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Regenerative Biomaterials · 2021 ·Vol. 8 ·期 2 · IF 6.353

Decellularized small intestine submucosa/polylactic-co-glycolic acid composite scaffold for potential application in hypopharyngeal and cervical esophageal tissue repair

Qiu Shijie,Liang Lijin,Zou Peng,Chen Qi

There has been an increase in the incidence of hypopharyngeal and cervical esophageal cancer worldwide, and hence growing needs for hypopharyngeal and cervical esophageal tissue repair. This work produced a bi-layer composite scaffold with decellularized small intestine submucosa and polylactic-co-glycolic acid, which resembled the layered architectures of its intended tissues. The decellularized small intestine submucosa contained minimal residual DNA (52.5 ± 1.2 ng/mg) and the composite scaffold exhibited satisfactory mechanical properties (a tensile modulus of 21.1 ± 4.8 MPa, an ultimate tensile strength of 14.0 ± 2.9 MPa and a failure strain of 26.9 ± 5.1%). The interactions between cells and the respective layers of the scaffold were characterized by CCK-8 assays, immunostaining and Western blotting. Desirable cell proliferation and phenotypic behaviors were observed. These results have provided an important basis for the next-step in vivo studies of the scaffold, and bode well for its future clinical applications.

CAS / MDL: 75-89-8
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Regenerative Biomaterials · 2021 ·Vol. 8 ·期 2 · IF 6.353

Therapeutic effects of EGF-modified curcumin/chitosan nano-spray on wound healing

Li Yue,Leng QingQing,Pang XianLun,Shi Huan,Liu YanLin,Xiao SuSu,Zhao Ling,Zhou Ping,Fu ShaoZhi

Dermal injury, including trauma, surgical incisions, and burns, remain the most prevalent socio-economical health care issue in the clinic. Nanomedicine represents a reliable administration strategy that can promote the healing of skin lesions, but the lack of effective drug delivery methods can limit its effectiveness. In this study, we developed a novel nano-drug delivery system to treat skin defects through spraying. We prepared curcumin-loaded chitosan nanoparticles modified with epidermal growth factor (EGF) to develop an aqueous EGF-modified spray (EGF@CCN) for the treatment of dermal wounds. In vitro assays showed that the EGF@CCN displayed low cytotoxicity, and that curcumin was continuously and slowly released from the EGF@CCN. In vivo efficacy on wound healing was then evaluated using full-thickness dermal defect models in Wistar rats, showing that the EGF@CCN had significant advantages in promoting wound healing. On day 12 post-operation, skin defects in the rats of the EGF@CCN group were almost completely restored. These effects were related to the activity of curcumin and EGF on skin healing, and the high compatibility of the nano formulation. We therefore conclude that the prepared nano-scaled EGF@CCN spray represents a promising strategy for the treatment of dermal wounds.

CAS / MDL: 458-37-7
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Regenerative Biomaterials · 2021 ·Vol. 8 ·期 1 · IF 6.353

Accelerating ESD-induced gastric ulcer healing using a pH-responsive polyurethane/small intestinal submucosa hydrogel delivered by endoscopic catheter

Zhao Long-Mei,Gong Mei,Wang Rui,Yuan Qi-Juan,Zhang Yi,Pi Jin-Kui,Lv Xiu-He,Xie Yan,Xie Hui-Qi

Endoscopic submucosal dissection (ESD) is the standard treatment for early-stage gastric cancer, but the large post-operative ulcers caused by ESD often lead to serious side effects. Post-ESD mucosal repair materials provide a new option for the treatment of post-ESD ulcers. In this study, we developed a polyurethane/small intestinal submucosa (PU/SIS) hydrogel and investigated its efficacy for accelerating ESD-induced ulcer healing in a canine model. PU/SIS hydrogel possessed great biocompatibility and distinctive pH-sensitive swelling properties and protected GES-1 cells from acid attack through forming a dense film in acidic conditions in vitro. Besides, PU/SIS gels present a strong bio-adhesion to gastric tissues under acidic conditions, thus ensuring the retention time of PU/SIS gels in vivo. In a canine model, PU/SIS hydrogel was easily delivered via endoscopy and adhered to the ulcer sites. PU/SIS hydrogel accelerated gastric ulcer healing at an early stage with more epithelium regeneration and slight inflammation. Our findings reveal PU/SIS hydrogel is a promising and attractive candidate for ESD-induced ulcer repair.

