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COLLOIDS AND SURFACES B-BIOINTERFACES · 2021 · IF 5.268

Three-dimensional porous reduced graphene oxide/hydroxyapatite membrane for guided bone regeneration

Wei Liu,Xingtong Dong,Han Qin,Lei Sui,Jian Wang

The guided bone regeneration (GBR) membrane is intended to provide sufficient space for alveolar bone regeneration and meanwhile prevent the invasion of gingival epithelium. In this study, three-dimensional porous reduced graphene oxide/hydroxyapatite (3D rGO/HA) membrane with two different sides was prepared using a two-step electrochemical method. One side of this composite membrane facing the bone defect was formed by 3D porous rGO with HA deposited on the frame of the 3D structure, and the other side of the membrane presented a dense 2D rGO surface to prevent the invasion of the gingival epithelium. The morphology, phase composition, and physical properties of the 3D rGO/HA composite membrane were characterized. Then the cell morphology, viability, and proliferation of pre-osteoblasts (MC3T3-E1 cells) on the 3D porous structure surface of membranes were evaluated and alkaline phosphatase (ALP) secretion as an indication of osteogenic differentiation was also investigated. Meanwhile, cell morphology, viability, and proliferation of HUVEC and L929 cells on the dense structure surface were examined. Finally, a cranial defect model of rat was employed to evaluate the effect of 3D rGO/HA as a GBR membrane in vivo. The results revealed the 3D rGO/HA membrane had good biocompatibility for MC3T3-E1 and HUVEC cells and could significantly enhance ALP secretion. Furthermore, this membrane also promoted the repair of calvarial defects in vivo . These results demonstrated that 3D porous rGO/HA composite membrane with a porous side and another dense side represents great application potential as an ideal GBR membrane.

研究领域: 生物材料 · 组织工程 · 生物医学工程 · 骨科 · 牙科材料
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A · 2024 · IF 3.9

Fabrication of vascularized tissue-engineered bone models using triaxial bioprinting

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 · 生物材料 · 再生医学
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Materials Science & Engineering C-Materials for Biological Applications · 2020 · IF 5.88

Biomimetic organic-inorganic hybrid hydrogel electrospinning periosteum for accelerating bone regeneration

Wenjuan Liu,Wei Bi,Yang Sun,Lei Wang,Xiaohua Yu,Ruoyu Cheng,Youcheng Yu,Wenguo Cui

Periosteum as an important component in the construct of bone is mainly responsible for providing nourishment and regulating osteogenic differentiation. When bone defect happens, the functionality of periosteum will also be influenced, furthermore, it will finally hamper the process of bone regeneration. However, fabrication of an artificial periosteum with the capabilities in accelerating angiogenesis and osteogenesis in the defect area is still a challenge for researchers. In this study, we fabricated an organic-inorganic hybrid biomimetic periosteum by electrospinning, which can induce mineralization in situ and control the ions release for long-term in local area. Further, this system exhibited potential capabilities in promoting in vitro, which means the potentiality in accelerating bone regeneration in vivo. Calcium phosphate nanoparticles (CaPs) were fabricated by emulsion method, then CaPs were further incorporated with gelatin-methacryloyl (GelMA) by electrospinning fibers to construct the hybrid hydrogel fibers. The fibers exhibited satisfactory morphology and mechanical properties, additionally, controlled ions release could be observed for over 10 days. Further, significant mineralization was proved on the surface of hybrid fibers after 7 days and 14 days' co-incubation with simulated body fluid (SBF). Then, favorable biocompatibility of the hybrid fibers was approved by co-cultured with MC3T3-E1 cells. Finally, the hybrid fibers exhibited potential capabilities in promoting angiogenesis and osteogenesis by co-culture with HUVECs and MC3T3-E1 cells. This biomimetic organic-inorganic hybrid hydrogel electrospinning periosteum provided a promising strategy to develop periosteum biomaterials with angiogenesis and osteogenesis capabilities.

