BIOMACROMOLECULES
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2013
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IF 5.371
Qingchun Zhang,Ke Tan,Yan Zhang,Zhaoyang Ye,Wen-Song Tan,Meidong Lang
In tissue engineering, incorporation of bone morphogenetic protein-2 (BMP-2) into biomaterial scaffolds is an attractive strategy to stimulate bone repair. However, suboptimal release of BMP-2 remains a great concern, which may cause unfavorable bone formation as well as severe inflammation. In this study, genipin-cross-linked gelatin entrapped with recombinant human BMP-2 (rhBMP-2) was exploited to decorate the interior surface of three-dimensional porous poly(ε-caprolactone) (PCL) scaffolds. With gelatin-coating, PCL scaffolds demonstrated enhanced water uptake and improved compressive moduli. Intriguingly, a unique release profile of rhBMP-2 composed of a transient burst release followed by a sustained release was achieved in coated scaffolds. These coated scaffolds well supported growth and osteogenesis of human mesenchymal stem cells (hMSCs) in vitro, indicating the retaining of rhBMP-2 bioactivity. When hMSCs-seeded scaffolds were implanted subcutaneously in nude mice for 4 weeks, better bone formation was observed in gelatin/rhBMP-2-coated scaffolds. Specifically, the spatial distribution of newly formed bone was more uniform in gelatin-coated scaffolds than in uncoated scaffolds, which displayed preferential bone formation at the periphery. These results collectively demonstrated that gelatin-coating of porous PCL scaffolds is a promising approach for delivering rhBMP-2 to stimulate improved bone regeneration.
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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DOI
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 .
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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DOI
PubMed
高影响因子
PLoS One
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2020
·Vol. 15
·期 1
·e0228247
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IF 2.74
Congcong Liu,Jingcheng Wang,Chengde Gao,Zhenting Wang,Xiaohua Zhou,Mingying Tang,Kun Yu,Youwen Deng
Magnesium-based biomaterials are attracting increasingly more attention for orthopedic applications based on their appropriate mechanical properties, biodegradability, and favorable biocompatibility. However, the high corrosion rate of these materials remains to be addressed. In this study, porous β-Ca 3 (PO 4 ) 2 /Mg-Zn (β-TCP/Mg-Zn) composites were fabricated via a powder metallurgy method. The β-TCP/Mg-Zn composites with 6% porosity exhibited optimal mechanical properties, and thus, they were selected for surface modification. A novel dopamine/gelatin/recombinant human bone morphogenetic protein-2 (rhBMP-2) coating with demonstrated stability was prepared to further improve the corrosion resistance of the composite and enhance early osteoinductivity. The homogeneously coated β-TCP/Mg-Zn composite showed significantly improved corrosion resistance according to electrochemical and immersion tests. In addition, extracts from the dopamine/gelatin/rhBMP-2–coated β-TCP/Mg-Zn composite not only facilitated cell proliferation but also significantly enhanced the osteogenic differentiation of Sprague–Dawley rat bone marrow-derived mesenchymal stem cells in vitro . Furthermore, in vivo experiments were performed to evaluate the biodegradation, histocompatibility, and osteoinductive potential of the coated composite. No obvious pathological changes in the vital visceral organs were observed after implantation, and radiography and hematoxylin-eosin staining showed strong promotion of new bone formation, matched composite degradation and bone regeneration rates, and complete absorption of the released hydrogen gas. Collectively, these results indicate that the dopamine/gelatin/rhBMP-2–coated β-TCP/Mg-Zn composite offers improved corrosion resistance, favorable biocompatibility, and enhanced osteoinductive potential for use in the fabrication of orthopedic implants.
