Biomaterials Advances
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2022
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IF 0
Yiwen Zhang,Zhixiang Li,Ziqi Wang,Bomin Yan,Ao Shi,Jinnuo Xu,Jianzhong Guan,Li Zhang,Pinghui Zhou,Yingji Mao
High-efficiency repair of critical bone defects is a pressing problem in clinical practice. However, most biological replacement materials do not simultaneously satisfy the dual requirements of mechanical strength and cell compatibility. In this study, chitosan methacryloyl (CSMA) and β-tricalcium phosphate (β-TCP) were subjected to photo-crosslinking to form the CSMA/β-TCP composite hydrogel, which has strong mechanical properties contributing to bone regeneration. In addition, its scaffold can alter the morphology of bone marrow mesenchymal stem cells (BMSCs), promote their proliferation, enhance the expression of alkaline phosphatase (ALP), and augment the nodular deposition of calcium. Meanwhile, the expressions of osteogenic proteins (ALP, osteocalcin, and osteopontin) were upregulated and the regulatory mechanism of the Hippo signaling pathway was verified. Moreover, animal experiments have confirmed that CSMA/β-TCP has adequate biocompatibility and bone regeneration. These results demonstrate the immense potential of the CSMA/β-TCP composite hydrogel in bone regeneration therapy.
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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骨科
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产品关联
DOI
PubMed
Materials Today Bio
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2023
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IF 8.2
Huimin Shi,Yang Li,Kailei Xu,Jun Yin
The development of cell-laden bioinks that possess high biocompatibility and printability is crucial in the field of bioprinting for the creation of cell-embedded tissue engineering scaffolds. As widely known, methacrylated gelatin (GelMA) is one of the most commonly used photo-crosslinkable bioink for cell-laden bioprinting with different printing methods, but GelMA is the derivative of gelatin, so it loses the unique triple-helix molecular structure of collagen and may not be able to successfully activate the cellular pathways or facilitate cell-matrix interaction as effectively as collagen. Recently, methacrylated collagen (CMA) was developed to be an alternative photocrosslinkable bioink with a good bioactivity, but its low printability and biocompatibility limited that application in tissue engineering. In this study, the synthetic process for CMA was improved by synthesizing under 4 °C and using acidic aqueous solution as solvent. Our CMA bioinks were demonstrated a similar printability as GelMA in extrusion bioprinting, while a better formability in digital light processing (DLP). To further analyze the bioactive properties, CMA bioinks were encapsulated with Schwann cells (SCs) and bone mesenchymal stem cells (BMSCs) for printing. SCs-laden CMA bioinks had a significantly higher proliferation rate and expression of neural stem cell-associated genes than GelMA in DLP bioprinting. While, BMSCs-laden CMA bioinks demonstrated >95% cellular viability, better cell spreading and higher expression of osteogenesis-related genes than that of GelMA. Overall, we speculate that the CMA-based bioink developed in this study could be potential bioinks for 3D cell-laden bioprinting in the future.
研究领域:
组织工程
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生物打印
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生物材料
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
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2023
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IF 8.2
Chunhui Ma,Tao Wang,Xinmeng Jin,Wanglin Zhang,Qi Lv
Repairing cartilage/subchondral bone defects that involve subchondral bone is a major challenge in clinical practice. Overall, the integrated repair of the structure and function of the osteochondral (OC) unit is very important. Some studies have demonstrated that the differentiation of cartilage is significantly enhanced by reducing the intake of nutrients such as lipids. This study demonstrates that using starvation can effectively optimize the therapeutic effect of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs). A hyaluronic acid (HA)-based hydrogel containing starved BMSCs-EVs displayed continuous release for more than 3 weeks and significantly promoted the proliferation and biosynthesis of chondrocytes around the defect regulated by the forkhead-box class O (FOXO) pathway. When combined with vascular inhibitors, the hydrogel inhibited cartilage hypertrophy and facilitated the regeneration of hyaline cartilage. A porous methacrylate gelatine (GelMA)-based hydrogel containing calcium salt loaded with thrombin rapidly promoted haematoma formation upon contact with the bone marrow cavity to quickly block the pores and prevent the blood vessels in the bone marrow cavity from invading the cartilage layer. Furthermore, the haematoma could be used as nutrients to accelerate bone survival. The in vivo experiments demonstrated that the multifunctional lineage-specific hydrogel promoted the integrated regeneration of cartilage/subchondral bone. Thus, this hydrogel may represent a new strategy for osteochondral regeneration and repair.
