to the Wnt signaling pathway. This work not only fabricated calcium silicate-based bioceramics with excellent mechanical and biological properties for bone tissue engineering but also provided a strategy for the combination of bionics and bioceramics.
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高影响因子
Regenerative Biomaterials
·
2022
·
IF 5.763
Guo Jiaxin,Wei Wenying,Zhao Yanan,Dai Honglian
Metal-based nanomaterials usually have broad-spectrum antibacterial properties, low biological toxicity and no drug resistance due to their intrinsic enzyme-like catalytic properties and external field (magnetic, thermal, acoustic, optical and electrical) responsiveness. Herein, iron oxide (Fe3O4) nanoparticles (IONPs) synthesized by us have good biosafety, excellent photothermal conversion ability and peroxidase-like catalytic activity, which can be used to construct a photothermal-enzymes combined antibacterial treatment platform. IONPs with peroxide-like catalytic activity can induce H2O2 to catalyze the production of •OH in a slightly acidic environment, thus achieving certain bactericidal effects and increasing the sensitivity of bacteria to heat. When stimulated by near-infrared light, the photothermal effect could destroy bacterial cell membranes, resulting in cleavage and inactivation of bacterial protein, DNA or RNA. Meanwhile, it can also improve the catalytic activity of peroxidase-like and promote IONPs to catalyze the production of more •OH for killing bacteria. After IONPs synergistic treatment, the antibacterial rate of Escherichia coli and Staphylococcus aureus reached nearly 100%. It also has an obvious killing effect on bacteria in infected wounds of mice and can effectively promote the healing of S. aureus-infected wounds, which has great application potential in clinical anti-infection treatment.
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高影响因子
Regenerative Biomaterials
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2022
·
IF 5.763
Meng Ziyu,Wang Binchao,Liu Yiqiang,Wan Yejian,Liu Qianshi,Xu Huasheng,Liang Renchuan,Shi Ying,Tu Peng,Wu Hong,Xu Chuan
Targeting mitochondria via nano platform emerged as an attractive anti-tumor pathway due to the central regulation role in cellar apoptosis and drug resistance. Here, a mitochondria-targeting nanoparticle (TOS-PDA-PEG-TPP) was designed to precisely deliver polydopamine (PDA) as the photothermal agent and alpha-tocopherol succinate (α-TOS) as the chemotherapeutic drug to the mitochondria of the tumor cells, which inhibits the tumor growth through chemo- and photothermal- synergistic therapies. TOS-PDA-PEG-TPP was constructed by coating PDA on the surface of TOS NPs self-assembled by α-TOS, followed by grafting PEG and triphenylphosphonium (TPP) on their surface to prolong the blood circulation time and target delivery of TOS and PDA to the mitochondria of tumor cells. In vitro studies showed that TOS-PDA-PEG-TPP could be efficiently internalized by tumor cells and accumulated at mitochondria, resulting in cellular apoptosis and synergistic inhibition of tumor cell proliferation. In vivo studies demonstrated that TOS-PDA-PEG-TPP could be efficiently localized at tumor sites and significantly restrain the tumor growth under NIR irradiation without apparent toxicity or deleterious effects. Conclusively, the combination strategy adopted for functional nanodrugs construction aimed at target-delivering therapeutic agents with different action mechanisms to the same intracellular organelles can be extended to other nanodrugs-dependent therapeutic systems.
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高影响因子
Regenerative Biomaterials
·
2022
·
IF 5.763
Wu Hao,Gao Yuan,Ma Jia,Hu Maosong,Xia Jing,Bao Shuting,Liu Yuxi,Feng Kai
Acute myelogenous leukemia (AML) remains a serious fatal disease for the patients and effective treatment strategies are urgently needed. Based on the characteristics of the AML, we developed the CD44 and bone targeting liposomes delivery system decorated with the redox-cleavable polymer. First, ALN-HA was obtained by amination between alendronate (ALN) and hyaluronic acid (HA), and cholesterol (Chol) was coupled by a disulfide linker (-SS-) with biological reducibility to obtain the goal polymer, ALN-HA-SS-Chol, decorated the liposomes loaded with the Cytarabine (AraC). ALN-HA-SS-AraC-Lip exhibited a spherical morphology with the diameter of 117.5 nm and expanded at the environment of 10 mM dithiothreitol. Besides, compared with other groups, ALN-HA-SS-AraC-Lip showed benign hydroxyapatite affinity in vitro and bone targeting in C57/BL6 mice, also, ALN-HA-SS-AraC-Lip exhibited encouraging antitumor which significantly reduced the white blood cell amount in bone marrow and blood smear caused by AML model, besides, the dual targeting liposomes also prolong the survival time of mice. In conclusion, the bone and CD44 dual targeting liposomes with redox sensitivity could target to the leukemia stem cells regions and then uptake by the tumor cells, which would be a valuable target for the treatment of the AML.