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Regenerative Biomaterials · 2020 ·Vol. 8 ·期 1 · IF 4.882

Strontium ranelate incorporated 3D porous sulfonated PEEK simulating MC3T3-E1 cell differentiation

Sun Yingxiao,Liu Xingdan,Tan Ji,Lv Dan,Song Wengang,Su Rui,Li Ling,Liu Xuanyong,Ouyang Liping,Liao Yun

Polyetheretherketone (PEEK) has been used as an implant material because it has similar mechanical properties to natural bone. However, inferior osseointegration and bioinertness hamper the clinical application of PEEK. In this study, the surfaces of sulfonated three-dimensional (3D) PEEK porous structures were loaded with different concentrations of strontium ranelate, a compound commonly used in the treatment or prevention of osteoporosis by promoting bone formation and inhibiting bone resorption. Field-emission scanning electron microscopy was used to characterize the topography of the structures, elemental carbon, oxygen and strontium contents were measured by X-ray photoelectron spectroscopy, and surface zeta potentials and water-contact angle were also measured. The results indicated that strontium ranelate was successfully loaded onto the 3D porous structures. In vitro cellular results showed that strontium ranelate-treated sulfonated PEEK (SP-SR) strengthened the adhesion of MC3T3-E1 cells. The activity of alkaline phosphatase, collagen secretion and extracellular matrix mineralization deposition of MC3T3-E1 cells were also improved on the surface of SP-SR. These results indicate that SP-SR could serve a new implant candidate for surgical treatment.

CAS / MDL: 123-03-5
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Regenerative Biomaterials · 2020 ·Vol. 7 ·期 3 ·303-311 · IF 4.882

Strontium-substituted sub-micron bioactive glasses inhibit ostoclastogenesis through suppression of RANKL-induced signaling pathway

Huang Deqiu,Zhao Fujian,Gao Wendong,Chen Xiaofeng,Guo Zhouyi,Zhang Wen

Strontium-substituted bioactive glass (Sr-BG) has shown superior performance in bone regeneration. Sr-BG-induced osteogenesis has been extensively studied; however, Sr-BG-mediated osteoclastogenesis and the underlying molecular mechanism remain unclear. It is recognized that the balance of osteogenesis and osteoclastogenesis is closely related to bone repair, and the receptor activators of nuclear factor kappaB ligand (RANKL) signaling pathway plays a key role of in the regulation of osteoclastogenesis. Herein, we studied the potential impact and underling mechanism of strontium-substituted sub-micron bioactive glass (Sr-SBG) on RANKL-induced osteoclast activation and differentiation in vitro. As expected, Sr-SBG inhibited RANKL-mediated osteoclastogenesis significantly with the experimental performance of decreased mature osteoclasts formation and downregulation of osteoclastogenesis-related gene expression. Furthermore, it was found that Sr-SBG might suppress osteoclastogenesis by the combined effect of strontium and silicon released through inhibition of RANKL-induced activation of p38 and NF-κB pathway. These results elaborated the effect of Sr-SBG-based materials on osteoclastogenesis through RANKL-induced downstream pathway and might represent a significant guidance for designing better bone repair materials.

