High Hydroxyapatite Content Research Articles

Preparation and Characterization of Hydroxyapatite Based Composite Material via Cold Sintering Process

This study focuses on the synthesis of hydroxyapatite (HA) from bovine bones through calcination and subsequent combination with Polyvinyl Alcohol (PVA) using the Cold Sintering Process (CSP). The CSP, operating at lower temperatures than conventional methods, aims to preserve the bioactivity and biocompatibility of HA, crucial for biomedical applications. The research investigates the influence of HA composition, sintering temperature, and PVA content on the porosity and compressive strength of the HA-PVA composite. The Hydroxyapatite powder, obtained from calcinated bovine bones, exhibits irregular shapes and sizes with a maximum grain size of 10µm, confirmed by SEM analysis. XRD analysis validates the successful production of Hydroxyapatite, showcasing characteristic peaks. The HA/PVA composite's XRD pattern indicates the dominance of HA, with PVA present as well. The study produces 27 specimens through the CSP, varying HA composition and sintering temperature. Porosity increases with higher HA content and sintering temperature, attributed to the role of PVA in binding HA particles. Compressive strength rises with increased HA content, emphasizing HA's role in enhancing mechanical strength. The presence of porosity is mitigated by a strong bond between HA and PVA, contributing to structural integrity. This research provides insights into tailoring HA-PVA materials for biomedical applications, considering controlled porosity and mechanical strength. The CSP, with its unique advantages, emerges as a promising method for developing customized materials to meet diverse biomedical needs.

Suitability of Gelatin Methacrylate and Hydroxyapatite Hydrogels for 3D-Bioprinted Bone Tissue.

Complex bone defects are challenging to treat. Autografting is the gold standard for regenerating bone defects; however, its limitations include donor-site morbidity and increased surgical complexity. Advancements in 3D bioprinting (3DBP) offer a promising alternative for viable bone grafts. In this experiment, gels composed of varying levels of gelatin methacrylate (GelMA) and hydroxyapatite (HA) and gelatin concentrations are explored. The objective was to increase the hydroxyapatite content and find the upper limit before the printability was compromised and determine its effect on the mechanical properties and cell viability. Design of Experiments (DoE) was used to design 13 hydrogel bioinks of various GelMA/HA concentrations. These bioinks were assessed in terms of their pipettability and equilibrium modulus. An optimal bioink was designed using the DoE data to produce the greatest stiffness while still being pipettable. Three bioinks, one with the DoE-designed maximal stiffness, one with the experimentally defined maximal stiffness, and a literature-based control, were then printed using a 3D bioprinter and assessed for print fidelity. The resulting hydrogels were combined with human bone-marrow-derived mesenchymal stromal cells (hMSCs) and evaluated for cell viability. The DoE ANOVA analysis indicated that the augmented three-level factorial design model used was a good fit (p < 0.0001). Using the model, DoE correctly predicted that a composite hydrogel consisting of 12.3% GelMA, 15.7% HA, and 2% gelatin would produce the maximum equilibrium modulus while still being pipettable. The hydrogel with the most optimal print fidelity was 10% GelMA, 2% HA, and 5% gelatin. There were no significant differences in the cell viability within the hydrogels from day 2 to day 7 (p > 0.05). There was, however, a significantly lower cell viability in the gel composed of 12.3% GelMA, 15.7% HA, and 2% gelatin compared to the other gels with a lower HA concentration (p < 0.05), showing that a higher HA content or print pressure may be cytotoxic within hydrogels. Extrusion-based 3DBP offers significant advantages for bone-tissue implants due to its high customizability. This study demonstrates that it is possible to create printable bone-like grafts from GelMA and HA with an increased HA content, favorable mechanical properties (145 kPa), and a greater than 80% cell viability.