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高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 5
·
IF 6.353
Wang Ying,Wang Qingshuai,Luo Shengchang,Chen Zhoujiang,Zheng Xiang,Kankala Ranjith Kumar,Chen Aizheng,Wang Shibin
Recently, hydrogels have gained enormous interest in three-dimensional (3D) bioprinting toward developing functional substitutes for tissue remolding. However, it is highly challenging to transmit electrical signals to cells due to the limited electrical conductivity of the bioprinted hydrogels. Herein, we demonstrate the 3D bioprinting-assisted fabrication of a conductive hydrogel scaffold based on poly-3,4-ethylene dioxythiophene (PEDOT) nanoparticles (NPs) deposited in gelatin methacryloyl (GelMA) for enhanced myogenic differentiation of mouse myoblasts (C2C12 cells). Initially, PEDOT NPs are dispersed in the hydrogel uniformly to enhance the conductive property of the hydrogel scaffold. Notably, the incorporated PEDOT NPs showed minimal influence on the printing ability of GelMA. Then, C2C12 cells are successfully encapsulated within GelMA/PEDOT conductive hydrogels using 3D extrusion bioprinting. Furthermore, the proliferation, migration and differentiation efficacies of C2C12 cells in the highly conductive GelMA/PEDOT composite scaffolds are demonstrated using various in vitro investigations of live/dead staining, F-actin staining, desmin and myogenin immunofluorescence staining. Finally, the effects of electrical signals on the stimulation of the scaffolds are investigated toward the myogenic differentiation of C2C12 cells and the formation of myotubes in vitro. Collectively, our findings demonstrate that the fabrication of the conductive hydrogels provides a feasible approach for the encapsulation of cells and the regeneration of the muscle tissue.
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高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 6
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IF 6.353
Jiang Yingying,Tan Shuo,Hu Jianping,Chen Xin,Chen Feng,Yao Qianting,Zhou Zhi,Wang Xiansong,Zhou Zifei,Fan Yunshan,Liu Junjian,Lin Yize,Liu Lijia,He Shisheng
The seek of bioactive materials for promoting bone regeneration is a challenging and long-term task. Functionalization with inorganic metal ions or drug molecules is considered effective strategies to improve the bioactivity of various existing biomaterials. Herein, amorphous calcium magnesium phosphate (ACMP) nanoparticles and simvastatin (SIM)-loaded ACMP (ACMP/SIM) nanocomposites were developed via a simple co-precipitation strategy. The physiochemical property of ACMP/SIM was explored using transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) and high-performance liquid chromatograph (HPLC), and the role of Mg2+ in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure (XANES). After that, the transformation process of ACMP/SIM in simulated body fluid (SBF) was also tracked to simulate and explore the in vivo mineralization performance of materials. We find that ACMP/SIM releases ions of Ca2+, Mg2+ and PO3−4, when it is immersed in SBF at 37°C, and a phase transformation occurred during which the initially amorphous ACMP turns into self-assembled hydroxyapatite (HAP). Furthermore, ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells. For the in vivo studies, lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria. ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12 weeks. The bioactive ACMP/SIM nanocomposites are promising as bone repair materials. Considering the facile preparation process and superior in vitro/vivo bioactivity, the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications.
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高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 6
·
IF 6.353
Yang Li,Fu Shengxiang,Cai Zhongyuan,Liu Li,Xia Chunchao,Gong Qiyong,Song Bin,Ai Hua
The T1−T2 dual-mode probes for magnetic resonance imaging (MRI) can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same time, making MRI a more flexible imaging modality for complicated applications. In this work, three Gadolinium-diethylene-triaminepentaaceticacid (Gd-DTPA) complex conjugated superparamagnetic iron oxide (SPIO) nanoparticles with different Gd/Fe molar ratio (0.94, 1.28 and 1.67) were prepared as T1–T2 dual-mode MRI probes, named as SPIO@PEG-GdDTPA0.94, SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67, respectively. All SPIO@PEG-GdDTPA nanocomposites with 8 nm spherical SPIO nanocrystals showed good Gd3+ chelate stability. SPIO@PEG-GdDTPA0.94 nanocomposites with lowest Gd/Fe molar ratio show no cytotoxicity to Raw 264.7 cells as compared to SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67. SPIO@PEG-GdDTPA0.94 nanocomposites with r1 (8.4 mM−1s−1), r2 (83.2 mM−1s−1) and relatively ideal r2/r1 ratio (9.9) were selected for T1–T2 dual-mode MRI of blood vessels and liver tissue in vivo. Good contrast images were obtained for both cardiovascular system and liver in animal studies under a clinical 3 T scanner. Importantly, one can get high-quality contrast-enhanced blood vessel images within the first 2 h after contrast agent administration and acquire liver tissue anatomy information up to 24 h. Overall, the strategy of one shot of the dual mode MRI agent could bring numerous benefits not only for patients but also to the radiologists and clinicians, e.g. saving time, lowering side effects and collecting data of different organs sequentially.
