Hydroxyapatite Research Articles

Effect of filler morphology on mechanical behaviour of Mg/HA nanocomposites for degradable implant applications

Abstract Magnesium (Mg) alloys exhibit promising potential for biodegradable orthopaedic applications, with the incorporation of hydroxyapatite (HA), which offers a means to tailor their bioactivity and biodegradation behavior. In this study, the effect of filler morphology on mechanical behaviour and biocorrosion of the Mg/HA composites is analysed. Two distinct morphologies of nano-hydroxyapatite (nHA), needle-like and flake-shaped, were incorporated into Mg using a stir-casting technique. The incorporation of nHA led to a notable increase in hardness, with enhancements of 15% for needle-like nHA and 29% for flake-like nHA. Moreover, the ultimate compressive strength exhibited a significant improvement of 29% for the flake-shaped nHA and 12% for the needle-like nHA. Interestingly, the morphological variation did not impact the degradation behaviour of the composites. Based on these findings, it is proposed that Mg metal matrix composites utilizing bioactive flake-shaped nHA as a filler material hold promise for enhancing the mechanical properties of Mg/HA nanocomposites, particularly for load-bearing implant applications.

Fabrication of ZnO-loaded, polycaprolactone -based, antibacterial 3D scaffolds for bone tissue engineering using melt-electrowriting

The potential of melt-electrowriting (MEW) to fabricate highly porous 3D composite scaffolds for bone tissue engineering (BTE) with antibacterial attachment properties was explored. Zinc oxide (ZnO) nanoparticles (NPs) were loaded into biodegradable medical grade Polycaprolactone (PCL) loaded with 10 wt% hydroxyapatite (HA) NPs to create antibacterial constructs by the MEW technique. The constructs’ morphology, chemical, thermal and mechanical properties, osteoblasts cell viability and bacterial attachment were investigated. Our results demonstrate a unique homogeneous dispersion of ZnO-HA NPs in the outer shell of the fabricated composite fibres by MEW, leading to significant inhibition of bacterial attachment against microorganisms. This novel composite MEW 3D scaffolds yielded promising multifunctional constructs with high potential in BTE.

A 3D in vitro model of biphasic calcium phosphate (BCP) scaffold combined with human osteoblasts, osteoclasts, and endothelial cells as a platform to mimic the oral microenvironment for tissue regeneration

Objectives: This study aimed to develop an innovative 3D in vitro model based on the biphasic calcium phosphate (BCP) scaffold combined with human osteoblasts (hOBs), osteoclasts (hOCs), and endothelial cells to evaluate its effects on bone and vascular cells behavior. Methods: To this end, an optimized mixture of hydroxyapatite (HA) and β-tricalcium phosphate (TCP) with a weight ratio of 30/70 was employed to develop a BCP scaffold using the computer-aided design (CAD) approach. The BCP scaffold was combined with primary cultures of hOBs, hOCs and human umbilical vein endothelial cells (HUVECs). Results: Morphometric analyses using scanning electron microscopy (SEM) and X-ray micro-computed tomography, along with biomechanical testing, revealed that BCP scaffold exhibited a regular 3D structure with large interconnected internal pores (700 µm) and high mechanical strength. In terms of biological behavior, after 14 days of tri-culture with hOBs, hMCs and HUVECs, SEM, immunofluorescence, and histological analyses showed that all cell types were viable and adhered well to the entire surface of the scaffold. Interestingly, SEM and energy-dispersive X-ray spectroscopy analyses also revealed on the BCP scaffold the presence of mineralized matrix crystals of Ca, P, O and C within a tissue-like cell layer produced by the interaction of the three cell types. Conclusions: Data confirmed the high performance of the BCP scaffold through biomechanical studies. Notably, for the first time, this study demonstrated the feasibility of combining BCP scaffold with hOBs, hOCs, and HUVEC, which remained viable and maintained their native phenotypes, creating also tissue-like cell layer. Clinical significanceAlthough further investigation is needed, these results underscore the potential to develop a 3D in vitro model that mimics the oral microenvironment, which could be valuable for BTE approaches in in vivo studies.