Porous hydroxyapatite-titanium dioxide composites prepared by a sol-gel / supercritical CO2-drying combined process

In this work, porous nanostructured materials based on hydroxyapatite (HA) and titanium dioxide (TiO2) were prepared by integrating the sol-gel process and supercritical CO2 drying. These combined processes constitute a synergistic methodology that allows modulating the porosity generated in the gel and preserving it after drying. HA nanoparticles and a pore-generating agent (Polyvinylpyrrolidone) were included without significant modifications to gel consolidation times or integrity by using this methodology. The presence of HA nanoparticles within the TiO2 matrix helped preserving the anatase phase after the calcination stage. No reactivity between the present phases was detected, indicating their successful integration in the final composite material structure, which was one of the most challenging aspects of the research. This allowed HA-TiO2 composites to improve the adhesion of MG63 osteoblast-like cells and their proliferation, being the sample with high HA content (∼37 % wt/wt) the one that presented the best response. The present work puts forward a new way for the synthesis of scaffolds composed of HA and TiO2 with retention of the anatase phase for applications in bone tissue engineering.

Processing of hydroxyapatite (HA)–Ti–6Al–4V composite powders via laser powder bed fusion (LPBF): effect of HA particle size and content on the microstructure and mechanical properties

This research study examines the influence of hydroxyapatite (HA) powder particle size and content on the processability, microstructure, and mechanical properties of the laser powder bed fusion (LPBF) fabricated Ti–6Al–4V (Ti64)-HA composites. For this purpose, various Ti64-HA composite powders were produced, and the effects of the HA particle size and content on the optical reflectance were investigated. Composite powders and the monolithic Ti64 powder (as the reference) were subjected to the LPBF process within a wide range of volumetric energy densities by varying the LPBF process parameters. Parts with the highest relative density for each material were assessed by studying their microstructure, nanohardness, and nanoindentation-derived yield strength. Results revealed that the incorporation of the highly reflective HA powder into the Ti64 slightly enhanced the reflectance of Ti64-HA composite powders over that of the monolithic Ti64 powder. The LPBF processability of the composite powders was found to highly depend on the content of the HA constituent. For any given volumetric energy density employed in this study, composites containing 1 wt%HA were crack-free. However, composite systems containing higher HA content (2.5 wt%) featured randomly distributed transgranular cracks. Addition of 1 and 2.5 wt%HA to the Ti64 resulted in a significant improvement in the nanohardness (∼30 and 75%) and yield strength (∼20 and 37%). The dominant strengthening mechanisms in composite samples were the Hall-Petch and geometrically necessary dislocations strengthening, accounting for 57–66% and 13–20% of the total yield strength improvement.

Additive manufactured polyether-ether-ketone composite scaffolds with hydroxyapatite filler and porous structure promoted the integration with soft tissue

Additive Manufactured (AM) Polyether-ether-ketone (PEEK) orthopaedic implants offer new opportunities for bone substitutes. However, owing to its chemical inertness, the integration between PEEK implants and soft tissue represents a major challenge threatening the early success of the PEEK implants. Here we investigated the influence of hydroxyapatite (HA) fillers and porous structure of AM HA/PEEK scaffolds on the integration with soft tissue through in-vitro cellular experiments and in-vivo rabbit experiments. Among the animal experiments, HA/PEEK composite scaffolds with HA contents of 0, 20 wt%, 40 wt% and pore sizes of 0.8 mm, 1.6 mm were manufactured by fused filament fabrication. The results indicated that HA promoted the proliferation and adhesion of myofibroblasts on PEEK-based composites by releasing Ca2+ to active FAK and its downstream proteins, while the surface morphology of the scaffolds was also roughened by the HA particles, both of which led to the tighter adhesion between HA/PEEK scaffolds and soft tissue in-vivo. The macroscopic bonding force between soft tissue and scaffolds was dominated by the pore size of the scaffolds but was hardly affected by neither the HA content and nor the surface morphology. Scaffolds with larger pore size bonded more strongly to the soft tissue, and the maximum bonding force reached to 5.61 ± 2.55 N for 40 wt% HA/PEEK scaffolds with pore size of 1.6 mm, which was higher than that between natural bone and soft tissue of rabbits. Although the larger pore size and higher HA content of the PEEK-based scaffolds facilitated the bonding with the soft tissue, the consequent outcome of reduced mechanical properties has to be compromised in the design of the porous PEEK-based composite implants. The present study provides engineering-accessible synergistic strategies on material components and porous architecture of AM PEEK orthopaedic implants for improving the integration with soft tissue.

