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Acta Biomaterialia · 2019 · IF 6.638

A strong, tough, and osteoconductive hydroxyapatite mineralized polyacrylamide/dextran hydrogel for bone tissue regeneration

Ju Fang,Pengfei Li,Xiong Lu,Liming Fang,Xiaoying Lü,Fuzeng Ren

The design of hydrogels with adequate mechanical properties and excellent bioactivity, osteoconductivity, and capacity for osseointegration is essential to bone repair and regeneration. However, it is challenging to integrate all these properties into one bone scaffold. Herein, we developed a strong, tough, osteoconductive hydrogel by a facile one-step micellar copolymerization of acrylamide and urethacrylate dextran (Dex-U), followed by the in situ mineralization of hydroxyapatite (HAp) nanocrystals . We show that the soft, flexible, and hydrophobically associated polyacrylamide (PAAm) network is strengthened by the stiff crosslinked Dex-U phase, and that the mineralized HAp simultaneously improves the mechanical properties and osteoconductivity. The obtained HAp mineralized PAAm/Dex-U hydrogel (HAp-PADH) has extremely high compressive strength (6.5 MPa) and enhanced fracture resistance (over 2300 J m −2 ), as compared with pure PAAm hydrogels. In vitro , we show that the mineralized HAp layer promotes the adhesion and proliferation of osteoblasts, and effectively stimulates osteogenic differentiation. Through the in vivo evaluation of hydrogels in a femoral condyle defect rabbit model, we show regeneration of a highly mineralized bone tissue and direct bonding to the HAp-PADH interface. These findings confirm the excellent osteoconductivity and osseointegration ability of fabricated HAp-PADH. The present HAp-PADH, with its superior mechanical properties and excellent osteoconductivity, should have great potential for bone repair and regeneration. Statement of Significance We developed a strong, tough, and osteoconductive hydrogel by a facile one-step micellar copolymerization of acrylamide and urethane methacrylate dextran (Dex-U), followed by the in situ mineralization of hydroxyapatite (HAp) nanocrystals. The hydrophobic micellar copolymerization and introduction of the stiff crosslinked Dex-U phase endowed the soft polyacrylamide (PAAm) network with enhanced strength and toughness. The in situ mineralized HAp nanocrystals on the hydrogels further improved the mechanical properties of the hydrogels and promoted osteogenic differentiation of cells. Mechanical tests together with in vitro and in vivo evaluations confirmed that the HAp mineralized PAAm/Dex-U hydrogel (HAp-PADH) achieved a combination of superior mechanical properties and excellent osseointegration, and thus may offer a promising candidate for bone repair and regeneration.

CAS / MDL: 151-21-3 79-06-1
研究领域: 生物材料 · 组织工程 · 生物医学工程
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E-POLYMERS · 2020 ·Vol. 20 ·期 1 ·69-75 · IF 1.675

Fabrication and characterization of hexadecyl acrylate cross-linked phase change microspheres

Haoran Yun,Xingxiang Zhang

Microspheres with phase change properties were fabricated by polymerization of hexadecyl acrylate (HA) and different cross-linking agents. The samples were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA). The results show that, the samples that added cross-linking agents have a smooth surface and the latent heat of them is different. The experiments show that all of the cross-linked copolymer shells can be made into temperature controlled release microspheres. These materials can be potentially applied in the field of thermal energy storage. β-tricalcium phosphate was encapsulated in microspheres to obtain one with a fast release effect. It will effectively promote bone conduction when these microspheres were implanted into a bone defect. This microsphere can be used for orthopedic implant or coating of instrument in the future.

研究领域: 材料科学 · 生物医学工程
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CARBOHYDRATE POLYMERS · 2021 · IF 9.381

Electrospun polyamide-6/chitosan nanofibers reinforced nano-hydroxyapatite/polyamide-6 composite bilayered membranes for guided bone regeneration

Xiaolian Niu,Longfei Wang,Mengjie Xu,Miao Qin,Liqin Zhao,Yan Wei,Yinchun Hu,Xiaojie Lian,Ziwei Liang,Song Chen,Weiyi Chen,Di Huang

