Calcium Phosphate-based Scaffolds Research Articles

Sustained drug release from sintering-free calcium phosphate-based scaffolds

Sustained drug release from sintering-free calcium phosphate-based scaffolds

Compressive properties and failure behavior of photocast hydroxyapatite gyroid scaffolds vary with porosity.

Hydroxyapatite is commonly used in tissue engineered scaffolds for bone regeneration due to its excellent bioactivity and slow degradation rate in the human body. A method of layer-wise, photopolymerized viscous extrusion, a type of additive manufacturing, was developed to fabricate hydroxyapatite gyroid scaffolds with 60%, 70%, and 80% porosities. This study uses this method to produce and evaluate calcium phosphate-based scaffolds. Gyroid topology was selected due to its interconnected porosity and superior, isotropic mechanical properties compared to typical rectilinear lattice structures. These 3D printed scaffolds were mechanically tested in compression and examined to determine the relationship between porosity, ultimate compressive strength, and fracture behavior. Compressive strength increased with decreasing porosity. Ultimate compressive strengths of the 60% and 70% porous gyroids are comparable to that of human cancellous bone, and higher than previously reported for hydroxyapatite rectilinear scaffolds. These gyroid scaffolds exhibited ultimate compressive strength increases between 1.5 and 6.5 times greater than expected, based on volume of material, as porosity is decreased. The Weibull moduli, a measure of failure predictability, were predictive of failure mode and found to be in the accepted range for engineering ceramics. The gyroid scaffolds were also found to be self-reinforcing such that initial failures due to minor manufacturing inconsistencies did not appear to be the primary cause of early failure of the scaffold. The porous gyroids exhibited scaffold failure characteristics that varied with porosity, ranging from monolithic failure to layer-by-layer failure, and demonstrated self-reinforcement in each porosity tested.

Use of ozone on regeneration of 3D critical size bone defects

Extensive bone loss is often experienced in the treatment of trauma, tumors, infections, congenital diseases, and disuse. Autologous bone grafting is considered the gold standard for solving these demands due to its osteogenic, osteoinductive, and osteoconductive characteristics. Thus, the need more surgical sites, volumetric limitations, risk of infections, and in some situations, the cost of hospitalization should be considered. 3D printing biomanufatured calcium phosphate-based scaffolds raises as osteoconductive materials for bone reconstructions. Volumetric disposability, biocompatible performance and easy handling are some benefits of these new options. Advances in biology and tissue engineering technologies are making it possible to use materials and techniques together to achieve better results. Osteogenic properties of ozone are being mapped which make this material a possible biofunctionalizer 3D scaffolds and other materials for tissue engineering. Thus, deficiencies such as the osteogenic potential and remodeling ability of the scaffolds still remains as limitations. Ozone therapy has been used as adjuvant in regeneration and repair processes by releasing free oxygen and increasing the responsiveness of cellular metabolism and generation of vital energy. Therefore, the release responses of inflammatory mediators, growth factors, and cytokines become more effective, especially in situations in which they are deficient, such as at advanced ages. The objective of this literature review is to evaluate the role of ozone therapy to optimize cellular response for the local response of bone formation at critical size defect sites reconstructed with 3D biomanufacturing scaffolds.

Nature-Inspired Unconventional Approaches to Develop 3D Bioceramic Scaffolds with Enhanced Regenerative Ability.

Material science is a relevant discipline in support of regenerative medicine. Indeed, tissue regeneration requires the use of scaffolds able to guide and sustain the natural cell metabolism towards tissue regrowth. This need is particularly important in musculoskeletal regeneration, such as in the case of diseased bone or osteocartilaginous regions for which calcium phosphate-based scaffolds are considered as the golden solution. However, various technological barriers related to conventional ceramic processing have thus far hampered the achievement of biomimetic and bioactive scaffolds as effective solutions for still unmet clinical needs in orthopaedics. Driven by such highly impacting socioeconomic needs, new nature-inspired approaches promise to make a technological leap forward in the development of advanced biomaterials. The present review illustrates ion-doped apatites as biomimetic materials whose bioactivity resides in their unstable chemical composition and nanocrystallinity, both of which are, however, destroyed by the classical sintering treatment. In the following, recent nature-inspired methods preventing the use of high-temperature treatments, based on (i) chemically hardening bioceramics, (ii) biomineralisation process, and (iii) biomorphic transformations, are illustrated. These methods can generate products with advanced biofunctional properties, particularly biomorphic transformations represent an emerging approach that could pave the way to a technological leap forward in medicine and also in various other application fields.