CAS / MDL: 760-93-0
研究领域: 材料科学 · 生物医学工程 · 组织工程 · 生物材料 · 再生医学
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Biomaterials Science · 2020 ·Vol. 9 ·期 6 ·2090-2102 · IF 6.183

Electrospun artificial periosteum loaded with DFO contributes to osteogenesis via the TGF-β1/Smad2 pathway

Rui Shi,Jingshuang Zhang,Kun Niu,Weiyang Li,Ni Jiang,Jianlin Li,Qingsong Yu,Chengai Wu

Deferoxamine (DFO), an iron chelator regarded as a hypoxic analogue, has been reported to be involved in angiogenesis and osteogenic differentiation. In this study, DFO was loaded into nanospheres, Then, DFO-loaded NPs and free DFO were co-encapsulated in nanofibers through coaxial electrospinning and its effects on cell viability, migration, and osteogenic differentiation, and the potential mechanisms were investigated. The results suggested that DFO maintained cell viability and promoted the migration of human mesenchymal stem cells (hMSCs) and MC3T3-E1 cells. ALP activity, calcium deposition, and expression of osteogenesis-related markers, including collagen, osteocalcin, and osteopontin, were all increased with DFO. Moreover, hypoxia-inducible factor-1α, transforming growth factor-β, and Smad2 were upregulated with DFO, which indicated activation of the TGF-β1/Smad2 signalling pathway. This may contribute to osteogenic differentiation of cells.

CAS / MDL: 68-12-2
研究领域: 生物材料 · 组织工程 · 再生医学 · 细胞生物学
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS · 2019 ·Vol. 108 ·期 4 ·1505-1517 · IF 2.674

In vitro and in vivo assessment of glucose cross-linked gelatin/zein nanofibrous scaffolds for cranial bone defects regeneration

Lingli Deng,Yang Li,Hui Zhang

The purpose of this study was to evaluate the glucose cross-linked gelatin/zein scaffolds for bone regeneration in vitro and in vivo. The nanofibrous scaffolds exhibited fast mineralization in the concentrated simulated body fluid with the deposited octacalcium phosphate and dicalcium phosphate dehydrate. The nanofibrous scaffolds exhibited no cytotoxic effect on MC3T3e1 cells in a CCK-8 test. Additionally, scanning electron microscope and confocal laser scanning microscopy images revealed that all the scaffolds were biocompatible and showed excellent support for MC3T3e1 cells. In the osteogenesis characterizations, Alizarin Red staining experiments indicated the improved calcium deposits on the cross-linked scaffolds, while the alkaline phosphatase activity showed no difference. Furthermore, the in vivo cranial bone regeneration results suggested that the cross-linked gelatin/zein scaffolds presented a strong positive effect on the cranial bone regeneration with the increased new bone volume and connective tissue formation, but the incorporation of zein in the gelatin scaffolds did not favor the bone regeneration. Moreover, the cross-linked gelatin scaffold retarded the bone resorption as indicated by the higher levels of IFN-γ and lower levels of IL-6, which restricted the differentiation of osteoclasts.

CAS / MDL: 9000-70-8
研究领域: 生物材料 · 组织工程 · 再生医学
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2022 · IF 5.062

Fusion of parathyroid hormone (1–34) to an albumin-binding domain improves osteogenesis