Periodontal defect poses a significant challenge in orthopedics. Guided Bone Regeneration (GBR) membrane is considered as one of the most successful methods applied to reconstruct alveolar bone and then to achieve periodontal defect repair/regeneration. In this paper, a novel polyamide-6/ [email protected] /polyamide-6 (PA6/ [email protected] /PA6) bilayered tissue guided membranes by combining a solvent casting and an electrospinning technique was designed. The developed PA6/ [email protected] /PA6 composites were characterized by a series of tests. The results show that n-HA/PA6 and electrospun PA6/CS layers are tightly bound by molecular interaction and chemical bonding, which enhances the bonding strength between two distinct layers. The porosity and adsorption average pore diameter of the PA6/ [email protected] /PA6 membranes are 36.90 % and 22.61 nm, respectively. The tensile strength and elastic modulus of PA6/ [email protected] /PA6 composites are 1.41 ± 0.18 MPa and 7.15 ± 1.09 MPa, respectively. In vitro cell culture studies demonstrate that PA6/ [email protected] /PA6 bilayered scaffolds have biological safety, good bioactivity, biocompatibility and osteoconductivity.

研究领域: 材料科学 · 生物医学工程 · 骨科 · 组织工程
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Gelatin hydrogel reinforced with mussel-inspired polydopamine-functionalized nanohydroxyapatite for bone regeneration

Wuchao Ma,Hongrui Chen,Shuzhen Cheng,Chao Wu,Lishu Wang,Ming Du

Developing high-strength hydrogels with biocompatibility and bone conductibility is still desirable for bone regeneration. The nanohydroxyapatite (nHA) was incorporated into a dopamine-modified gelatin (Gel-DA) hydrogel system to create a highly biomimetic native bone tissue microenvironment. In addition, to further increase the cross-linking density between nHA and Gel-DA, nHA was functionalized by mussel-inspired polydopamine (PDA). Compared with nHA, adding polydopamine functionalized nHA (PHA) increased the compressive strength of Gel-Da hydrogel from 449.54 ± 180.32 kPa to 611.18 ± 211.86 kPa without affecting its microstructure. Besides, the gelation time of Gel-DA hydrogels with PHA incorporation (GD-PHA) was controllable from 49.47 ± 7.93 to 88.11 ± 31.18 s, contributing to its injectable ability in clinical applications. In addition, the abundant phenolic hydroxyl group of PHA was beneficial to the cell adhesion and proliferation of Gel-DA hydrogels, leading to the excellent biocompatibility of Gel-PHA hydrogels. Notably, the GD-PHA hydrogels could accelerate the bone repair efficiency in the rat model of the femoral defect. In conclusion, our results suggest the Gel-PHA hydrogel with osteoconductivity, biocompatibility, and enhanced mechanical properties is a potential bone repair material.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 生物材料 · 组织工程 · 生物医学工程 · 材料科学
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APPLIED SURFACE SCIENCE · 2019 · IF 5.155

Nano-hydroxyapatite crystal formation based on calcified TiO2 nanotube arrays

Qiaoxia Lin,Di Huang,Jingjing Du,Yan Wei,Yinchun Hu,Xiaojie Lian,Xin Xie,Weiyi Chen,Yu Shrike Zhang

The lack of biological activity of pure titanium as a dental implant has attracted increasing attention. This condition can be improved by preparing a layer of nano-hydroxyapatite (nano-HA) coating that is stable and does not easily fall off, which however, remains a challenge. Here, we report the preparation of nano-HA crystals on calcified titanium oxide (TiO 2 ) nanotube arrays by means of anodization, heat treatment, calcification in vacuum and hydrothermal phosphorylation, achieving the chemical bonding between the nano-HA coating and TiO 2 substrate. The mechanism of coating formation was also investigated. The results confirmed that annealing at 450 °C could convert the amorphous nanotubes to the anatase structure. Calcium titanate (CaTiO 3 ) was formed on the surface of nanotubes by heat treatment after calcification, which could provide nucleation sites for the formation of nano-HA. Needle-like nano-HA crystals were subsequently formed on the surface of the TiO 2 nanotube arrays. The scratch test showed that the adhesion strength between the formed nano-HA coating and the TiO 2 nanotube arrays was higher than 29.17 ± 1.07 N. In vitro cell proliferation and adhesion experiments showed that the nano-HA coating had good biocompatibility. Alkaline phosphatase (ALP) activity and osteocalcin (OCN) expressions highlighted the higher osteoconductivity of the nano-HA coating on the surface of TiO 2 nanotube arrays compared to the pure Ti.

