•Multi-component organic/inorganic composite double-network BC-GEL/HAp platform was synthesized and investigated for the first time.•BC-GEL/HAp composite demonstrated higher mechanical strength than conventional BC/GEL double-network composite as well as BC/HAp composite.•The rationale behind high mechanical strength of the BC-GEL/HAp composite was discussed in detail.•The rBMSCs cultured on the BC-GEL/HAp composite showed positive adhesion, proliferation, and differentiation potential.Bacterial cellulose/hydroxyapatite (BC/HAp) composite had good bioaffinity but its poor mechanical strength limited its widespread applications in bone tissue engineering (BTE). Bacterial cellulose/gelatin (BC/GEL) double-network (DN) composite had excellent mechanical properties but was seldom used in biomedical fields. In this regard, a multi-component organic/inorganic composite BC-GEL/HAp DN composite was synthesized, which combined the advantages of BC/HAp and BC/GEL. Compared with BC/GEL, the BC-GEL/HAp exhibited rougher surface topography and higher thermal stability. Compression and tensile testing indicated that the mechanical strength of the BC-GEL/HAp was greatly reinforced compared with BC/HAp and was even higher than that of BC/GEL. In vitro cell culture demonstrated that the rat bone marrow-derived mesenchymal stem cells (rBMSCs) cultured on the BC-GEL/HAp showed better adhesion and higher proliferation and differentiation potential than the cells cultured on BC/GEL. We hope the BC-GEL/HAp composite could be used as ideal bone scaffold platform or biomedical membrane in the future.

In load-bearing bone tissue engineering (BTE), ionic doping is a promising strategy to make up for the inherent defects of hydroxyapatite (HAp). However, the influence of doped elements on the structures and properties of in vitro mineralized HAp has not been investigated in detail so far. In addition, no systematic investigations have been found comparing the properties of different kinds of element doped HAp-based organic/inorganic composites. In this work, the hydroxyapatite/chitosan composite (CS/HAp) and Mg, Zn, Sr, and Si doped hydroxyapatite/chitosan composites (Mg-CS/HAp, Zn-CS/HAp, Sr-CS/HAp, and Si-CS/HAp) were synthesized by using a facile in situ precipitation method. The impacts of different kinds of doped elements on the crystallinity, crystal morphology, and crystal structure of the mineralized HAp were carefully studied. In addition, we also investigated and compared the surface morphology, surface roughness, thermal stability, mechanical strength, and in vitro cytocompatibility of the five samples in detail. We anticipate that our work could shed new light on the influence of ionic doping on the mineralization of HAp and inspire researchers to prepare an HAp-based organic/inorganic composite load-bearing bone substitute in the future.

In load-bearing bone tissue engineering (BTE), ionic doping is a promising strategy to make up for the inherent defects of hydroxyapatite (HAp). However, the influence of doped elements on the structures and properties of in vitro mineralized HAp has not been investigated in detail so far. In addition, no systematic investigations have been found comparing the properties of different kinds of element doped HAp-based organic/inorganic composites. In this work, the hydroxyapatite/chitosan composite (CS/HAp) and Mg, Zn, Sr, and Si doped hydroxyapatite/chitosan composites (Mg-CS/HAp, Zn-CS/HAp, Sr-CS/HAp, and Si-CS/HAp) were synthesized by using a facile in situ precipitation method. The impacts of different kinds of doped elements on the crystallinity, crystal morphology, and crystal structure of the mineralized HAp were carefully studied. In addition, we also investigated and compared the surface morphology, surface roughness, thermal stability, mechanical strength, and in vitro cytocompatibility of the five samples in detail. We anticipate that our work could shed new light on the influence of ionic doping on the mineralization of HAp and inspire researchers to prepare an HAp-based organic/inorganic composite load-bearing bone substitute in the future.

•A novel method was applied to generate anisotropic pores in chitosan hydrogels.•A speculative explanation for the pore formation was provided.•Diverse chitosan-based anisotropic porous scaffolds were prepared.•Micron-scale pores and nano-scale pores were obtained simultaneously.•These scaffolds showed great potential for tissue engineering applications.To date, great efforts have been made to prepare different kinds of isotropic tissue engineering (TE) scaffolds. However, little attention has been paid to anisotropic porous scaffolds in spite of many examples of their excellent performances. In this work, a facile method termed “ammonia-induced method” (AIM) was proposed and applied to generate anisotropic pores in chitosan (CS)-based scaffolds. The pore structures of these scaffolds were studied in detail. In order to clarify the rationale behind this process, a speculative explanation was provided on basis of the experimental results and the theory of Uras (Uras & Devlin, 2000). Compression tests indicated that the mechanical strengths of these scaffolds were sufficient for TE applications. In vitro cell culture showed that MC3T3-E1 cells cultivated in the pores of these scaffolds had positive proliferation potential. We anticipated that this novel AIM could inspire research not only in TE but also in other fields.