研究领域:
组织工程
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再生医学
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骨科
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干细胞生物学
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生物材料
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
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IF 5.3
Chun Liu,Chengqiang Wang,Yang Liu,Jiahui Huang,Wenning Xu,Jianjun Li,Yihan Wang,Yizhou Xu,Lixin Zhu,Haixia Xu
Oxidative stress plays a crucial role in steroid-induced osteonecrosis of the femoral head (SONFH). Although several antioxidant strategies have been investigated for treating SONFH, their antioxidant efficiencies and therapeutic effects remain unsatisfactory. Here, we developed a selenium nanoparticles/carboxymethyl chitosan/alginate (SeNPs/CMC/Alg) antioxidant hydrogel and evaluated its ability to treat SONFH. In vitro assays indicated that the SeNPs/CMC/Alg hydrogel exhibited excellent properties, such as low cytotoxicity, sustained SeNPs release, and favorable antioxidant activity. Under oxidative stress, the SeNPs/CMC/Alg hydrogel promoted reactive oxygen species (ROS) elimination and enhanced the osteogenic and proangiogenic abilities of bone marrow mesenchymal stem cells (BMSCs). After establishing a rabbit model of SONFH, the SeNPs/CMC/Alg hydrogel was transplanted into the femoral head after core decompression (CD) surgery. Radiographic and histological analyses revealed that the hydrogel treatment alleviated SONFH by eliminating ROS and promoting osteogenesis and angiogenesis compared to those in the CD and CMC/Alg groups. In vitro and in vivo studies indicated that the Wnt/β-catenin signaling pathway was activated by the SeNPs/CMC/Alg hydrogel in both hydrogen peroxide-conditioned BMSCs and necrotic femoral heads. These findings indicate that local transplantation of the SeNPs/CMC/Alg hydrogel is beneficial for treating SONFH, as it promotes ROS elimination and activation of the Wnt/β-catenin signaling pathway.
研究领域:
生物材料
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纳米技术
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骨科
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组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Yi He,Lejia Zhang,Siyuan Huang,Yuquan Tang,Yiming Li,Hongyu Li,Guanhui Chen,Xun Chen,Xiliu Zhang,Wei Zhao,Feilong Deng,Dongsheng Yu
Background The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism.Methods The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites.Results We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites.Conclusion We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects.
研究领域:
生物材料
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组织工程
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骨再生
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分子生物学
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纳米技术
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2020
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IF 2.69
Jianping Mao,Pengfei Wei,Zuoying Yuan,Wei Jing,Jingjing Cao,Guangping Li,Jianxun Guo,Honggang Wang,Dafu Chen,Qing Cai
There are intensive needs for scaffolds with new designs to meet the diverse requirements of bone repairing. Biodegradable microspheres are highlighted as injectable micro-scaffolds thanks to their advantages in filling irregular defects via a minimally invasive surgery. In this study, microspheres with surface micropores were made via the W1/O/W2 double emulsion method using amphiphilic triblock copolymers (PLLA-PEG-PLLA) composed of poly(L-lactide) (PLLA) and poly(ethylene glycol) (PEG) segments. When the PEG fraction was controlled as 10 wt.%, the microspheres demonstrated higher cell affinity than the smooth-surfaced PLLA microspheres. After being further functionalized with polydopamine coating and apatite deposition, the PLLA-PEG-PLLA microspheres could up-regulate the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) significantly. Before subcutaneous implantation, bone morphogenetic protein-2 (BMP-2) was adsorbed onto the biomineralized microspheres by taking advantages of the strong affinity of apatite to BMP-2. The resulted microspheres induced ectopic osteogenesis efficiently without causing biocompatibility problems. In summary, this study provided a simple strategy to prepare functionalized microspheres with osteoconductivity and osteoinductivity, which showed great potential in promoting bone regeneration as injectable micro-scaffolds.
