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JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY · 2022 · IF 10.319

Lanthanum doped octacalcium phosphate/polylactic acid scaffold fabricated by 3D printing for bone tissue engineering

Zeya Xu,Bin Lin,Chaoqian Zhao,Yanjin Lu,Tingting Huang,Yan Chen,Jungang Li,Rongcan Wu,Wenge Liu,Jinxin Lin

Lanthanum (La) has tremendous potential in the treatment and prevention of bone diseases especially osteoporosis and metabolic disorders. However, controlling its distribution and keeping the release of La 3+ ions sustained and steady in the body is still a big challenge. In this study, we prepared La-OCP powders via co-precipitation method, and further prepared La-OCP/PLA porous scaffolds by 3D printing . La 3+ was successfully introduced into the OCP crystal structure and substituted Ca 2+ at the Ca-5 and Ca-8 sites. In particular, some La 3+ ions were deposited on the crystal surface in the form of nanoparticles. Both octacalcium phosphate (OCP, Ca 8 H 2 (PO 4 ) 6 ·5H 2 O) crystals and nanoparticles played as the carriers for La 3+ ions. The La-OCP/PLA scaffolds displayed obvious mineralization effects and sustained release of La 3+ . The scaffolds contained a uniform structure with rough micro surface topography which acted as a suitable pathway for BMSCs cells to adhere, grow and proliferation. At a certain La 3+ concentration, the extracts from La-OCP/PLA scaffolds increased the expression of osteogenesis-related genes, thus promoting the osteogenic differentiation of BMSCs. Moreover, the extracts regulated the immune responses. The experiment in vivo proved that La-OCP/PLA porous scaffolds were safe and could enhance bone defect regeneration in vivo . These findings suggest that 3D printed La-OCP/PLA porous scaffolds have promising potentials in bone tissue engineering.

研究领域: 生物材料学 · 骨科医学 · 组织工程学
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ACS Applied Nano Materials · 2021 · IF 5.097

Polyaniline Protrusions on MoS2 Nanosheets for PVDF Scaffolds with Improved Electrical Stimulation

Fangwei Qi,Xiuwen Gao,Shuping Peng,Wenjing Yang,Guowen Qian,Sheng Yang,Cijun Shuai

Piezoelectric polyvinylidene fluoride (PVDF) provided an opportunity for non-invasive in situ electrical stimulation of cell behavior, yet its electroactive β phase was difficult to obtain due to its instability in the molten state. Herein, polyaniline (PANI) protrusions were in situ oxidation-polymerized on molybdenum disulfide (MoS2) nanosheets (PANI-MoS2). Then, PANI-MoS2 was introduced into laser additive-manufactured PVDF scaffolds. On the one hand, PANI protrusions produced steric hindrance between adjacent MoS2 nanosheets and inhibited the stacking and aggregating of MoS2. On the other hand, PANI-MoS2 could serve as a platform to achieve interfacial polarization locking. Specifically, Mo–S dipoles in MoS2 and π electron clouds over the N atom in PANI locked −CH2 dipoles in PVDF through electrostatic and hydrogen bond interactions, respectively, which forced −CH2 to align perpendicularly to the basal plane of MoS2 and bialy to one side of the PVDF main chain, thereby forming a full-reverse planar zigzag configuration of the polarized β phase and maintaining its stable existence. The results demonstrated that the β phase of the scaffolds was significantly increased from 43 to 90%, which resulted in an enhanced electrical output performance. The improved electrical output greatly promoted osteoblast-like cell proliferation and differentiation. Furthermore, owing to the pulling-out effect of MoS2 and improved interfacial stress transfer between MoS2 and the polymer matrix, the mechanical properties of scaffolds were also enhanced. These findings suggested that the piezoelectric scaffolds had great potential in bone tissue engineering.

