Regenerative Biomaterials
·
2019
·Vol. 6
·期 6
·361-371
·
IF 3.382
Lei Xiongxin,Gao Jianping,Xing Fangyu,Zhang Yang,Ma Ye,Zhang Guifeng
The use of various types of calcium phosphate has been reported in the preparation of repairing materials for bone defects. However, the physicochemical and biological properties among them might be vastly different. In this study, we prepared two types of calcium phosphates, nano-hydroxyapatite (nHA) and natural bone ceramic (NBC), into 3D scaffolds by mixing with type I collagen (CoL), resulting in the nHA/CoL and NBC/CoL scaffolds. We then evaluated and compared the physicochemical and biological properties of these two calcium phosphates and their composite scaffold with CoL. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD) and compressive tests were used to, respectively, characterize the morphology, composition, distribution and the effect of nHA and NBC to collagen. Next, we examined the biological properties of the scaffolds using cytotoxicity testing, flow cytometry, immunofluorescence staining, biocompatibility testing, CCK-8 assays and RT-PCR. The results reflected that the Ca2+ released from nHA and NBC could bind chemically with collagen and affect its physicochemical properties, including the infrared absorption spectrum and compression modulus, among others. Furthermore, the two kinds of scaffolds could promote the expression of osteo-relative genes, but showed different gene induction properties. In short, NBC/CoL could promote the expression of early osteogenic genes, while nHA/CoL could upregulate late osteogenic genes. Conclusively, these two composite scaffolds could provide MC3T3-E1 cells with a biomimetic surface for adhesion, proliferation and the formation of mineralized extracellular matrices. Moreover, nHA/CoL and NBC/CoL had different effects on the period and extent of MC3T3-E1 cell mineralization.
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高影响因子
Regenerative Biomaterials
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2022
·
IF 5.763
Chen Lin-Fei,Chen Ying,Duan You-Yu,Zhang Man-Man,Xu Pei-Yao,Kankala Ranjith Kumar,Wang Shi-Bin,Chen Ai-Zheng
Aripiprazole (ARI), a second-generation atypical antipsychotic drug approved for schizophrenia treatment, shows good efficacy against depression. However, the poorly aqueous solubility of ARI leads to low bioavailability and increased dose-related side effects, seriously limiting its application in pharmaceutics. Herein, we demonstrated the fabrication of ARI and poly (methyl vinyl ether-co-maleic anhydride) (PVMMA) composite nanoparticles (PA NPs) using the supercritical antisolvent (SAS) process for enhancing its water-solubility and curative anti-depressant effects. Initially, the optimal experimental conditions (ARI/PVMMA mass ratio of 1:6, pressure of 10 MPa, and solution flow rate of 0.75 ml min−1) were determined by a 23 factorial experimental design, resulting in the PA NPs with an excellent particle morphology. In vitro cell experiments showed that PA NPs significantly inhibited the inflammatory response caused by the microglia activation induced by lipopolysaccharide (LPS). Similarly, mice behavioral tests demonstrated that PA NPs significantly improved LPS-induced depression-like behavior. Importantly, compared with free ARI, the LPS-induced activation of microglia in the mouse brain and the expression of inflammatory factors in serum were significantly reduced after treatment with PA NPs. Together, the innovative PA NPs designed by SAS process might provide a candidate for developing new ARI-based nano-formulations.
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高影响因子
Regenerative Biomaterials
·
2025
·
IF 8.1
Xia Hangbin,Yang Chen,Li Huili,Huang Lingwei,Zeng Zhen,Chi Runrun,Yang Ziwei,Wang Yuzen,Chang Jiang,Jiao Yiren,Li Wenzhong
Muscle satellite cells (MuSCs) play a vital role in skeletal muscle regeneration. However, in intractable muscle diseases such as volumetric muscle loss (VML), the quantity and function of MuSCs are significantly reduced, severely limiting the body's inherent muscle regeneration capability. In this study, we propose a novel strategy to modulate the fate of MuSCs using a combination of bioactive magnesium (Mg) and silicon (Si) ions, sustainably delivered through magnesium silicate (MgSiO3, MS) bioceramic-based scaffolds. In vitro, Mg and Si ions synergistically promote the proliferation and differentiation of MuSCs. Similarly, Mg and Si ions derived from MS/poly (L-lactic acid) (MS/PLLA) composite scaffold also increases the proliferation and differentiation ability of MuSCs. Furthermore, MS/PLLA composite scaffolds facilitate the activation of MuSCs, regeneration of muscle fiber, and neovascularization, while inhibiting fibrosis, thereby effectively restoring muscle function and promoting tibialis anterior muscle functional regeneration in a VML mouse model. Mechanistically, the combination of Mg and Si ions promotes the activation and proliferation of MuSCs by activating the Notch1-Hes1 pathway. Besides, the combination of Mg and Si ions also improves the differentiation of MuSCs by up-regulating Myod and Myog, and enhances fusion by up-regulating Mymk and Mymx expression. The outcomes of our research introduce a promising approach to the treatment of skeletal muscle injuries and related diseases.
