BIOMATERIALS
·
2019
·
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 .
研究领域:
生物材料
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组织工程
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再生医学
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细胞生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
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
Frontiers of Materials Science
·
2015
·Vol. 9
·期 1
·38-50
·
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
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
Journal of Materials Chemistry B
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2017
·Vol. 5
·期 44
·8770-8779
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IF 4.543
Jiachen Sun,Yanxia Zhang,Bin Li,Yong Gu,Liang Chen
Stimulating the adhesion and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is crucial for the scaffold materials used in bone tissue engineering. In this study, a silk fibroin (SF)/nano-hydroxyapatite (nHAp) scaffold was prepared, embedded with SF microspheres containing bone morphogenetic protein-2 (BMP-2) and surface-modified through chemical conjugation with the type I collagen-mimetic peptide GFOGER. Surface-bound GFOGER and sustained BMP-2 release promoted the adhesion and osteogenic differentiation, respectively, of BMSCs. Our results indicated that this system released low doses of BMP-2 in a sustained manner, thereby avoiding cost and safety problems. The biological responses to this scaffold were investigated both in vitro and in vivo. Our results indicated that the synergistic effect of GFOGER and BMP-2 promoted the adhesion and osteogenic differentiation of BMSCs, thus leading to complete bone bridging of rat cranial defects after 12 weeks of implantation. This system might provide a powerful platform for treating bone defects and for bone tissue engineering.
研究领域:
组织工程
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生物医用材料
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再生医学
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Han Sun,Jian Dong,Yangyufan Wang,Siyu Shen,Yong Shi,Lei Zhang,Jie Zhao,Xiaoliang Sun,Qing Jiang
The periosteum plays an important role in vascularization and ossification during bone repair. However, in most studies, an artificial periosteum cannot restore both functions of the periosteum concurrently. In this study, a novel nanofiber that can sustain the release of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) was fabricated to enhance the durability of angiogenesis and osteogenesis during bone regeneration. A cell-free tissue engineered periosteum based on an electrospinning poly-l-lactic acid (PLLA) nanofiber was fabricated, on which VEGF and BMP-2 were immobilized through a polydopamine (PDA) coating conveniently and safely (BVP@PLLA membrane). The results indicated a significantly improved loading rate as well as a slow and sustained release of VEGF and BMP-2 with the help of the PDA coating. BMP-2 immobilized on nanofibers successfully induced the osteogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs) in vitro with high expression of runt-related transcription factor 2 (Runx2), osteopontin (OPN), and alkaline phosphatase (ALP). Similarly, angiogenic differentiation of BMSCs with the expression of fetal liver kinase-1 (Flk-1) and vascular endothelial cadherin (VE-cadherin) was observed under the environment of VEGF sustained release. Moreover, an in vivo study revealed that the BVP@PLLA membrane could enhance vascular formation and new bone formation, which accelerates bone regeneration in rat femoral defects along with a massive periosteum defect. Therefore, our study suggests that the novel artificial periosteum with dual growth factor controlled release is a promising system to improve bone regeneration in bone defects along with a massive periosteum defect.
研究领域:
组织工程
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生物材料
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再生医学
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骨修复
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产品关联
DOI
PubMed
高影响因子
Materials Today Advances
·
2023
·
IF 10
Weiye Cai,Xiaoping Xu,Yingcun Jiang,Kang Cheng,Fei Liu,Chao Song,Daru Guo,Zhenming Hu,Zhihong Liu,Zongchao Liu
Bone tissue repair is influenced by the synergistic interaction between acute immune microenvironment and osteogenesis. In this study will be independently by film dispersion method and static loading shell polymers and resveratrol liposome preparation CS - Res @ Lipo (CRL) and microfluidic technology preparation of HAMA@HepMA hydrogel microspheres (MS) by condensation reaction of chemical grafting, and then the non-covalent binding site of the MS microsphere was used to skillfully bind BMP-2, construct procedural release of hydrogel microspheres (CRL @ BMP - 2 @ MS). CRL@BMP-2@MS inhibit the acute immune peak by rapidly releasing Res, in addition, the sustained liberation of BMP-2 synchronizes osteoimmunity and osteogenesis, thereby accelerating bone repair. The results showed that Res was released with an increased cumulative rate of 72.4 ± 3.6% in the first 24 h, TNF-α and IL-1β levels were significantly decreased by 4.27 times and 3.65 times as compared to the control group, respectively. Furthermore, continuous release of approximately 40.26 ± 6.8% of BMP-2 occurred within the first 72 h, CRL@BMP-2@MS microspheres significantly increased osteogenic activity compared with the control group by 2.98 and 2.82 times, respectively. In conclusion, the programmed CRL@BMP-2@MS constructed in this study can realize the programmed synergistic linkage of immunity and osteogenesis, dynamically regulate bone repair, and the treatment of clinical bone repair will be based on a new strategy for diagnosis and treatment.
