CHEMICO-BIOLOGICAL INTERACTIONS
·
2016
·
IF 2.618
Xiaonan Zhang,Kang Chen,Bo Wei,Xingwang Liu,Zeming Lei,Xizhuang Bai
Glucocorticoid-induced osteoporosis (GIOP) is the primary cause of secondary osteoporosis and the existing therapeutic strategies are limited. The aim of this study is to evaluate the effects of ginsenosides (GS) Rg3 on dexamethasone (DEX)-induced osteoporosis in vivo and in vitro. GIOP rat was established by DEX injection for 5 weeks and treated by GS Rg3 10 or 20 mg/kg. Body weight and bone mineral density (BMD) of rats were measured at the beginning and the end of the experiment. Histological changes of femurs were observed using HE staining. The in vitro model was established on primary osteoblasts induced by DEX. CCK-8 assay was used to test the cell viability. Bone metabolism markers in serum or primary osteoblasts were detected using biochemical kits. Real time PCR and western blot were used to measure nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), bone morphogenic protein-2 (BMP-2), BMP receptor 1A (BMPR1A) and Runx2 expression. The results demonstrated that GS Rg3 prevented DEX-induced body weight and BMD reduction, enhanced secretion of bone formation markers and decreased bone resorption markers. In addition, GS Rg3 was found to prevent the suppression of BMP-2/BMPR1A/Runx2 signals induced by DEX both in GIOP rats and primary osteoblasts. Inhibition of BMP-2 by noggin completely blocked the bone-alkaline phosphatase-secretion-promoted effect of GS Rg3 in vitro. These data suggest that GS Rg3 attenuates GIOP through regulating BMP-2 signaling pathway. This study provides a potential drug candidate for GIOP therapy.
研究领域:
药理学
·
骨科
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2024
·
IF 5.8
Zhonglian Wu,Haidi Sun,Xu Hu,Jian Yang,Zehao Gu,Chirun Wang,Hui Chong,Jihang Dai,Hang Yao,Dong-An Wang
Osteochondral defects pose significant challenges in tissue regeneration due to the complex structure and composition of native tissue. Restoring the intricate structure and functional capacity of tissues remains a formidable task in osteochondral transplantation. In this study, a novel composite crosslinked 3D printing ink was designed to construct a biomimetic osteochondral scaffold with a sustained release bone morphogenetic protein 2 (BMP-2) hydrogel system of dopamine-modified hyaluronic acid (HAD) and BMP-2 interaction. The enzyme-linked immunosorbent assay results showed a cumulative release of BMP-2 reaching 48.3 %±6.1 % at 28 days. Theoretical calculations indicated that the binding affinity of HAD and BMP-2 was −41.8 ± 1.27 kJ/mol. These findings corroborated the outstanding sustained release efficacy of the hydrogel scaffolds due to the HAD and BMP-2 interaction. Biological function evaluations revealed that the scaffolds possessed significant osteogenesis and chondrogenesis abilities in vitro . This effect is attributed to the hydrophilic nature of the upper layer of the scaffold and the sustained release of BMP-2 from the lower layer. Ultimately, the bilayer scaffolds achieved integrated osteochondral regeneration in a rat model. These results demonstrated the potential of the 3D-printed biomimetic scaffolds with a sustained release BMP-2 hydrogel system for osteochondral repair.