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高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Xie Lijun,Zhang Yan,Cao Binji,Jiao Xiaoyi,Yue Xusong,Xu Yan,Yang Xianyan,Yang Guojing,Wang Yingjie,Shen Jian,Wang Cong,Weng Xisheng,Gou Zhongru
It is known that magnesium phosphate cements (MPCs) show appreciable mechanical strength and biocompatibility, but the hydration reaction processes often lead to intense heat release while the hydration products present weak resistance to mechanical decay and low bioactivity. Herein we developed an MPC-based system, which was low-heat-releasing and fast-curing in this study, by compounding with self-curing calcium silicate cements (CSCs). The MPC composed of magnesium oxide (MgO), potassium dihydrogen phosphate (KH2PO4), disodium hydrogen phosphate (Na2HPO4), magnesium hydrogen phosphate trihydrate (MgHPO4·3H2O) and chitosan were weakly basic, which would be more stable in vivo. The physicochemical properties indicated that the addition of CSCs could increase the final setting time while decrease the heat release. Meanwhile, the CSCs could endow MPC substrate with apatite re-mineralization reactivity, especially, which add 25 wt.% CSCs showed the most significant apatite deposition. What’s more, the mechanical evolution in buffer demonstrated CSCs could enhance and sustain the mechanical strength during degradation, and the internal constructs of cement implants could still be reconstructed by μCT analysis in rabbit femoral bone defect model in vivo. Particularly, appropriate CSCs adjusted the biodegradation and promoted new bone tissue regeneration in vivo. Totally, the MPC/CSCs composite system endows bioactivity and sustain mechanical strength of the MPC, which may be promising for expending the clinical applications of MPC-based bone cements.
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高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Sun Yage,Zhao Xinrui,Zhang Qian,Yang Rong,Liu Wenguang
The hypoxia microenvironment post myocardial infarction (MI) critically disturbs cellular metabolism and inflammation response, leading to scarce bioenergy supplying, prolonged inflammatory phase and high risk of cardiac fibrosis during cardiac restoration. Herein, an injectable hydrogel is prepared by Schiff-base reaction between fructose-1,6-bisphosphate (FBP)-grafted carboxymethyl chitosan (CF) and oxidized dextran (OD), following by loading fucoidan-coated baicalin (BA)-encapsulated zein nanoparticles (BFZ NPs), in which immunoregulatory and metabolism improving functions are integrally included. The grafted FBP serves to enhance glycolysis and provide more bioenergy for cardiomyocytes survival under hypoxia microenvironment, and elevating cellular antioxidant capacity via pentose phosphate pathway. OD with intrinsic anti-inflammatory effect can induce M2 polarization of macrophages to accelerate inflammatory elimination. While facing the possibility of endothelial-to-mesenchymal transition (EndoMT) caused by excessive expressed TGF-β1 secreted from M2 macrophages, BFZ NPs can target endothelia cells and intracellularly release BA to regulate the level of fatty acid oxidation, resulting in retained endothelial features and decreased risk of cardiac fibrosis. After being injecting the hydrogel into rats’ infarcted cardiac, the 28 day-post surgical outcomes demonstrate its benign effects on restoring cardiac functions and attenuating adverse left ventricular remodeling. This study shows a promising measure for MI treatment with immunoregulating and metabolism regulation comprehensively.
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高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Zhang Peng,Wang Tiehua,Qian Junyu,Qin Haotian,Liu Peng,Xiong Ao,Udduttula Anjaneyulu,Wang Deli,Zeng Hui,Chen Yingqi
Microbial infections of bones, particularly after joint replacement surgery, are a common occurrence in clinical settings and often lead to osteomyelitis (OM). Unfortunately, current treatment approaches for OM are not satisfactory. To address this issue, this study focuses on the development and evaluation of an injectable magnesium oxide (MgO) nanoparticle-coordinated phosphocreatine-grafted chitosan hydrogel (CMPMg-VCM) loaded with varying amounts of vancomycin (VCM) for the treatment of OM. The results demonstrate that the loading of VCM does not affect the formation of the injectable hydrogel, and the MgO-incorporated hydrogel exhibits anti-swelling properties. The release of VCM from the hydrogel effectively kills staphylococcus aureus bacteria, with CMPMg-VCM (50) showing the highest antibacterial activity even after prolonged immersion in PBS solution for 12 days. Importantly, all the hydrogels are non-toxic to MC3T3-E1 cells and promote osteogenic differentiation through the early secretion of alkaline phosphatase and calcium nodule formation. Furthermore, in vivo experiments using a rat OM model reveal that the CMPMg-VCM hydrogel effectively kills and inhibits bacterial growth, while also protecting the infected bone from osteolysis. These beneficial properties are attributed to the burst release of VCM, which disrupts bacterial biofilm, as well as the release of Mg ions and hydroxyl by the degradation of MgO nanoparticles, which inhibits bacterial growth and prevents osteolysis. Overall, the CMPMg-VCM hydrogel exhibits promising potential for the treatment of microbial bone infections.
