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
RSC Advances
·
2016
·Vol. 6
·期 24
·20202-20210
·
IF 3.289
Tianlin Gao,Weiwei Cui,Zongliang Wang,Yu Wang,Ya Liu,Ponnurengam Sivakumar Malliappan,Yoshihiro Ito,Peibiao Zhang
Lack of bioactivity has seriously restricted the development of biodegradable implants in bone tissue engineering. In this study, Bone Morphogenic Protein 2 (BMP-2) was photo-immobilized on the poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and pure PLGA composites via photo-reactive gelatin (Az-Gel). The results demonstrate that the Az-Gel facilitates efficient and long-term immobilization of peptides on the surface of PLGA. The immobilization of Az-Gel enhanced the adhesion and proliferation of Mouse Adipose-Derived Stem Cells (ADSCs), while HA incorporation facilitated cellular osteodifferentiation. The immobilization of BMP-2 induced the osteogenesis of the ADSCs, indicated by alkaline phosphatase activity, quantitative real-time polymerase chain reaction (qRT-PCR) analysis and mineralization on the deposited substrates. Furthermore, the surface immobilization of BMP-2 could not only reduce the amount of growth factor, but also have a long-term osteoinductive effect. Therefore, it is considered that the surface modification method has a great potential for the enhancement of osteointegration of biodegradable bone implants.
研究领域:
组织工程
·
生物材料科学
·
干细胞研究
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Yulei Tai,Meng Zhang,Yuning Han,Hui Hu,Shan Lin,Fangya Zhai,Menglun Tian,Xiaojun Song,Shuangshuang Wan,Yu Chen,Dazhi Jin
Introduction: Niclosamide (NIC) has significant potential as a clinical therapeutic agent for Clostridioides difficile infection (CDI); however, its strong hydrophobicity hampers its oral bioavailability, and its active effects against C. difficile remain unclear.Methods: Niclosamide-loaded controlled-release hyaluronic acid-modified poly (lactic-co-glycolic acid) naosphernes (NIC@PLGA-HAs) were synthesized using an oil-in-water emulsion technique and their effects on C. difficile cell growth, spore germination, biofilm formation, and NIC interaction sites with C. difficile toxin B (TcdB) were analyzed.Results: NIC@PLGA-HAs exhibited enhanced solubility and stability, with a water contact angle on a hydrophilic surface of 65.1° and a zeta potential of 31.57 ± 2.08 mV, and pH-responsive (pH 7.4) controlled-release characteristics compared to free NIC. The NIC@PLGA-HAs killed C. difficile vegetative cells at a minimum inhibitory concentration (MIC) of 4 μg/mL. When C. difficile cells were treated with NIC@PLGA-HAs at the 1/4 MIC, spore germination and biofilm formation were significantly inhibited compared to those in untreated cells (P < 0.01). NIC was found to interact with the receptor-binding domain of TcdB at 24 amino acid sites via an enthalpy-driven reaction (enthalpy change, 36.21 kJ/mol and entropy change, 212.9 J⋅mol/K). In vivo experimental findings in Mongolian gerbils indicated that NIC@PLGA-HAs outperformed free NIC in reducing pathological damage, diarrhea severity, weight loss, and TcdB production and enhanced the survival rate.Conclusion: These findings presented the therapeutic potential of NIC@PLGA-HAs with high solubility and stability, which simultaneously exerted multiple biological activities against C. difficile.
研究领域:
药剂学
·
微生物学
·
纳米技术
·
药物递送
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-13
·
IF 4.259
Fu Chuan,Yang Xiaoyu,Tan Shulian,Song Liangsong
Lack of bioactivity has seriously restricted the development of biodegradable implants for bone tissue engineering. Therefore, surface modification of the composite is crucial to improve the osteointegration for bone regeneration. Bone morphogenetic protein-2 (BMP-2), a key factor in inducing osteogenesis and promoting bone regeneration, has been widely used in various clinical therapeutic trials. In this study, BMP-2 was successfully immobilized on graphene oxide-incorporated PLGA/HA (GO-PLGA/HA) biodegradable microcarriers. Our study demonstrated that the graphene oxide (GO) facilitated the simple and highly efficient immobilization of peptides on PLGA/HA microcarriers within 120 min. To further test in vitro , MC3T3-E1 cells were cultured on different microcarriers to observe various cellular activities. It was found that GO and HA significantly enhanced cell adhesion and proliferation. More importantly, the immobilization of BMP-2 onto the GO-PLGA/HA microcarriers resulted in significantly greater osteogenic differentiation of cells in vitro , as indicated by the alkaline phosphate activity test, quantitative real-time polymerase chain reaction analysis, immunofluorescence staining and mineralization on the deposited substrates. Findings from this study revealed that the method to use GO-PLGA/HA microcarriers for immobilizing BMP-2 has a great potential for the enhancement of the osseointegration of bone implants.
