ACS Biomaterials Science & Engineering
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2019
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IF 4.511
Ping Sun,Qianqian Zhang,Wei Nie,Xiaojun Zhou,Liang Chen,Haibo Du,Shuguang Yang,Zhengwei You,Jiawen He,Chuanglong He
In the repair of large segmental bone defects, bone tissue is often unable to heal due to the destruction of the vascular network near the wound site. An ideal bone repair material should have both angiogenic and osteogenic capabilities. To achieve this goal, we used biodegradable mesoporous silica nanoparticles (MSNs) as a delivery vehicle for dexamethasone (DEX), a small-molecule drug that induces osteogenic differentiation. Subsequently, chitosan was covalently modified onto the surface of the nanoparticles by glycidoxypropyltrimethoxysilane (GPTMS) to construct nanoparticulate delivery systems (DEX@chi-MSNs) that induce osteoblast formation. The QK peptide, which mimics the α-helical structure of vascular endothelial growth factor (VEGF) binding to the receptor, was adsorbed to the surface of chitosan-modified MSNs nanoparticles (QK@chi-MSNs) to render them with angiogenic ability. The QK@chi-MSNs can promote the formation of the tubular structure of human umbilical vein endothelial cells (HUVECs) and angiogenesis in vivo, as demonstrated by a chicken embryo chorioallantoic test (CAM) and subcutaneous embedding test. The DEX@chi-MSNs can improve alkaline phosphatase (ALP) activity, mineralized nodule formation, and the expression of osteogenic-related genes and proteins by BMSCs. Furthermore, the ability of bone repair and angiogenesis was evaluated in a critical size skull defect model in rats by using nanocarriers loaded with both DEX and QK (QK/DEX@chi-MSNs). The results of computed tomography (CT) scan, histological examination, and immunofluorescence staining indicated that QK/DEX@chi-MSNs can promote bone formation and angiogenesis in vivo, which has broad application prospects in bone tissue engineering.
研究领域:
生物材料学
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再生医学
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组织工程学
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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
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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
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生物医学材料
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再生医学
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骨科
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2020
·
IF 4.152
MingLi Xiang,Mengyuan Zhu,Zun Yang,Ping He,Jingjing Wei,Xiang Gao,Jinlin Song
The development of biomimetic bone graft materials for periodontal tissue engineering is a field of topical interest. In this study, we designed a dual-functionalized apatite nanocomposite, which could integrate multiple molecular cues for manipulating the fate of periodontal ligament stem cells (PDLSCs). Briefly, inspired by mussels, a biomimetic nanohydroxyapatite was fabricated using a polydopamine structure as a template (named as tHA) and then surface-modified with bone-forming peptide-1 (BFP-1) and vascular endothelial growth factor-mimicking peptide (QK) via a single step of catechol chemistry. Our study showed that the biofunctions of tethered peptides were not compromised on the surface of apatite nanoparticles. Because of the synergistic effect of BFP-1 and QK peptides, the dual-functionalized apatite nanocomposite showed improved cytocompatibility compared to controls. Moreover, it can boost the proliferation and osteogenic differentiation of PDLSCs, indicating excellent bioactivity of tHA–BFP/QK nanoparticles on cell fate decision. More importantly, animal experiments showed that dual-functionalized apatite nanocomposites could dramatically promote the regeneration of periodontal bone. It is concluded that our work provides an instructive insight into the design of biomimetic apatite nanocomposites, which holds a great potential for applications in periodontal bone repair.
研究领域:
组织工程学
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生物材料科学
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牙科材料
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再生医学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 30
·6056-6067
·
IF 6.331
Qian Li,He Zhang,Jijia Pan,Binhong Teng,Ziqian Zeng,Yang Chen,Yu Hei,Siqi Zhang,Shicheng Wei,Yuhua Sun
Due to the ability to combine multiple osteogenic induction “cues” at the same time, hydrogels are widely used in the three-dimensional (3D) culture of human mesenchymal stem cells (hMSCs) and osteoinduction. However, the survival and proliferation of stem cells in a 3D culture system are limited, which reduces their osteogenic differentiation efficiency. In addition, the cells inside the hydrogel are prone to apoptosis due to hypoxia, which is a serious challenge for tissue engineering based on stem cells. In this study, a tripeptide-based macroporous alginate hydrogel was prepared to improve the osteogenic microenvironment of stem cells. The arginine–glycine–aspartate (RGD) peptide promoted the adhesion and proliferation of stem cells, and the degradation of gelatin microspheres (GMs) produced a macroporous structure to enhance further the migration and aggregation of stem cells. Mesoporous silica nanoparticles (MSNs) sustained-release bone-forming peptide-1 (BFP-1) induced osteogenic differentiation, and the sustained release of the QK peptide from the GMs promoted angiogenesis. In vitro experiments have shown that this functionalized hydrogel stimulates the proliferation of hMSCs, encourages larger cell cluster formation, and enhances the osteogenic differentiation efficiency. The released QK facilitates the proliferation and migration of endothelial cells. In vivo experiments have also verified that this system has a better osteogenic effect, and more blood vessels were observed inside the hydrogel, than in other systems. In general, this research has led to the development of a tripeptide macroporous hydrogel that can simultaneously promote osteogenesis and angiogenesis, showing great promise for applications of 3D cultures and stem cell-based tissue engineering.