Highly efficient phosphate adsorption using calcium silicate hydrate-embedded calcium crosslinked polyvinyl alcohol thin film

The removal of phosphate from water is necessary to avoid eutrophication. In this work, a novel composite film of calcium silicate hydrate (CSH) immobilized within calcium cross-linked polyvinyl alcohol (CSH–PVA) was developed for efficient phosphate removal from water using a simple and environmentally friendly preparation method. The characterization showed that flake crystal-like CSH nanoparticles were immobilized on a PVA film (86–106 μm). Amorphous calcium phosphate and hydroxyapatite were observed after phosphate adsorption. The adsorption efficiency and capability of phosphate were examined under various conditions using batch experiments. The phosphate removal data fitted well to the pseudo-second-order kinetic model (R2 = 0.9903–0.9999) and the Langmuir isotherm model (R2 = 0.9958), which estimated a maximum removal capacity (99.01 mg g−1). Phosphate adsorption was found to be endothermic with spontaneous adsorption via chemisorption with strong affinity (ΔG° = −3.96 to −8.62 kJ mol−1, ΔH° = 65.4 kJ mol−1, and ΔS° = 232.94 J mol−1 K−1). Additionally, significant amounts of fluoride and carbonate ions affected phosphate adsorption at levels exceeding 5-fold and 20-fold that of phosphate, respectively. An excellent removal efficiency was achieved in the range of 72.06%–97.87% using phosphate-containing real samples. Therefore, the proposed CSH–PVA film showed great potential for effective phosphate removal from water, with potential for further use as a fertilizer.

Optimizing biomimetic hydroxyapatite coating on Ti-6Al-6Mo alloy: influence of immersion time

This study investigates the formation and characteristics of hydroxyapatite (HAp) coating on Ti-6Al-6Mo alloy through immersion in a supersaturated calcification solution (SCS) for 3, 7, and 14 days. X-ray diffraction (XRD) and secondary electron microscopy (SEM) with electron dispersive spectroscopy (EDS) were used to identify the phases and characterize the morphology and composition of the HAp layer. Atomic force microscopy (AFM) and contact angle tests were used to evaluate the surface properties, while potentiodynamic corrosion testing in Hanks’ solution was used to assess corrosion behavior. It is confirmed that the sample immersed for 14 days formed an HAp layer on the Ti-6Al-6Mo substrate with a Ca/P ratio of 2.5, approaching the ideal value of 1.67. This HAp film exhibits a smooth and homogeneous crystal structure, with a surface roughness of 31.47 nm and an appreciable corrosion rate of 0.0005 mm y−1. This study signifies the impact of immersion time on the microstructural properties and biocompatibility of biomimetic HAp coatings applied to Ti-6Al-6Mo alloy, contributing to the progress of HAp coatings in biomedical engineering.

Spirulina protein concentrate hydrogel reinforced by hydroxyapatite nanoparticles and hydroxychloroquin: A novel platform for bone regeneration

