International Journal of Nanomedicine
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2018
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IF 4.37
Shuying Hu,Hanbang Chen,Xuefeng Zhou,Gang Chen,Ke Hu,Yi Cheng,Lili Wang,Feimin Zhang
Introduction Scaffold structure plays a vital role in cell behaviors. Compared with two-dimensional structure, 3D scaffolds can mimic natural extracellular matrix (ECM) and promote cell–cell and cell–matrix interactions. The combination of osteoconductive scaffolds and osteoinductive growth factors is considered to have synergistic effects on bone regeneration. Materials and methods In this study, core–shell poly(lactide-co-glycolide) (PLGA)/polycaprolactone (PCL)–BMP-2 (PP–B) fibrous scaffolds were prepared through coaxial electrospinning. Next, we fabricated 3D scaffolds based on PP–B fibers with thermally induced self-agglomeration (TISA) method and compared with conventional PLGA/PCL scaffolds in terms of scaffold morphology and BMP-2 release behaviors. Then, rat adipose-derived stem cells (rADSCs) were seeded on the scaffolds, and the effects on cell proliferation, cell morphology, and osteogenic differentiation of rADSCs were detected. Results The results demonstrated that 3D scaffold incorporated with BMP-2 significantly increased proliferation and osteogenic differentiation of rADSCs, followed by PP–B group. Conclusion Our findings indicate that scaffolds with 3D structure and osteoinductive growth factors have great potential in bone tissue engineering.
研究领域:
生物医学工程
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组织工程
·
干细胞研究
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Xiaofeng Shen,Yanxia Zhang,Yong Gu,Yun Xu,Yong Liu,Bin Li,Liang Chen
In this study, a cell-free bone tissue engineering system based on a silk fibroin (SF)/nano-hydroxyapatite (nHAp) scaffold was developed, in which two bioactive molecules , stromal cell derived factor-1 (SDF-1) and bone morphogenetic protein-2 (BMP-2), were embedded and released in a sequential and controlled manner to facilitate cell recruitment and bone formation, respectively. BMP-2 was initially loaded into SF microspheres , and these BMP-2 containing microspheres were subsequently encapsulated into the SF/nHAp scaffolds, which were successively functionalized with SDF-1 via physical adsorption. The results indicated rapid initial release of SDF-1 during the first few days, followed by slow and sustained release of BMP-2 for as long as three weeks. The composite scaffold significantly promoted the recruitment of bone marrow mesenchymal stem cells (BMSCs) and osteogenic differentiation of them in vitro . Further, the in vivo studies using D-Luciferin-labeled BMSCs indicated that implantation of this composite scaffold markedly promoted the recruitment of BMSCs to the implanted sites. Enhanced bone regeneration was identified at 12 weeks' post-implantation. Taken together, our findings suggested that the sequential and sustained release of SDF-1 and BMP-2 from the SF/nHAp scaffolds resulted in a synergistic effect on bone regeneration. Such a composite system , therefore, shows promising potential for cell-free bone tissue engineering applications .
研究领域:
生物医学工程
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组织工程
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再生医学
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PubMed
高影响因子
Bioactive Materials
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2025
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IF 20.3
Rongpu Liu,Guifang Wang,Li Ma,Guangzheng Yang,Sihan Lin,Ningjia Sun,Jiajia Wang,Huijing Ma,Xinquan Jiang,Wenjie Zhang
Guided bone regeneration (GBR) is widely applied in implant dentistry, employing barrier membranes to create an osteogenic space by preventing gingival tissue ingrowth. However, this method does not enhance the osteogenic capacity of osteoblasts, limiting sufficient bone volume in larger defects. Inspired by axolotl limb regeneration, abundant soft tissue-derived stem cells mobilized to the defect may facilitate comprehensive osteogenesis within a BMP-2-enriched environment. We developed a biomimetic channel system (BCS) to promote alveolar bone regeneration, using channel structures to activate gingival-derived stem cells under a BMP-2-enriched biological barrier. In a cell-tracing mouse model, Prrx1 + stem cells demonstrated a critical role in BMP-2-induced subcutaneous osteogenesis. Sequencing and histological analyses revealed that channel structures significantly enhance soft tissue cell proliferation and migration. Attributable to the biological barrier, BCS applications markedly improved bone formation in beagle mandibular defects. These results suggest a novel osteoinductive strategy for alveolar bone regeneration that functions without a traditional barrier membrane.