Development of pH-sensitive biomaterial-based nanocomposite for highly controlled drug release

Combining non-toxic biomaterials to obtain high effective hybrids is a promising approach in medicine and drug delivery. This study aims to combine the biomaterial with different swelling behavior to attain high controlled release. Hydroxyapatite (HA) nanoparticles do not possess swelling properties and are stable in different pH solutions. HA was used to prevent the unwanted sudden release in acidic media by modifying the swelling properties of chitosan-based hydrogels (CTS). CTS being soluble in acidic pHs causes drug release as it dissolves, resulting in burst release behavior. The experiments confirmed that the introduction of HA remarkably reduced the swelling ratio, which independent of the pH led to a decrease in the release amount (approximately 38–73%) and prevented the burst release. The metronidazole-loaded CTS/MMt/HA1 with low content HA showed a high sustained pH-responsive release. However, the metronidazole-loaded CTS/MMt/HA2 with high content of HA didn't show sustained release. Indeed, the release rate was sustained by modifying the HA content. The kinetic investigations indicated the release mechanisms were changed from dissolution in CTS/MMt to diffusion in CTS/MMt/HA by introducing HA, which is compatible with the swelling ratio reduction. As well as CTS/MMt, HA grafted samples showed high encapsulation efficiency (>96%) and pH-sensitive properties. The biocompatibility of Metronidazole-loaded nanocomposites was confirmed by the cytotoxicity tests on the human nasopharyngeal carcinoma L929 cells.

Additive Fabrication and Characterization of Biomimetic Composite Bone Scaffolds with High Hydroxyapatite Content.

With the increased incidence of bone defects following trauma or diseases in recent years, three-dimensional porous scaffolds fabricated using bioprinting technologies have been widely explored as effective alternatives to conventional bone grafts, which provide cell-friendly microenvironments promoting bone repair and regeneration. However, the limited use of biomaterials poses a significant challenge to the robust and accurate fabrication of bioprinted bone scaffolds that enable effective regeneration of the target tissues. Although bioceramic/polymer composites can provide tunable biomimetic conditions, their effects on the bioprinting process are unclear. Thus, in this study, we fabricated hydroxyapatite (HA)/gelatin composite scaffolds containing large weight fractions of HA using extrusion-based bioprinting, with the aim to provide an adequate biomimetic environment for bone tissue regeneration with compositional and mechanical similarity to the natural bone matrix. The overall features of the bioprinted HA/gelatin composite scaffolds, including rheological, morphological, physicochemical, mechanical, and biological properties, were quantitatively assessed to determine the optimal conditions for both fabrication and therapeutic efficiency. The present results show that the bioprinted bioceramic/hydrogel scaffolds possess excellent shape fidelity; mechanical strength comparable to that of native bone; and enhanced bioactivity in terms of cell proliferation, attachment, and osteogenic differentiation. This study provides a suitable alternative direction for the fabrication of bioceramic/hydrogel-based scaffolds for bone repair based on bioprinting.

Characterization of Polycaprolactone Nanohydroxyapatite Composites with Tunable Degradability Suitable for Indirect Printing.