Among the fabrication methods, hydrogels have received significant attention due to their excellent ability to mimic the extracellular matrix structure. Spirulina is a type of unicellular blue-green algae. It is an excellent source of protein and a wide variety of other nutrients. Hydroxychloroquin (HCQ) reduces bone resorption and osteoclasts growth. This study hypothesized that the hydrogel, which is composed of Spirulina protein cross-linked by transglutaminase and reinforced by hydroxyapatite (HAP) nanoparticles loaded with HCQ, could potentially aid in bone regeneration. The protein from Spirulina was extracted using the probe sonication method. Afterwards, hydrogels were prepared by incorporating the Spirulina protein with gelatin and cross-linked with varying percentages of transglutaminase. HCQ-loaded HAP nanoparticles were used to enhance not only the mechanical properties of the hydrogels but also to stimulate bone mineralization. Hydrogels were studied for their mechanical and rheological properties in vitro, as well as their ability to swell, break down, injectability, and release HCQ. Cell adhesion, proliferation, and bone mineralization on MG-63 osteoblast cells were also studied using Alizarine red and alkaline phosphatase markers. The loading efficiency of HCQ in HAP nanoparticles was about 97 %. The HCQ release rate from hydrogel containing HAP was 85 % in 9 hours. The tensile strength and injectability force of the optimized hydrogel were in the range of 530.75 KPa and 21 N, respectively. The results showed that hydrogels made with 10 % protein, 150 units of transglutaminase, 6 % gelatin, and HAP loaded with HCQ had the best cell behavior and improved markers of bone regeneration. The promising results obtained suggest that the prepared hydrogel may act as a suitable construct for accelerating bone regeneration.

Engineering Triphasic Nanocomposite Coatings on Pretreated Mg Substrates for Biomedical Applications.

Biodegradable polymer-based nanocomposite coatings provide multiple advantages to modulate the corrosion resistance and cytocompatibility of magnesium (Mg) alloys for biomedical applications. Biodegradable poly(glycerol sebacate) (PGS) is a promising candidate used for medical implant applications. In this study, we synthesized a new PGS nanocomposite system consisting of hydroxyapatite (HA) and magnesium oxide (MgO) nanoparticles and developed a spray coating process to produce the PGS nanocomposite layer on pretreated Mg substrates, which improved the coating adhesion at the interface and their cytocompatibility with bone marrow derived mesenchymal stem cells (BMSCs). Prior to the spray coating process of polymer-based nanocomposites, the Mg substrates were pretreated in alkaline solutions to enhance the interfacial adhesion strength of the polymer-based nanocomposite coatings. The addition of HA and MgO nanoparticles (nHA and nMgO) to the PGS matrix, as well as the alkaline pretreatment of the Mg substrates, significantly enhanced the interfacial adhesion strength when compared with the PGS coating on the nontreated Mg control. The average BMSC adhesion densities were higher on the PGS/nHA/nMgO coated Mg than the noncoated Mg controls under direct contact conditions. Moreover, the addition of nHA and nMgO to the PGS matrix and coating the nanocomposite onto Mg substrates increased the average BMSC adhesion density when compared with the PGS/nHA/nMgO coated titanium (Ti) and PGS coated Mg controls under direct contact. Therefore, the spray coating process of PGS/nHA/nMgO nanocomposites on Mg substrates or other biodegradable metal substrates could provide a promising surface treatment strategy for biodegradable implant applications.

Hydroxyapatite-polymer composites with tannin as a chelating agent: crystal structure and mechanical properties

Hydroxyapatite is the main minerals in the bone as a biomaterial. The synthesis of hydroxyapatite requires additional materials to improve its mechanical properties. This research aimed to observe the ability of tannins as a chelating agent in hydroxyapatite synthesis. Hydroxyapatite was synthesized from Ca(OH)2, (NH4)2HPO4, Ca(OH)2, H3PO4, and tannin as chelating agents with precipitation method. Hydroxyapatite made from calcium and phosphate as a precursor and control the pH was 12 with the addition of Sodium Hydroxide. Then, added tannin and stirrer about 1 hour. The precipitate was dried in oven at 40°C for Hydroxyapatite using H3PO4 precursor. All the samples were characterized using FTIR, XRD, SEM and Hardness tester. Two compounds (calcium carbonate and hydroxyapatite) were obtained by using XRD analysis. The crystal size of the hydroxyapatite of 15-27 nm and hydroxyapatite-tannin of 10-29 nm. The SEM results show the surface morphology of hydroxyapatite was obtained as agglomerates or clumping. Hydroxyapatite-tannin was obtained with particle size in fields from 0.1-0.4 µm. The Hardness Tester received an average value was 28.36 N and 27.81 N for hydroxyapatite and 34.43 N dan 33.92 N for hydroxyapatite-tannin. Tannin acts as a chelating agent in the synthesis process of hydroxyapatite by the precipitation method.

