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Frontiers in Bioengineering and Biotechnology · 2020 · IF 3.644

Customized Borosilicate Bioglass Scaffolds With Excellent Biodegradation and Osteogenesis for Mandible Reconstruction

Zhang Peng,Yang Kang,Zhou Ziyu,Zhu Xingrong,Li Wenchao,Cao Chuanliang,Zhou Kui,Liao Lan,Ai Fanrong

Graft reconstruction of the mandible is an important approach that aims at improving the appearance and functionality of defected mandibles. The traditional implant materials are generally bioinert, non-degradable, and that they lack favorable pore structures for cell proliferation, which limit their clinical application. In this study, we used boron-containing bioactive glass which was combined with a three-dimensional (3D) printing technology to construct an osteoinductive implant scaffold, according to the imaging instructions of CT scan on bone defects. Here, the boron-containing bioglass scaffold (B-BGs) was prepared through sol-gel processing and a 3D print technique. Different boron content of borosilicate bioglass was prepared by incorporating B2O3 (molar: 19.4 and 38.8%) into 58S bioglass to replace parts of SiO2. For fabricated mandible implants through three-dimensional 3D printing of B-BGs (size: 8 × 2 mm; pore size: 250 μm) modified with borosilicate bioglass powder and sodium alginate. Notably, the compressive strength of the B-BGs was about 3.8 Mpa, which supported mandibular activity. Subsequently, the excellent biocompatibility of B-BGs was confirmed using cytotoxicity in vitro studies. Finally, data from in vivo experiments demonstrated that the B-BGs could promote bone regeneration and they could almost get completely degraded within 4 weeks. Our results showed that the boron-containing bioglass could repair mandibular defects.

研究领域: 材料科学 · 生物医学工程 · 组织工程
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JOURNAL OF MOLECULAR STRUCTURE · 2021 · IF 3.196

RETRACTED: Two new Co(II)/Zn(II) coordination polymers: Photocatalytic and luminescent property, and application value on alveolar bone reconstruction

Zhiyuan Feng,Lin Cheng,Hong Fan,Jia Liu,Fusheng Han

This article has been retracted: please see Elsevier Policy on Article Withdrawal ( http://www.elsevier.com/locate/withdrawalpolicy ). This article has been retracted at the request of the Editor-in-Chief. In investigating concerns brought up regarding the authenticity of the article, the editors reached out to the corresponding author for an explanation and to request the original data. Per journal policy, the editors, at their discretion, may request deposition of any or all original data files for examination by the reviewers and/or editors. As a result of the author’s unsatisfactory explanation and failure to provide these data—in violation of journal policy—the editors feel that the findings of the manuscript cannot be relied upon. The corresponding author agrees to this retraction.

研究领域: 材料科学 · 生物学 · 医学
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Research · 2023 · IF 11

Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone Reconstruction

Zhenyu Zhao,Huitong Ruan,Aopan Chen,Wei Xiong,Mingzhu Zhang,Ming Cai,Wenguo Cui

Genetic engineering technology can achieve specific gene therapy for a variety of diseases, but the current strategy still has some flaws, such as a complex system, single treatment, and large implantation trauma. Herein, the genetic engineering injectable hydrogels were constructed by ultrasonic technology for the first time to realize in vivo ultrasound-triggered in situ cross-linking and cell gene transfection, and finally complete in situ gene therapy to promote bone reconstruction. First, ultrasound-triggered calcium release was used to activate transglutaminase and catalyze the transamidation between fibrinogen. Simultaneously, liposome loaded with Zinc-finger E-box-binding homeobox 1 (ZEB1) gene plasmid (Lip-ZEB1) was combined to construct an ultrasound-triggered in situ cross-linked hydrogels that can deliver Lip-ZEB1. Second, ultrasound-triggered injectable hydrogel introduced ZEB1 gene plasmid into endothelial cell genome through Lip-ZEB1 sustained release, and then acted on the ZEB1/Notch signal pathway of cells, promoting angiogenesis and local bone reconstruction of osteoporosis through genetic engineering. Overall, this strategy provides an advanced gene delivery system through genetic engineered ultrasound-triggered injectable hydrogels.