研究领域:
材料科学
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生物医学工程
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骨科
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2025
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IF 6.5
A li mu Ke re mu,Maimaitiaili Abulikemu,Zhilin Liang,Abudurusuli Abulikemu,Aikebaier Tuxun
Background Given the limitations of traditional therapies, the treatment of infected bone defects (IBD) remains a great challenge. It is urgent to find a novel method that can simultaneously eradicate infection and promote new bone formation. With the increasing application of personalized scaffolds in orthopedics, novel biomaterials with both antibacterial and osteoinductive properties have provided a viable option for IBD treatment. Through the three-dimensional (3D) printing technology, we fabricated a poly(lactic-co-glycolic acid)(PLGA)/nano-hydroxyapatite (n-HA) composite scaffold grafted with the antibiotic vancomycin and loaded with the osteoinductive agent recombinant human bone morphogenic protein-2 (rhBMP-2) via polydopamine (DOPA) chemistry, whose therapeutic effects on IBD were determined.Methods After examining the hydrophilicity, surface chemical composition, mechanical properties, and drug release of the PLGA/n-HA, PLGA/n-HA/VAN, and PLGA/n-HA/VAN+DOPA/rhBMP-2 composite scaffolds, pre-osteoblast MC3T3-E1 cells were seeded onto the scaffold surface to assess the biocompatibility and osteoconductive properties of the scaffolds in vitro. For in vivo experiments, the composite scaffolds contaminated with Staphylococcus aureus were implanted into the defect sites of rabbit radius. After 12 weeks, micro-CT analysis, H&E and Masson staining, immunohistochemistry, and viable bacteria counting were conducted to compare the effects of three composite scaffolds on new bone formation and bone infection.Results The surface modification with DOPA/rhBMP-2 increased the hydrophilicity of PLGA/n-HA scaffolds. Vancomycin and BMP-2 were continuously and regularly eluted from the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds. The PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds promoted MC3T3-E1 cell survival and proliferation and enhanced ALP activity and calcium deposition compared with the PLGA/n-HA and PLGA/n-HA/VAN scaffolds. Additionally, the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds significantly facilitated new bone formation and inhibited bone infection in IBD rabbit models. The rabbits implanted with the PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds exhibited normal heart, lung, and kidney histologies and normal serum biochemical indices, suggesting the safety of the scaffolds.Conclusion The 3D-printed PLGA/n-HA/VAN+DOPA/rhBMP-2 scaffolds exhibited both antibacterial and osteoinductive activities in IBD.
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2021
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IF 13.273
Wentao Liu,Chengde Liu,Cheng Liu,Yizheng Li,Liang Pan,Jinyan Wang,Xigao Jian
Failure of poly(aryl ether ketone) (PAEK) bone implants results mainly from poor osteogenesis and bacterial infection. One promising strategy for enhancing osteointegration involves developing a bioactive surface of PAEK implants through chemical modification. Poly(phthalazinone ether nitrile ketone) (PPENK) is considered a potential PAEK bone implant because it possesses mechanical properties similar to those of natural bone and its cyano group has high reactivity which provides a surface modification strategy. In this work, recombinant human bone morphogenetic protein-2 (rhBMP-2) and newly synthesized cationic antimicrobial polypeptides (AMPs) were chemically conjugated to a PPENK substrate surface to enhance osteogenic and antibacterial activities. The molecular structures of AMP-1 and AMP-2 containing PEG segments were confirmed by nuclear magnetic resonance spectroscopy. The surface roughness of each substrate was reduced by rhBMP-2 and AMP immobilization. In situ, real-time quartz crystal microbalance with dissipation studies revealed that the loading amount increased with the successive immobilization of rhBMP-2 and AMPs. In vitro antibacterial assay confirmed that the AMP-modified PPENK surfaces provided an effective antibacterial effect and the number of residential bacteria remaining on the substrate was reduced by the PEG segments in AMP-2. In vitro osteogenic properties of the rhBMP-2-modified PPENK surface presented favorable cytocompatibility and osteo-inductive activity. In vivo studies confirmed that the rhBMP-2 and AMP immobilization led to decrease amounts of fibrous tissues around the implant and improved bone regeneration. This study provides a strategy for surface modification that enhances the antibacterial and osteogenic activities to develop a bone implant material with considerable potential for clinical application.