Hyaluronic Acid and Calcium Hydroxyapatite in the Context of Hypertrophic Photoaging. Evaluation by 2D, 3D Photographs and Reflectance Confocal Microscopy (RCM).

Hyaluronic Acid and Calcium Hydroxyapatite in the Context of Hypertrophic Photoaging. Evaluation by 2D, 3D Photographs and Reflectance Confocal Microscopy (RCM).

Leveraging Machine Learning for Optimized Mechanical Properties and 3D Printing of PLA/cHAP for Bone Implant.

This study explores the fabrication and characterisation of 3D-printed polylactic acid (PLA) scaffolds reinforced with calcium hydroxyapatite (cHAP) for bone tissue engineering applications. By varying the cHAP content, we aimed to enhance PLA scaffolds' mechanical and thermal properties, making them suitable for load-bearing biomedical applications. The results indicate that increasing cHAP content improves the tensile and compressive strength of the scaffolds, although it also increases brittleness. Notably, incorporating cHAP at 7.5% and 10% significantly enhances thermal stability and mechanical performance, with properties comparable to or exceeding those of human cancellous bone. Furthermore, this study integrates machine learning techniques to predict the mechanical properties of these composites, employing algorithms such as XGBoost and AdaBoost. The models demonstrated high predictive accuracy, with R2 scores of 0.9173 and 0.8772 for compressive and tensile strength, respectively. These findings highlight the potential of using data-driven approaches to optimise material properties autonomously, offering significant implications for developing custom-tailored scaffolds in bone tissue engineering and regenerative medicine. The study underscores the promise of PLA/cHAP composites as viable candidates for advanced biomedical applications, particularly in creating patient-specific implants with improved mechanical and thermal characteristics.

Fabrication of 3D Bioactive Melt Electrowriting Composite Scaffold with High Osteogenic Potential

A key challenge in using melt electrowriting (MEW) technology is incorporating large amounts of bioactive inorganic materials, such as hydroxyapatite (HA). In the present study, following optimization of the fabrication parameters, 40%-HA (HA40) nanoparticles were pre-mixed into medical-grade polycaprolactone (PCL) and processed using the MEW (MEW) technique to mimic the structure and function of the natural extracellular matrix (ECM) for bone regeneration. The HA40 fibrous composite scaffolds showed continuous writing and obtained a well-connected and orderly stacked fibre with a small diameter size (67 ± 8.5µm). A major result of the present study was the successful enrichment and accumulation of the HA particles, which mostly occurred on the MEW fibre external surfaces. This design allows for direct interfacial interaction with human periodontal ligament cells (hPDLCs). We systematically investigated the behaviour and function of hPDLCs on the HA40 composite scaffold, alongside parameters related to mineralization. The HA40 scaffold demonstrated significantly higher metabolic activity and enhanced expression of osteonectin and RUNX2 compared to PCL-only scaffolds, as well as increased levels of ALP and COL1. The study’s findings demonstrate that bioactive composite scaffolds, incorporating 40% HA into m-PCL via MEW, effectively enhance the biological response of the ECM and are promising for potential applications in bone regeneration.

Dental Applications of Ion-Substituted Hydroxyapatite: A Review of the Literature.

Hydroxyapatite (HA) forms an essential constituent of human teeth and bone. Its distinctive characteristic features, such as bioactivity and osteoconductivity, make it an ideal candidate to be used as an implant coating in restorative dentistry and maxillofacial surgery for bone regeneration. However, low fracture toughness and brittleness are a few of the inherent features of HA, which limit its application in load-bearing areas. The potential of HA to engage its lattice structure with either partial or complete substitution with external ions has become an increasing area of research as this phenomenon has the potential to enhance the biological and functional properties of the material. Consequently, this review aimed to highlight the role of various substituted ions in dental applications. Data indicate that the newly formed HA-substituted biomaterials demonstrate enhanced remineralization and antimicrobial activity along with improved hardness. Ion-substituted HA offers a promising strategy for future clinical research as these materials may be incorporated into various dental products for therapeutic treatments.