研究领域:
生物医学工程
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组织工程
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免疫学
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药剂学
✓ 已验证
DOI
高影响因子
Journal of Orthopaedic Surgery and Research
·
2026
·Vol. 21
·期 1
·101
·
IF 3.8
Li Gui,Song Qianbo,Song Ye,Liao Wenxing,Zhao Dong,Hong Binqing,Cao Guangru
Background To meet the needs of local treatment for spinal tuberculosis, this study developed a thermosensitive gel microsphere composite with both anti-tuberculosis and osteogenesis-promoting functions for efficient drug sustained release. The composite consists of anti-tuberculosis drugs (Pretomanid, Pa-824; Moxifloxacin, M; Pyrazinamide, Z) and bone morphogenetic protein-2 (BMP-2) to optimize drug release kinetics and enhance local therapeutic effects. Methods PaMZ/BMP-2 microspheres were prepared using microfluidics and characterized by SEM, particle size analysis, and XRD. LC–MS and ELISA measured drug and BMP-2 release. The thermosensitive gel (P407/P188) ratio was optimized to ensure it remained liquid at room temperature and formed a gel at 37 °C for sustained release. Results Microspheres were spherical with an average size of 203.92 ± 27.76 μm. Encapsulation rates were 112.69%, 24.15%, and 15.18% for Pa, M, and Z, respectively. In vitro release showed Pa and M sustained release for over 17 days, with the gel prolonging drug release. Conclusion This study successfully prepared PaMZ/BMP-2 microspheres with good morphology and drug loading capacity, achieving controlled sustained release through thermosensitive gel. This offers a potential formulation approach for future localized therapy of spinal tuberculosis and lays the foundation for subsequent in vivo experiments and clinical translation.
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.9
Wei Ma,Xinyue Zhang,Jiajia Cen,Qin Chen,Kai Chen,Cunao Feng,Hongyu Zhang,Dekun Zhang
Efficient bone regeneration requires scaffolds that combine mechanical strength with controlled osteoinductive factor delivery. Here, we present a porous Ti6Al4V scaffold (PXTC4) functionalized with polydopamine and integrated with dual-level BMP2–PLA–Alg core–shell microspheres (BMP2-HPLA-Alg) for sustained BMP2 release. The PXTC4 scaffold exhibited high porosity (∼75%) and an elastic modulus (∼6.5 GPa) compatible with cortical bone, while the microspheres ensured heparin-mediated BMP2 adsorption, tunable degradation, and reduced initial burst release by 53.5% compared to the single-level BMP2-Alg microspheres. In vitro studies demonstrated enhanced MC3T3-E1 adhesion, proliferation, cytoskeletal organization, early osteogenic differentiation, and late-stage matrix mineralization. These results indicate that BMP2 synergizes with scaffold topography to create a favorable osteogenic microenvironment. This BMP2-HPLA-Alg microsphere-functionalized porous Ti6Al4V scaffold provides a robust platform with mechanical stability and sustained pro-osteogenic activity, offering a promising strategy for bone regeneration that warrants further in vivo investigation.
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DOI
PubMed
高影响因子
American Journal of Translational Research
·
2019
·
IF 3.266
Zhao Wang,Hong-Wei Bao
Our aim was to study the osteogenic effect of cnidium lactone for bone marrow mesenchymal stem cells (BMSCs) and its potential mechanism. BMSCs were isolated and identified by flow cytometry and multidirectional differentiation capacity. Cell Counting Kit-8 (CCK-8) was used to identify the optimal concentration of cnidium lactone. Alkaline Phosphatase (ALP) and Alizarin Red S (ARS) was performed to identify whether cnidium lactone has effect on osteogenesis at early and late phase respectively. Moreover, we used estrogen receptor antagonist, ICI182780, to identify the receptor of cnidium lactone. The expression of Runt-related transcription factor 2 (RUNX2), Osterix (OSX), osteopontin (OPN), estrogen receptor (ER), Smad4, p-Smad1, Smad1 and bone morphogenetic protein 2 (BMP-2) protein were measured by PCR and western blot. Cnidium lactone (2 μM) demonstrated increased osteogenesis after osteogenic inducible medium (OIM) induction, as evidenced by more ALP activity and mineralization. When blocked with ICI182780, osteogenesis capacity was decreased. Moreover, the polymerase chain reaction (PCR) and western blotting results indicated that cnidium lactone enhanced ER, BMP2, Smad1, Smad4, RUNX2, OSX, and OPN expression and Smad1 phosphorylation. Cnidium lactone can effectively stimulates osteogenic differentiation of BMSCs via BMP-2/Smad-Signaling cascades mediated by ER.