Degradable bone implants are designed to foster the complete regeneration of natural tissue after large-scale loss trauma. Polycaprolactone (PCL) and hydroxyapatite (HA) composites are promising scaffold materials with superior mechanical and osteoinductive properties compared to the single materials. However, producing three-dimensional (3D) structures with high HA content as well as tuneable degradability remains a challenge. To address this issue and create homogeneously distributed PCL-nanoHA (nHA) scaffolds with tuneable degradation rates through both PCL molecular weight and nHA concentration, we conducted a detailed characterisation and comparison of a range of PCL-nHA composites across three molecular weight PCLs (14, 45, and 80 kDa) and with nHA content up to 30% w/w. In general, the addition of nHA results in an increase of viscosity for the PCL-nHA composites but has little effect on their compressive modulus. Importantly, we observe that the addition of nHA increases the rate of degradation compared to PCL alone. We show that the 45 and 80 kDa PCL-nHA groups can be fabricated via indirect 3D printing and have homogenously distributed nHA even after fabrication. Finally, the cytocompatibility of the composite materials is evaluated for the 45 and 80 kDa groups, with the results showing no significant change in cell number compared to the control. In conclusion, our analyses unveil several features that are crucial for processing the composite material into a tissue engineered implant.

Development of three-dimensional printing filaments based on poly(lactic acid)/hydroxyapatite composites with potential for tissue engineering

Injured bone tissues can be healed with scaffolds, which could be manufactured using the fused deposition modeling (FDM) strategy. Poly(lactic acid) (PLA) is one of the most biocompatible polymers suitable for FDM, while hydroxyapatite (HA) could improve the bioactivity of scaffold due to its chemical composition. Therefore, the combination of PLA/HA can create composite filaments adequate for FDM and with high osteoconductive and osteointegration potentials. In this work, we proposed a different approache to improve the potential bioactivity of 3D printed scaffolds for bone tissue engineering by increasing the HA loading (20-30%) in the PLA composite filaments. Two routes were investigated regarding the use of solvents in the filament production. To assess the suitability of the FDM-3D printing process, and the influence of the HA content on the polymer matrix, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) were performed. The HA phase content of the composite filaments agreed with the initial composite proportions. The wettability of the 3D printed scaffolds was also increased. It was shown a greener route for obtaining composite filaments that generate scaffolds with properties similar to those obtained by the solvent casting, with high HA content and great potential to be used as a bone graft.

An interference screw made using a silk fibroin-based bulk material with high content of hydroxyapatite for anterior cruciate ligament reconstruction in a rabbit model.

Upgradation is still in need for the clinically applied interference screws in anterior cruciate ligament reconstruction for more reliable fixation. Silk fibroin bulk materials offer a promising opportunity for this application except lacking osteoinductivity to some extent. Here we report a novel silk-based bulk material with high content of hydroxyapatite-silk fibroin (HA-SF) hybrid particles, which is prepared via a dual-network hydrogel. This composite bulk material possesses a compression modulus of 3.2 GPa, comparable to that of the natural compact bone, and presents satisfactory cytocompatibility and osteoinductivity in vitro when combined with the HA-SF nanoparticles particularly. This composite bulk material shaped into interference screws exhibits remarkable biomechanical properties and significant new-bone ingrowth in the host bone tunnel in a rabbit anterior cruciate ligament reconstruction (ACLR) model at 4 weeks and 12 weeks post-operatively. Moreover, considering that this "hydrogel method" allows the material to be formed in a mold, avoiding complicated post fabrication, it is a potential candidate for clinical translation.

Biodegradable Composite Nanofiber Containing Fish-Scale Extracts.

