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Biomaterials Advances · 2022 · IF 0

Porous hydroxyapatite scaffold orchestrated with bioactive coatings for rapid bone repair

Yingzheng Zhao,Hangbo Chen,Kunjie Ran,Yingying Zhang,Hanxiao Pan,Jianxun Shangguan,Mengqi Tong,Jiaojiao Yang,Qing Yao,Helin Xu

Current bioceramic scaffolds for critical-size bone defects are still facing various challenges such as the poor capability of self-resorption, vascularization and osteogenesis. Herein, a composite scaffold (HOD) is fabricated by integrating bioactive coatings of konjac glucomannan (KGM) and deferoxamine (DFO) into porous hydroxyapatite scaffold (HA), where KGM coating induces the self-resorption of HOD after implanting and DFO promoted the vascularization at the defected bone. Porous HA scaffolds with 200–400 μm of pore sizes were prepared and these bioactive coatings were successfully deposited on the scaffold, which was confirmed by SEM. MC3T3-E1 cells could be tightly attached to the pore wall of HOD and the obvious osteogenic differentiation was clearly displayed after 14 days of co-culture. Besides, HOD displayed the potential of promoting the vascularization of HUVECs. Importantly, the accelerated degradation of HOD was observed in a macrophage-associated acidic medium, which led to the self-resorption of HOD in vivo . Micro-CT images showed that HOD was gradually replaced by newly formed bone, achieving a balance between the new bone formation and the scaffold degradation. The rapid bone repairing of the femoral defects in rats was displayed for HOD in comparison to the HA scaffold. Moreover, the therapeutic mechanism of HOD was highly associated with promoted osteogenesis and vascularization. Collectively, the porous ceramic scaffold orchestrated with bioactive coatings may be a promising strategy for repairing of the large bone defect.

研究领域: 生物医学工程 · 组织工程 · 生物材料科学 · 骨科
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International Journal of Nanomedicine · 2020 · IF 5.115

The Fabrication and Function of Strontium-modified Hierarchical Micro/Nano Titanium Implant

Haiyan Wang,Qiuping Xu,Hui Hu,Chunling Shi,Ziyan Lin,Huixi Jiang,Huaipu Dong,Jing Guo

Background Relying on surface topography alone to enhance the osteointegration of implants is still inadequate. An effective way to combine long-term ion release and surface topography to enhance osteogenic property is urgently needed. Purpose The objective of this study is to fabricate a long-term strontium ion release implant system and confirm the biological function in vitro and in vivo. Methods The biomimic surface was fabricated through alkali-heat treatment and magnetron sputtering. The in vitro biological function assays were determined by MTT, fluorescence staining, alkaline phosphatase activity, extracellular mineralization, and quantitative real-time polymerase chain reaction assays. The in vivo experiments were detected by micro-CT, HE staining and Masson staining. Results The biomimic surface structure has been successfully fabricated. The in vitro cell assays determined that AH-Ti/Sr90 possessed the best biological function. The in vivo experiments demonstrated that AH-Ti/Sr90 could promote osteointegration significantly under both in normal and osteoporotic conditions. Conclusion We determined that AH-Ti/Sr90 possesses the best osteogenic property, long-term ion release capacity and osteointegration promotion ability. It has potential clinic application prospects.

CAS / MDL: 1310-73-2
研究领域: 生物材料 · 生物医学工程 · 骨科 · 材料科学
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Journal of Materials Research and Technology-JMR&T · 2023 · IF 6.4

Effect of La3+ and Mg2+ combined system on bioactivity and osteogenesis of bioinspired La-doped magnesium phosphate composites prepared utilizing the precursor method