研究领域:
材料科学
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生物材料
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组织工程
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生物医学工程
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产品关联
DOI
高影响因子
Bioengineered
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2022
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IF 6.832
Wenbo Zhang,Pu Xu,Yanan Cheng,Yanlan Yang,Qiuhua Mao,Zuogeng Chen
A nanopearl powder/C-HA (chitosan-hyaluronic acid)/rhBMP-2 (recombinant human bone morphogenetic protein-2) composite artificial bone material was prepared, and its biological properties were evaluated. The nanopearl powder/C-HA/rhBMP-2 composite porous artificial bone material was prepared using the freeze-drying method after the nanopearl powder was prepared using mechanical ball milling. The particle was measured with a transmission electron microscope, its surface morphology and pore size were observed under a scanning electron microscope. The porosity of the artificial bone was determined using pycnometry, a compression performance test was conducted with a universal testing machine, and XRD (X-ray diffraction) patterns were recorded to examine the crystal form of the pearl powder in the composite artificial bone. Finally, the artificial bone was cocultured with mouse MC3T3-E1 cells to investigate its effects on cell proliferation and differentiation and the expression of osteogenesis-related genes. The pearl powder prepared in this experiment had a particle size in the nanometer range. This nanopearl powder, along with C-HA and rhBMP-2, was compounded into the nanopearl powder/C-HA/rhBMP-2 composite artificial bone, showing pore sizes of 188.53 ± 15.32 μm, a porosity of 86.43 ± 2.78% and a compressive strength of 0.342 ± 0.024 MPa. Notably, rhBMP-2 was released from the artificial bone in a sustained manner. Moreover, this artificial bone promoted the adhesion, proliferation, and differentiation of MC3T3-E1 cells and upregulated the expression of ColαI (collagen α1), OCN (osteocalcin), OPN (osteopontin) and Runx2 (runt-related gene 2). Conclusively, this nanopearl powder/C-HA/rhBMP-2 composite artificial bone material showed good performance and cytocompatibility, suggesting that it can be used for bone tissue engineering.
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DOI
PubMed
高影响因子
Bioactive Materials
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2024
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IF 18
Lili Sun,Haoyi Niu,Yuqiong Wu,Shiyan Dong,Xuefeng Li,Betty Y.S. Kim,Changsheng Liu,Yifan Ma,Wen Jiang,Yuan Yuan
Repair of large bone defects caused by severe trauma, non-union fractures, or tumor resection remains challenging because of limited regenerative ability. Typically, these defects heal through mixed routines, including intramembranous ossification (IMO) and endochondral ossification (ECO), with ECO considered more efficient. Current strategies to promote large bone healing via ECO are unstable and require high-dose growth factors or complex cell therapy that cause side effects and raise expense while providing only limited benefit. Herein, we report a bio-integrated scaffold capable of initiating an early hypoxia microenvironment with controllable release of low-dose recombinant bone morphogenetic protein-2 (rhBMP-2), aiming to induce ECO-dominated repair. Specifically, we apply a mesoporous structure to accelerate iron chelation, this promoting early chondrogenesis via deferoxamine (DFO)-induced hypoxia-inducible factor-1α (HIF-1α). Through the delicate segmentation of click-crosslinked PEGylated Poly (glycerol sebacate) (PEGS) layers, we achieve programmed release of low-dose rhBMP-2, which can facilitate cartilage-to-bone transformation while reducing side effect risks. We demonstrate this system can strengthen the ECO healing and convert mixed or mixed or IMO-guided routes to ECO-dominated approach in large-size models with clinical relevance. Collectively, these findings demonstrate a biomaterial-based strategy for driving ECO-dominated healing, paving a promising pave towards its clinical use in addressing large bone defects.
研究领域:
组织工程
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骨再生
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生物材料
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）