Incorporation of functionalized reduced graphene oxide/magnesium nanohybrid to enhance the osteoinductivity capability of 3D printed calcium phosphate-based scaffolds

Improving bone regeneration is one of the most pressing problems facing bone tissue engineering (BTE) which can be tackled by incorporating different biomaterials into the fabrication of the scaffolds. The present study aims to apply the 3D-printing and freeze-drying methods to design an ideal scaffold for improving the osteogenic capacity of Dental pulp stem cells (DPSCs). To achieve this purpose, hybrid constructs consisted of 3D-printed Beta-tricalcium phosphate (β-TCP)-based scaffolds filled with freeze-dried gelatin/reduced graphene oxide-Magnesium-Arginine (GRMA) matrix were fabricated through a novel green method. The effect of different concentrations of Reduced graphene oxide-Magnesium-Arginine (RMA) (0, 0.25% and 0.75%wt) on the morphology, mechanical properties, and biological activity of the 3D scaffolds were completely evaluated. Our findings show that the incorporation of RMA hybrid into the scaffold can remarkably enhance its mechanical features and improve cell proliferation and differentiation simultaneously. Of all scaffolds, β-TCP/0.25GRMA showed not only the highest ALP activity and cell proliferation after 14 days but it up-regulated bone-related genes and proteins (COL-I, RUNX2, OCN). Hence, the fabricated 3D printed β-TCP/0.25GRMA porous scaffolds can be considered as a high-potential candidate for BTE.

The effect of platelet-rich plasma on human mesenchymal stem cell-induced bone regeneration of canine alveolar defects with calcium phosphate-based scaffolds.

Objective(s):Autologous bone transplantation known as the “gold standard” to reconstruction of osseous defects has known disadvantages. This study was designed to explore the effects of hydroxy-apatite/tricalcium-phosphate (HA/TCP) and platelet-rich plasma (PRP) on the osteogenesis ability of human adipose-derived mesenchymal stem cells (hAdMSCs) in vitro and in vivo.Materials and Methods:hAdMSCs were incubated with HA/TCP granules and/or PRP in vitro and then, cell proliferation and differentiation was assessed by MTT assay, AZR S staining and SEM examination. In vivo, four cylindrical defects were drilled in the mandibular bones of 5 mongrel dogs and divided randomly into the following groups: I-autologous crushed bone, II- no filling material, III- HA/TCP and PRP, IV- PRP-enriched hAdMSCs seeded on HA/TCP granules. Inserted hAdMSCs were labeled to trace their contribution to bone tissue regeneration. Finally, cell tracing and tissue regeneration were evaluated by immunohistochemistry and histomorphometry methods, respectively.Results:In vitro, co-incubation with HA/TCP granules significantly reduced proliferation and osteogenic differentiation ability of hAdMSCs; while PRP application promoted these capacities (P<0.05). In vivo, PRP-enriched hAdMSCs seeded on HA/TCP granules induced considerable bone formation in osseous defects (P<0.05). It was obviously shown that hAdMSCs were incorporated into the newly-formed bone.Conclusion:Based on this study, application of stem cells could offer a helpful therapeutic tool in bone tissue regeneration. Although inserted hAdMSCs were identifiable throughout the newly-formed bone tissue, their few number could be an indicator of indirect role of hAdMSCs in tissue regeneration.

Simulation of cortico-cancellous bone structure by 3D printing of bilayer calcium phosphate-based scaffolds

Traditional methods of fabrication for porous bone scaffolds are unable to accurately mimic the desirable cortico-cancellous morphology and the structure of the bone. In this study, 3D printing of a β-Tricalcium phosphate (TCP)-based paste was used to develop scaffolds simulating the two distinct cortical and cancellous layers of the natural bone. Laser microscope imaging showed that the pore sizes were 242.2±24.3µm and 410.5±27.9µm for the cortical and cancellous layers, respectively. Micro CT analysis revealed overall porosity and interconnectivity of 61.8±1.4% and 208707.5±52405, respectively. Mechanical properties were within the range of human cancellous bone with 10.0±2.4MPa strength and 55.5±5.7MPa young's modulus. The X-ray diffraction (XRD) analysis showed that the phase composition of the printed scaffolds was almost identical to pure TCP. Scanning electron microscopy (SEM) and cell vitality assessment indicated significant osteoblastic proliferation on the surface of the scaffolds. The gene expression analysis showed an increase in the level of Collagen I (Col I), Osteonectin (ON), Ostocalcin (OC), and Osteopontin (OPN) with a significant increase in OC and OPN at day 10. In conclusion, 3D printing can be used to develop a TCP-based scaffold with controllable and reproducible microstructures and favourable in vitro biological properties with potential to be further developed to be used for clinical bone regeneration.