Self-crosslinked gelatin-oxidized hyaluronic acid/ hydroxyapatite (GEL-OHA/HAp) composite bone substitute was successfully prepared with a novel in situ precipitation method without using any toxic chemical cross-linkers, and its characterizations, including elemental composition, surface morphology, crystallinity, and structure of crystalline phase, were carried out. In order to evaluate its corresponding performances, comparisons with glutaraldehyde crosslinked gelatin/hydroxyapatite (GEL-Glu/ HAp) composite were made in detail. The results indicate that nano-HAp crystallites are homogeneously dispersed in both GEL-OHA/HAp and GEL-Glu/HAp composites, and the HAp crystallites in the former take larger particle size than those in the latter. Mechanical property tests show the acceptable mechanical strength at high strain of GEL-OHA/HAp composite. Study of in vitro degradation and swelling demonstrate that the two composites have similar degradation rate and water absorption capability. By in vitro cell culture, it has been found out that the cells on the GEL-OHA/HAp composite show higher proliferative potential than the cells on the GEL-Glu/HAp composite. Compared with GEL-Glu/HAp composite, GEL-OHA/HAp composite provides an excellent strategy for preparation of non-toxic bone substitute with acceptable corresponding properties.

A simple and effective approach was developed to synthesize chitosan–silk sericin/hydroxyapatite nanocomposites by in situ precipitation and two methods of alkali diffusion were carried out in this study. The objective of this paper was to investigate the different properties of the nanocomposites. SEM showed that the rod-like hydroxyapatite particles with a diameter of 20–50 nm were distributed homogeneously within the chitosan–silk sericin matrix, and the formation mechanism was also investigated. The results of FTIR and XRD indicated that the inorganic phase in the nanocomposite was carbonate-substituted hydroxyapatite with low crystallinity. In terms of mechanical properties, chitosan–silk sericin/hydroxyapatite nanocomposites exhibited a higher elastic modulus and compressive strength than that of the chitosan/hydroxyapatite nanocomposites. In vitro cytocompatibility of the nanocomposite was evaluated by CCK-8 assay and SEM through MG63 osteoblast cells cultured on the samples, which demonstrated that they are non-toxic and support cell growth. These results suggest that the chitosan–silk sericin/hydroxyapatite nanocomposites are promising biomaterials for bone tissue engineering.

In this research, gelatin-tussah silk fibroin/hydroxyapatite (GEL-TSF/HAp), gelatin-Bombyx mori silk fibroin/hydroxyapatite (GEL-BMSF/HAp), and gelatin/hydroxyapatite (GEL/HAp) nano-composites were synthesized by a novel in situ precipitation method. Characterizations, including surface morphology, elemental composition and distribution, structure of the crystalline phase, mechanical strength, thermal stability, and in vitro cytocompatibility, were carried out. Investigations on the crystalline phase showed that rod-like HAp crystallites in the GEL-TSF/HAp composite had a higher aspect ratio than those in the GEL-BMSF/HAp composite and the GEL/HAp composite. In addition, the GEL-TSF/HAp composite also presented better thermal stability than the other two composites revealed by differential thermal analysis (DTA) and thermogravimetric analysis (TGA). Mechanical properties testing indicated that the GEL-TSF/HAp composite had a higher elastic modulus at low strain and higher compressive modulus at high strain simultaneously than the other two composites. An in vitro cell culture showed that MG63 osteoblast-like cells on the GEL-TSF/HAp membrane took on higher proliferative potential than those on the GEL-BMSF/HAp membrane. These results indicated that compared to the GEL-BMSF/HAp composite, the GEL-TSF/HAp composite was more suitable for bone tissue engineering (BTE) applications.

