Ailing Li

Bioactive Nanoparticle–Gelatin Composite Scaffold with Mechanical Performance Comparable to Cancellous Bones

Mechanical properties are among the most concerned issues for artificial bone grafting materials. The scaffolds used for bone grafts are either too brittle (glass) or too weak (polymer), and therefore composite scaffolds are naturally expected as the solution. However, despite the intensive studies on composite bone grafting materials, there still lacks a material that could be matched to the natural cancellous bones. In this study, nanosized bioactive particles (BP) with controllable size and good colloidal stability were used to composite with gelatin, forming macroporous scaffolds. It was found that the mechanical properties of obtained composite scaffolds, in terms of elastic modulus, compressive strength, and strain at failure, could match to that of natural cancellous bones. This is ascribed to the good distribution of particle in matrix and strong interaction between particle and gelatin. Furthermore, the incorporation of BPs endues the composite scaffolds with bioactivity, forming HA upon reacting with simulated body fluid (SBF) within days, thus stimulating preosteoblasts attachment, growth, and proliferation in these scaffolds. Together with their good mechanical properties, these composite scaffolds are promising artificial bone grating materials.

Bioactive organic/inorganic hybrids with improved mechanical performance

New sol-gel functionalized poly-ethylene glycol (PEGM)/SiO2-CaO hybrids were prepared with interpenetrating networks of silica and PEGM through the formation of Si-O-Si bonds. Bioactive and mechanical properties were investigated for a series of hybrids containing varying organic/inorganic ratios and PEG molecular weights. In contrast to the unmodified PEG/SiO2-CaO hybrids, which rapidly dissolved and crumbled, the epoxy modified hybrids exhibited good mechanical properties and bioactivity. The compressive strength and Youngs modulus were greater for higher molecular weight PEGM hybrids (PEGM600 compared to PEGM300). Compressive strengths of 138 MPa and 81 MPa were found for the 50 : 50 and 60 : 40 organic/inorganic hybrid samples respectively, which are comparable with cortical bone. Youngs modulus values of ∼800 MPa were obtained for the 50 : 50 and 60 : 40 organic/inorganic hybrids. Bioactivity tests were conducted by immersing the hybrids into simulated body fluid and observing the formation of apatite. Apatite formation was observed within 24 hours of immersion. PEGM600 hybrids showed enhanced apatite formation compared to PEGM300 hybrids. Increased apatite formation was observed with increasing organic/inorganic ratio. 70 : 30 and 60 : 40 hybrids exhibited the greatest apatite formation. All PEGM hybrids samples had good cell viability and proliferation. The 60 : 40 PEGM600 hybrids displayed the optimal combination of bioactivity and mechanical strength. The bioactivity of these hybrids, combined with the enhanced mechanical properties, demonstrate that these materials have significant potential for bone regeneration applications.

Bioactive Nanoparticle through Postmodification of Colloidal Silica

Bioactive nanoparticles with controllable size and good colloidal stability were synthesized through surface modification of colloidal silica nanoparticles with Ca(OH)2 as the modifier. These modified nanoparticles showed good bioactivity, showing evidence of hydroxyapatite formation when incubated in simulated body fluid within 3 days. Comparison of bioactivity was made among different sized particles from nanoscale to microscale. It was found the bioactivity of these calcium modified colloidal silica particles generally decreased with particle size in the explored size range (40 nm particles showed bioactivity within 1 day). These particles were also found to be noncytotoxic but promote preosteoblast growth, thus making them promising bioactive additives for bone repair materials.

An easy-to-use wound dressing gelatin-bioactive nanoparticle gel and its preliminary in vivo study

Beyond promoting hard tissue repairing, bioactive glasses (BGs) have also been proved to be beneficial for wound healing. Nano-scale BGs prepared by sol-gel method were found to have a better performance as they have a larger specific surface area. In this work, bioactive nanoparticles (nBPs) with mean diameter of 12 nm (BP-12) instead of conventional BGs were mixed with gelatin to form an easy-to-use hydrogel as a dressing for skin wound. It was found that the composite of BP-12 and gelatin could form a hydrogel (BP-12/Gel) under 25 °C, which showed pronounced thixotropy at a practically accessible shear rate, therefore become easy to be used for wound cover. In vitro, the composite hydrogel of BP-12 and gelatin had good biocompatibility with the fibroblast cells. In vivo, rapid cutaneous-tissue regeneration and tissue-structure formation within 7 days was observed in the wound-healing experiment performed in rats. This hydrogel is thus a promising easy-to-use wound dressing material.Graphical Abstract

A Novel Composite PMMA-based Bone Cement with Reduced Potential for Thermal Necrosis

Percutaneous vertebroplasty (VP) and balloon kyphoplasty (BKP) are now widely used to treat patients who suffer painful vertebral compression fractures. In each of these treatments, a bone cement paste is injected into the fractured vertebral body/bodies, and the cement of choice is a poly(methyl methacrylate) (PMMA) bone cement. One drawback of this cement is the very high exothermic temperature, which, it has been suggested, causes thermal necrosis of surrounding tissue. In the present work, we prepared novel composite PMMA bone cement where microcapsules containing a phase change material (paraffin) (PCMc) were mixed with the powder of the cement. A PCM absorbs generated heat and, as such, its presence in the cement may lead to reduction in thermal necrosis. We determined a number of properties of the composite cement. Compared to the values for a control cement (a commercially available PMMA cement used in VP and BKP), each composite cement was found to have significantly lower maximum exothermic temperature, increased setting time, significantly lower compressive strength, significantly lower compressive modulus, comparable biocompatibility, and significantly smaller thermal necrosis zone. Composite cement containing 20% PCMc may be suitable for use in VP and BKP and thus deserves further evaluation.