研究领域:
生物材料
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组织工程
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干细胞生物学
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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
ACS Biomaterials Science & Engineering
·
2022
·
IF 5.395
He Zhang,Xiaoming Fu,Siqi Zhang,Qian Li,Yang Chen,Hao Liu,Wen Zhou,Shicheng Wei
The use of human bone marrow mesenchymal stem cells (hBMSCs) to regenerate and repair bone tissue defects is a complex research field of bone tissue engineering; nevertheless, it is a hot topic. One of the biggest problems is the limited survival and osteogenic capacity of the transplanted cells within the host tissue. Even for hBMSCs with their low immunogenicity, the body will still cause a local immune-inflammatory response directed against the allogeneic cells and thereby reduce the activity of the transplanted cells. Even in the case of successful transplantation, the lack of vascularization at the transplantation site makes it difficult for the transplanted cells to exchange nutrients and metabolic wastes that ultimately affects bone regeneration. In this study, we covalently modified alginate with RGD and QK peptides that were injected subcutaneously into immunocompetent mice. Histological analysis, as well as ELISA techniques, proved that this method is able to provide bioactive stem cell transplant beds containing functionalized biomaterials and vascularized surrounding tissues. Inflammation-related factors, such as IL-2, IL-6, TNF-α, and IFN-γ, around the cell graft beds decreased with time and were lowest at the second week. Then, the hBMSCs were injected into the cell transplantation beds intended to form vascularized bonelike tissues that were evaluated by micro-computed tomography (Micro CT), histological, and immunohistochemical analyses. The results showed that the expression of osteogenesis-related proteins RUNX2, COL1A1, and OPN, as well as the expression of angiogenic factor vWF and cartilage-related protein COL2A1 were significantly upregulated in the hBMSC-derived osteogenic tissue. These results suggest that the stem cell transplantation strategy by constructing bioactive cell transplant beds is effective to enhance the bone regeneration capacity of hBMSCs and holds great potential in bone tissue engineering.
研究领域:
组织工程
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干细胞生物学
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生物材料科学
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免疫学
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再生医学
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DOI
PubMed
高影响因子
Research
·
2023
·
IF 11
Jiaying Li,Jinjin Ma,Qian Feng,En Xie,Qingchen Meng,Wenmiao Shu,Junxi Wu,Liming Bian,Fengxuan Han,Bin Li
The critical factor determining the in vivo effect of bone repair materials is the microenvironment, which greatly depends on their abilities to promote vascularization and bone formation. However, implant materials are far from ideal candidates for guiding bone regeneration due to their deficient angiogenic and osteogenic microenvironments. Herein, a double-network composite hydrogel combining vascular endothelial growth factor (VEGF)-mimetic peptide with hydroxyapatite (HA) precursor was developed to build an osteogenic microenvironment for bone repair. The hydrogel was prepared by mixing acrylated β-cyclodextrins and octacalcium phosphate (OCP), an HA precursor, with gelatin solution, followed by ultraviolet photo-crosslinking. To improve the angiogenic potential of the hydrogel, QK, a VEGF-mimicking peptide, was loaded in acrylated β-cyclodextrins. The QK-loaded hydrogel promoted tube formation of human umbilical vein endothelial cells and upregulated the expression of angiogenesis-related genes, such as Flt1, Kdr, and VEGF, in bone marrow mesenchymal stem cells. Moreover, QK could recruit bone marrow mesenchymal stem cells. Furthermore, OCP in the composite hydrogel could be transformed into HA and release calcium ions facilitating bone regeneration. The double-network composite hydrogel integrated QK and OCP showed obvious osteoinductive activity. The results of animal experiments showed that the composite hydrogel enhanced bone regeneration in skull defects of rats, due to perfect synergistic effects of QK and OCP on vascularized bone regeneration. In summary, improving the angiogenic and osteogenic microenvironments by our double-network composite hydrogel shows promising prospects for bone repair.