Dongzhi Xu,Haihao Wu,Chunguang Zhou

Osteoporosis is a common severe orthopedic disease that can lead to bone fractures and significantly reduce a patient's quality of life. Teriparatide (parathyroid hormone, PTH (1–34)) has been approved for the treatment of osteoporosis. However, PTH (1–34) needs to be injected once daily due to its short half-life of 1 h. To improve the pharmacokinetic and pharmacodynamic profiles of PTH (1–34), a G148-ABD3 (GA3) domain, which can bind to albumin non-covalently, was employed to modify PTH (1–34). The resultant PTH 34 -GA3-GS1 and PTH 34 -GA3-GS3 fusion proteins were constructed by fusing PTH (1–34) to the N-terminus of GA3 via (G 4 S) 1 and (G 4 S) 3 linkers, respectively. The fusion proteins were highly expressed in Escherichia coli . In vitro results showed that both PTH 34 -GA3-GS1 and PTH 34 -GA3-GS3 could bind to human serum albumin (HSA) with high affinity. The fusion proteins significantly increased the proliferation and differentiation of osteoblastic MC3T3-E1 cells, thereby promoting osteogenesis. PTH 34 -GA3-GS3 increased intracellular and serum calcium levels more than PTH 34 -GA3-GS1 did. The half-lives of PTH 34 -GA3-GS1 and PTH 34 -GA3-GS3 were 8.4 h and 9.1 h, respectively, which are significantly longer than that of PTH (1–34). Injection of PTH 34 -GA3-GS3 every three days increased bone mineral density and improved trabecular structure in ovariectomized mice, indicating that PTH 34 -GA3-GS3 has the potential to alleviate osteoporosis in humans. In conclusion, the fusion proteins maintained the biological activity of native PTH (1–34) and were not affected by the GA3 moiety, which extended the half-life of PTH (1–34). Long-acting GA3-fusion PTH (1–34) proteins have therapeutic effects on osteoporosis by improving osteogenesis and by enhancing the proliferation and differentiation of osteoblasts.

CAS / MDL: 50-81-7
研究领域: 骨科 · 药理学 · 生物技术
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2023 · IF 5.8

A 3D-printed orthopedic implant with dual-effect synergy based on MoS2 and hydroxyapatite nanoparticles for tumor therapy and bone regeneration

Wenyu Dai,Yunfei Zheng,Bin Li,Fan Yang,Wanxi Chen,Yunfei Li,Yi Deng,Ding Bai,Rui Shu

Treatments for malignant bone tumors are urgently needed to be developed due to the dilemma of precise resection of tumor tissue and subsequent bone defects. Although polyether-ether-ketone (PEEK) has widely attracted attention in the orthopedic field, its bioinertness and poor osteogenic properties significantly restrict its applications in bone tumor treatment. To tackle the daunting issue, we use a hydrothermal technique to fabricate novel PEEK scaffolds modified with molybdenum disulfide (MoS 2 ) nanosheets and hydroxyapatite (HA) nanoparticles . Our dual-effect synergistic PEEK scaffolds exhibit perfect photothermal therapeutic (PTT) property dependent on molybdous ion (Mo 2+ ) concentration and laser power density, superior to conventional PEEK scaffolds. Under near-infrared (NIR) irradiation, the viability of MG63 osteosarcoma cells is significantly reduced by modified PEEK scaffolds, indicating a tumor-killing potential in vitro . Furthermore, the incorporation of HA nanoparticles on the surface of PEEK bolsters proliferation and adherence of MC3T3-E1 cells, boosting mineralization for further bone defect repair. The results of micro-computed tomography (micro-CT) and histological analysis of 4-week treated rat femora demonstrate the preeminent photothermal and osteogenesis capacity of 3D-printed modified scaffolds in vivo . In conclusion, the dual-effect synergistic orthopedic implant with photothermal anticancer property and osteogenic induction activity strikes a balance between tumor treatment and bone development promotion, offering a promising future therapeutic option.

研究领域: 骨科 · 生物材料 · 纳米技术 · 癌症治疗 · 再生医学
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Shape Memory Polyester Scaffold Promotes Bone Defect Repair through Enhanced Osteogenic Ability and Mechanical Stability

Rui Du,Bin Zhao,Kun Luo,Man-Xi Wang,Quan Yuan,Lei-Xiao Yu,Ke-Ke Yang,Yu-Zhong Wang

Bone tissue engineering involving scaffolds is recognized as the ideal approach for bone defect repair. However, scaffold materials exhibit several limitations, such as low bioactivity, less osseointegration, and poor processability, for developing bone tissue engineering. Herein, a bioactive and shape memory bone scaffold was fabricated using the biodegradable polyester copolymer’s four-dimensional fused deposition modeling. The poly(ε-caprolactone) segment with a transition temperature near body temperature was selected as the molecular switch to realize the shape memory effect. Another copolymer segment, i.e., poly(propylene fumarate), was introduced for post-cross-linking and improving the regulation effect of the resulting bioadaptable scaffold on osteogenesis. To mimic the porous structures and mechanical properties of the native spongy bone, the pore size of the printed scaffold was set as ∼300 μm, and a comparable compression modulus was achieved after photo-cross-linking. Compared with the pristine poly(ε-caprolactone), the scaffold made from fumarate-functionalized copolymer considerably enhanced the adhesion and osteogenic differentiation of MC3T3-E1 cells in vitro. In vivo experiments indicated that the bioactive shape memory scaffold could quickly adapt to the defect geometry during implantation via shape change, and bone regeneration at the defect site was remarkably promoted, providing a promising strategy to treat bone defects in the clinic, substantial bone defects with irregular geometry.

