Biomedical Materials
·
2024
·Vol. 19
·期 6
·065004
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IF 3.9
Zhao Qianjuan,Shan Rong,Liu Shengxi,Liu Xuanhao,Liu Bin,Song Fuxiang
Artificial bone is the alternative candidate for the bone defect treatment under the circumstance that there exits enormous challenge to remedy the bone defect caused by attributes like trauma and tumors. However, the impact of pore size discrepancy for regulating new bone generation is still ambiguous. Using direct 3D printing technology, customized 3D polycaprolactone/β-tricalcium phosphate (PCL/β-TCP) artificial bones with different structural pore sizes (1.8, 2.0, 2.3, 2.5, and 2.8 mm) were successfully prepared, abbreviated as the 3D PCL/β-TCP. 3D PCL/β-TCP exhibited a 3D porous structure morphology similar to natural bone and possessed outstanding mechanical properties. Computational fluid dynamics analysis indicated that as the structural pore size increased from 1.8 to 2.8 mm, both velocity difference (from 4.64 × 10−5 to 7.23 × 10−6 m s−1) and depressurization (from 7.17 × 10−2 to 2.25 × 10−2 Pa) decreased as the medium passed through. In vitro biomimetic mineralization experiments confirmed that 3D PCL/β-TCP artificial bones could induce calcium–phosphate complex generation within 4 weeks. Moreover, CCK-8 and Calcein AM live cell staining experiments demonstrated that 3D PCL/β-TCP artificial bones with different structural pore sizes exhibited advantageous cell compatibility, promoting MC3T3-E1 cell proliferation and adhesion. In vivo experiments in rats further indicated that 3D PCL/β-TCP artificial bones with different structural pore sizes promoted new bone formation, with the 2.5 mm group showing the most significant effect. In conclusion, 3D PCL/β-TCP artificial bone with different structural pore sizes could promote new bone formation and 2.5 mm group was the recommended for the bone defect repair.
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PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 17
·3344-3356
·
IF 7.571
Linxue Zhang,Zhuo Wan,Zuoying Yuan,Jun Yang,Yunfan Zhang,Qing Cai,Jianyong Huang,Yuming Zhao
Multicellular aggregates have been widely utilized for regenerative medicine; however, the heterogeneous structure and undesired bioactivity of cell-only aggregates hinder their clinical translation. In this study, we fabricated an innovative kind of microparticle-integrated cellular aggregate with multifunctional activities in angiogenesis and osteogenesis, by combining stem cells from human exfoliated deciduous teeth (SHEDs) and bioactive composite microparticles. The poly(lactide-co-glycolide) (PLGA)-based bioactive microparticles (PTV microparticles) were ∼15 μm in diameter, with dispersed β-tricalcium phosphate (β-TCP) nanoparticles and surface-modified vascular endothelialcadherin fusion protein (hVE-cad-Fc). After co-culturing with microparticles in U-bottomed culture plates, SHEDs could firmly attach to the microparticles with a homogeneous distribution. The PTV microparticle-integrated SHED aggregates (PTV/SHED aggregates) showed significant positive CD31 and ALP expression, as well as the significantly upregulated osteogenesis makers (Runx2, ALP, and OCN) and angiogenesis makers (Ang-1 and CD31), compared with PLGA, PLGA/β-TCP (PT) and PLGA/hVE-cad-Fc (PV) microparticle-integrated SHED aggregates. Finally, in mice, 3 mm calvarial defects filled with the PTV microparticle-integrated SHED aggregates achieved abundant vascularized neo-bone regeneration within 4 weeks. Overall, we believe that these multifunctional PTV/SHED aggregates could be used as modules for bottom-up regenerative medicine, and provide a promising method for vascularized bone regeneration.
研究领域:
再生医学
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组织工程
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生物材料
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干细胞生物学
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高影响因子
CERAMICS INTERNATIONAL
·
2026
·
IF 6
Yanlong Wu,Jiangyong Wu,Jianfeng Kang,Jingwei Yang,Shuanglong Zhang,Jian Qiao,Xiaoxi Shao,Xu Chen
Bioactive ceramics are ideal materials for bone substitutes owing to their excellent osteoconductivity, but the application in load-bearing conditions is limited by their intrinsic brittleness. Inspired by the interpenetrating organic-inorganic structure of natural bone, we developed ceramic/polymer interpenetrating phase composites (C/P-IPCs) by vacuum-assisted microporous infiltration of polycaprolactone (PCL) molten into the interconnected micropores in vat photopolymerization printed β-tricalcium phosphate (β-TCP) samples. The C/P-IPCs achieved a synergy of mechanical properties and bioactivity compared with the pure ceramic β-TCP and the conventional ceramic particle-reinforced polymer (CPR-P) from the same materials. Specifically, the composites exhibited dramatically enhanced mechanical properties over pure ceramic, with strength increases of approximately 2.1- to 2.4-fold and strain energy density improvements of 2.4- to 5.5- fold. Meanwhile, the C/P-IPCs demonstrated a moderate degradation rate and superior mechanical stability during degradation. Furthermore, their biological performance of C/P-IPCs was markedly superior to that of CPR-P, including cell proliferation, differentiation, and bone repair. These results indicate that the C/P-IPCs are a promising candidate for bone repair under load-bearing conditions.