Fabrication of 3D microfibrous composite polycaprolactone/hydroxyapatite scaffolds loaded with piezoelectric poly (lactic acid) nanofibers by sequential near-field and conventional electrospinning for bone tissue engineering

Near-field electrospinning (NFES) has recently gained considerable interest in fabricating tissue engineering scaffolds. This technique combines the advantages of both 3D printing and electrospinning. It allows for the production of fibers with smaller resolution and the ability to make regular structures with suitable pores. In this study, a microfibrous composite scaffold of polycaprolactone (PCL)/hydroxyapatite (HA) was prepared by NFES in the first step. The microfibrous scaffold had a fiber spacing of 414.674 ± 24.9 μm with an average fiber diameter of 94.695 ± 16.149 μm. However, due to the large fiber spacing, the surface area was insufficient for cell adhesion. Therefore, the hybrid scaffold was prepared by adding aligned and random electrospun poly (L-lactic acid) (PLLA) nanofibers to the microfibrous scaffold. Cellular studies showed that cell adhesion to the hybrid scaffold increased by 334 % compared to the microfibrous scaffold. These nanofibers also exhibited piezoelectric properties, which helped stimulate bone regeneration. Aligned nanofibers in the hybrid scaffold enhanced alkaline phosphatase activity and the intensity of alizarin red staining 1.5 and 1.6 times, respectively, compared to the microfibrous scaffold. Furthermore, the elastic modulus and ultimate tensile strength increased by 268 % and 130 %, respectively, by adding aligned nanofibers to the microfibrous scaffold. Therefore, the hybrid microfibrous composite scaffold of PCL/HA containing aligned electrospun PLLA nanofibers with improved properties showed the potential for bone regeneration.

Development of a Monte Carlo simulation platform for the systematic evaluation of photon-counting detector-based micro-CT

PurposeThis study aimed to develop a photon-counting detector (PCD) based micro-CT simulation platform for assessing the performance of three different PCD sensor materials: cadmium telluride (CdTe), gallium arsenide (GaAs), and silicon (Si). The evaluation encompasses the components of primary and scatter signals, performance of imaging contrast agents, and detector efficiency. MethodsSimulations were performed using the Geant4 Monte Carlo toolkit, and a micro-PCD-CT system was meticulously modeled based on realistic geometric parameters. Results.The simulation can obtain HU values consistent with measured results for iodine and calcium hydroxyapatite contrast agents. The two major components of scatter signals for CdTe and GaAs based PCD are fluorescent X-ray photons and photoelectrons, whereas for Si, the components are photoelectrons and Compton electrons. Scattering counts of CdTe and GaAs sensors can be effectively reduced by using energy thresholds, whereas those of Si sensor are insensitive to the applied threshold. The optimal threshold values for CdTe and GaAs are 30 and 15 keV, respectively. For contrast agent imaging, GaAs exhibits enhanced sensitivity to low photon energies compared to CdTe, while it’s contrast-to-noise ratio (CNR) values are slightly lower than those of CdTe at the same contrast agent concentration. Among the three sensor materials, Si has the lowest CNR and detector efficiency; CdTe exhibits the highest efficiency, except in low-energy ranges (< 45 keV), where GaAs has superior efficiency. ConclusionsThe proposed methods are expected to benefit PCD optimization and applications, including energy threshold selection, scattering correction, and may reduce the need for large-scale experiments.