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高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Li Bingyi,He Mei,Xu Zichen,Zhang Qianting,Zhang Liyuan,Zhao Shuang,Cao Yu,Mou Nianlian,Wang Yi,Wang Guixue
Atherosclerosis (AS), an inflammatory disease characterized by lipid accumulation, has a high global incidence and mortality rate. Recently, nanotherapeutic approaches that target pathological sites and improve drug bioavailability and biocompatibility hold great promise for AS treatment. In this study, a biomimetic ROS-responsive hyaluronic acid–based nanomaterial was prepared for targeted anti-AS. Specifically, a safe ROS-responsive carrier based on hyaluronic acid (HSP) was prepared to load methotrexate (MTX), a drug known for its ability to enhance lipid excretion, resulting in the formation of MTX-loaded nanoparticles (MTXNPs). Furthermore, the macrophage membrane was coated on the surface of MTXNPs to obtain MM/MTXNPs. Both MTXNPs and MM/MTXNPs exhibited ROS responsiveness and demonstrated excellent biocompatibility. In vitro experiments revealed that MM/MTXNPs could evade macrophage phagocytosis and exhibited high uptake rates by inflamed endothelial cells. MM/MTXNPs also reduced lipid accumulation in foam cells. In vivo experiments showed that MM/MTXNPs exhibited superior accumulation at AS plaque sites, facilitated by the surface membrane layer containing integrin α4β1 and CD47, resulting in an enhanced therapeutic effect in inhibiting plaque development compared to free MTX and MTXNPs. Therefore, HSP represents a promising nanocarrier to load hydrophobic MTX, enabling effective and biocompatible enhancement of AS treatment.
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高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Wang Zhiwei,Sun Lingshun,Wang Weixing,Wang Zheng,Shi Ge,Dai Honglian,Yu Aixi
Diabetic wounds are a difficult medical challenge. Excessive secretion of matrix metalloproteinase-9 (MMP-9) in diabetic wounds further degrades the extracellular matrix (ECM) and growth factors and causes severe vascular damage, which seriously hinders diabetic wound healing. To solve these issues, a double-network porous hydrogel composed of poly (methyl methacrylate-co-acrylamide) (p(MMA-co-AM)) and polyvinyl alcohol (PVA) was constructed by the high internal phase emulsions (HIPE) technique for the delivery of potassium sucrose octasulfate (PSO), a drug that can inhibit matrix metalloproteinases (MMPs), increase angiogenesis, and improve microcirculation. The hydrogel possessed a typical polyHIPE hierarchical microstructure with interconnected porous morphologies, high porosity, high specific surface area, excellent mechanical properties, and suitable swelling properties. Meanwhile, the p(MMA-co-AM)/PVA@PSO hydrogel showed high drug-loading performance and effective PSO release. In addition, both in vitro and in vivo studies showed that the p(MMA-co-AM)/PVA@PSO hydrogel had good biocompatibility and significantly accelerated diabetic wound healing by inhibiting excessive MMP-9 in diabetic wounds, increasing growth factor secretion, improving vascularization, increasing collagen deposition, and promoting re-epithelialization. Therefore, this study provided a reliable therapeutic strategy for diabetic wound healing, some theoretical basis, and new insights for the rational design and preparation of wound hydrogel dressings with high porosity, high drug-loading performance, and excellent mechanical properties.