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PLoS One
·
2020
·Vol. 15
·期 1
·e0228247
·
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
·
骨科
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PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2024
·
IF 5.8
Yuxin Niu,Fuxiang Song,Rong Shan,Qianjuan Zhao,Zhuang Chen,Na Wang,Weibo Xie
The use of 3D printing technology has advanced the bone tissue engineering, and constructing large artificial bones for repairing large-scale bone defects is highly significant. This study aimed to construct large artificial bones in a precise and controllable manner, focusing on repairing critical-sized bone defects. The researchers used 3D printing technology to synthesize 3D PCL/β-TCP, and then evaluated its ability to promote MC3T3-E1 cell adhesion, proliferation, and new bone formation through a series of characterizations. The results confirmed that 3D PCL/β-TCP, presented as a lattice structure similar to natural bone, could be used to prepare personalized artificial bone blocks based on the actual range of bone defects. The researchers also experimented with dipping 3D PCL/β-TCP bone blocks in different proportions of β-TCP and found that PT2 showed better mechanical and hydrophilic properties. Further experiments showed that PT2 presented excellent biocompatibility and outstanding capacity to promote MC3T3-E1 cell proliferation and adhesion, and that 3D PCL/β-TCP bone blocks possessed good osteogenic activity. Finally, it was suggested that PT2 exhibited the property of promoting new bone formation. These findings provide experimental data support for the repair of critical-sized bone defects.
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Bioactive Materials
·
2023
·
IF 18.9
Qiji Lu,Jingjing Diao,Yingqu Wang,Jianlang Feng,Fansen Zeng,Yan Yang,Yudi Kuang,Naru Zhao,Yingjun Wang
Bone bionics and structural engineering have sparked a broad interest in optimizing artificial scaffolds for better bone regeneration. However, the mechanism behind scaffold pore morphology-regulated bone regeneration remains unclear, making the structure design of scaffolds for bone repair challenging. To address this issue, we have carefully assessed diverse cell behaviors of bone mesenchymal stem cells (BMSCs) on the β-tricalcium phosphate (β-TCP) scaffolds with three representative pore morphologies (i.e., cross column, diamond, and gyroid pore unit, respectively). Among the scaffolds, BMSCs on the β-TCP scaffold with diamond pore unit (designated as D-scaffold) demonstrated enhanced cytoskeletal forces, elongated nucleus, faster cell mobility, and better osteogenic differentiation potential (for example, the alkaline phosphatase expression level in D-scaffold were 1.5–2 times higher than other groups). RNA-sequencing analysis and signaling pathway intervention revealed that Ras homolog gene family A (RhoA)/Rho-associated kinase-2 (ROCK2) has in-depth participated in the pore morphology-mediated BMSCs behaviors, indicating an important role of mechanical signaling transduction in scaffold-cell interactions. Finally, femoral condyle defect repair results showed that D-scaffold could effectively promote endogenous bone regeneration, of which the osteogenesis rate was 1.2–1.8 times higher than the other groups. Overall, this work provides insights into pore morphology-mediated bone regeneration mechanisms for developing novel bioadaptive scaffold designs.
研究领域:
生物医学工程
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组织工程
·
细胞生物学
·
再生医学
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PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2023
·
IF 13.1
Renliang Zhao,Yifan Shen,Xiangtian Deng,Yunfeng Tang,Zilu Ge,Dong Wang,Zhencheng Xiong,Qian Fang,Zhang Zhen,Xiaolin Li,Xiaotian Du,Wei Lin,Shichang Zhao,Guanglin Wang
The clinical indications reveal that traumatic brain injury (TBI) accelerates the process of limb bone regeneration. However, the mechanisms underlying this phenomenon remain ambiguous. In this inquiry, the activation of endogenous neural stem cells in the hippocampus post TBI led to the secretion of extracellular vesicles (NSC-EV) that targeted bone marrow mesenchymal stem cells, ultimately promoting bone healing. The enrichment of miR-9-5p in NSC-EV facilitated osteogenesis through the activation of the MAP3K3 pathway. We also present a novel hydrogel formulation for clinical application of NSC-EVs by means of ROS-responsive EV delivery. The hydrogel was cross-linked with EVs to create a water-based gel encapsulation, which was applied to a 3D-printed β-TCP scaffold for controlled long-term release that corresponded to those of physiological bone tissue. Our investigation represents the inaugural usage of EVs derived from neural stem cells in bone tissue engineering. These EVs were found to encourage information exchange between the central nervous system and bone tissue regeneration. Our composite scaffold demonstrated impressive bone regeneration qualities in rats with cranial defects, highlighting its potential for pioneering approaches in bone tissue engineering and innovative medical technologies for clinical applications.