研究领域:
组织工程
·
生物医学工程
·
再生医学
·
生物材料科学
✓ 已验证
产品关联
DOI
高影响因子
European Review for Medical and Pharmacological Sciences
·
2017
·Vol. 21
·期 10
·2316-2328
·
IF 1.778
An G,Zhang WB,Ma DK,Lu B,Wei GJ,Guang Y,Ru CH,Wang YS
Objective To investigate the influence of VEGF/BMP-2 on the proliferation and osteogenic differentiation of rat bone mesenchymal stem cells BMSCs) on PLGA/gelatin composite scaffold. Materials and methods Randomly-oriented nanofibers with different ratios of Poly Lactic-co-Glycolic Acid (PLGA)/gelatin were produced through electrospinning. The mixture of nanofibers and BMSCs was pipetted onto the surface of the scaffolds, and BMSCs/PLGA/gelatin composite was obtained. The surface morphology, chemical structure, hydrophilicity and mechanical property of PLGA/gelatin nanofibers were revealed by scanning electron microscope. In vitro release kinetics of bone morphogenetic protein (BMP-2) and vascular endothelial growth factor (VEGF) were studied using ELISA kits. The cell adhesion, growth and proliferation of BMSCs on scaffolds were observed by scanning electron microscopy. The CCK-8 assay was used to evaluate the effects of VEGF/BMP-2 slow release system on the proliferation of BMSCs on scaffolds. RT-PCR was used to examine the activities of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX-2), and osteocalcin (OCN). Results In each group of cells in the in-vitro experiment, through electron microscope scanning, fiber scaffolds were interconnected three-dimensional reticular structure, BMSCs firmly attached to the fiber surface and internal stent, cells experienced a long spindle, polygon change, and branch-like protrusions on the cell surface were connected. Under the electron microscope, cell proliferation curve and osteogenesis markers (ALP, RUNX-2, OCN) expression in the dual factor group on cell adhesion, proliferation and differentiation were much better than those of blank control group and single factor groups. Conclusions In the successfully constructed gelatin/PLGA nanofiber scaffold, VEGF and BMP-2 can be sequentially released, during which VEGF and BMP-2 can promote the adhesion, proliferation, and differentiation of BMSCs.
研究领域:
生物医学工程
·
组织工程
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2019
·
IF 0
Xiang Li,Hua-Mo Yin,En Luo,Songsong Zhu,Peng Wang,Zhen Zhang,Gui-Qing Liao,Jia-Zhuang Xu,Zhong-Ming Li,Ji-Hua Li
Although artificial polymeric scaffolds act as vital characters in bone repair, their application is limited due to their inferior bioactivity. Herein, osteoinductive poly(ε-caprolactone) (PCL) composite scaffolds were prepared by synchronously enlisting bioactive nanohydroxyapatite (nHA), bioglass (BG), and bone morphogenetic protein-2 (BMP-2), which was bound up with polydopamine (pDA). It was found that pDA deposition not only significantly enhanced hydrophilicity and cell affinity of composite scaffolds but also endowed steady immobilization of BMP-2 with long-term yet sustained release. Compared to pure PCL and PCL/nHA/BG (PHB) scaffolds, the designed PHB-pDA-BMP-2 scaffolds significantly induced the differentiation of bone marrow stromal cells toward an osteogenic lineage. Meanwhile, in vivo examinations revealed the prominent osteogenic capability of PHB-pDA-BMP-2 scaffolds, which enabled complete bone healing of calvarial bone defects in rabbits by 12 weeks. This finding indicates that the developed porous composite scaffolds hold great potential for bone regeneration.
研究领域:
组织工程
·
生物材料
·
再生医学
·
骨科
✓ 已验证
DOI
PubMed
Communications Biology
·
2021
·Vol. 4
·期 1
·1-14
·
IF 6.268
Geng Yingnan,Duan Huichuan,Xu Liang,Witman Nevin,Yan Bingqian,Yu Zheyuan,Wang Huijing,Tan Yao,Lin Liqin,Li Dong,Bai Shanshan,Fritsche-Danielson Regina,Yuan Jie,Chien Kenneth,Wei Min,Fu Wei
Bone has a remarkable potential for self-healing and repair, yet several injury types are non-healing even after surgical or non-surgical treatment. Regenerative therapies that induce bone repair or improve the rate of recovery are being intensely investigated. Here, we probed the potential of bone marrow stem cells (BMSCs) engineered with chemically modified mRNAs (modRNA) encoding the hBMP-2 and VEGF-A gene to therapeutically heal bone. Induction of osteogenesis from modRNA-treated BMSCs was confirmed by expression profiles of osteogenic related markers and the presence of mineralization deposits. To test for therapeutic efficacy, a collagen scaffold inoculated with modRNA-treated BMSCs was explored in an in vivo skull defect model. We show that hBMP-2 and VEGF-A modRNAs synergistically drive osteogenic and angiogenic programs resulting in superior healing properties. This study exploits chemically modified mRNAs, together with biomaterials, as a potential approach for the clinical treatment of bone injury and defects.
