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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 5 · IF 6.353

3D bioprinting of conductive hydrogel for enhanced myogenic differentiation

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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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 · 2021 ·Vol. 8 ·期 3 · IF 6.353

Cisplatin and paclitaxel co-delivery nanosystem for ovarian cancer chemotherapy

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.

CAS / MDL: 33069-62-4 14913-33-8
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Regenerative Biomaterials · 2021 ·Vol. 8 ·期 3 · IF 6.353

Tetraphenylethylene-conjugated polycation covered iron oxide nanoparticles for magnetic resonance/optical dual-mode imaging

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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Regenerative Biomaterials · 2021 ·Vol. 8 ·期 5 · IF 6.353

Gelatin methacrylate hydrogel scaffold carrying resveratrol-loaded solid lipid nanoparticles for enhancement of osteogenic differentiation of BMSCs and effective bone regeneration

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.

CAS / MDL: 10102-40-6
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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 · 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.

研究领域: 材料科学 · 生物医学工程
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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.

研究领域: 药学 · 材料科学 · 肿瘤学
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