Qiaoyun Liu,Yifeng Yu,Changjiang Liu,Yuhang Liu,Liangjie Yuan,Zheng Wang,Aixi Yu

Lanthanum (La) compounds have attracted much attention because of low toxicity and biocompatibility. In this study, a series of La-doped magnesium phosphate composites bone repair materials (LMPCs) were prepared by the precursor method, in which the molar ratio of lanthanum was 1%, 3% and 5%, respectively. The results of X-ray powder diffraction, scanning electron microscope and compressive strength test show that La-doped magnesium phosphates (LMPs) synthesized by the precursor method have uniform particle distribution, high purity and excellent degradability. In vitro research results show that LMPCs exhibited reliable biosafety and excellent bioactivity. The introduction of lanthanum enhances the antibacterial activity of Escherichia coli and Staphylococcus aureus of the composite. Furthermore, the combined system of released La 3+ and Mg 2+ is more conducive to promoting the proliferation of mesenchymal stromal cells (MSC) and angiogenesis of human umbilical vein endothelial cells (HUVECs) when the content of lanthanum is 3% (referred to as LMPC-2). By up-regulating the expression of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (RUNX2), LMPC-2 is prominent in promoting osteogenic differentiation, and mineralized calcium deposition in vitro . Moreover, the results of micro-CT, H&E and Masson staining confirmed the beneficial effect of the combined system of La 3+ and Mg 2+ on the repair of rat skull defects in vivo . These achievements will provide new strategies for improving the biological activity of LMPCs and provide reference value for bone repairing in the clinic.

CAS / MDL: 54451-24-0 1309-42-8
研究领域: 生物材料 · 生物医学工程 · 组织工程 · 骨再生
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ACS Biomaterials Science & Engineering · 2023 · IF 5.8

Potential of an Aligned Porous Hydrogel Scaffold Combined with Periodontal Ligament Stem Cells or Gingival Mesenchymal Stem Cells to Promote Tissue Regeneration in Rat Periodontal Defects

Wenhao Wang,Ao Wang,Gaofu Hu,Mengyao Bian,Lili Chen,Qian Zhao,Weilian Sun,Yanmin Wu

Periodontal tissue regeneration is a major challenge in tissue engineering due to its regenerated environment complexity. It aims to regenerate not only the supporting alveolar bone and cementum around teeth but also the key connecting periodontal ligament. Herein, a constructed aligned porous hydrogel scaffold carrying cells based on chitosan (CHI) and oxidized chondroitin sulfate (OCS) treated with a freeze-casting technique was fabricated, which aimed to induce the arrangement of periodontal tissue regeneration. The microscopic morphology and physical and chemical properties of the hydrogel scaffold were evaluated. The biocompatibilities with periodontal ligament stem cells (PDLSCs) or gingival-derived mesenchymal stem cells (GMSCs) were verified, respectively, by Live/Dead staining and CCK8 in vitro. Furthermore, the regeneration effect of the aligned porous hydrogel scaffold combined with PDLSCs and GMSCs was evaluated in vivo. The biocompatibility experiments showed no statistical significance between the hydrogel culture group and blank control (P > 0.05). In a rat periodontal defect model, PDLSC and GMSC hydrogel experimental groups showed more pronounced bone tissue repair than the blank control (P < 0.05) in micro-CT. In addition, there was more tissue repair (P < 0.05) of PDLSC and GMSC hydrogel groups from histological staining images. Higher expressions of OPN, Runx-2, and COL-I were detected in both of the above groups via immunohistochemistry staining. More importantly, the group with the aligned porous hydrogel induced more order periodontal ligament formation than that with the ordinary hydrogel in Masson’s trichrome analysis. Collectively, it is expected to promote periodontal tissue regeneration utilizing an aligned porous hydrogel scaffold combined with PDLSCs and GMSCs (CHI–OCS–PDLSC/GMSC composite), which provides an alternative possibility for clinical application.