研究领域: 材料科学 · 生物医学工程 · 组织工程
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MEDICAL ENGINEERING & PHYSICS · 2017 · IF 1.819

Functional testing on engineered cartilage to identify the role played by shearing

Ling Wang,Hao Shen,Jichang Nie,Dichen Li,Hongbin Fan,Zhongmin Jin,Chaozong Liu

Compressive loading is crucial for tissue regeneration in cartilage; however, the role played by shearing induced from translational or rotational motion of the knee joint has yet to be identified. This study aims at investigating the effects of in vivo like dynamic load–compression integrated with shearing on tissue regeneration, particularly to identify the role played by shearing induced from rotational motion. Tissue samples fabricated from a calcium alginate hydrogel embedded with chondrocytes were subjected to a dynamic tissue culture. Three culturing regimes were included: a static culture control (CON), compression combined with shearing induced from translational motion (CS), and compression combined with shearing induced from both translational and rotational motion (CSR). The results indicate that the CS group has a significantly larger chondrocyte proliferation rate ( p  < .01), and that the CSR group has no advantages over the CS group. However, the CSR group was found to have a marked influence on the matrix synthesis compared to that of the CS group ( p  < .01). It can be concluded that shearing from individual joint motions offers a different contribution to the chondrocyte proliferation, matrix synthesis, and phenotype maintenance, and better insight into these individual roles will be necessary for determining the efficacy of in vivo/vitro cartilageous tissue functionalization.

CAS / MDL: 9001-73-4
研究领域: 生物医学工程 · 再生医学
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BIOMATERIALS · 2015 · IF 8.557

Injectable glycopolypeptide hydrogels as biomimetic scaffolds for cartilage tissue engineering

Kaixuan Ren,Chaoliang He,Chunsheng Xiao,Gao Li,Xuesi Chen

Glycopolypeptides are an emerging class of bioinspired polymers that mimic naturally occurring glycopeptides or glycoproteins , and therefore are expected to exhibit great potential for biomedical applications . In this study, a glycopolypeptide was synthesized by conjugation of poly(γ-propargyl- l -glutamate) (PPLG) with azido-modified mannose and 3-(4-hydroxyphenyl) propanamide (HPPA), via click chemistry. Injectable hydrogels based on the glycopolypeptide were developed through enzymatic crosslinking reaction in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H 2 O 2 ). The physicochemical properties of the hydrogels, such as gelation time, storage modulus , swelling and degradation time , could be controlled by varying the concentrations of HRP and H 2 O 2 . The glycopolypetide copolymer as well as the extracts of the glycopolypetide hydrogels displayed good cytocompatibility in vitro . After subcutaneous injection into rats, the glycopolypeptide hydrogels were rapidly formed in situ , and exhibited acceptable biocompatibility accompanying the degradation of the hydrogels in vivo . The rabbit chondrocytes inside the glycopolypeptide hydrogels showed spherical morphology with high viability during the incubation period of 3 weeks in vitro , and exhibited a higher proliferation rate than within the hydrogel counterparts of PPLG grafted with 2-(2-(2-methoxyethoxy)ethoxy)ethane (MEO 3 ) and HPPA. Biochemical analysis demonstrated that the production of glycosaminoglycans (GAG) and type II collagen were significantly enhanced after incubation for 2 and 3 weeks in vitro . Moreover, the chondrocyte-containing glycopolypeptide hydrogels in subcutaneous model of nude mice maintained chondrocyte phenotype and produced the cartilaginous specific matrix. These results indicated that the biomimetic glycopolypeptide-based hydrogels hold potential as three-dimensional scaffolds for cartilage tissue engineering .

研究领域: 生物材料学 · 再生医学 · 组织工程
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Injectable Self-Healing Oxidized Starch/Gelatin Hybrid Hydrogel for Preventing Aseptic Loosening of Bone Tissue Engineering

Xi Chen,Chang Xu,Tianxiang Geng,Yi Geng,Zhenghui Li,Yanqing Li,Peng Wu,Ningning Lei,Xijing Zhuang,Sijia Zhao

Aseptic loosening presents a formidable challenge within the realm of bone tissue engineering, playing a pivotal role in the occurrence of joint replacement failures. The development of therapeutic materials characterized by an optimal combination of mechanical properties and biocompatibility is imperative to ensure the enduring functionality of bone implants over extended periods. In this context, this study introduced an injectable, temperature-sensitive irisin/oxidized starch/gelatin hybrid hydrogel (I-OG) system. The hierarchical cross-linked structure endows the I-OG hydrogel with controlled and adjustable physical and chemical properties, making it easy to adapt to different clinical environments. This hydrogel exhibits satisfactory injectable properties, excellent biocompatibility, and good temperature sensitivity. The sol–gel point of the I-OG hydrogel, close to the body temperature, allows it to cushion the shaking of the implant and maintain an intact state during compression of bone tissue. Significantly, the I-OG hydrogel effectively filled the gap between the implant and bone tissue, successfully inhibiting aseptic loosening induced by titanium particles, a result that confirmed the slow release of the irisin protein from the gel. Collectively, the findings from this study strongly support the proposition that functional hydrogels, typified by the I-OG system, hold substantial promise as an accessible and efficient treatment strategy for mitigating aseptic loosening.