CAS / MDL: 111-30-8
研究领域: 材料科学 · 生物材料 · 纳米技术 · 牙科种植学
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APL Materials · 2024 ·Vol. 12 ·期 9 · IF 5.3

Magnetic casein/CaCO3/Fe3O4 microspheres stimulate osteogenic differentiation

Zhang Mingjie,Li Xiaolei,Lin Han

The quality of life is significantly impacted by bone defects, which calls for the creation of optimum restorative materials with particular qualities. Current repair materials, such as metal alloys, polymer scaffolds, and bone cement, have a number of drawbacks, such as poor fracture toughness, non-degradability, and insufficient osteogenic ability. To address these challenges, we designed a novel magnetic casein/CaCO 3 /Fe 3 O 4 microspheres (CCFM), combining biodegradability, osteoinductivity, osteoconductivity, and osteogenesis properties together. In vitro studies confirmed the outstanding biocompatibility and osteogenic differentiation effects on MC3T3-E1 cells of CCFM, highlighting their potential as a promising bone regeneration platform for clinical applications. As a novel bone repair material with superparamagnetic properties, CCFM not only possess good osteoinductivity, osteoconductivity, and osteogenesis properties but also can remain in the lesion location for a long time under an external magnetic field, representing a significant advancement in the field of bone tissue engineering and offering new possibilities for effective bone defect remediation and patient care.

研究领域: 生物材料 · 组织工程 · 生物医学工程 · 骨科
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COMPOSITES PART B-ENGINEERING · 2021 · IF 9.078

3D-printed pre-tapped-hole scaffolds facilitate one-step surgery of predictable alveolar bone augmentation and simultaneous dental implantation

Cuicui Zhang,Zhigang Chen,Juan Liu,Mingming Wu,Jirong Yang,Yaomin Zhu,William Weijia Lu,Changshun Ruan

Despite the convenience of one-step surgery for alveolar bone augmentation and simultaneous dental implantation, achieving a suitable bone graft for predictable alveolar bone augmentation and stable dental implant placement via one-step surgery remains a huge challenge. Herein, a novel personalized scaffold with a pre-tapped-hole that could perfectly fit the dental implant was precisely fabricated by 3D printing technology. The biocompatible organic poly(lactic- co -glycolic acid) (PLGA) and osteoconductive inorganic materials (hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP)) were used as composite materials with an appropriate viscosity for pre-tapped-hole scaffold fabrication (PLGA/HA/β-TCP, PHT). The PHT composite scaffold demonstrated a well-designed structure that could match perfectly with bone defect areas and the titanium screw, and proper mechanical property as high as 67.18 ± 7.40 MPa in Young's modulus and 4.85 ± 0.39 MPa in compression stress. Meanwhile, PHT scaffold exhibited excellent in vitro cellular biocompatibility and proper in vivo osteoconductivity in a rabbit bone augmentation model. In addition, results of micro-CT and histological analysis further confirmed that PHT scaffold was able to obtain adequate primary stability provided by the titanium screw, and offer adequate space maintenance ability for new bone formation. Therefore, this study provided a robust and effective strategy of precise 3D printing technology for one-step surgery of predictable alveolar bone augmentation and simultaneous dental implantation.

CAS / MDL: 1306-06-5 123-91-1
研究领域: 牙科学 · 生物医学工程 · 材料科学 · 组织工程
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Advanced Healthcare Materials · 2022 ·Vol. 11 ·期 14 ·2200287 · IF 11.092

Bamboo-Based Biomaterials for Cell Transportation and Bone Integration

Jianmin Xue,Hongshi Ma,Erhong Song,Fei Han,Tian Li,Meng Zhang,Yufang Zhu,Jianjun Liu,Chengtie Wu