研究领域: 组织工程 · 生物材料 · 骨科研究 · 再生医学
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HUMAN GENE THERAPY · 2023 · IF 4.2

Direct Knockdown of PDZ and LIM Domain 1 Using an Adenoviral Delivery System Accelerates Osteogenesis and Fracture Healing in Mice

Dr. Zhiguang Chen,Ms. Qi Zhao,Mr. Ran Zhang,Dr. Lianghong Chen,Mr. Songlan Gao,Dr. Yu Wang,Dr. Tiegang Li,Dr. Jinqi Xue

Substantial advances have been made in understanding the role of partial PDZ and LIM domain (PDLIM) family’s proteins in skeletal-related diseases. Yet, little is known about the effect of Pdlim1 on osteogenesis and fracture repair. This study aimed to investigate whether direct gene delivery using an adenovirus vector carrying Pdlim1 (Ad-oePdlim1) or encoding shRNA-Pdlim1 (Ad-shPdlim1) could affect the osteogenic activity of pre-osteoblastic MC3T3-E1 cells in vitro, and influence the fracture healing of mice in vivo. We found that Ad-shPdlim1 transfection contributed to the calcified nodule formation in MC3T3-E1 cells. Downregulation of Pdlim1 enhanced the alkaline phosphatase (ALP) activity and increased the expression of osteogenic markers (Runx2, Col1A1, osteocalcin and osteopontin). Further analysis indicated that Pdlim1 knockdown could activate β-catenin signaling, as evidenced by the accumulation of β-catenin in the nucleus and the increase levels of downstream regulators such as Lef1/Tcf7, Axin2, Cyclin D1 and Sox9. By contrast, Pdlim1 overexpression resulted in inhibition of the osteogenic activity of MC3T3-E1 cells. In vivo, at day 3 after fracture, Ad-shPdlim1 adenovirus particles were injected into the fracture site of the femur of mice, and the process of fracture healing was evaluated by X-ray, Micro-CT and histological examination. Local injection of Ad-shPdlim1 promoted the early cartilage callus formation, restored bone mineral density and accelerated cartilaginous ossification, with the upregulation of osteogenic gene (Runx2, Col1A1, osteocalcin and osteopontin) expression and activation of β-catenin signaling. Thus, we concluded that inhibition of Pdlim1 contributed to osteogenesis and fracture healing by activating the β-catenin signaling pathway.

CAS / MDL: 50-81-7 47165-04-8
研究领域: 分子生物学 · 骨科 · 再生医学 · 基因治疗
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MATERIALS & DESIGN · 2023 · IF 8.4

Surface bisphosphonation of polyetheretherketone to manipulate immune response for advanced osseointegration

Weifang Zhang,Lvhua Liu,Huang Zhou,Chanjuan He,Xueli Yang,Jingjing Fu,Huaiyu Wang,Ying Liu,Yanyan Zheng

Polyetheretherketone (PEEK) is deemed to be a promising alternative to biomedical metals for orthopedic and dental implantation attributed to its bone-like elastic modulus and good biocompatibility. Nevertheless, the bioinert PEEK elicits an acute and irreducible inflammatory immune response after implantation, resulting in fibrous encapsulation and ultimately inferior osseointegration. Therefore, endowing the PEEK surface with immunomodulatory function is essential for advanced osseointegration. Herein, surface bisphosphonation of PEEK is achieved by using mussel-inspired chemistry together with alendronate, which can not only mitigate the early servious inflammatory immune response by promoting macrophages polarization toward the pro-healing M2 phenotype, but also construct a favorable osteoimmune microenvironment to promote the angiogenesis of human umbilical vein endothelial cells (HUVECs) and the osteogenesis of MC3T3-E1 osteoblasts. In vivo evaluation reveals an ameliorative osseointegration of PEEK implant after surface bisphosphonation, confirming the in vitro results. Our findings elucidate that the PEEK implant after surface bisphosphonation can positively regulate early immune reaction to facilitate subsequent angiogenesis and osteogenesis processes, which is desirable for orthopedic and dental implantation.