CAS / MDL: 7790-28-5 9005-84-9
研究领域: 生物材料学 · 骨科医学 · 组织工程学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2016 · IF 3.902

Degradation pattern of porous CaCO3 and hydroxyapatite microspheres in vitro and in vivo for potential application in bone tissue engineering

Qiwei Zhong,Wenhua Li,Xiuping Su,Geng Li,Ying Zhou,Subhas C. Kundu,Juming Yao,Yurong Cai

Despite superior clinical handling, excellent biocompatibility, biodegradation property of calcium phosphate needs to be improved to coincide with the rate of new bone formation. In this study, spherical CaCO 3 are fabricated in the presence of the silk sericin and then transformed into porous hydroxyapatite (HAP) microspheres via hydrothermal method. The degradation behavior of obtained CaCO 3 , HAP and their mixture is first investigated in vitro . The result demonstrates that the weight loss of HAP microspheres are almost 24.3% after immersing in pH 7.40 Tris-HCl buffer solution for 12 weeks, which is far slower than that of spherical CaCO 3 (97.5%). The degradation speed of the mixtures depends on the proportion of CaCO 3 and HAP. The mixture with higher content of CaCO 3 possesses a quicker degradation speed. The obtained CaCO 3 and HAP microspheres are injected into subcutaneous tissue of ICR mice with the assistance of sodium alginate. The result in vivo also shows an obvious difference of degradation speed between the obtained CaCO 3 and HAP microspheres, implying it is feasible to modulate the degradation property of the mixture through changing the proportion of CaCO 3 and HAP The good cytocompatibility of the two kinds of microspheres is proved and a mild inflammation response is observed only at early stage of implantation. The job offers a simple method to modify the degradation properties of biomaterial for potential use in bone tissue engineering.

研究领域: 材料科学 · 生物材料 · 组织工程
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Journal of Materials Chemistry B · 2016 ·Vol. 4 ·期 37 ·6200-6212 · IF 4.872

3D plotting of highly uniform Sr5(PO4)2SiO4 bioceramic scaffolds for bone tissue engineering

Huiying Zhu,Dong Zhai,Chucheng Lin,Yali Zhang,Zhiguang Huan,Jiang Chang,Chengtie Wu

Bioceramics play an important role in bone regeneration. However, it is challenging to design bioceramic scaffolds with suitable ionic components and beneficial osteo/angio-stimulation ability for enhanced bone regeneration. In this study, we successfully synthesized a pure-phase Sr5(PO4)2SiO4 (SPS) bioactive ceramic through a solid-state reaction method and further prepared highly uniform SPS bioceramic scaffolds with controlled macropore sizes and mechanical strength by a 3D-plotting technique, and the biological responses of rabbit bone marrow stromal cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs) after culturing with different concentrations of SPS extracts and porous scaffolds were systematically studied. The results showed that the ionic products from SPS bioceramics significantly stimulated the proliferation, alkaline phosphate (ALP) activity and osteogenesis-related gene expression (Runx2, ALP, OCN, OPN) of rBMSCs as well as the proliferation and angiogenesis-related gene expression (VEGF, KDR, eNOS, HIF 1α) of HUVECs. 3D-plotted SPS scaffolds could effectively support the attachment and proliferation of both rBMSCs and HUVECs, and the proliferation rates of the two kinds of cells in SPS scaffolds were distinctively higher than those in β-tricalcium phosphate (β-TCP) scaffolds prepared by the same method. In addition, the compressive strength of SPS scaffolds could be well controlled in the range 8–30 MPa when their pore size varied from 100 to 300 μm, which was significantly higher than those of β-TCP scaffolds with similar pore sizes (∼1.5 times). Our results demonstrated that 3D-plotted SPS bioceramic scaffolds with such a specific ionic combination and high mechanical strength as well as good degradability possessed the ability to stimulate both osteogenic and angiogenic differentiation of tissue cells, indicating that they might be promising biomaterials for bone tissue engineering.