The construction of hierarchical porous structure in biomaterials is of great significance for improving nutrient transport and biological performance. However, it is still challenging to design porous bone substitutes with high strength and biological properties, which limits their clinical applications in load-bearing bone regeneration. Herein, based on hierarchical porous structure of renewable bamboo, the mineralized calcium phosphate/bamboo composite scaffolds with high strength and excellent transport performance are successfully prepared in combination of biotemplated approach and biomimetic mineralization. The mineralized biomaterials have simultaneously achieved high mechanical strength and low modulus, similar to those of cortical bone. Furthermore, the mineralized biomaterials exhibit good liquid transport capacity and can transport cells along anti-gravity direction. Based on density functional theory (DFT) calculations, the mineralized calcium phosphate reveals the optimal H 2 O adsorption energy (−0.651 eV) and low diffusion energy barrier (0.743 eV), which is conducive to enhance hydrophilicity and liquid transport performance. Moreover, owing to the synergistic effect of the porous structure of biotemplate and bioactive mineralized components, the mineralized biomaterials possess enhanced bone integration and osteoconduction properties. The present study shed light on deeper understanding of mineralized biosourced materials, offering a strategy of combining green chemistry with tissue engineering to prepare eco-friendly biomaterials.

CAS / MDL: 7758-19-2
研究领域: 材料科学 · 生物材料 · 组织工程 · 生物力学 · 生物医学工程
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2020 · IF 2.69

Osteoconductive and osteoinductive biodegradable microspheres serving as injectable micro-scaffolds for bone regeneration

Jianping Mao,Pengfei Wei,Zuoying Yuan,Wei Jing,Jingjing Cao,Guangping Li,Jianxun Guo,Honggang Wang,Dafu Chen,Qing Cai

There are intensive needs for scaffolds with new designs to meet the diverse requirements of bone repairing. Biodegradable microspheres are highlighted as injectable micro-scaffolds thanks to their advantages in filling irregular defects via a minimally invasive surgery. In this study, microspheres with surface micropores were made via the W1/O/W2 double emulsion method using amphiphilic triblock copolymers (PLLA-PEG-PLLA) composed of poly(L-lactide) (PLLA) and poly(ethylene glycol) (PEG) segments. When the PEG fraction was controlled as 10 wt.%, the microspheres demonstrated higher cell affinity than the smooth-surfaced PLLA microspheres. After being further functionalized with polydopamine coating and apatite deposition, the PLLA-PEG-PLLA microspheres could up-regulate the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) significantly. Before subcutaneous implantation, bone morphogenetic protein-2 (BMP-2) was adsorbed onto the biomineralized microspheres by taking advantages of the strong affinity of apatite to BMP-2. The resulted microspheres induced ectopic osteogenesis efficiently without causing biocompatibility problems. In summary, this study provided a simple strategy to prepare functionalized microspheres with osteoconductivity and osteoinductivity, which showed great potential in promoting bone regeneration as injectable micro-scaffolds.

研究领域: 生物医学工程 · 组织工程 · 材料科学 · 再生医学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Bioinspired self-healing injectable nanocomposite hydrogels based on oxidized dextran and gelatin for growth-factor-free bone regeneration

Wuchao Ma,Meilian Yang,Chao Wu,Shaoyun Wang,Ming Du

Hydrogels with great biocompatibility, biodegradability, and mechanical properties, combined with osteoconductivity, osteoinductivity, and osteointegration as biomaterials for bone regeneration without adding exogenous growth factors and cells are highly appealing but challenging. Here, inspired by organic-inorganic analogues of natural bone tissue and the adhesion chemistry of mussels, nanocomposite hydrogels with self-healing, injectable, adhesive, antioxidant, and osteoinductive properties (termed GO-PHA-CPs) were constructed by Schiff base cross-linking between dopamine-modified gelatin (Gel-DA) and oxidized dextran (ODex). Furthermore, the hydrogel network was enhanced by the introduction of polydopamine-functionalized nanohydroxyapatite (PHA) by improving the interfacial compatibility between the rigid inorganic particles and the flexible hydrogel matrix. Bioactive cod peptides (CPs) with osteogenic activity from Atlantic cod were further incorporated into the nanocomposite hydrogel. As a result, the multicomponent nanocomposite hydrogel favored the adhesion and spreading of MC3T3-E1 cells. The increased ALP activity suggested that GO-PHA-CPs hydrogels contributed to the osteogenic differentiation of MC3T3-E1 cells. The suitability of GO-PHA-CPs hydrogels for enhancing bone regeneration in vivo was further confirmed by the rat femoral defect model. Our results indicate that the multifunctional GO-PHA-CPs nanocomposite hydrogels without growth factors are a promising and effective candidate material for bone regeneration.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 材料科学 · 生物医学工程 · 组织工程 · 生物材料
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