研究领域: 生物医学工程 · 基因治疗 · 材料科学 · 组织工程
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Materials Science & Engineering C-Materials for Biological Applications · 2019 · IF 4.959

Characterization and cytocompatibility of hierarchical porous TiO2 coatings incorporated with calcium and strontium by one-step micro-arc oxidation

Yada Li,Weiqiang Wang,Fengyun Yu,Dongjiao Wang,Shiwei Guan,Yan Li,Min Qi

Calcium (Ca) and strontium (Sr) are beneficial for bone reconstruction. This study incorporated Ca and Sr into the TiO 2 coatings by one-step micro-arc oxidation (MAO) treatment with CaO and SrO added in tetraborate electrolytes. The structure, composition, hydrophilicity, ion release, and cytocompatibility of the coatings were studied. The coatings combine layered micron-scale pores in various sizes and nano-scaled pores, forming a hierarchical structure. This hierarchical structure is highly porous and super-hydrophilic. The coatings are composed of Ti, O, and B, as well as Ca or Sr. Ca and Sr mainly distribute in the outer layer of the coatings and exist in the forms of carbonates and oxides. The formation of the coatings was discussed. Ca and Sr incorporated into the coatings are readily released into aqueous solutions. The homogeneous surface structure of the coatings leads to an excellent and approximating performance in hydrophilicity, as well as the adhesion and spreading of the human bone marrow-derived mesenchymal stem cells (hBMSCs). The simultaneous incorporation of Ca and Sr incorporation exhibits superior facilitation in the proliferation of hBMSCs compared with single Ca or Sr incorporation. This study shows a promising method to incorporate bioactive elements into the MAO coatings on titanium surfaces.

CAS / MDL: 1314-11-0
研究领域: 生物材料 · 生物医学工程 · 材料科学
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Cell Death & Disease · 2025 ·Vol. 16 ·期 1 ·1-16 · IF 9.6

Targeting Irgm1 to combat osteoporosis: suppressing ROS and restoring bone remodeling

Cui Zichen,Gu Guanghui,Chen Fei,Li Jianyi,Du Xiaofan,Chen Shuqing,Zhang Han,Li Chenxu,Shao Jiale,Xi Jiayi,Du Yukun,Zhao Qinghua,Xi Yongming

The accumulation of reactive oxygen species (ROS) leads to enhanced osteoclast activity, causing severe bone destruction in postmenopausal osteoporosis. Immunity-related GTPase family M member 1 (Irgm1) plays an essential role in affecting the production of intracellular ROS. To detect whether deletion of Irgm1 could suppress osteoclastogenesis through cellular redox regulation, we first evaluated whether the Irgm1 level was significantly elevated in mice bone marrow-derived monocytes/macrophages (BMDMs) from ovariectomy (OVX)-induced osteoporosis mice. Moreover, bioinformatics network analysis was performed to identify Irgm1 as a key upregulated gene during osteoclast differentiation. Next, we found that macrophage-specific Irgm1 knockout (Irgm1-cKO, Lyz2-Cre; Irgm1 flox/flox ) in OVX mice resulted in slower bone loss compared with OVX mice from the control group (Irgm1 flox/flox ). We then demonstrated that loss of Irgm1 inhibited osteoclast differentiation and bone resorption function via suppressing ROS accumulation. Further mechanism revealed that Irgm1 could endogenously bind to kelch-like ECH-associated protein 1 (Keap1) and keep Keap1 from ubiquitination and degradation. In the absence of Irgm1, Keap1 was downregulated and causing nuclear factor erythroid 2-related factor 2 (Nrf2) to translocate to the nucleus, thereby activating the level of the antioxidant system to combat oxidative stress. Moreover, Irgm1 deficiency in RAW264.7 promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) through inhibiting the M1 phenotype polarization. Taken together, our results revealed that loss of Irgm1 significantly alleviates OVX-induced bone loss, thus laying the foundation for exploring Irgm1 as a novel targeting approach for the treatment of osteoporosis.

CAS / MDL: 5142-23-4
研究领域: 分子生物学 · 细胞生物学 · 免疫学 · 遗传学 · 药理学 · 生物医学研究
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Advanced Healthcare Materials · 2024 · IF 10

Ultrasound-Triggered Mg2+ Blasting Release Hydrogel Microspheres for Promoting Bone Reconstruction