研究领域:
口腔医学
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再生生物学
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组织工程
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PubMed
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2025
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IF 5.4
Xue Chen,Jiemei Bi,Haoyang Zhang,Mengtong Yuan,Jianjiao Wang,Narisu Hu
Periodontitis is a chronic inflammatory disease caused by dental plaque biofilm. To prevent disease progression and achieve successful periodontal tissue repair, it is necessary to simultaneously address the need for antibacterial, anti-inflammatory, and osteogenic effects within deep lesions. This study proposes a novel approach using a NIR light-responsive nanocomposite for enhanced ossification and combating bacterial biofilm infections in periodontitis. The nanocomposite incorporates polydopamine-coated calcium carbonate nanoparticles and BMP-2, which exhibits excellent photothermal conversion efficiency for bacterial eradication. Additionally, polydopamine also serves as an efficient ROS scavenger, thereby reducing the inflammatory response associated with periodontal disease. The core CaCO 3 interacts with BMP-2 to promote bone regeneration. This strategy demonstrates a synergistic effect by integrating PTT, ROS therapy, and osteogenic therapy in treating biofilm-induced periodontitis. Moreover, the CaCO 3 @BMP-2/PDA NPs reduced the protein expression levels of pro-inflammatory cytokines TNF-α and IL-1β and mitigated LPS-induced inflammation. This combination not only achieved critical protective effects but also fostered the promotion of osteoblast differentiation.
研究领域:
生物医学工程
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口腔医学
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材料科学
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DOI
高影响因子
iScience
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2022
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IF 6.107
Yang Liu,Gong-ming Gao,Kai-yuan Yang,Lu-ming Nong
Summary Intervertebral disc (IVD) degeneration, which is common among elderly individuals, mainly manifests as low back pain and is caused by structural deterioration of the nucleus pulposus (NP) due to physiological mechanical stress. NP mesenchymal stem cells (NPMSCs) around the IVD endplate have multidirectional differentiation potential and can be used for tissue repair. To define favorable conditions for NPMSC proliferation and differentiation into chondroid cells for NP repair, the present study simulated periodic mechanical stress (PMS) of the NP under physiological conditions using MSC chondrogenic differentiation medium and recombinant human BMP-2 (rhBMP-2). rhBMP-2 effectively promoted NPMSC proliferation and differentiation. To clarify the mechanism of action of rhBMP-2, integrin alpha 1 (ITG A1) and BMP-2 were inhibited. PMS regulated the BMP-2/Smad1/RUNX2 pathway through ITG A1 and promoted NPMSC proliferation and differentiation. During tissue-engineered NP construction, PMS can effectively reduce osteogenic differentiation and promote extracellular matrix protein synthesis to enhance structural NP recovery.
研究领域:
骨科
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组织工程
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干细胞研究
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力学生物学
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PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2016
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IF 1.733
Bingjie Niu,Bin Li,Yong Gu,Xiaofeng Shen,Yong Liu,Liang Chen
Bone tissue engineering by using osteoinductive scaffolds seeded with stem cells to promote bone extracellular matrix (ECM) production and remodeling has evolved into a promising approach for bone repair and regeneration. In order to mimic the ECM of bone tissue structurally and compositionally, nanofibrous silk fibroin (SF) scaffolds containing hydroxyapatite (HAP) nanoparticles and bone morphogenetic protein 2 (BMP-2) were fabricated in this study using electrospinning technique. The microstructure, mechanical property, biocompatibility, and osteogenic characteristics were examined. It was found that the HAP nanoparticles were successfully incorporated in the SF nanofibers (diameter, 200–500 nm). The mechanical properties of SF/HAP/BMP-2 composite scaffolds increased with HAP content when it was less than 20 wt%, after which the mechanical properties dropped as HAP content increased. Cell culture tests using bone marrow mesenchymal stem cells (BMSCs) showed that the scaffolds had good biocompatibility and promoted the osteogenic differentiation of BMSCs. Therefore, the electrospun SF/HAP/BMP-2 scaffolds may serve as a promising biomaterial for bone tissue engineering.
研究领域:
组织工程
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材料科学
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生物材料
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再生医学
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PubMed
高影响因子
BIOMATERIALS
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2019
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IF 10.273
Haoyi Niu,Yifan Ma,Guangyu Wu,Bing Duan,Ying Wang,Yuan Yuan,Changsheng Liu
Synchronization of material resorption and new bone formation is vital to achieve harmonious bone regeneration in the treatment of large bone defects. To exposit the resorption/osteogenesis properties in the guided bone repairing, rhBMP-2-loaded trimodal macro/micro/nano-porous bioactive glass scaffolds (TMS-rhBMP-2) were set as substrate model. We penetratingly investigated the particular function of hierarchical structure and incorporated rhBMP-2 in the resorption/osteogenesis, and dissected the cellular interplay throughout the regenerative procedure. The results suggested that rhBMP-2 significantly facilitated osteoclastogenesis-mediated scaffold degradation and strikingly up-regulated mesenchymal stem cells (MSCs)-involved osteogenesis in vitro. Further gene microarray and related proteins expression indicated that in the presence of rhBMP-2, MSCs rather than differentiated MSCs could exert synergistic effects on osteoclastogenesis , osteoclasts maturation and resorptive function; meanwhile, rhBMP-2-induced MSCs osteogenesis was also strengthened by the osteoclasts. In vivo micro-CT, X-ray, kinetic and histological analyses qualitatively and quantitively demonstrated the optimized coupling of bioresorption/osteogenesis and the most rapid regeneration in TMS-rhBMP-2. Consequently, with rhBMP-2 acted as ignitor and MSCs/osteoclasts interaction as booster, a harmonious bone regeneration was obtained. Besides, long-term magnetic resonance imaging (MRI) in virtue of Gd 3+ suggested that the degradation products mainly distributed in liver and spleen, verifying the accumulation/discharge profiles and safety application of TMS-rhBMP-2 system in vivo. This study will not merely provide guidance for the design of clinical bone repairing materials, but shed substantial light on the multicell-mediated tissue regeneration .