CAS / MDL: 9007-28-7 39455-18-0
研究领域: 组织工程 · 牙科材料 · 干细胞生物学 · 再生医学 · 生物医学工程
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Evidence-based Complementary and Alternative Medicine · 2021 · IF 2.63

Tanshinone I Mitigates Steroid-Induced Osteonecrosis of the Femoral Head and Activates the Nrf2 Signaling Pathway in Rats

Xilin Xu,Yiwei Shen,Hang Lv,Jun Zhao,Xiaodong Li,Lu Gao,Shujun Ren,Xiaofeng Zhang

Steroid-induced osteonecrosis of the femoral head (SIONFH) is a frequent orthopedic disease caused by long-term or high-dose administration of corticosteroids. Tanshinone I (TsI), a flavonoid compound isolated from Salvia miltiorrhiza Bunge, has been reported to inhibit osteoclastic differentiation in vitro. This study aimed to investigate whether TsI can ameliorate SIONFH. Herein, SIONFH was induced by intraperitoneal injection of 20 μg/kg lipopolysaccharide every 24 h for 2 days, followed by an intramuscular injection of 40 mg/kg methylprednisolone every 24 h for 3 days. Four weeks after the final injection of methylprednisolone, the rats were intraperitoneally administrated with low-dose (5 mg/kg) and high-dose (10 mg/kg) TsI once daily for 4 weeks. Results showed that TsI significantly alleviated osteonecrotic lesions of the femoral heads as determined by micro-CT analysis. Furthermore, TsI increased alkaline phosphatase activity and expressions of osteoblastic markers including osteocalcin, type I collagen, osteopontin, and Runt-related transcription factor 2 and decreased tartrate-resistant acid phosphatase activity and expressions of osteoclastic markers including cathepsin K and acid phosphatase 5. TsI also reduced inflammatory response and oxidative stress and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in the femoral heads. Taken together, our findings show that TsI can relieve SIONFH, indicating that it may be a candidate for preventing SIONFH.

CAS / MDL: 1493-13-6
研究领域: 骨科 · 药理学 · 分子生物学
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RSC Advances · 2023 ·Vol. 13 ·期 2 ·1267-1277 · IF 3.9

A more accurate indicator to evaluate oxidative stress in rat plasma with osteoporosis

Wei-Chong Dong,Jia-Liang Guo,Xin-Hui Jiang,Lei Xu,Huan Wang,Xiao-yu Ni,Ying-Ze Zhang,Zhi-Qing Zhang,Ye Jiang

Background: oxidative stress is linked to various human diseases which developed into the idea of “disrupted redox signaling”. Osteoporosis (OP) is a chronic skeletal disorder characterized by low bone mineral density and deterioration of bone microarchitecture among which estrogen deficiency is the main cause. Lack of estrogen leads to the imbalance between oxidation and anti-oxidation in patients, and oxidative stress is an important link in the pathogenesis of OP. The ratio of the reduced to the oxidized thiols can characterize the redox status. However, few methods have been reported for the simultaneous determination of reduced forms and their oxidized forms of thiols in plasma. Methods: we developed a hollow fiber centrifugal ultrafiltration (HFCF-UF) method for sample preparation and validated a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method to determine two reduced forms of thiols-homocysteine (Hcy), cysteine (Cys) levels and their respective oxidized compounds, homocystine (HHcy) and cystine (Cyss) in rat plasma simultaneously for the first time. Thirty-six female rats were randomly divided into three groups: normal control (NC), oxidative stress (ovariectomy, OVX) and ovariectomy with hydrogen-rich saline administration (OVX + HRS). Results: the validation parameters for the methodological results were within the acceptance criteria. There were both significant differences of Hcy/HHcy (Hcy reduced/oxidized) and Cys/Cyss (Cys reduced/oxidized) in rat plasma between three groups with both p < 0.05 and meanwhile, the p values of malondialdehyde, superoxide dismutase and glutathione peroxidase were all less than 0.01. The value of both Hcy/HHcy and Cys/Cyss were significantly decreased with the change of Micro-CT scan result of femoral neck in OVX group (both the trabecular thickness and trabecular number significantly decreased with a significant increase of trabecular separation) which demonstrate OP occurs. The change of Hcy/HHcy is more obvious and prominent than Cys/Cyss. Conclusions: the Hcy/HHcy and Cys/Cyss could be suitable biomarkers for oxidative stress and especially Hcy/HHcy is more sensitive. The developed method is simple and accurate. It can be easily applied in clinical research to further evaluate the oxidative stress indicator for disease risk factors.