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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生物医学工程
✓ 已验证
DOI
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Abdullrahman M. Al-Bishari,Tingting Liu,Jiatong Zhuang,Qihong Zhang,Jiaquan Chen,Yan Wang,Chuanyang Liu,Peng Gao,Jinsong Liu,Lei Lu
Advancements in guided bone regeneration (GBR) rely on the development of membranes that can effectively control drug delivery and facilitate bone repair. This study introduces a triple-layered multi-functional membrane (MFM), with each layer serving a specific release profile and function. These layers consist of Qk peptide, strontium (Sr), and vancomycin (Van) for angiogenesis, bone growth, and infection control. The MFM was meticulously designed to ensure sustained drug release kinetics and improved bone regeneration. The membrane morphology was analyzed via SEM, and its mechanical properties were measured via stress–strain curves. In vitro studies confirmed the controlled release of the agents for 21 days. These findings indicate significant enhancements needed for GBR, as supported by in vitro results. The synergy of the membrane's components contributes to a greater therapeutic impact. Furthermore, in vivo results further supported the exceptional performance of MFM in GBR. Within 5 days of implantation, notable improvements in revascularization were observed. After 1 month, micro-CT scans displayed accelerated bone regeneration, while the membrane effectively prevented bacterial growth within 3 days. The MFM/Van-Sr-Qk membrane shows excellent potential for advancing bone regeneration and GBR therapies, warranting further research and development in this promising field.
研究领域:
生物医学工程
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材料科学
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组织工程
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药学
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骨科
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Guansong Hu,Junjian Chen,Yan Fan,Haiyan Zhou,Kunzhong Guo,Zhou Fang,Liangxu Xie,Lin Wang,Yingjun Wang
As an effective strategy to develop novel implants with a biomolecule, the efficiency of a copper-catalysed azide-alkyne cycloaddition (CuAAC) urgently requires improvement. Herein, we constructed a facile CuAAC system with catalytic CuSO 4 /sodium borohydride (CuAAC-Bor). As Cu nanoclusters (CuNCs) formed in situ , they showed stronger efficiency in immobilizing 41 types of peptides on Ti implants than traditional CuAAC with CuSO 4 /sodium ascorbate. Then, we mechanically revealed the significance of peptide size on CuAAC efficiency by all-atom molecular dynamics simulation and machine learning, and found that larger peptides preferred to adhere to Ti and CuNCs to increase their reaction opportunity. With CuAAC-Bor, HHC36-engineered implants strongly inhibited 5 types of clinical bacteria in vitro and prevented infection in vivo , and RGD-, DGEA-, QK- or YGFGG-engineered implants had high biocompatibilities with HUVECs / hBMSCs in vitro . Moreover, we demonstrated that QK-engineered implants prepared with CuAAC-Bor promoted the osteogenic differentiation of hBMSCs via the PI3K/Akt signalling pathway and triggered angiogenesis and osteogenesis in vivo . Our study shows that this facile and highly efficient CuAAC-Bor system holds high promise for the preparation of novel biomaterial surfaces.
研究领域:
生物材料
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生物医学工程
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分子生物学
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Junjian Chen,Guansong Hu,Tianjie Li,Yunhua Chen,Meng Gao,Qingtao Li,Lijing Hao,Yongguang Jia,Lin Wang,Yingjun Wang
Although antimicrobial titanium implants can prevent biomaterial-associated infection (BAI) in orthopedics, they display cytotoxicity and delayed osseointegration . Therefore, versatile implants are desirable for simultaneously inhibiting BAI and promoting osseointegration, especially “statically-versatile” ones with nonessential external stimulations for facilitating applications. Herein, we develop a “statically-versatile” titanium implant by immobilizing an innovative fusion peptide (FP) containing HHC36 antimicrobial sequence and QK angiogenic sequence via sodium borohydride reduction promoted Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC-SB), which shows higher immobilization efficiency than traditional CuAAC with sodium ascorbate reduction (CuAAC-SA). The FP-engineered implant exhibits over 96.8% antimicrobial activity against four types of clinical bacteria ( S. aureus , E. coli , P. aeruginosa and methicillin-resistant S. aureus ), being stronger than that modified with mixed peptides. This can be mechanistically attributed to the larger bacterial accessible surface area of HHC36 sequence. Notably, the implant can simultaneously enhance cellular proliferation , up-regulate expressions of angiogenesis-related genes/proteins (VEGF and VEGFR-2) of HUVECs and osteogenesis-related genes/proteins (ALP, COL-1, RUNX-2, OPN and OCN) of hBMSCs . In vivo assay with infection and non-infection bone-defect model reveals that the FP-engineered implant can kill 99.63% of S. aureus , and simultaneously promote vascularization and osseointegration. It is believed that this study presents an excellent strategy for developing “statically-versatile” orthopedic implants .
研究领域:
骨科
·
材料科学
·
生物材料
·
组织工程
·
生物医学工程
✓ 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）