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2015
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IF 4.152
Zhenzhen Liu,Yong Tang,Ting Kang,Minyu Rao,Kejia Li,Qin Wang,Changyun Quan,Chao Zhang,Qing Jiang,Huiyong Shen
HA and bone morphogenetic protein-2 (BMP-2) possess superior osteoinductive and osteoconductive activities in the repair of bone defects. In this study, a BMP-2 mimicking oligopeptide (serine–serine–valine–proline–threonine, SSVPT) was introduced to the surface of nano-sized HA as the reinforcement phase of a poly(methyl methacrylate) (PMMA) cement, and the synergistic action of HA and oligopeptide on the bioactivity of HA/PMMA bone cement was investigated. Incorporated with 3-trimethoxysilyl propyl methacrylate (MPS)-modified HA, the compressive strength, flexural strength, and flexural modulus of HA/PMMA complied with the international standardization organization 5833 standard. Adherence measurement demonstrated that the introduction of HA and SSVPT could promote the adhesion and proliferation of human fetal osteoblast (hFOB) on the surface of HA/PMMA cement. The increased alkaline phosphatase (ALP) activity indicated that HA/PMMA could promote osteogenic differentiation of hFOB. All of the results illuminated that the HA/PMMA cement could be used as a bioactive material for regeneration and reconstruction of load-bearing bone.
研究领域:
材料科学
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骨科医学
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2020
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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.
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Oxidative Medicine and Cellular Longevity
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2019
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IF 4.868
Yang Zhao,Yan Cai,Li-Yan Cui,Wen Tang,Bo Liu,Jia-Jia Zheng,Wen-Zhe Si,Xian Wang,Ming-Jiang Xu
Aims. Vascular calcification (VC) is a primary risk factor for cardiovascular mortality in chronic renal failure (CRF) patients; thus, effective therapeutic targets are urgently needed to be explored. Here, we identified the role of intestinal bacterial translocation in CRF-related VC. Methods and Results. Antibiotic supplementation by oral gavage significantly suppressed intestinal bacterial translocation, CRF-related VC, and aortic osteogenic gene and Toll-like receptor (TLR) gene expression in CRF rats. Furthermore, TLR4 and TLR9 activation in vascular smooth muscle cells (VSMCs) aggravated inorganic phosphate- (Pi-) induced calcification. TLR9 inhibition, but not TLR4 inhibition, by both a pharmacological inhibitor and genetic methods could significantly reduce CRF rats’ serum or CRF-induced VC. Interestingly, bone morphogenic protein-2 (BMP-2) levels were increased in the aorta and sera from CRF rats. Increased BMP-2 levels were also observed in VSMCs treated with TLR9 agonist, which was blocked by NF-κB inhibition. Both siRNA knockdown of BMP-2 and NF-κB inhibitor significantly blocked TLR9 agonist-induced VSMC calcification. Conclusions. Gut bacterial translocation inhibited by oral antibiotic significantly reduces CRF-related VC through inhibition of TLR9/NF-κB/BMP-2 signaling.
研究领域:
心血管疾病
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肾脏生理学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers of Materials Science
·
2015
·Vol. 9
·期 1
·38-50
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IF 1
Du Ya-Wei,Zhang Li-Nan,Ye Xin,Nie He-Min,Hou Zeng-Tao,Zeng Teng-Hui,Yan Guo-Ping,Shang Peng
Polyetheretherketone (PEEK) is regarded as one of the most potential candidates of biomaterials in spinal implant applications. However, as a bioinert material, PEEK plays a limited role in osteoconduction and osseointegration. In this study, recombinant human bone morphogenetic protein-2 (rhBMP-2) was immobilized onto the surface of collagen-coated PEEK in order to prepare a multi-functional material. After adsorbed onto the PEEK surface by hydrophobic interaction, collagen was cross-linked with N-(3-dimethylaminopropyl)-N′-ethyl carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). EDC/NHS system also contributed to the immobilization of rhBMP-2. Water contact angle tests, XPS and SEM clearly demonstrated the surface changes. ELISA tests quantified the amount of rhBMP-2 immobilized and the release over a period of 30 d. In vitro evaluation proved that the osteogenesis differentiation rate was higher when cells were cultured on modified PEEK discs than on regular ones. In vivo tests were conducted and positive changes of major parameters were presented. This report demonstrates that the rhBMP-2 immobilized method for PEEK modification increase bioactivity in vitro and in vivo , suggesting its practicability in orthopedic and spinal clinical applications.
研究领域:
生物医学工程
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骨科
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材料科学
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DOI
高影响因子
Communications Biology
·
2021
·Vol. 4
·期 1
·1-14
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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.
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