研究领域:
生物医学工程
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组织工程
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材料科学
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2022
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IF 10.633
Jiayuan Wang,Huan Wang,Yong Wang,Zhao Liu,Zexi Li,Jiaying Li,Qixin Chen,Qingchen Meng,Wenmiao Will Shu,Junxi Wu,Can Xiao,Fengxuan Han,Bin Li
In bone tissue engineering, vascularization is one of the critical factors that limit the effect of biomaterials for bone repair . While various approaches have been tried to build vascular networks in bone grafts, lack of endothelialization still constitutes a major technical hurdle. In this study, we have developed a facile technique to fabricate endothelialized biomimetic microvessels (BMVs) from alginate-collagen composite hydrogels within a single step using microfluidic technology. BMVs with different sizes could be readily prepared by adjusting the flow rate of microfluids. All BMVs supported perfusion and outward penetration of substances in the tube. Endothelial cells could adhere and proliferate on the inner wall of tubes. It was also found that the expression of CD31 and secretion of BMP-2 and PDGF-BB were higher in the rat umbilical vein endothelial cells (RUVECs) in BMVs than those cultured on hydrogel. When co-cultured with bone marrow mesenchymal stem cells (BMSCs), endothelialized BMVs promoted the osteogenic differentiation of BMSCs compared to those in acellular BMV group. In vivo , markedly enhanced new bone formation was achieved by endothelialized BMVs in a rat critical-sized calvarial defect model compared to those with non-endothelialized BMVs or without BMVs. Together, findings from both in vitro and in vivo studies have proven that endothelialized BMVs function to facilitate osteogenesis and promote bone regeneration , and therefore might present an effective strategy in bone tissue engineering. Statement of significance In bone tissue engineering, limited vascularization is one of the critical factors that limit the effect of biomaterials for bone repair. In this study, we developed a facile technique to fabricate endothelialized biomimetic microvessels (BMVs) from alginate-collagen composite hydrogels within a single step using microfluidic technology. Both in vitro and in vivo studies have proven that endothelialized BMVs function to facilitate osteogenesis and promote bone regeneration, and therefore might present an effective strategy in bone tissue engineering.
研究领域:
组织工程
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生物医学工程
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再生医学
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骨生物学
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微流控技术
✓ 已验证
DOI
PubMed
高影响因子
MATERIALS & DESIGN
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2022
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IF 9.417
Wen Hou,Jiaxin Guo,Jiawei Liu,Yanan Zhao,Wenying Wei,Dan Shu,Honglian Dai
Vascularisation and mineralisation are indispensable conditions for bone repair materials. The introduction of magnesium ions into calcium phosphate-based materials can give them angiogenic and mineralising capabilities. However, the optimum calcium to magnesium ratio has yet to be determined. Microspheres have received much attention from researchers due to their flexibility, non-agglomeration and other advantages. We prepared calcium-magnesium phosphate biphasic microspheres (CMBS) using the water-in-oil emulsion cross-linking method to achieve osteogenic differentiation and vascularisation. The simultaneous use of the sacrificial template method and heat treatment endow the microspheres with a rich micro-pore structure. In addition, we investigated the compounding ratio of calcium phosphate to magnesium phosphate and determined the optimal compounding ratio (Ca/Mg = 3/1–1/1) for this material. The prepared microspheres promoted the attachment, proliferation and directed differentiation of bone marrow mesenchymal stromal cells (BMSCs) and human umbilical vein cells (HUVECs). CMBS-I (Ca/Mg = 3/1) and CMBS-II (Ca/Mg = 1/1) microspheres showed the best promotion effect among all groups. These microspheres were implanted under the skin of Sprague- Dawley (SD) rats, and the composite microspheres significantly induced vascular regeneration compared to pure phase microspheres.