研究领域:
再生医学
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干细胞生物学
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组织工程
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神经科学
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骨生物学
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生物医学工程
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高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2024
·
IF 3.9
Junbiao Zhang,Srisurang Suttapreyasri,Chidchanok Leethanakul,Bancha Samruajbenjakun
Bone tissue is a highly vascularized tissue. When constructing tissue-engineered bone models, both the osteogenic and angiogenic capabilities of the construct should be carefully considered. However, fabricating a vascularized tissue-engineered bone to promote vascular formation and bone generation, while simultaneously establishing nutrition channels to facilitate nutrient exchange within the constructs, remains a significant challenge. Triaxial bioprinting, which not only allows the independent encapsulation of different cell types while simultaneously forming nutrient channels, could potentially emerge as a strategy for fabricating vascularized tissue-engineered bone. Moreover, bioinks should also be applied in combination to promote both osteogenesis and angiogenesis. In this study, employing triaxial bioprinting, we used a blend bioink of gelatin methacryloyl (GelMA), sodium alginate (Alg), and different concentrations of nano beta-tricalcium phosphate (nano β-TCP) encapsulated MC3T3-E1 preosteoblasts as the outer layer, a mixed bioink of GelMA and Alg loaded with human umbilical vein endothelial cells (HUVEC) as the middle layer, and gelatin as a sacrificial material to form nutrient channels in the inner layer to fabricate vascularized bone constructs simulating the microenvironment for bone and vascular tissues. The results showed that the addition of nano β-TCP could adjust the mechanical, swelling, and degradation properties of the constructs. Biological assessments revealed the cell viability of constructs containing different concentrations of nano β-TCP was higher than 90% on day 7, The cell-laden constructs containing 3% (w/v) nano β-TCP exhibited better osteogenic (higher Alkaline phosphatase activity and larger Osteocalcin positive area) and angiogenic (the gradual increased CD31 positive area) potential. Therefore, using triaxial bioprinting technology and employing GelMA, Alg, and nano β-TCP as bioink components could fabricate vascularized bone tissue constructs, offering a novel strategy for vascularized bone tissue engineering.
研究领域:
组织工程
·
生物打印
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生物材料
·
再生医学
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DOI
PubMed
高影响因子
Biomaterials Advances
·
2022
·
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
·
生物材料
·
再生医学
·
骨科
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DOI
PubMed
MATERIALS & DESIGN
·
2024
·
IF 7.6
Yifan Lu,Ze-Yu Wang,Jianhong Xiao,Zhengyi Zhao,Xiaoyu Liao,Huai-Ling Gao,Duohong Zou
Treatment of osteochondral (OC) defects is still an immense challenge in clinic due to lack of satisfactory strategy to simultaneously regenerate both cartilage and subchondral bone. Herein, we propose an effective bottom-up strategy by developing a type of multifunctional chitosan-based nanocomposite microgels as the building blocks to repair OC defects. The microgels are biocompatible, and biodegradable, and have a hierarchical nanofibrous structure, mimicking the structural feature of extracellular matrix (ECM) to facilitate cell attachment and proliferation. Additionally, β-tricalcium phosphate (β-TCP) nanoparticles are incorporated in the microgels not only to promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), but also to facilitate the loading of transforming growth factor beta 1 (TGF-β1). For reconstructing OC defects, pure microgels are implanted at the bottom layer of the OC defects in rat knee joints to promote osteogenesis, while the microgels loaded with TGF-β1 are implanted at the top layer of the OC defects to promote cartilage regeneration. This modular microgel system results in simultaneous regeneration of cartilage and subchondral bone in OC defects, which is expected as a promising way for repairing other complex tissue defects in the field of tissue engineering.
研究领域:
组织工程
·
生物材料
·
再生医学
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DOI
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Lei Huang,Shihao Zhang,Mengxuan Bian,Xingdong Xiang,Lan Xiao,Jiayi Wang,Shunyi Lu,Weisin Chen,Cheng Zhang,Guokang Mo,Libo Jiang,Yulin Li,Jian Zhang
The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and β-Tricalcium Phosphate (β-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo . Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. Statement of significance Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into β-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro . Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.
研究领域:
生物医学工程
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材料科学
·
组织工程
·
骨科
·
生物材料
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PubMed
高影响因子
危险品化学品经营许可证（带存储）