CAS / MDL: 1314-11-0
研究领域: 生物材料学 · 骨科医学 · 细胞生物学
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MOLECULES · 2019 ·Vol. 24 ·期 9 ·1669 · IF 3.06

Fabrication and Application of Novel Porous Scaffold in Situ-Loaded Graphene Oxide and Osteogenic Peptide by Cryogenic 3D Printing for Repairing Critical-Sized Bone Defect

Yidi Zhang,Chong Wang,Li Fu,Shan Ye,Min Wang,Yanmin Zhou

Osteogenic peptides have been reported as highly effective in directing mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo. Therefore, developing novel biomaterials for the controlled delivery of osteogenic peptides in scaffolds without lowering the peptide’s biological activity is highly desirable. To repair a critical-sized bone defect to efficiently achieve personalized bone regeneration, a novel bioactive poly(lactic-co-glycolic acid) (PLGA)/β-tricalcium phosphate (β-TCP) composite scaffold, in which graphene oxide (GO) and bone morphogenetic protein (BMP)-2-like peptide were loaded in situ (PTG/P), was produced by an original cryogenic 3D printing method. The scaffolds were mechanically comparable to human cancellous bone and hierarchically porous. The incorporation of GO further improved the scaffold wettability and mechanical strength. The in situ loaded peptides retained a high level of biological activity for an extended time, and the loading of GO in the scaffold further tuned the peptide release so that it was more sustained. Our in vitro study showed that the PTG/P scaffold promoted rat bone marrow-derived mesenchymal stem cell ingrowth into the scaffold and enhanced osteogenic differentiation. Moreover, the in vivo study indicated that the novel PTG/P scaffold with sustained delivery of the peptide could significantly promote bone regeneration in a critical bone defect. Thus, the novel bioactive PTG/P scaffold with a customized shape, improved mechanical strength, sustainable peptide delivery, and excellent osteogenic ability has great potential in bone tissue regeneration.Keywords:osteogenic peptide;sustained delivery;bone tissue engineering;scaffolds;graphene oxide

CAS / MDL: 75-09-2
研究领域: 生物医学工程 · 材料科学 · 组织工程
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Polymers · 2021 ·Vol. 13 ·期 2 ·270 · IF 4.329

Additive-Manufactured Gyroid Scaffolds of Magnesium Oxide, Phosphate Glass Fiber and Polylactic Acid Composite for Bone Tissue Engineering

Lizhe He,Xiaoling Liu,Chris Rudd

Composites of biodegradable phosphate glass fiber and polylactic acid (PGF/PLA) show potential for bone tissue engineering scaffolds, due to their ability to release Ca, P, and Mg during degradation, thus promoting the bone repair. Nevertheless, glass degradation tends to acidify the surrounding aqueous environment, which may adversely affect the viability and bone-forming activities of osteoblasts. In this work, MgO was investigated as a neutralizing agent. Porous network-phase gyroid scaffolds were additive-manufactured using four different materials: PLA, MgO/PLA, PGF/PLA, and (MgO + PGF)/PLA. The addition of PGF enhanced compressive properties of scaffolds, and the resultant scaffolds were comparably strong and stiff with human trabecular bone. While the degradation of PGF/PLA composite induced considerable acidity in degradation media and intensified the degradation of PGF in return, the degradation media of (MgO + PGF)/PLA maintained a neutral pH close to a physiological environment. The experiment results indicated the possible mechanism of MgO as the neutralizing agent: the local acidity was buffered as the MgO reacted with the acidic degradation products thereby inhibiting the degradation of PGF from being intensified in an acidic environment. The (MgO + PGF)/PLA composite scaffold appears to be a candidate for bone tissue engineering.