CAS / MDL: 123-03-5
研究领域: 生物材料 · 生物医学工程 · 免疫学 · 骨科 · 牙科种植
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Materials Today Bio · 2024 · IF 8.7

Dual-functional thermosensitive hydrogel for reducing infection and enhancing bone regeneration in infected bone defects

Yuhang Tian,Yutao Cui,Guangkai Ren,Yi Fan,Minghan Dou,Shaorong Li,Gan Wang,Yanbing Wang,Chuangang Peng,Dankai Wu

The contamination of bone defects is a serious therapeutic problem. The treatment of infected bone defects involves rigorous infection control followed by bone reconstruction. Considering these two processes, the development of biomaterials possessing antibacterial and osteogenic properties offers a promising approach for the treatment of infected bone defects. In this study, a dual-functional, thermosensitive, and injectable hydrogel composed of chitosan (CS), quaternized CS (QCS), and nano-hydroxyapatite (nHA) was designed, and the ratio of CS to QCS in the hydrogel was optimized to enhance the antibacterial efficacy of CS while reducing the cytotoxicity of QCS. In vitro studies demonstrated that the hydrogel with an 85 %:15 % ratio of CS to QCS exhibited excellent biocompatibility and antibacterial properties while also possessing suitable mechanical characteristics and degradability. The incorporation of nHA into the hydrogel enhanced MC3T3-E1 proliferation and osteogenic differentiation. Moreover, this hydrogel demonstrated superior in vivo therapeutic effectiveness in a rabbit model of infected bone defect. In summary, this study provides a promising material design and a comprehensive one-step treatment strategy for infected bone defects.

研究领域: 生物材料 · 组织工程 · 骨科 · 传染病 · 生物医学工程
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Materials Science & Engineering C-Materials for Biological Applications · 2021 · IF 7.328

Thermosensitive -hydrogel-coated titania nanotubes with controlled drug release and immunoregulatory characteristics for orthopedic applications

Baoe Li,Lei Zhang,Donghui Wang,Feng Peng,Xuefeng Zhao,Chunyong Liang,Haipeng Li,Hongshui Wang

Although Ti is widely used in orthopedic implants, its bio-inert characteristics and poor antibacterial activity may result in implant failure. To counter this problem, in this study, we loaded simvastatin, a bioactive compound that promotes osteogenesis, in TiO 2 nanotubes and a thermosensitive chitosan-glycerin-hydroxypropyl methyl cellulose hydrogel (CGHH) was then layered on top of these nanotubes. At normal human-body temperature (37 °C), CGHH was present in a sol state, thus facilitating the controlled release of simvastatin to enhance differentiation in MC3T3-E1 osteoblasts. In vitro cell-culture studies suggested that CGHH in a gel state would induce macrophage polarization to the pro-inflammatory M1 phenotype. In vitro testing against Escherichia coli and Staphylococcus aureus indicated no antibacterial activity in CGHH in both sol and gel states. However, the results of subcutaneous infection animal models suggested that CGHH showed excellent in vivo antibacterial activity, which can be explained by the fact at high temperatures induced by an infection, CGHH transitioned into a gel state and released large amounts of glycerin. Such a high glycerin dosage induced an acute inflammatory reaction and antibacterial activity. Thus, due to their enhanced osteogenesis capacity at normal body temperature and antibacterial characteristics in the presence of infection, the newly designed simvastatin-loaded CGHH-encapsulated TiO 2 nanotubes are promising materials for application in orthopedic implants.

CAS / MDL: 9004-65-3
研究领域: 生物材料 · 药物递送系统 · 骨科 · 免疫学 · 纳米技术
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