研究领域:
再生医学
·
组织工程
·
分子生物学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 89
·56732-56742
·
IF 3.108
Jun Zhang,Jianan Li,Guoliang Jia,Yikun Jiang,Qinyi Liu,Xiaoyu Yang,Su Pan
To engineer bone tissue, an ideal biodegradable implant should be biocompatible, biodegradable, osteoinductive and osteoconductive. However, the lack of bioactivity has seriously restricted the development of biodegradable implants in bone tissue engineering. In this study, we have developed a three-dimensional porous poly(L-lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA) scaffold based on the dual delivery of bone morphogenic protein 2 (BMP-2) and insulin-like growth factor 1 (IGF-1) via polydopamine (PDA) coating. The aim of this study was to improve the osteoinductivity of biodegradable implants for clinical bone repair via a PDA-assisted BMP-2 and IGF-1 surface modification strategy. Our study demonstrated that PDA layer surface modification could more efficiently immobilize BMP-2 and IGF-1 on the scaffold surfaces than physical adsorption, and the immobilized growth factor was released slowly and steadily from the scaffold in a sustained manner. MC3T3-E1 cell attachment and proliferation on IGF-1 and BMP-2-immobilized porous scaffolds were much higher than other groups. According to an in vitro osteogenesis assay, alkaline phosphatase (ALP) activity, the expression of osteogenesis-related genes and the mineralization capacity of MC3T3-E1 cells were increased by the incorporation of BMP-2 and IGF-1. In vivo, digital radiograph evaluation demonstrated that there was the most rapid healing in the defects treated with the IGF-1 and BMP-2 immobilized porous scaffold compared with the other groups eight weeks after implantation. In vitro and in vivo results of this study revealed that the PDA-assisted surface modification method can be a useful tool to graft biomolecules onto biodegradable implants, and the dual release of BMP-2 and IGF-1 could promote cell proliferation and osteogenesis differentiation. Based on the results, the surface modification strategy with growth factors has great potential for the enhancement of osteointegration of biodegradable bone implants.
研究领域:
生物医学工程
·
材料科学
·
组织工程
·
骨再生
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2020
·
IF 4.152
Honglei Wang,Xue Qu,Zheng Zhang,Miao Lei,Haoqi Tan,Chunyan Bao,Shaoliang Lin,Linyong Zhu,Joachim Kohn,Changsheng Liu
The construction of a biomaterial matrix with biological properties is of great importance to developing functional materials for clinical use. However, the site-specific immobilization of growth factors to endow materials with bioactivities has been a challenge to date. Considering the wide existence of glycosylation in mammalian proteins or recombinant proteins, we establish a bioaffinity-based protein immobilization strategy (bioanchoring method) utilizing the native sugar–lectin interaction between concanavalin A (Con A) and the oligosaccharide chain on glycosylated bone morphogenetic protein-2 (GBMP-2). The interaction realizes the site-specific immobilization of GBMP-2 to a substrate modified with Con A while preserving its bioactivity in a sustained and highly efficient way, as evidenced by its enhanced ability to induce osteodifferentiation compared with that of the soluble GBMP-2. Moreover, the surface with Con A-bioanchored GBMP-2 can be reused to stimulate multiple batches of C2C12 cells to differentiate almost to the same degree. Even after 4 month storage at 4 °C in phosphate-buffered saline (PBS), the Con A-bioanchored GBMP-2 still maintains the bioactivity to stimulate the differentiation of C2C12 cells. Furthermore, the ectopic ossification test proves the in vivo bioactivity of bioanchored GBMP-2. Overall, our results demonstrate that the tag-free and site (i.e., sugar chain)-specific protein immobilization strategy represents a simple and generic alternative, which is promising to apply for other glycoprotein immobilization and application. It should be noted that although the lectin we utilized can only bind to d-mannose/d-glucose, the diversity of the lectin family assures that a specific lectin could be offered for other sugar types, thus expanding the applicable scope further.