研究领域:
药理学
·
干细胞生物学
·
骨骼再生
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DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
·
2022
·Vol. 110
·期 9
·2075-2088
·
IF 3.405
Shuang Qin,Zhengkuan Lu,Kang Gan,Chunyan Qiao,Baosheng Li,Tianjie Chen,Yunbo Gao,Lingling Jiang,Hong Liu
Polyetheretherketone (PEEK) has been widely investigated for improving its biological inert to enable it to achieve stronger osteogenic capability and to be a promising material in implant fields. The most important mechanism that makes a successful implantation is osteointegration. Surface modification is an appropriate method to maintain the excellent mechanical properties of PEEK and simultaneously endow PEEK certain biological characters. In this work, we attempted to shape the nano-topography of PEEK surface by nitrogen low-temperature plasma and polydopamine coating on the surface as a secondary reaction platform to bond the aminated poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating the BMP-2 gene for enhancing the biological activity. Scanning electron microscope, atomic force microscopy, X-ray photoelectron spectroscopy and water contact angle (CA) measurements were applied to characterize the surface of modified or untreated PEEK. Surface characterization showed that the modification was successfully performed on PEEK including a rougher and more hydrophilic surface with nanotopographic features. The influence on cell adhesion, proliferation and differentiation was evaluated by culturing of rat bone marrow mesenchymal stem cells on different modified PEEK substrates in vitro. The biological results indicated that the low-temperature plasma treatment and PDA-coating on PEEK significantly promoted cell adhesion and proliferation. And the osteogenic differentiation was effectively improved by BMP-2 gene releasing from PLGA-NH 2 microspheres. The results showed that this novel biological surface modification endowed PEEK with outstanding bioactivity and osteogenic ability, providing a theoretical basis for application in the field of implantation.
研究领域:
生物材料
·
组织工程
·
骨科
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2019
·
IF 4.511
Lixia Zheng,Dejian Li,Weizhong Wang,Qianqian Zhang,Xiaojun Zhou,Dinghua Liu,Jingtian Zhang,Zhengwei You,Jundong Zhang,Chuanglong He
Recently, a bilayered scaffold with an anisotropic structure mimicking a native osteochondral tissue shows considerable potential for treating osteochondral defects. Herein, a bilayered scaffold consisting of biomimetic cartilage and a subchondral bone architecture was constructed for repairing osteochondral defect. A hydrogel prepared by the Schiff base reaction of gelatin, silk fibroin, and oxidized dextran was designed as the cartilage layer, while a nanofibrous scaffold with a macroporous structure prepared from the polymer blend of poly(l-lactic acid)/poly(lactic-co-glycolic acid)/poly(ε-caprolactone) using the dual phase separation technique served as a subchondral layer. The subchondral layer was then treated with polydopamine coating for osteogenic factor immobilization. To facilitate the chondrogenic and osteogenic differentiation of bone marrow mesenchymal stem cells on the bilayered scaffold, the cartilage-inducing drug kartogenin (KGN) and osteogenic-inducing factor bone morphogenetic protein 2-derived peptides (P24 peptides) were, respectively, loaded on the subchondral layer. Next, the in vitro release of KGN and P24 peptide from the corresponding layer was monitored, respectively, and the results showed that both the release time of KGN and P24 peptides would last for more than 28 days. The in vitro results indicated that the KGN-loaded cartilage layer and P24 peptides-loaded subchondral layer were capable of supporting cell proliferation, and induced the chondrogenic and osteogenic differentiation, respectively. Furthermore, the in vivo experiments suggested that the bilayered scaffold significantly accelerated the regeneration of the osteochondral tissue in the rabbit knee joint model. Consequently, this bilayered scaffold loaded with KGN and P24 peptides would be a promising candidate for repairing osteochondral defect.
研究领域:
生物材料学
·
组织工程
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
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