Computational modelling of local calcium ions release from calcium phosphate-based scaffolds.

A variety of natural or synthetic calcium phosphate (CaP)-based scaffolds are currently produced for dental and orthopaedic applications. These scaffolds have been shown to stimulate bone formation due to their biocompatibility, osteoconductivity and osteoinductivity. The release of the [Formula: see text] ions from these scaffolds is of great interest in light of the aforementioned properties. It can depend on a number of biophysicochemical phenomena such as dissolution, diffusion and degradation, which in turn depend on specific scaffold characteristics such as composition and morphology. Achieving an optimal release profile can be challenging when relying on traditional experimental work alone. Mathematical modelling can complement experimentation. In this study, the in vitro dissolution behaviour of four CaP-based scaffold types was investigated experimentally. Subsequently, a mechanistic finite element method model based on biophysicochemical phenomena and specific scaffold characteristics was developed to predict the experimentally observed behaviour. Before the model could be used for local [Formula: see text] ions release predictions, certain parameters such as dissolution constant ([Formula: see text]) and degradation constant ([Formula: see text]) for each type of scaffold were determined by calibrating the model to the in vitro dissolution data. The resulting model showed to yield release characteristics in satisfactory agreement with those observed experimentally. This suggests that the mathematical model can be used to investigate the local [Formula: see text] ions release from CaP-based scaffolds.

Fabrication of porous scaffolds by three-dimensional plotting of a pasty calcium phosphate bone cement under mild conditions

The major advantage of hydroxyapatite (HA)-forming calcium phosphate cements (CPCs) used as bone replacement materials is their setting under physiological conditions without the necessity for thermal treatment that allows the incorporation of biological factors. In the present study, we have combined the biocompatible consolidation of CPCs with the potential of rapid prototyping (RP) techniques to generate calcium phosphate-based scaffolds with defined inner and outer morphology. We demonstrate the application of the RP technique three-dimensional (3D) plotting for the fabrication of HA cement scaffolds. This was realized by utilizing a paste-like CPC (P-CPC) which is stable as a malleable paste and whose setting reaction is initiated only after contact with aqueous solutions. The P-CPC showed good processability in the 3D plotting process and allowed the fabrication of stable 3D structures of different geometries with adequate mechanical stability and compressive strength. The cytocompatibility of the plotted P-CPC scaffolds was demonstrated in a cell culture experiment with human mesenchymal stem cells. The mild conditions during 3D plotting and post-processing and the realization of the whole procedure under sterile conditions make this approach highly attractive for fabrication of individualized implants with respect to patient-specific requirements by simultaneous plotting of biological components.

A finite element study of mechanical stimuli in scaffolds for bone tissue engineering

Mechanical stimuli are one of the factors that affect cell proliferation and differentiation in the process of bone tissue regeneration. Knowledge on the specific deformation sensed by cells at a microscopic level when mechanical loads are applied is still missing in the development of biomaterials for bone tissue engineering. The objective of this study was to analyze the behavior of the mechanical stimuli within some calcium phosphate-based scaffolds in terms of stress and strain distributions in the solid material phase and fluid velocity, fluid pressure and fluid shear stress distributions in the pores filled of fluid, by means of micro computed tomographed (CT)-based finite element (FE) models. Two samples of porous materials, one of calcium phosphate-based cement and another of biodegradable glass, were used. Compressive loads equivalent to 0.5% of compression applied to the solid material phase and interstitial fluid flows with inlet velocities of 1, 10 and 100 μm/s applied to the interconnected pores were simulated, changing also the inlet side and the viscosity of the medium. Similar strain distributions for both materials were found, with compressive and tensile strain maximal values of 1.6% and 0.6%, respectively. Mean values were consistent with the applied deformation. When 10 μm/s of inlet fluid velocity and 1.45 Pa s viscosity, maximal values of fluid velocity were 12.76 mm/s for CaP cement and 14.87 mm/s for glass. Mean values were consistent with the inlet ones applied, and mean values of shear stress were around 5×10 −5 Pa. Variations on inlet fluid velocity and fluid viscosity produce proportional and independent changes in fluid velocity, fluid shear stress and fluid pressure. This study has shown how mechanical loads and fluid flow applied on the scaffolds cause different levels of mechanical stimuli within the samples according to the morphology of the materials.