Development of hydroxyapatite/poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate)/gelatin composite nanofibers to improve bone‐forming cell proliferation and mineral deposition

AbstractCalcium phosphate hydroxyapatite (HA) was successfully incorporated into poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate)/gelatin (PHBV/GEL) nanofibers through an electrospinning process in a hexafluoroisopropanol solvent (HFIP). The PHBV/GEL was electrospun and collected using a rotating metallic network to develop highly ordered nonwoven mats. The effects of HA addition on the morphologies of the obtained fibers were investigated using SEM. The average diameter of the fibers ranged around 700–900 nm, depending on the HA content. From a mechanical perspective, the addition of HA nanoparticles showed variations in tensile strength and elastic modulus values. The lowest tensile strength measured for neat PHBV/GEL was 0.37 ± 0.08 MPa with an elastic modulus of 9.45 ± 0.65 MPa, whereas the highest tensile strength reported for 5% HA‐loaded PHBV/GEL mats was 1.1 ± 0.4 MPa with an elastic modulus of 16.9 ± 0.39 MPa. In addition, cell viability, and mineral deposition were also studied using MC3T3‐E1 pre‐osteoblasts. The in vitro experiment results showed that the HA loaded‐PHBV/GEL mats provide optimal conditions for cell growth and osteogenic differentiation of MC3T3‐E1 cells. This study reveals the potential of PHBV/GEL/HA matrices in the development of novel guided bone‐regeneration (GBR) membranes for orthopedic and craniomaxillofacial surgery, by providing favorable structural features for attachment, growth, and differentiation of osteoblast cells.Highlights Simple and cheap electrospinning strategy toward network‐like fibrous mats. Microstructure, mechanical, and biological features were evaluated. Electrospun PHBV/GEL/HA promoted calcium phosphate deposition by MC3T3‐E1 cells.

Effect of Tin (Sn) Addition on the Corrosion Behavior of Hydroxyapatite (HAP) Coated Mg/MgSn Alloys using Different Coating Methods

Effect of Tin (Sn) Addition on the Corrosion Behavior of Hydroxyapatite (HAP) Coated Mg/MgSn Alloys using Different Coating Methods

Exploring the effect of hydroxyapatite nanoparticle shape on red blood cells and blood coagulation.

Aim: In this study, we evaluated the effects of two types of hydroxyapatite (HAP) nanoparticles, sharing the same surface chemistry but differing in shape, on the biological characteristics of plasma, platelets and red blood cells.Materials & methods: Initially, two different shapes (rod-shaped and sphere-shaped) of HAPs were characterized. These HAPs were then co-cultured with plasma and red blood cells to examine their impact on coagulation and hemolysis. The impact of HAPs on white blood cells count in mice were evaluated following gavage and tail vein injection.Results: Sphere-shaped HAP is more likely to adsorb onto platelet surfaces, while rod-shaped HAP is more likely to cause hemolysis. Although there are differences in the in vitro experimental results between sphere-shaped HAP and rod-shaped HAP, both types demonstrate good blood compatibility at a 20mM concentration. Furthermore, in vivo experiments showed that sphere-shaped nano-HAP induced a more pronounced increase in white blood cell count, suggesting that it may exhibit greater toxicity.Conclusion: While differences exist in the blood compatibility test results between the two HAPs, these differences are minimal, with both results falling within a safe range. Overall, HAP demonstrates excellent blood compatibility.

Trends in Injectable Biomaterials for Vocal Fold Regeneration and Long-Term Augmentation.