A biodegradable composite nanofiber containing polyhydroxyalkanoate (PHA) or modified PHA (MPHA) and treated fish-scale powder (TFSP) was prepared and characterized. The powder (20-80 nm) was prepared by grinding after treating FSP with water, acid, and heat (450 °C) to yield the TFSP. Composite nanofibers (100-500 nm long) of TFSP/PHA and TFSP/MPHA were fabricated by electrospinning using a biaxial feed method. The TFSP, which had a high hydroxyapatite content, was suitable as a filler for composites. The Ca/P ratio of the TFSP was similar to that of the human bone. Particle size analysis and analysis of scanning electron microscopy images indicated that, compared with the PHA/TFSP composite, the MPHA/TFSP nanofibers were more uniform and bonded more strongly in the matrix. The tensile strength at failure of the MPHA/TFSP specimens was enhanced and increased with increasing TFSP content. The elongation at failure was lower and decreased with increasing TFSP concentration. The water contact angle decreased with increasing TFSP content in PHA/TFSP and MPHA/TFSP nanofiber membranes. The TFSP enhanced the hydrophilic effect of the PHA/TFSP and MPHA/TFSP nanofiber membranes and provided a more suitable environment for cell growth. This composite nanofiber has potential in many biomedical applications.

Porous 3D hydroxyapatite/polyurethane composite scaffold for bone tissue engineering and its in vitro degradation behavior

In this study, a novel hydroxyapatite (HA)/polyurethane (PU) composite porous 3D scaffold was developed by in situ polymerization. Aliphatic hexamethylene diisocyanate (HDI) as a nontoxic and safe agent was adopted to produce the rigid segment in PU polymerization. HA powder was compounded in a PU polymer matrix during the polymeric process. The macrostructure and morphology as well as mechanical strength of the scaffolds were characterized by FTIR, XRD and SEM. The results show that the HDI can react mildly with hydroxyl (–OH) groups of polytetramethylene ether glycol and a mild foaming action caused by the release of CO2 gas occurred simultaneously in the reactive process, thus producing a uniform porous structure of HA/PU scaffold. The HA/PU composite scaffold with a high HA content of about 30 wt% has a porosity of more than 60% and a pore size from 100 to 800 μm. After immersed in simulated body fluid, the scaffolds were investigated by weight loss experiments and FTIR. The results show that polymerized component of HA/PU scaffolds degraded gradually in vitro, while HA component presented a classic trend of dissolution then deposition procedure. Three hydrolysis processes may happen in the PU degradation. The HA/PU scaffolds should be a promising material for bone tissue regeneration in clinic.

The Effect of Hydroxyapatite Prepared by In Situ Synthesis on the Properties of Poly(Vinyl Alcohol)/Cellulose Nanocrystals Biomaterial

Polyvinyl alcohol/cellulose nanocrystals (CNC) and hydroxyapatite (HA) (PCH) were combined using an in situ method to fabricate porous scaffolds. CNC was extracted from sugarcane bagasse and the effect of HA on PVA/CNC composites was varied with 0, 0.5, 1 and 3 wt%. The scanning electron microscopy images of the PCH composites showed interior pores with pore channels, while the energy dispersive spectroscopy (EDS) results confirmed the increased HA content in the nanocomposite with a Ca/P ratio of 1.67. Porosity and the equilibrium swelling ratio were slightly affected by the HA content. The Fourier transform infrared spectra supported the EDS results by identifying significant peaks belonging to the HA curves of the PCH composites. The crystallinity revealed decreased crystal regions at higher HA content, whereas the mechanical behavior showed the improvement at 0.5 wt% of HA. Cytotoxicity with L929 demonstrated the compatibility of the PCH composites, with 85 ± 0.92% cell viability.

Characterization of Mechanical and Micro-Architectural Properties of Porous Hydroxyapatite Bone Scaffold Using Green MicroAlgae as Binder