Chitosan–multiwalled carbon nanotubes/hydroxyapatite nanocomposites were synthesized by a novel in situ precipitation method. The electrostatic adsorption between multiwalled carbon nanotubes and chitosan was investigated and explained by Fourier transform infrared spectroscopy analysis. Morphology studies showed that uniform distribution of hydroxyapatite particles and multiwalled carbon nanotubes in the polymer matrix was observed. In chitosan–multiwalled carbon nanotubes/hydroxyapatite nanocomposites, the diameters of multiwalled carbon nanotubes were about 10 nm. The mechanical properties of the composites were evaluated by measuring their compressive strength and elastic modulus. The elastic modulus and compressive strength increased sharply from 509.9 to 1089.1 MPa and from 33.2 to 105.5 MPa with an increase of multiwalled carbon/chitosan weight ratios from 0 to 5 %, respectively. Finally, the cell biocompatibility of the composites was tested in vitro, which showed that they have good biocompatibility. These results suggest that the chitosan–multiwalled carbon nanotubes/hydroxyapatite nanocomposites are promising biomaterials for bone tissue engineering.

•Homogeneous agarose/hydroxyapatite (agar/HA) nanocomposites were synthesized without any crosslinking agent via a facile in situ precipitation method.•The inorganic nanoparticles were uniformly dispersed in the organic matrix, and the mechanical properties of the nanocomposites were enhanced significantly.•The biocompatibility of the nanocomposites was desirable, which have the potential to be used for the bone regeneration and repair of the bone defect.•The structural role of agarose in agar/HA nanocomposites was investigated.•The advantage of gel media for preparing biomaterials was presented.Agarose/hydroxyapatite (agar/HA) nanocomposites for load-bearing bone substitutes were successfully fabricated via a novel in situ precipitation method. Observation via SEM and TEM revealed that the spherical inorganic nanoparticles of approximately 50 nm were well dispersed in the organic matrix, and the crystallographic area combined closely with the amorphous area. The uniform dispersion of HA nanoparticles had prominent effect on improving the mechanical properties of the agar/HA nanocomposites (the highest elastic modulus: 1104.42 MPa; the highest compressive strength: 400.039 MPa), which proved to be potential load-bearing bone substitutes. The thermal stability of agarose and nanocomposites was also studied. The MG63 osteoblast-like cells on the composite disks displayed fusiform and polygonal morphology in the presence of HA, suggesting that the cell maturation was promoted. The results of cell proliferation and cell differentiation indicated that the cells cultured on the agar/HA composite disks significantly increased the alkaline phosphatase activity and calcium deposition. The structural role of agarose in the composite system was investigated to better understand the effect of biopolymer on structure and properties of the composites. The optimal properties were the result of a comprehensive synergy of the components.Download high-res image (153KB)Download full-size image

In load-bearing bone tissue engineering (BTE), ionic doping is a promising strategy to make up for the inherent defects of hydroxyapatite (HAp). However, the influence of doped elements on the structures and properties of in vitro mineralized HAp has not been investigated in detail so far. In addition, no systematic investigations have been found comparing the properties of different kinds of element doped HAp-based organic/inorganic composites. In this work, the hydroxyapatite/chitosan composite (CS/HAp) and Mg, Zn, Sr, and Si doped hydroxyapatite/chitosan composites (Mg-CS/HAp, Zn-CS/HAp, Sr-CS/HAp, and Si-CS/HAp) were synthesized by using a facile in situ precipitation method. The impacts of different kinds of doped elements on the crystallinity, crystal morphology, and crystal structure of the mineralized HAp were carefully studied. In addition, we also investigated and compared the surface morphology, surface roughness, thermal stability, mechanical strength, and in vitro cytocompatibility of the five samples in detail. We anticipate that our work could shed new light on the influence of ionic doping on the mineralization of HAp and inspire researchers to prepare an HAp-based organic/inorganic composite load-bearing bone substitute in the future.

In load-bearing bone tissue engineering (BTE), ionic doping is a promising strategy to make up for the inherent defects of hydroxyapatite (HAp). However, the influence of doped elements on the structures and properties of in vitro mineralized HAp has not been investigated in detail so far. In addition, no systematic investigations have been found comparing the properties of different kinds of element doped HAp-based organic/inorganic composites. In this work, the hydroxyapatite/chitosan composite (CS/HAp) and Mg, Zn, Sr, and Si doped hydroxyapatite/chitosan composites (Mg-CS/HAp, Zn-CS/HAp, Sr-CS/HAp, and Si-CS/HAp) were synthesized by using a facile in situ precipitation method. The impacts of different kinds of doped elements on the crystallinity, crystal morphology, and crystal structure of the mineralized HAp were carefully studied. In addition, we also investigated and compared the surface morphology, surface roughness, thermal stability, mechanical strength, and in vitro cytocompatibility of the five samples in detail. We anticipate that our work could shed new light on the influence of ionic doping on the mineralization of HAp and inspire researchers to prepare an HAp-based organic/inorganic composite load-bearing bone substitute in the future.