CAS / MDL: 64-18-6
研究领域: 药理学 · 生物化学 · 临床研究 · 骨骼疾病 · 氧化应激
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Materials Today Bio · 2024 · IF 8.7

TPG-functionalized PLGA/PCL nanofiber membrane facilitates periodontal tissue regeneration by modulating macrophages polarization via suppressing PI3K/AKT and NF-κB signaling pathways

Xiang Han,Feiyang Wang,Yuzhuo Ma,Xuerong Lv,Kewei Zhang,Yue Wang,Ke Yan,Youmin Mei,Xiaoqian Wang

Traditional fibrous membranes employed in guided tissue regeneration (GTR) in the treatment of periodontitis have limitations of bioactive and immunomodulatory properties. We fabricated a novel nTPG/PLGA/PCL fibrous membrane by electrospinning which exhibit excellent hydrophilicity, mechanical properties and biocompatibility. In addition, we investigated its regulatory effect on polarization of macrophages and facilitating the regeneration of periodontal tissue both in vivo and in vitro. These findings showed the 0.5%TPG/PLGA/PCL may inhibit the polarization of RAW 264.7 into M1 phenotype by suppressing the PI3K/AKT and NF-κB signaling pathways. Furthermore, it directly up-regulated the expression of cementoblastic differentiation markers (CEMP-1 and CAP) in periodontal ligament stem cells (hPDLSCs), and indirectly up-regulated the expression of cementoblastic (CEMP-1 and CAP) and osteoblastic (ALP, RUNX2, COL-1, and OCN) differentiation markers by inhibiting the polarization of M1 macrophage. Upon implantation into a periodontal bone defect rats model, histological assessment revealed that the 0.5%TPG/PLGA/PCL membrane could regenerate oriented collagen fibers and structurally intact epithelium. Micro-CT (BV/TV) and the expression of immunohistochemical markers (OCN, RUNX-2, COL-1, and BMP-2) ultimately exhibited satisfactory regeneration of alveolar bone, periodontal ligament. Overall, 0.5%TPG/PLGA/PCL did not only directly promote osteogenic effects on hPDLSCs, but also indirectly facilitated cementoblastic and osteogenic differentiation through its immunomodulatory effects on macrophages. These findings provide a novel perspective for the development of materials for periodontal tissue regeneration.

研究领域: 牙科材料 · 组织工程 · 免疫学 · 再生医学
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS · 2024 · IF 2.5

Laponite Modified Methacryloyl Gelatin Hydrogel with Controlled Release of Vascular Endothelial Growth Factor A for Bone Regeneration

Baoguo Mi,Jitao Zhang,Hailan Meng,Yixin Xu,Jiajun Xie,Dingjun Hao,Lequn Shan

Reconstruction of bone defects has long been a major clinical challenge. Limited by the various shortcomings of conventional treatment like autologous bone grafting and inorganic substitutes, the development of novel bone repairing strategies is on top priority. Injectable biomimetic hydrogels that deliver stem cells and growth factors in a minimally invasive manner can effectively promote bone regeneration and thus represent a promising alternative. Therefore, in this study, we designed and constructed an injectable nanocomposite hydrogel co-loaded with Laponite (Lap) and vascular endothelial growth factor (VEGF) through a simplified and convenient scheme of physical co-mixing (G@Lap/VEGF). The introduced Lap not only optimized the injectability of GelMA by the electrostatic force between the nanoparticles, but also significantly delayed the release of VEGF-A. In addition, Lap promoted high expression of osteogenic biomarkers in mesenchymal stem cells (MSCs) and enhanced the matrix mineralization. Besides, VEGF-A exerted chemotactic effects recruiting endothelial progenitor cells (EPCs) and inducing neovascularization. Histological and micro-CT results demonstrated that the critical-sized calvarial bone defect lesions in the SD rats after treated with G@Lap/VEGF exhibited significant in vivo bone repairing. In conclusion, the injectable G@Lap/VEGF nanocomposite hydrogel constructed in our study is highly promising for clinical transformation and applications, providing a convenient and simplified scheme for clinical bone repairing, and contributing to the further development of the injectable biomimetic hydrogels.