研究领域: 生物材料学 · 医学工程 · 骨科
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JOM · 2021 ·Vol. 73 ·期 6 ·1745-1753 · IF 2.474

Fabrication and Characterization of Sr-doped Hydroxyapatite Porous Scaffold

Li Ke,Li Shuiyuan,Ai Fanrong,Yan Jinchao,Zhou Kui

Strontium (Sr) is a trace metal ion that exists in natural bones. It not only regulates metabolism but also promotes osteoblast differentiation and the formation of new bones. In this study, a new method was developed to prepare Sr-doped hydroxyapatite (HA) three-dimensional (3D) porous scaffolds. A preliminary scaffold was obtained by an extrusion 3D printing method using HA–sodium alginate composite slurry as printing ink. Then, the obtained scaffolds were immersed in a strontium chloride (SrCl 2 ·6H 2 O) solution of different concentrations (1 wt.%, 5 wt.%, 10 wt.%, and 15 wt.%) for 24 h. Finally, the scaffolds were dried and then sintered at 1200°C to obtain the final scaffolds. The Sr-doped scaffolds were characterized by scanning electron microscopy, x-ray diffraction, Fourier-transform infrared spectroscopy, mechanical testing, and cell culture testing. The results show that the Sr-doped HA scaffold has better compactness and compressive strength than the HA-0Sr scaffold, and promotes cell proliferation and osteoblast differentiation. This indicates that the alternative method is suitable for preparing ion-doping ceramic scaffolds for bone tissue engineering.

CAS / MDL: 9005-38-3
研究领域: 生物材料学 · 医学工程 · 细胞生物学
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International Journal of Surgery · 2014 · IF 1.65

Cytocompatibility and osteogenesis evaluation of HA/GCPU composite as scaffolds for bone tissue engineering

Jingjing Du,Qin Zou,Yi Zuo,Yubao Li

Porous scaffolds for bone repair were prepared from newly designed segmented aliphatic polyurethane based on glyceride of castor oil and isophorone diisocyanate. To promote the scaffolds' biological and mechanical properties, hydroxyapatite powder was incorporated into the polymer matrix. The scaffold (named as HA/GCPU) with 40 wt% HA had an average pore size of 500 μm and a compressive strength of 4.6 MPa. The in vitro cell culture studies demonstrated that the HA/GCPU scaffold owned good cytocompatibility. The scaffold and cell-seeded scaffold were implanted in defects (Ф3 mm × 3 mm) of femoral condyle of Sprague–Dawley rats, respectively. New bone could extensively form in both the scaffold and cell-seeded scaffold. It indicates that the HA/GCPU composite scaffold has good prospect for bone repair and regeneration.

研究领域: 生物材料学 · 组织工程学 · 医学
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Frontiers in Materials · 2022 · IF 3.985

A 3D-printed Sn-doped calcium phosphate scaffold for bone tissue engineering

Liang Hong,Fu Gaosheng,Liu Jinrui,Tang Yueting,Wang Yujue,Chen Shan,Zhang Yanjie,Zhang Chen

Recent developments in 3D printing technology have been applied in the field of tissue engineering to fabricate customized bone repair scaffolds. β-tricalcium phosphate (β-TCP) is a bioceramic material with excellent potential as a scaffold foundation. Doping metallic ions with β-TCP will significantly enhance the mechanical property and bone regeneration performance compared with pure β-TCP specimens. In this study, we proposed a protocol for the fabrication of a Sn-doped β-TCP (Sn@TCP) scaffold using 3D printing technology, and the effect of Sn-doping on the physicochemical properties of the material and its in vitro bioactivity were investigated. Polyethylene glycol and polyvinyl alcohol were used as binder to construct Sn@TCP scaffolds which have good biocompability and can break down into H2O and CO2 after scaffolds sintering. The appearance of the scaffold constructed by 3D printing technology closely matched the computer design. The incorporation of Sn into β-TCP improved the compressive strength of the scaffold. Moreover, the Sn@TCP scaffold retained the inherently good biocompatibility of β-TCP and exhibited better osteoinduction capability than pure β-TCP scaffolds. Notably, the osteoinduction ability of Sn@TCP scaffolds were dependent on the Sn content. In conclusion, the 3D printing of Sn@TCP scaffolds with enhanced mechanical properties and osteoblast-inducing activity show great promise as scaffold materials in bone tissue engineering applications.

CAS / MDL: 7440-31-5
研究领域: 生物材料学 · 组织工程学 · 医学
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