研究领域:
生物材料
·
组织工程
·
生物医学工程
·
蛋白质工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2025
·
IF 6
Long Yang,Yufei Liu,Yong Yang,Yuhu Zhou,Zihao Zou,Min He,Changlei Yang,Daizhu Yuan,Jieheng Wu,Chuan Ye
Artificial bone substitutes have garnered significant attention within the field of biomaterials, and the use of tissue engineering technology to repair bone defects has emerged as a promising alternative. However, when artificial bone substitutes are implanted in the body, they can induce many adverse cellular and tissue immune responses. In this study, we use coaxial electrospinning technology to fabricate microfiber with controllable diameter, excellent mechanical properties and surface porous structure. Poly(3-hydroxybutyrate- co -4-hydroxybutyrate) (P34HB) and polyethylene glycol (PEG) were used as shell solutions and polyvinyl alcohol (PVA) and bone morphogenetic protein-2 (BMP-2) peptides as core solutions. Compared to PVA/P34HB-PEG (P/P-P) scaffolds, PVA-BMP-2/P34HB-PEG (P-B/P-P) scaffolds polarized more human monocytic leukemia cell line (THP-1 cells) toward alternatively activated macrophages (M2), as demonstrated by increased M2 and decreased classically activated macrophage (M1) phenotypic marker expression in the cells. P-B/P-P microfibers have the potential to regulate the polarization state of macrophages, induce them to differentiate into an M2 phenotype and inhibit the inflammatory response of surrounding tissues. In addition, microfibers with a hollow porous structure facilitate the controlled release of BMP-2 peptides by regulating the fiber diameter, enhancing the differentiation of pre-osteoblastic cell line derived from mouse calvaria (MC3T3-E1) cells in an osteogenic direction and facilitating the repair of bone defects in vivo. This study presents microfibers essential for modulating the osteoimmune microenvironment, facilitating efficient bone regeneration.
研究领域:
生物材料
·
组织工程
·
免疫调节
·
骨再生
·
纳米纤维技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SURFACE & COATINGS TECHNOLOGY
·
2024
·
IF 5.3
Xue'e Zhang,Xu Zhang,Wuchao Zhou,MengZhen Tang,Tiebiao Wang,Ketong Le,Weihong Xi
As is generally known, the lack of osteoinductive properties in titanium scaffolds has been a major barrier to bone defects repair. In our previous studies, we found that silicon-doped porous coatings prepared via micro-arc oxidation (MAO) had the potential application of Si-doped coatings in dental and orthopedic fields. We are currently focused on developing more advanced surface coatings to maximize their osteoinductive efficacy. Bone morphogenetic protein-2 (BMP-2), known for its ability to induce bone and cartilage development, has also been extensively studied. Therefore, in this study, macroporous titanium alloy scaffolds were fabricated using 3D printing technology, silicon ions were introduced onto the surface of customized macroporous titanium alloy scaffolds through MAO to enhance the bioactivity of the scaffolds, and BMP-2 was loaded onto the Si-doped coating to further improve the osseointegration of the titanium alloy scaffolds post-implantation. Results demonstrated that silicon-doped coating-loaded BMP2-modified multi-level porous titanium scaffolds exhibited improved hydrophilicity and biocompatibility. In-vivo and vitro studies further confirmed the superior bone regeneration capabilities of these scaffolds. This study demonstrates an optional strategy to combine two surface modification treatments, offering substantial potential as an advanced bone defect repair material with improved and accelerated bone regeneration.
研究领域:
材料科学
·
生物医学工程
·
骨科
·
组织工程
✓ 已验证
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Ziyang Yang,Li Xie,Boqing Zhang,Gang Zhang,Fangjun Huo,Changchun Zhou,Xi Liang,Yujiang Fan,Weidong Tian,Yinghui Tan
Digital light processing (DLP)-based 3D printing is suitable to fabricate bone scaffolds with small size and high precision. However, the published literature mainly deals with the fabrication procedure and parameters of DLP printed bioceramic scaffold, but lacks the subsequent systematic biological evaluations for bone regeneration application. In this work, a biphasic calcium phosphate (BCP) macroporous scaffold was constructed by DLP-based 3D printing technique. Furthermore, bone morphogenetic protein-2 (BMP-2) was facilely incorporated into this scaffold through a facile polydopamine (PDA) modification process. The resultant scaffold presents an interconnected porous structure with pore size of ∼570 μm, compressive strength (∼3.6 MPa), and the self-assembly Ca-P/PDA nanocoating exhibited excellent sustained-release property for BMP-2. Notably, this BMP-2/PDA-BCP scaffold presents favorable effects on the adhesion, proliferation, osteogenic differentiation, and mineralization of bone marrow stromal cells (BMSCs). Furthermore, in vivo experiments conducted on rats demonstrated that the scaffolds could induce cell layer aggregation adjacent to the scaffolds and continuous new bone generation within the scaffold. Collectively, this work demonstrated that the BMP-2/PDA-BCP scaffold is of immense potential to treat small craniofacial bone defects in demand of high accuracy.