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高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Zhang Sulei,Sun Jun,Guo Shuaihang,Wang Yichen,Zhang Yuheng,Lei Jiao,Liu Xiaoli,Chen Hong
Surface endothelialization is a promising way to improve the hemocompatibility of biomaterials. However, current surface endothelialization strategies have limitations. For example, various surface functions are not well balanced, leading to undesirable results, especially when multiple functional components are introduced. In this work, a multifunctional surface was constructed by balancing the functions of antifouling, nitric oxide release and endothelial cell promotion via layer−by−layer self−assembly. Poly(sodium p−styrenesulfonate−co−oligo(ethylene glycol) methacrylate) (negatively charged) and polyethyleneimine (positively charged) were deposited on silicon substrates to construct multilayers by layer−by−layer self−assembly. Then, organic selenium, which has a nitric oxide-releasing function, and the cell-adhesive peptide Gly-Arg-Glu-Asp-Val-Tyr, which selectively promotes endothelial cells, were introduced on the assembled multilayers. Poly(oligo(ethylene glycol) methacrylate) is a hydrophilic component for antifouling properties, and poly(sodium p−styrenesulfonate) is a heparin analog that provides negative charges. By modulating the contents of poly(oligo(ethylene glycol) methacrylate) and poly(sodium p−styrenesulfonate) in the copolymers, the nitric oxide release rates catalyzed by the modified surfaces were regulated. Moreover, the behaviors of endothelial cells and smooth muscle cells on modified surfaces were well controlled. The optimized surface strongly promoted endothelial cells and inhibited smooth muscle cells to achieve endothelialization effectively.
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高影响因子
Regenerative Biomaterials
·
2015
·Vol. 2
·期 2
·97-105
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IF 0
Li Xiaomeng,Qin Jinli,Ma Jun
A silk fibroin/poly (vinyl alcohol) porous scaffold with a water vapor transmission rate of 2125 ± 464 g/m2/day has been developed via thermally induced phase separation (gelation) and freeze-drying process. A hierarchical architecture of micropores and nanofibers was observed inside the scaffolds, and the related structures were analyzed. The viability and proliferation of 3T3 fibroblasts were examined, which indicated that the scaffolds exerted low cytotoxicity. After loading curcumin, the scaffolds can suppress the growth of 3T3 fibroblasts. The release behavior of curcumin from the scaffolds was investigated. At pH = 7.2, the release profiles showed no significant difference for the loading amounts of 0.5 mg and 0.25 mg per sample. Meanwhile, the cumulative amount of released drug at pH = 5.7 was significantly more than that in neutral solution due to more degradation of the scaffolds. It was suggested that the silk fibroin/poly (vinyl alcohol) blend scaffolds could be potentially used as wound dressing materials.
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Regenerative Biomaterials
·
2016
·Vol. 3
·期 5
·299-307
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IF 0
Sun Hong-Ji,Wang Yan,Hao Tong,Wang Chang-Yong,Wang Qi-Yu,Jiang Xiao-Xia
Glutathione (GSH) depletion has been an important contributor to the dysfunction of dopamine neurons. Polyamidoamine-GSH (PAMAM-GSH) was synthesized and the delivery effect of GSH into PC12 cells was tested. MTT assessment for cytotoxicity and reactive oxygen species (ROS) as well as nitrite oxide (NO) and intracelluar superoxide dismutase (SOD) detection for antioxidative ability were performed. Furthermore, the antiapoptotic ability was analysed by assessing caspase-3, JNK1/2 and Erk1/2 expression. Our data indicated that PAMAM-GSH is an effective agent to replenish GSH into PC12 cells. PAMAM-GSH developed its antioxidative and protective ability for 1-methyl-4-phenylpyridinium (MPP)-induced PC12 cells by reducing the intracellular levels of ROS and SOD activity as well as decreasing the release of NO. Meanwhile, PAMAM-GSH could inhibit caspase-3 activation and might show its antiapoptotic ability to MPP-induced PC12 cells through JNK2/Erk1/2 pathway. In summary, these studies suggest that PAMAM-GSH conjugate has an intrinsic ability to penetrate PC12 cells and deliver GSH into these cells which may provide a new strategy for clinical applications in the treatment of Parkinson’s disease.
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Regenerative Biomaterials
·
2014
·Vol. 1
·期 1
·27-35
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IF 0
Cai Teng-Teng,Lei Qi,Yang Bin,Jia Hui-Zhen,Cheng Hong,Liu Li-Han,Zeng Xuan,Feng Jun,Zhuo Ren-Xi,Zhang Xian-Zheng
A novel Uralic (U)-rich linear-hyperbranched mono-methoxy poly (ethylene glycol)-hyperbranched polyglycerol-graft-Uralic (mPEG-HPG-g-U) nanoparticle (NP) was prepared as drug carrier for antitumor methotrexate (MTX). Due to the H-bond interaction of U with MTX and hydrophobic interaction, this NP exhibited high drug loading efficiency of up to 40%, which was significantly higher than that of traditional NPs based on U-absent copolymers (<15%). In addition, MTX-loaded mPEG-HPG-g-U NPs also demonstrated an acidity-accelerated drug release behavior.
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