Novel bioactive glass based injectable bone cement with improved osteoinductivity and its in vivo evaluation

Recently, more and more attention has been paid to the development of a new generation of injectable bone cements that are bioactive, biodegradable and are able to have appropriate mechanical properties for treatment of vertebral compression fractures (VCFs). In this study, a novel PSC/CS composite cement with high content of PSC (a phytic acid-derived bioactive glass) was prepared and evaluated in both vitro and vivo. The PSC/CS cement showed excellent injectability, good resistance to disintegration, radiopacity and suitable mechanical properties. The in vitro test showed that the cement was bioactive, biocompatible and could maintain its shape sustainably, which made it possible to provide a long-term mechanical support for bone regeneration. Radiography, microcomputed tomography and histology of critical sized rabbit femoral condyle defects implanted with the cements proved the resorption and osteoinductivity of the cement. Compared with the PMMA and CSPC, there were more osteocyte and trabeculae at the Bone-Cement interface in the group PSC/CS cement. The volume of the residual bone cement suggested that PSC/CS had certain ability of degradation and the resorption rate was much lower than that of the CSPC cement. Together, the results indicated that the cement was a promising bone cement to treat the VCFs.

Porous Particle-Reinforced Bioactive Gelatin Scaffold for Large Segmental Bone Defect Repairing

Large segmental bone defect repairing remains a big challenge in clinics, and synthetic bone grafts suitable for this purpose are still highly demanded. In this article, hydrophilic composite scaffolds (bioactive hollow particle (BHP)-gel scaffold) composed of bioactive hollow nanoparticles and cross-linked gelatin have been developed. The bioactive nanoparticles have a porous structure as well as high specific surface area; thus, they interact strongly with gelatin to overcome the swelling problem that a hydrophilic polymer scaffold will usually face. With this combination, these BHP-gel scaffolds showed porous structure and mechanical properties similar to those of the cancellous bone. They also showed excellent bioactivity and cell growth promotion performance in vitro. The best of them, namely, 10BHP-gel scaffold, was evaluated in vivo on a rat femur model, where it was found that the 5 mm segmental bone defect almost healed with new bone tissue formed in 12 weeks and the scaffold itself degraded at the same time. Thus, 10BHP-gel scaffold may become a potential bone graft for large segmental bone defect healing in the future.

Synthesis of Hybrid Hollow Sub-microspheres Assisted by Pre-added Colloidal SiO2

A novel method was developed to synthesize organic-inorganic hybrid hollow sub-microspheres (HHSs) through the addition of colloidal SiO2. The hydrolysis rate of 3-(methacryloyloxy)propyltrimethoxysilane (MPS) was accelerated by SiO2 particles; meanwhile, the condensation rate of the hydrolytic species was decelerated. Thus, the hydrolytic monomers and oligomers of MPS were preserved as emulsifiers. These emulsifiers can then emulsify the isopentyl acetate (PEA) to form a steady O/W emulsion. The HHSs were produced by subsequent free radical polymerization and removal of the oil core. The hydrolytic MPS acted as emulsifiers and polymerizable monomers at the emulsification and polymerization stage, respectively. Thus, extra emulsifiers, co-emulsifiers, and organic monomers were omitted, which simplified the synthesis process. The good dispersion of HHSs in water and oil, as well as the EDX results, indicated the organic-inorganic hybrid structure of HHSs.

Regeneration of dental–pulp complex-like tissue using phytic acid derived bioactive glasses

Phytic acid derived bioactive calcium phosphosilicate (PSC) glasses with a high phosphate content were synthesised by using non-toxic phytic acid as a phosphorus precursor. This study aimed to verify the effects of PSC on the odontogenic differentiation and dentin–pulp complex-like tissue regeneration of dental pulp cells (DPCs). Nitrogen adsorption, field-emission scanning electron microscopy, Fourier transform infrared spectroscopy, pH measurement, and inductively coupled plasma optical emission spectroscopy analyses were performed to characterise PSC. Classical 45S5 bioactive glasses (45S5) were used as positive control. Cell proliferation (1, 3, 5, 7 and 9 days), odontogenic-related gene expression levels (3 and 7 days) and mineralisation ability (21 days) of human DPCs (hDPCs) were evaluated with methylthiazol tetrazolium assay, real-time polymerase chain reaction and alizarin red staining after hDPCs from third molars were treated with PSC or 45S5 extractions. Rat molar crowns with pulp tissues covered by PSC or 45S5 were transplanted subcutaneously into nude mice for 2 and 6 weeks to demonstrate their biological effects in vivo. Results revealed that the specific surface area of PSC was larger than that of 45S5. The PSC also induced hydroxycarbonate apatite precipitation earlier than 45S5. pH was slightly increased when the amount and dissolution time of PSCs were increased. By comparison, pH was remarkably increased by 45S5. The amounts of Si and P ions released by PSC (0.1 mg mL−1) were larger than those released by 45S5. Cell proliferation, mRNA expression levels of dentin sialophosphoprotein, dentin matrix protein 1 and osteocalcin and mineralisation of hDPCs were also more strongly promoted by PSC than by 45S5. In vivo, the amount of induced typical dentin-like tissues with odontoblast-like cells generated on the interface between materials and pulp tissues was higher in PSC than in 45S5. Only collagen-like tissues were observed in groups without bioactive glasses. These findings suggested that PSC enhanced the odontogenic differentiation of DPCs and dentin–pulp complex-like tissue regeneration. The PSC might be a potential candidate for vital pulp preservation and regeneration of the dentin–pulp complex.