Wenlin Huang,Xu Wang,Zhenyu Zhao

Mg 2+ (Magnesium ion) can affect bone tissue metabolism by regulating related signaling pathways in bone metabolism. However, how to realize precise controlled release of Mg 2+ in bone regeneration treatment still presents a challenge. Herein, for the first time, the GelMA-BP (Gelatin Methacryloyl-Bisphosphonate) and the composite nano-bubble system are fused to construct the Mg 2+ blasting controlled-release hydrogel microspheres, the stability of the nano-bubbles in the microspheres is enhanced through metal coordination complexation, and the burst of the nano-bubbles is controlled by using ultrasonic cavitation to achieve the precise controlled release of Mg 2+ , ultimately effectively promoting bone reconstruction. First, GelMA-BP composite is prepared by Schiff base reaction. Second, the nanobubble BP (Bisphosphonate) system is constructed, and Mg 2+ is combined with the ligand coordination to prepare the composite nanobubble system. Thirdly, through Mg 2+ co-coordination, the ultrasound-triggered Mg 2+ blasting controlled release microspheres were prepared to achieve bone repair. Overall, this innovative strategy effectively solves the problem of accurate controlled release of Mg 2+ , and finally effectively activates in situ bone tissue regeneration.

研究领域: 生物医学工程 · 材料科学 · 组织工程 · 骨科
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ACS Nano · 2020 · IF 14.588

Bioactive Core–Shell CaF2 Upconversion Nanostructure for Promotion and Visualization of Engineered Bone Reconstruction

Zhihao Li,Haoran Liu,Rui Wang,Chenhui Ji,Yan Wei,Miusi Shi,Yingqian Wang,Yaping Du,Yufeng Zhang,Quan Yuan,Chunhua Yan

Inorganic ion metabolism plays significant roles in various life processes including signal transduction, substance exchange, and cellular constructions. Regulation and monitoring of ion metabolism offer great promise to modulate biological activities and provide insights into related mechanisms. Here, a synergistic nanodepot based on a bioactive core–shell CaF2 upconversion nanostructure that integrates multiple mineral ions for metabolic regulation was built for the acceleration and monitoring of the biomineralization process. Multiple mineral ions released from the nanodepots can accelerate the growth of inorganic crystals and enhance the production of organic matrixes, synergistically facilitating the regeneration of bone defects in vivo. During the process, such a nanodepot can be constructed to specifically recognize osteoblasts for the monitoring of biomineralization. This nanoprobe represents an efficient strategy to promote and monitor biomineralization-related metabolic activities with applications in fundamental research, disease diagnosis, and regenerative medicine.

研究领域: 材料科学 · 生物材料 · 生物医学工程 · 再生医学 · 纳米技术
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CERAMICS INTERNATIONAL · 2019 · IF 3.45

Superior biological performance and osteoinductive activity of Si-containing bioactive bone regeneration particles for alveolar bone reconstruction

Zhe Mao,Yifan Gu,Jing Zhang,Will Wenmiao Shu,Yingqiu Cui,Tao Xu

Bone grafting materials for repair of alveolar bone deficits have improved markedly in recent years, increasing the applicability and success of oral implantology. The long-term success rate of dental implant surgery is strongly dependent on the quality and stability of residual bone tissue. Therefore, reconstruction of resorbed alveolar bone is a challenge for clinicians. In the present study, we have developed bioactive bone regeneration particles (BRPs) using amorphous calcium phosphate and 58S bioglass as raw materials. The structural characteristics, biocompatibility, and osteoinductivity of these BRPs were compared to commercially available bovine spongy bone (BSB) without organic components. X-ray diffractometry (XRD) and scanning electron microscopy (SEM) showed that BRPs were composed of β-tricalcium phosphate (β-TCP) and calcium silicate in the form of hexagonal crystals, while BSB was mainly hydroxyapatite (HA) arranged in orderly nano-sized crystals. The viability of human bone marrow mesenchymal stem cells (hBMSCs) cultured in BRP-containing medium was roughly equal to that of hBMSCs in control medium. Moreover, hBMSCs in BRP medium exhibited greater proliferation rates, substrate attachment, alkaline phosphatase (ALP) activity, alizarin red staining intensity, and expression levels of osteogenic-related genes (COL-I, OCN, Runx-2, ALP, BSP) than hBMSCs in BSB medium, indicating the superior osteoinductivity of BRPs. Silicon ions released from BRPs during cell culture were crucial for these enhanced biological properties. BRPs also demonstrated superior osteoconduction and osteoinduction properties for bone defect repair, suggesting promise for alveolar bone repair surgery.