Human vocal folds (VF), a pair of small, soft tissues in the larynx, have a layered mucosal structure with unique mechanical strength to support high-level tissue deformation by phonation. Severe pathological changes to VF have causes including surgery, trauma, age-related atrophy, and radiation, and lead to partial or complete communication loss and difficulty in breathing and swallowing. VF glottal insufficiency requires injectable VF biomaterials such as hyaluronan, calcium hydroxyapatite, and autologous fat to augment VF functions. Although these biomaterials provide an effective short-term solution, significant variations in patient response and requirements of repeat reinjection remain notable challenges in clinical practice. Tissue engineering strategies have been actively explored in the search of an injectable biomaterial that possesses the capacity to match native tissue's material properties while promoting permanent tissue regeneration. This review aims to assess the current status of biomaterial development in VF tissue engineering. The focus will be on examining state-of-the-art techniques including modification with bioactive molecules, cell encapsulation, composite materials, as well as, in situ crosslinking with click chemistry. We will discuss potential opportunities that can further leverage these engineering techniques in the advancement of VF injectable biomaterials.

GDF10 is a negative regulator of vascular calcification

Cardiovascular mortality is particularly high and increasing in patients with chronic kidney disease, with vascular calcification (VC) as a major pathophysiologic feature. VC is a highly regulated biological process similar to bone formation involving osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). We have previously demonstrated that loss of T-cell death-associated gene 51 (TDAG51) expression leads to an attenuation of medial VC. We now show a significant induction of circulating levels of growth differentiation factor 10 (GDF10) in TDAG51-/- mice, which was of interest due to its established role as an inhibitor of osteoblast differentiation. The objective of this study was to examine the role of GDF10 in the osteogenic transdifferentiation of VSMCs. Using primary mouse and human VSMCs, as well as exvivo aortic ring cultures, we demonstrated that treatment with recombinant human (rh) GDF10 mitigated phosphate-mediated hydroxyapatite (HA) mineral deposition. Furthermore, exvivo aortic rings from GDF10-/- mice exhibited increased HA deposition compared to C57BL/6J controls. To explain our observations, we identified that rhGDF10 treatment reduced protein expression of runt-related transcription factor 2, a key driver of osteogenic transdifferentiation of VSMCs and VC. In support of these findings, invivo treatment with rhGDF10 attenuated VD3-induced VC. Furthermore, we demonstrated an increase in circulating GDF10 in patients with chronic kidney disease with clinically defined severe VC, as assessed by coronary artery calcium score. Thus, our studies identify GDF10 as a novel inhibitor of mineral deposition and as such, may represent a potential novel biomarker and therapeutic target for the detection and management of VC.

Enhancing alginate dialdehyde-gelatin (ADA-GEL) based hydrogels for biofabrication by addition of phytotherapeutics and mesoporous bioactive glass nanoparticles (MBGNs)

This study explores the 3D printing of alginate dialdehyde-gelatin (ADA-GEL) inks incorporating phytotherapeutic agents, such as ferulic acid (FA), and silicate mesoporous bioactive glass nanoparticles (MBGNs) at two different concentrations. 3D scaffolds with bioactive properties suitable for bone tissue engineering (TE) were obtained. The degradation and swelling behaviour of films and 3D printed scaffolds indicated an accelerated trend with increasing MBGN content, while FA appeared to stabilize the samples. Determination of the degree of crosslinking validated the increased stability of hydrogels due to the addition of FA and 0.1% (w/v) MBGNs. The incorporation of MBGNs not only improved the effective moduli and conferred bioactive properties through the formation of hydroxyapatite (HAp) on the surface of ADA-GEL-based samples but also enhanced VEGF-A expression of MC3T3-E1 cells. The beneficial impact of FA and low concentrations of MBGNs in ADA-GEL-based inks for 3D (bio)printing applications was corroborated through various printing experiments, resulting in higher printing resolution, as also confirmed by rheological measurements. Cytocompatibility investigations revealed enhanced MC3T3-E1 cell activity and viability. Furthermore, the presence of mineral phases, as confirmed by an in vitro biomineralization assay, and increased ALP activity after 21 days, attributed to the addition of FA and MBGNs, were demonstrated. Considering the acquired structural and biological properties, along with efficient drug delivery capability, enhanced biological activity, and improved 3D printability, the newly developed inks exhibit promising potential for biofabrication and bone TE.