研究领域:
材料科学
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生物医学工程
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组织工程
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产品关联
DOI
高影响因子
POULTRY SCIENCE
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2022
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IF 4.014
Zhengtian Lyu,Haifang Li,Xin Li,Hui Wang,Hongchao Jiao,Xiaojuan Wang,Jingpeng Zhao,Hai Lin
ABSTRACT Fibroblast growth factor 23 ( FGF23 ), a bone-derived hormone, is involved in the reabsorption of phosphate ( P ) and the production of vitamin D hormones in the kidney. However, whether and how FGF23 regulates chicken bone metabolism remains largely unknown. In the present study, we investigated the effect of FGF23 on osteogenic differentiation and mineralization of chicken bone marrow mesenchymal stem cells ( BMSCs ). First, we found that the transcription of FGF23 was inhibited by β-glycerophosphate sodium ( GPS , 5 mM, 10 mM, 20 mM) and 10 −9 M 1, 25-dihydroxyvitamin D3 ( 1, 25(OH) 2 D 3 ), but was stimulated by 10 −7 M 1, 25(OH) 2 D 3 and parathyroid hormone ( PTH , 10 −9 M, 10 −8 M, 10 −7 M). Second, overexpression of FGF23 by the FGF23 adenovirus ( Adv-FGF23 ) suppressed the formation of mineralized nodules ( P < 0.001) and alkaline phosphatase ( ALP ) activity ( P < 0.05) in both differentiated and mineralized osteoblasts. Administration of FGF receptor 3 ( FGFR3 ) inhibitor (50 nM) was sufficient to restore the FGF23-decreased ALP activity ( P < 0.05), but not for the formation of mineralized nodules. In addition, the phosphorylation of ERK increased considerably with Adv-FGF23 overexpression ( P < 0.05). Administration of an ERK-specific inhibitor (10 μM) could down-regulate the phosphorylation of ERK ( P-ERK ) ( P < 0.05) and slightly restored the Adv-FGF23-reduction of ALP activity ( P = 0.08). In summary, our data suggest that GPS, 1, 25(OH) 2 D 3 , and PTH could regulate FGF23 mRNA expression in vitro. FGF23 is a negative regulator of bone remodeling. FGF23 not only inhibits BMSCs osteogenesis through the FGFR3-ERK signaling pathway but also suppresses the mineralization of mature osteoblasts.
研究领域:
骨生物学
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细胞生物学
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分子生物学
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2023
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IF 5.7
Ding Wenbin,Zhou Qirong,Lu Yifeng,Wei Qiang,Tang Hao,Zhang Donghua,Liu Zhixiao,Wang Guangchao,Wu Dajiang
Stem cell-based therapy has drawn attention as an alternative option for promoting prosthetic osteointegration in osteoporosis by virtue of its unique characteristics. However, estrogen deficiency is the main mechanism of postmenopausal osteoporosis. Estrogen, as an effective antioxidant, deficienncy also results in the accumulation of reactive oxygen species (ROS) in the body, affecting the osteogenic differentiation of stem cells and the bone formation i osteoporosis. In this study, we prepared a ROS-scavenging hydrogel by crosslinking of epigallocatechin-3-gallate (EGCG), 3-acrylamido phenylboronic acid (APBA) and acrylamide. The engineered hydrogel can scavenge ROS efficiently, enabling it to be a cell carrier of bone marrow-derived mesenchymal stem cells (BMSCs) to protect delivered cells from ROS-mediated death and osteogenesis inhibition, favorably enhancing the tissue repair potential of stem cells. Further in vivo investigations seriously demonstrated that this ROS-scavenging hydrogel encapsulated with BMSCs can prominently promote osteointegration of 3D printed microporous titanium alloy prosthesis in osteoporosis, including scavenging accumulated ROS, inducing macrophages to polarize toward M2 phenotype, suppressing inflammatory cytokines expression, and improving osteogenesis related markers (e.g., ALP, Runx-2, COL-1, BSP, OCN, and OPN). This work provides a novel strategy for conquering the challenge of transplanted stem cells cannot fully function in the impaired microenvironment, and enhancing prosthetic osteointegration in osteoporosis.