研究领域: 牙科材料 · 组织工程 · 生物医学工程 · 口腔种植学
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Journal of Materials Chemistry B · 2020 ·Vol. 9 ·期 4 ·1107-1122 · IF 5.344

HA/MgO nanocrystal-based hybrid hydrogel with high mechanical strength and osteoinductive potential for bone reconstruction in diabetic rats

Rui Chen,Hang-Bo Chen,Peng-Peng Xue,Wai-Geng Yang,Lan-Zi Luo,Meng-Qi Tong,Bin Zhong,He-Lin Xu,Ying-Zheng Zhao,Jian-Dong Yuan

Bone repair and regeneration processes are markedly impaired in diabetes mellitus (DM). Intervening approaches similar to those developed for normal healing conditions have been adopted to combat DM-associated bone regeneration. However, limited outcomes were achieved for these approaches. Hence, together with osteoconductive hydroxyapatite (HA) nanocrystals, osteoinductive magnesium oxide (MgO) nanocrystals were uniformly mounted into the network matrix of an organic hydrogel composed of cysteine-modified γ-polyglutamic acid (PGA-Cys) to construct a hybrid and rough hydrogel scaffold. It was hypothesized that the HA/MgO nanocrystal hybrid hydrogel (HA/MgO-H) scaffold can significantly promote bone repair in DM rats via the controlled release of Mg2+. The HA/MgO-H scaffold exhibited a sponge-like morphology with porous 3D networks inside it and displayed higher mechanical strength than a PGA-Cys scaffold. Meanwhile, the HA/MgO-H scaffold gradually formed a tough hydrogel with G′ of more than 1000 Pa after hydration, and its high hydration swelling ratio was still retained. Moreover, after the chemical degradation of the dispersed MgO nanocrystals, slow release of Mg2+ from the hydrogel matrix was achieved for up to 8 weeks because of the chelation between Mg2+ and the carboxyl groups of PGA-Cys. In vitro cell studies showed that the HA/MgO-H scaffold could not only effectively promote the migration and proliferation of BMSCs but could also induce osteogenic differentiation. Moreover, in the 8th week after implanting the HA/MgO-H scaffold into femur bone defect zones of DM rats, more effective bone repair was presented by micro-CT imaging. The bone mineral density (397.22 ± 16.36 mg cm−3), trabecular thickness (0.48 ± 0.07 mm), and bone tissue volume/total tissue volume (79.37 ± 7.96%) in the HA/MgO-H group were significantly higher than those in the other groups. Moreover, higher expression of COL-I and OCN after treatment with HA/MgO-H was also displayed. The bone repair mechanism of the HA/MgO-H scaffold was highly associated with reduced infiltration of pro-inflammatory macrophages (CD80+) and higher angiogenesis (CD31+). Collectively, the HA/MgO-H scaffold without the usage of bioactive factors may be a promising biomaterial to accelerate bone defect healing under diabetes mellitus.

研究领域: 生物材料 · 组织工程 · 生物医学工程 · 骨科 · 糖尿病研究
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

A sodium alginate/carboxymethyl chitosan dual-crosslinked injectable hydrogel scaffold with tunable softness/hardness for bone regeneration

Hui Wang,Jueying Yang,Wei Tian,Kelin Peng,Yun Xue,Haosen Zhao,Xilan Ma,Rui Shi,Yu Chen

Recently, injectable dual-crosslinked (DC) hydrogel scaffolds have attracted many attentions as a class of excellent bone regeneration biomaterials with in-situ tunable functions. However, the design of injectable DC hydrogels with cell behavior-compatible network structure and mechanical property remains a bottleneck. Herein, based on the in-situ gelling method, we constructed an injectable CMCS/PEG+SA/CaCl 2 (CPSC) chemical/physical DC hydrogel scaffold with tunable softness/hardness mechanical properties and good biocompatibility. The formation mechanism and properties of the CPSC hydrogel scaffold were investigated by FTIR , XRD, rheometry, and mechanical testing. It is found that proper softness/hardness mechanical properties can be obtained by adjusting the secondary network structure of the hydrogel. The CPSC hydrogel scaffold prepared under optimal conditions can effectively promote cell infiltration , nutrient transport, and the osteogenic differentiation of rat bone mesenchymal stem cells (rBMSCs). The in vivo experiments show that the rBMSCs-loaded injectable CPSC hydrogels with appropriate mechanical properties can effectively promote bone reconstruction . This study has provided important guidance for the construction of injectable DC hydrogels with adjustable softness/hardness to promote osteogenesis for bone defect repair.

研究领域: 材料科学 · 生物材料 · 组织工程 · 生物医学工程 · 骨再生
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