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Regenerative Biomaterials · 2020 ·Vol. 7 ·期 2 ·153-160 · IF 4.882

Cu∥-loaded polydopamine coatings with in situ nitric oxide generation function for improved hemocompatibility

Zhou Lei,Li Xin,Wang Kebing,Shen Fangyu,Zhang Lu,Li Peichuang,Shang Tengda,Wang Jin,Huang Nan

NO is the earliest discovered gas signal molecule which is produced by normal healthy endothelial cells, and it has many functions, such as maintaining cardiovascular homeostasis, regulating vasodilation, inhibiting intimal hyperplasia and preventing atherosclerosis in the blood system. Insufficient NO release is often observed in the pathological environment, for instance atherosclerosis. It was discovered that NO could be released from the human endogenous NO donor by many compounds, and these methods can be used for the treatment of certain diseases in the blood system. In this work, a series of copper-loaded polydopamine (PDA) coatings were produced through self-polymerization time for 24, 48 and 72 h. The chemical composition and structure, coating thickness and hydrophilicity of the different copper-loaded PDA coatings surfaces were characterized by phenol hydroxyl quantitative, X-ray photoelectron spectroscopy, ellipsometry atomic force microscopy and water contact angles. The results indicate that the thickness and the surface phenolic hydroxyl density of the PDA coatings increased with the polymerization time.This copper-loaded coating has glutathione peroxidase-like activity, and it has the capability of catalyzing NO releasing from GSNO. The surface of the coating showed desirable hemocompatibility, the adhesion and activation of platelets were inhibited on the copper-loaded coatings. At the same time, the formation of the thrombosis was also suppressed. These copper-loaded PDA coatings could provide a promising platform for the development of blood contact materials.

CAS / MDL: 7447-39-4
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Regenerative Biomaterials · 2019 ·Vol. 6 ·期 6 ·361-371 · IF 3.382

Comparative evaluation of the physicochemical properties of nano-hydroxyapatite/collagen and natural bone ceramic/collagen scaffolds and their osteogenesis-promoting effect on MC3T3-E1 cells

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.

CAS / MDL: 1306-06-5 12167-74-7
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Regenerative Biomaterials · 2022 · IF 5.763

Preparation of aripiprazole-poly(methyl vinyl ether-co-maleic anhydride) nanocomposites via supercritical antisolvent process for improved antidepression therapy

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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Regenerative Biomaterials · 2016 ·Vol. 3 ·期 5 ·299-307 · IF 0

Efficient GSH delivery using PAMAM-GSH into MPP-induced PC12 cellular model for Parkinson’s disease

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.

CAS / MDL: 70-18-8
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Regenerative Biomaterials · 2017 ·Vol. 4 ·期 4 ·223-231 · IF 0

Facile synthesis of nano-sized CuFe2S3: morphology and diverse functional tuning and crystal growth mechanism exploring

Zhang Xiao,Zhao Huan,Zhu Yuda,Yang You,Jiang Dongli,Chen Xiaoqin,Sun Jing,Luo Jiaoming,Cai Bing,Fan Hongsong

Ternary chalcogenide compounds are such promising and have been used for much practical applications. As a sort of these compounds, cubanite (CuFe2S3) possess some unique properties which can be used in different fields. In our study, we developed a facile one pot synthesis of CuFe2S3 nanocrystals (NCs) at a low reaction temperature, and achieved a morphology and phase composition tuning of the NCs through changing a variety of precursors and surfactants, meanwhile improved their magnetism and optical properties. Eventually, well-ordered and ‘nano-brick’ like CuFe2S3 NCs were obtained and showed best magnetism and near-infrared fluorescence properties. Furthermore, the NCs were proved with good biocompatibility and possibility for cell labeling. This kind of materials with lower toxicity and potential of magnetic is bound to remedy the defects of photoluminescence quantum dots (QDs) and be with higher potential in the field of biological diagnosis and multi-functional system construction.

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Regenerative Biomaterials · 2015 ·Vol. 2 ·期 2 ·97-105 · IF 0

Silk fibroin/poly (vinyl alcohol) blend scaffolds for controlled delivery of curcumin

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.

CAS / MDL: 9002-89-5
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Regenerative Biomaterials · 2014 ·Vol. 1 ·期 1 ·27-35 · IF 0

Utilization of H-bond interaction of nucleobase Uralic with antitumor methotrexate to design drug carrier with ultrahigh loading efficiency and pH-responsive drug release

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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