Novel Hydroxyapatite (HA)-based porous bone scaffold is developed using green microalgae as binding as well as pore-forming agent. The composite scaffolds are developed at 1:2, 2:1 and 1:1 (w/w) compositions of HA and binder, respectively, using solvent-casting technique and their mechanical and micro-architectural properties are investigated. Material characterization of the scaffold shows improved mechanical strength with a maximum compressive strength of 2.89 MPa and maximum interconnected porosity of 65.29%. FT-IR and XRD results confirm formation of crystalline nano-HA in the scaffolds. SEM and TEM micrographs of the scaffolds show pore morphology with a maximum pore diameter of 258 microns and minimum pore diameter of 6 microns and uniformly dispersed rod-shaped nano-HA particles of length 3.95–99.11 nm, respectively. TG/DTG analysis shows high thermal stability of scaffolds with high HA content. Comparative study of the three types of scaffolds shows composites with equal weight ratio of HA, and binder yields the highest porosity and mechanical strength desired for cell growth and support. XRF analysis confirms Ca and P as the major constituent elements of the scaffold. The study highlights the potential of natural biomass as an alternative to synthetic and naturally derived polymeric binders for development of HA-based bone scaffolds.

Preparation of ex-situ Mixed Sintered Biphasic Calcium Phosphate Ceramics from Its Co-Precipitated Precursors and Their Characterization

ABSTRACTBiphasic calcium phosphate (BCP) ceramics was synthetically prepared by ex-situ method using hydroxyapatite (HAp) and beta tricalcium phosphate (β-TCP) powders. Both HAp and β-TCP were prepared by wet chemical co-precipitation and calcination method and were then mixed at two different weight ratios of 60:40 and 70:30. The mixed BCPs were then pressed and sintered at 1200o and 1250oC. Sintered pure HAp and β-TCP were also prepared for comparison purpose. Sintered products were then characterized for various properties. Higher density and strength values were found for the composition with higher HAp content and also the bioactivity on immersion in SBF (simulated body fluid) solution was found to be higher for HAp containing composition.

Hybrid core–shell scaffolds for bone tissue engineering

The tissue engineering applications of coaxial electrospinning are growing due to the potential increased functionality of the fibres compared to basic electrospinning. Previous studies of core and shell scaffolds have placed the active elements in the core, however, the surface response to a biomaterial affects the subsequent behaviour, thus here hydroxyapatite (HA) was added to the shell. Coaxial electrospun polycaprolactone (PCL)-polylactic acid (PLA)/HA (core–shell) scaffolds were produced in 2D sheets using a plate collector, or 3D tubes for bone tissue engineering using a rotating needle collector. The scaffolds include high hydroxyapatite content while retaining their structural and mechanical integrity. The effect of the collector type on fibre diameter, fibre alignment and mechanical properties have been evaluated, and the impact of HA incorporation on bioactivity, BMP-2 release, cell behaviour and mechanical properties for up to 12 weeks degradation were assessed. Fibre uniformity in coaxial electrospinning depends on the relative flow rate of the core and shell solutions. Using a rotating needle collector increased fibre alignment compared to a stationary collector, without affecting fibre diameter significantly, while HA content increased fibre non-uniformity. Coaxial PCL-PLA/HA fibres exhibited significantly higher bioactivity compared to PCL-PLA scaffolds due to the surface exposure of the HA particles. Apatite formation increased with increasing SBF immersion time. Coaxial tubular scaffolds with and without HA incorporation showed gradual reductions in their mechanical properties over 12 weeks in PBS or SBF but still retained their structural integrity. Coaxial scaffolds with and without HA exhibited gradual and sustained BMP-2 release and supported MSCs proliferation and differentiation with no significant difference between the two scaffolds types. These materials therefore show potential applications as bone tissue engineering scaffolds.

Electrophoretic co-deposition of PEEK-hydroxyapatite composite coatings for biomedical applications.

This study focuses on the optimization of electrophoretic deposition (EPD) and suspension parameters for producing PEEK-hydroxyapatite (HA) coatings with feasible microstructure, adhesion strength, and in-vitro bioactivity. Nanostructured hydroxyapatite (HA) micro-granules were incorporated with PEEK to form PEEK-hydroxyapatite composite coatings via EPD. After EPD, a heat-treatment at 375 °C was applied for densification of the coatings and for enhancing the adhesion between the coatings and the substrates. It was found that both adhesion strength and in-vitro bioactivity of the coatings were dependent on the PEEK and HA relative contents. Thus, increasing the amount of HA improved the bioactivity while decreased the adhesion strength of the coatings. Apatite-like layer formation was observed on coatings with high HA content after incubation for three days in simulated body fluid (SBF). Finally, a deposition mechanism was proposed for the EPD of the PEEK-hydroxyapatite composite system.