CAS / MDL: G477880 G477881 G477882
研究领域: 生物材料 · 组织工程 · 再生医学 · 生物医学工程 · 骨科
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Nature Communications · 2018 ·Vol. 9 ·期 1 ·1-14 · IF 12.353

Cationic nanoparticle as an inhibitor of cell-free DNA-induced inflammation

Liang Huiyi,Peng Bo,Dong Cong,Liu Lixin,Mao Jiaji,Wei Song,Wang Xinlu,Xu Hanshi,Shen Jun,Mao Hai-Quan,Gao Xiaohu,Leong Kam W.,Chen Yongming

Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here we show that ~40 nm cationic nanoparticles (cNP) can scavenge cfDNA derived from RA patients and inhibit the activation of primary synovial fluid monocytes and fibroblast-like synoviocytes. Using clinical scoring, micro-CT images, MRI, and histology, we show that intravenous injection of cNP into a CpG-induced mouse model or collagen-induced arthritis rat model can relieve RA symptoms including ankle and tissue swelling, and bone and cartilage damage. This culminates in the manifestation of partial mobility recovery of the treated rats in a rotational cage test. Mechanistic studies on intracellular trafficking and biodistribution of cNP, as well as measurement of cytokine expression in the joints and cfDNA levels in systemic circulation and inflamed joints also correlate with therapeutic outcomes. This work suggests a new direction of nanomedicine in treating inflammatory diseases.

研究领域: 纳米医学 · 炎症性疾病 · 风湿病学 · 生物医学工程
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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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Frontiers in Bioengineering and Biotechnology · 2023 · IF 5.7

Injectable FHE+BP composites hydrogel with enhanced regenerative capacity of tendon-bone interface for anterior cruciate ligament reconstruction

Eunshinae Cho,Yi Qiao,Changan Chen,Junjie Xu,Jiangyu Cai,Yamin Li,Jinzhong Zhao

Features of black phosphorous (BP) nano sheets such as enhancing mineralization and reducing cytotoxicity in bone regeneration field have been reported. Thermo-responsive FHE hydrogel (mainly composed of oxidized hyaluronic acid (OHA), poly-ε-L-lysine (ε-EPL) and F127) also showed a desired outcome in skin regeneration due to its stability and antibacterial benefits. This study investigated the application of BP-FHE hydrogel in anterior cruciate ligament reconstruction (ACLR) both in in vitro and in vivo , and addressed its effects on tendon and bone healing. This BP-FHE hydrogel is expected to bring the benefits of both components (thermo-sensitivity, induced osteogenesis and easy delivery) to optimize the clinical application of ACLR and enhance the recovery. Our in vitro results confirmed the potential role of BP-FHE via significantly increased rBMSC attachment, proliferation and osteogenic differentiation with ARS and PCR analysis. Moreover, In vivo results indicated that BP-FHE hydrogels can successfully optimize the recovery of ACLR through enhancing osteogenesis and improving the integration of tendon and bone interface. Further results of Biomechanical testing and Micro-CT analysis [bone tunnel area (mm2) and bone volume/total volume (%)] demonstrated that BP can indeed accelerate bone ingrowth. Additionally, histological staining (H&E, Masson and Safranin O/fast green) and immunohistochemical analysis (COL I, COL III and BMP-2) strongly supported the ability of BP to promote tendon-bone healing after ACLR in murine animal models.

研究领域: 组织工程 · 再生医学 · 骨科手术 · 生物材料科学
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