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Regenerative Biomaterials
·
2021
·Vol. 8
·期 3
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IF 6.353
Yang Li,Fu Shengxiang,Liu Li,Cai Zhongyuan,Xia Chunchao,Song Bin,Gong Qiyong,Lu Zhiyun,Ai Hua
Magnetic resonance (MR)/optical dual-mode imaging with high sensitivity and high tissue resolution have attracted many attentions in biomedical applications. To avert aggregation-caused quenching of conventional fluorescence chromophores, an aggregation-induced emission molecule tetraphenylethylene (TPE)-conjugated amphiphilic polyethylenimine (PEI) covered superparamagnetic iron oxide (Alkyl-PEI-LAC-TPE/SPIO nanocomposites) was prepared as an MR/optical dual-mode probe. Alkyl-PEI-LAC-TPE/SPIO nanocomposites exhibited good fluorescence property and presented higher T2 relaxivity (352 Fe mM−1s−1) than a commercial contrast agent Feridex (120 Fe mM−1s−1) at 1.5 T. The alkylation degree of Alkyl-PEI-LAC-TPE effects the restriction of intramolecular rotation process of TPE. Reducing alkane chain grafting ratio aggravated the stack of TPE, increasing the fluorescence lifetime of Alkyl-PEI-LAC-TPE/SPIO nanocomposites. Alkyl-PEI-LAC-TPE/SPIO nanocomposites can effectively labelled HeLa cells and resulted in high fluorescence intensity and excellent MR imaging sensitivity. As an MR/optical imaging probe, Alkyl-PEI-LAC-TPE/SPIO nanocomposites may be used in biomedical imaging for certain applications.
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高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 3
·
IF 6.353
Wang Qiaoying,Wu Changqiang,Li Xiaoting,Yang Dixiao,Shi Liangjun
We have designed and developed an effective drug delivery system using biocompatible polymer of poly (ethylene glycol)-polyaspartic acid (mPEG-PAsp) for co-loading the chemotherapy drugs paclitaxel (PTX) and cisplatin (CP) in one nano-vehicle. This study aimed to improve the anti-cancer efficacy of combinations of chemotherapy drugs and reduce their side effects. mPEG-PAsp-(PTX/Pt) nano-micelles disperse well in aqueous solution and have a narrow size distribution (37.8 ± 3.2 nm) in dynamic light scattering (DLS). Drug release profiles found that CP released at pH 5.5 was significantly faster than that at pH 7.4. MPEG-PAsp-(PTX/Pt) nano-micelles displayed a significantly higher tumor inhibitory effect than mPEG-PAsp-PTX nano-micelles when the polymer concentrations reached 50 μg/mL. Our data indicated that polymer micelles of mPEG-PAsp loaded with the combined drug exert synergistic anti-tumor efficacy on SKOV3 ovarian cells via different action mechanisms. Results from our studies suggested that mPEG-PAsp-(PTX/Pt) nano-micelles are promising alternatives for carrying and improving the delivery of therapeutic drugs with different water solubilities.
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高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 5
·
IF 6.353
Wei Bangguo,Wang Wenrui,Liu Xiangyu,Xu Chenxi,Wang Yanan,Wang Ziqi,Xu Jinnuo,Guan Jianzhong,Zhou Pinghui,Mao Yingji
Critical-sized bone defects caused by traumatic fractures, tumour resection and congenital malformation are unlikely to heal spontaneously. Bone tissue engineering is a promising strategy aimed at developing in vitro replacements for bone transplantation and overcoming the limitations of natural bone grafts. In this study, we developed an innovative bone engineering scaffold based on gelatin methacrylate (GelMA) hydrogel, obtained via a two-step procedure: first, solid lipid nanoparticles (SLNs) were loaded with resveratrol (Res), a drug that can promote osteogenic differentiation and bone formation; these particles were then encapsulated at different concentrations (0.01%, 0.02%, 0.04% and 0.08%) in GelMA to obtain the final Res-SLNs/GelMA scaffolds. The effects of these scaffolds on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone regeneration in rat cranial defects were evaluated using various characterization assays. Our in vitro and in vivo investigations demonstrated that the different Res-SLNs/GelMA scaffolds improved the osteogenic differentiation of BMSCs, with the ideally slow and steady release of Res; the optimal scaffold was 0.02 Res-SLNs/GelMA. Therefore, the 0.02 Res-SLNs/GelMA hydrogel is an appropriate release system for Res with good biocompatibility, osteoconduction and osteoinduction, thereby showing potential for application in bone tissue engineering.
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