Hydroxyapatite Microspheres as an Additive to Enhance Radiopacity, Biocompatibility, and Osteoconductivity of Poly(methyl methacrylate) Bone Cement.

This study demonstrates the utility of hydroxyapatite (HA) microspheres as an additive to enhance the radiopaque properties, biocompatibility, and osteoconductivity of poly(methyl methacrylate) (PMMA)-based bone cements. HA microspheres were synthesized using spray drying. They had well-defined spherical shapes, thus allowing for the production of PMMA/HA composites with a very high HA content (20 vol % and 40 vol %). The uniform distribution of these HA microspheres in the PMMA matrix resulted in a remarkable increase in compressive modulus (p < 0.05), while preserving a reasonably high compressive strength. The PMMA/HA bone cements showed much higher radiopacity than PMMA containing BaSO4 as the additive. This was attributed to the high HA content up to 40 vol %. In addition, the biocompatibility and osteoconductivity of PMMA/HA bone cements were significantly enhanced compared to those of PMMA bone cements containing BaSO4, which were assessed using in vitro tests and in vivo animal experiments.

An electrospun poly(ε-caprolactone) nanocomposite fibrous mat with a high content of hydroxyapatite to promote cell infiltration.

Electrospun polymer/inorganic biomimetic nanocomposite scaffolds have emerged for use in a new strategy for bone regeneration. In this study, a poly(ε-caprolactone) (PCL)/hydroxyapatite (HAp) nanocomposite mat with a HAp content as high as 60% was prepared via one-step electrospinning using trifluoroethanol as the solvent, and it has superior dispersibility and spinnability. The structure and physicochemical properties of the scaffolds were studied using scanning electron microscopy and spectroscopic techniques. X-ray diffraction and Fourier transformed infrared spectroscopy confirmed the presence of HAp in the composite PCL fibers. The results of cell culturing suggested that the incorporation of HAp with PCL could regulate the cytoskeleton and the differentiation of cells. More interestingly, the high content of HAp was also found to be conducive to the infiltration of MC-3T3 cells into the mat. The results indicated the potential of PCL/HAp scaffolds as a promising substitute for bone regeneration.

Three-Dimensional Printing of Nano Hydroxyapatite/Poly(ester urea) Composite Scaffolds with Enhanced Bioactivity.

Polymer-bioceramic composites incorporate the desirable properties of each material while mitigating the limiting characteristics of each component. 1,6-Hexanediol l-phenylalanine-based poly(ester urea) (PEU) blended with hydroxyapatite (HA) nanocrystals were three-dimensional (3D) printed into porous scaffolds (75% porosity) via fused deposition modeling and seeded with MC3T3-E1 preosteoblast cells in vitro to examine their bioactivity. The resulting 3D printed scaffolds exhibited a compressive modulus of ∼50 MPa after a 1-week incubation in PBS at 37 °C, cell viability >95%, and a composition-dependent enhancement of radio-contrast. The influence of HA on MC3T3-E1 proliferation and differentiation was measured using quantitative real-time polymerase chain reaction, immunohistochemistry and biochemical assays. After 4 weeks, alkaline phosphatase activity increased significantly for the 30% HA composite with values reaching 2.5-fold greater than the control. Bone sialoprotein showed approximately 880-fold higher expression and 15-fold higher expression of osteocalcin on the 30% HA composite compared to those of the control. Calcium quantification results demonstrated a 185-fold increase of calcium concentration in mineralized extracellular matrix deposition after 4 weeks of cell culture in samples with higher HA content. 3D printed HA-containing PEU composites promote bone regeneration and have the potential to be used in orthopedic applications.