研究领域:
生物医学工程
·
组织工程
·
骨再生
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 20
·15403
·
IF 5.6
Li Chen,Meng Tian,Jing Yang,Zhenxu Wu
Polymer microspheres have recently shown outstanding potential for bone tissue engineering due to their large specific surface area, good porosity, injectable property, good biocompatibility, and biodegradability. Their good load-release function and surface modifiability make them useful as a carrier of drugs or growth factors for the repair of bone defects in irregularly injured or complex microenvironments, such as skull defects. In this study, berberine (BBR)-encapsulated poly(lactic-co-glycolic acid) (PLGA)/hydroxyapatite (HA) microspheres were fabricated using electrified liquid jets and a phase-separation technique, followed by modification with the 3,4-hydroxyphenalyalanine-containing recombinant insulin-like growth–factor-1 (DOPA-IGF-1). Both the BBR and the IGF-1 exhibited sustained release from the IGF-1@PLGA/HA-BBR microspheres, and the composite microspheres exhibited good biocompatibility. The results of the alkaline phosphatase (ALP) activity assays showed that the BBR and IGF-1 in the composite microspheres synergistically promoted the osteogenic differentiation of MC3T3-E1 cells. Furthermore, it was confirmed that immobilized IGF-1 enhances the mRNA expression of an osteogenic-related extracellular matrix and that BBR accelerates the mRNA expression of IGF-1-mediated osteogenic differentiation and cell mineralization. Further cellular studies demonstrate that IGF-1 could further synergistically activate the IGF-1R/PI3K/AKT/mTOR pathway using BBR, thereby enhancing IGF-1-mediated osteogenesis. Rat calvarial defect repair experiments show that IGF-1@PLGA/HA-BBR microspheres can effectively promote the complete bony connection required to cover the defect site and enhance bone defect repair. These findings suggest that IGF-1@PLGA/HA-BBR composite microspheres show a great potential for bone regeneration.Keywords:polymer microspheres;berberine (BBR);IGF-1;bone regeneration;osteogenic differentiation
研究领域:
生物医学工程
·
组织工程
·
骨再生
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2016
·
IF 2.267
Jie Hou,Huichang Gao,Yingjun Wang,Delin Cheng,Xiaodong Cao
Modifying substrates through mineralization is a popular way to improve the osteogenic performance. Screening of the best mineralization characteristics on specific substrates for stem cells is meaningful but not fully studied. In this paper, poly(lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA, PH) microsphere scaffolds with superficial pores were fabricated by a low-temperature fusion method. After the mineralization in the 5× stimulated body fluid (SBF) for 0, 7, 12 and 24 h, four mineralized scaffolds (MPH-0, MPH-7, MPH-12 and MPH-24) with different apatite topographies were obtained. It was found that the surface of MPH-7 was evenly decorated with abundant micro-pores, MPH-12 with dense and plain apatite layer, and MPH-24 with small spherical bumps. The responses of mouse bone mesenchymal stem cells (mBMSCs) to the four scaffolds were further studied. The results showed that MPH-7 and MPH-24 had more obvious effects on mBMSCs attachment, proliferation and differentiation than MPH-0 and MPH-12. This work indicated that to obtain the maximum improvement, the mineralization characteristics had to be carefully chosen. This was noteworthy in the chemical modification of surfaces to form the functionalized scaffolds for bone repair.
研究领域:
生物材料
·
组织工程
·
干细胞研究
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 48
·27191-27200
·
IF 2.936
Qinli Xu,Ye Li,Yuhang Zhu,Kunchi Zhao,Rui Gu,Qingsan Zhu
Poly(lactic-co-glycolic acid) (PLGA) and hydroxyapatite (HA) are considered potential osteoinductive materials because of their biodegradability and mineralization features. However, the hydrophobicity of scaffold surfaces is less supportive of cell attachment and proliferation because of poor wettability. The mode of binding of growth factors to the scaffold also affects cell differentiation into osteoblasts. The half-life of a growth factor in vivo can be increased by binding the factor to the scaffold surface. In this work, we prepared a porous PLGA/HA scaffold grafted with recombinant human bone morphogenic protein-7 (rhBMP-7) attached via polydopamine (pDA) for bone repair. The pDA coated PLGA/HA (pDA-PLGA/HA) scaffolds were characterized by energy dispersive X-ray analysis and Fourier-transform infrared spectroscopy. The microstructure and porosity of PLGA/HA scaffolds were analyzed by scanning electron microscopy and micro-computed tomography. The release profile of rhBMP-7 grafted onto the pDA-PLGA/HA (pDA-PLGA/HA/BMP-7) scaffolds was examined for 21 days. The attachment efficiency, cell proliferation rate, alkaline phosphatase activity, calcium deposition, and osteoblast-related gene expression of bone marrow-derived stem cells to PLGA/HA, pDA-PLGA/HA, and pDA-PLGA/HA/BMP-7 scaffolds were evaluated. To assess the ability of bone repair in vivo, scaffolds were implanted into critical-sized calvarial defects created in mice, and the in vivo tissue-engineered bone was monitored by micro-computed tomography and histology. In vivo experiments revealed rapid healing of the defects treated with the pDA-PLGA/HA/BMP-7 scaffolds compared with pDA-PLGA/HA and PLGA/HA scaffolds at week 8 post-surgery. These results collectively demonstrate that the rhBMP-7-immobilized PLGA/HA scaffold via pDA is a promising candidate for calvarial repair.
研究领域:
生物医学工程
·
组织工程
·
材料科学
·
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）