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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骨科
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干细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2023
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IF 10
Zhuyun Cai,Xiaohao Liu,Miao Hu,Yichen Meng,Jianquan Zhao,Yixuan Tan,Xiong Luo,Ce Wang,Jun Ma,Zhongyi Sun,Yingying Jiang,Bingqiang Lu,Rui Gao,Feng Chen,Xuhui Zhou
Bone is a naturally mineralized tissue with a remarkable hierarchical structure, and the treatment of bone defects remains challenging. Microspheres with facile features of controllable size, diverse morphologies, and specific functions display amazing potentials for bone regeneration. Herein, inspired by natural biomineralization, a novel enzyme-catalyzed reaction is reported to prepare magnesium-based mineralized microspheres. First, silk fibroin methacryloyl (SilMA) microspheres are prepared using a combination of microfluidics and photo-crosslinking. Then, the alkaline phosphatase (ALP)-catalyzed hydrolysis of adenosine triphosphate (ATP) is successfully used to induce the formation of spherical magnesium phosphate (MgP) in the SilMA microspheres. These SilMA@MgP microspheres display uniform size, rough surface structure, good degradability, and sustained Mg 2+ release properties. Moreover, the in vitro studies demonstrate the high bioactivities of SilMA@MgP microspehres in promoting the proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Transcriptomic analysis shows that the osteoinductivity of SilMA@MgP microspheres may be related to the activation of the PI3K/Akt signaling pathway. Finally, the bone regeneration enhancement units (BREUs) are designed and constructed by inoculating BMSCs onto SilMA@MgP microspheres. In summary, this study demonstrates a new biomineralization strategy for designing biomimetic bone repair materials with defined structures and combination functions.
研究领域:
生物医学工程
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组织工程
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材料科学
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细胞生物学
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
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2025
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IF 14.1
Chenglong Wang,Zeyu Shou,Chengwei Xu,Kaiyuan Huo,Wenjie Liu,Hao Liu,Xingjie Zan,Qing Wang,Lianxin Li
Osteointegration, the effective coupling between an implant and bone tissue, is a highly intricate biological process. The initial stages of bone-related immunomodulation and cellular colonization play crucial roles, but have received limited attention. Herein, a novel supramolecular co-assembled coating of strontium (Sr)-doped metal polyphenol networks (MPN) modified with c(RGDfc) is developed and well-characterized, for eliciting an early immunomodulation and cellular colonization. The results showed that the (Sr-MPN)@RGD coating significantly regulated the polarization of macrophages to the M2 phenotype by controllable release of Sr, and promote the initial adhesion of bone marrow mesenchymal stem cells (BMSCs) by RGD presented on MPN. Notably, the (Sr-MPN)@RGD attenuated osteoclast differentiation and oxidative stress as well as enhanced osteoblast differentiation and angiogenesis due to macrophage polarization toward M2 phenotype, which in turn has a profound effect on neighboring cells through paracrine signaling. In vivo results showed that the (Sr-MPN)@RGD coating manifested superior osseointegration and bone maturation to the bare Ti-rod or Ti-rod coated with MPN and Sr-MPN. This work contributed to the design of multifunctional implant coatings that address the complex biological process of osteointegration from the perspective of orchestrating stem cell recruitment with immunomodulatory strategies.
研究领域:
生物材料
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组织工程
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免疫学
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细胞生物学
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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）