研究领域:
生物医学工程
·
组织工程
·
材料科学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Tissue Engineering and Regenerative Medicine
·
2022
·Vol. 16
·期 12
·1223-1237
·
IF 4.323
Zecheng Li,Shi Cheng,Ang Li,Chengchao Song,Anlong Jiang,Fangxing Xu,Hui Chi,Jinglong Yan,Guanghua Chen
The microenvironment in the healing process of large bone defects requires suitable conditions to promote osteogenesis and angiogenesis. Coaxial electrospinning is a mature method in bone tissue engineering (BTE) and allows functional modification. Appropriate modification methods can be used to improve the bioactivity of scaffolds for BTE. In this study, coaxial electrospinning with QK peptide (a Vascular endothelial growth factor mimetic peptide) and BMP-2 peptide–DFO (BD) was performed to produce double-modified PQBD scaffolds with vascularizing and osteogenic features. The morphology of coaxially electrospun scaffolds was verified by scanning electron microscopy (SEM) and transmission electron microscopy. Laser scanning confocal microscopy and Fourier transform infrared spectroscopy confirmed that BD covalently bound to the surface of the P and PQ scaffolds. In vitro, the PQBD scaffold promoted the adhesion and proliferation of bone marrow stromal cells (BMSCs). Both QK peptide and BD showed sustainable release and preservation of biological activity, enhancing the osteogenic differentiation of BMSCs and the migration of human umbilical vein endothelial cells and promoting angiogenesis. The combined ability of these factors to promote osteogenesis and angiogenesis is superior to that of each alone. In vivo, the PQBD scaffold was implanted into the bone defect, and after 8 weeks, the defect area was almost completely covered by new bone tissue. Histology showed more mature bone tissue and more blood vessels. PQBD scaffolds promote both angiogenesis and osteogenesis, offering a promising approach to enhance bone regeneration in the treatment of large bone defects.
研究领域:
组织工程
·
生物医学材料
·
再生医学
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yuping Wang,Yiting Lei,Nan Wang,Jun Zhang,Wenguo Cui,Xiaoji Luo
The challenge of achieving graded regeneration of adjacent tissues remains significant in tissue repair and regeneration. For instance, the disruption of the microenvironment caused by “osteogenesis mobilization” often results in fibrosis of the regenerated cartilage, ultimately leading to osteoarthritis. Inspired by the utilization of activated carbon for adsorbing and filtering small particles in air purification and water treatment, we have designed an integrated hydrogel scaffold capable of absorbing the endogenous BMP-2 produced by “osteogenesis mobilization”, confining it to the bone defect area, and preventing its diffusion into the cartilage region, thereby facilitating physiological osteochondral gradient regeneration. The osteogenic layer of this integrated scaffold is NHAP-AHAMA-B2A, which captures the BMP-2 produced by “osteogenesis mobilization” and amplifies its osteogenic effect through the grafted peptide B2A. This upregulation enhances the expression of ALP, OCN, and OPN in MSCs within the osteogenic layer, promoting osteogenic differentiation. The chondrogenic layer, HAMA-B2A, utilizes the peptide B2A to upregulate the expression of COL II and ACAN in MSCs, fostering chondrogenic differentiation. This integrated HAMA-B2A/NHAP-AHAMA-B2A hydrogel scaffold confines the BMP-2 produced by “osteogenesis mobilization” to the bone defect area, prevents its diffusion into the cartilage defect area, and effectively utilizes it to induce stem cell osteogenic differentiation. Simultaneously, it induces stem cell chondrogenic differentiation in the cartilage defect area, achieving transparent cartilage regeneration. In summary, the osteogenic and chondrogenic layers of this integrated scaffold collaborate to achieve a physicochemical gradient regeneration of bone-cartilage.
研究领域:
组织工程
·
再生医学
·
生物材料科学
·
骨科
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）