Bioactive Particles Research Articles

Sustainable drug release from highly porous and architecturally engineered composite scaffolds prepared by 3D printing.

Additive manufacturing techniques have evolved novel opportunities for the fabrication of highly porous composite scaffolds with well-controlled and interconnected pore structures which is notably important for tissue engineering. In this work, poly (ε-caprolactone) (PCL)-based composite scaffolds (average pore diameter of 450 μm and strut thickness of 400 μm) reinforced with 10 vol% bioactive glass particles (BG; ∼6 μm) or TiO2 nanoparticles (∼21 nm), containing different concentrations of tetracycline hydrochloride (TCH) as an antimicrobial agent, were prepared by 3D printing. In order to investigate the effect of fabrication process and scaffold geometry on the biocompatibility, drug release kinetics, and antibacterial activity, polymer and composite films (2D structures) were also prepared by solvent casting method. We demonstrate that even without any additional coating layer, sustainable release can be attained on highly porous scaffolds prepared by 3D printing due to chemical interactions between functional groups of TCH and the bioactive particles. Herein, the effect of TiO2 nanoparticles on the release rate is substantially more pronounced than BG particles. Nevertheless, agar well-diffusion and MTT assays determine better cellular viability and higher antibacterial effect for PCL/BG composite. Although all the drug-eluting composite scaffolds exhibit acceptable hemocompatibility, in vitro cellular and bacterial studies also determine that the maximum amount of TCH that can inhibit gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) bacteria without cytotoxicity effect (≥95% viability) is 0.57 mg/ml. These findings may pave the way for designing structurally engineered composite scaffolds with sustainable drug release profile by additive manufacturing techniques for tissue engineering applications.

Orthodontic resin containing bioactive glass: Preparation, physicochemical characterization, antimicrobial activity, bioactivity and bonding to enamel

ObjectivesTo synthesize experimental orthodontic resins used for bracket bonding containing different concentrations of niobophosphate (NbG) and 45S5 glasses. MethodsExperimental resins (Bis-GMA + UDMA + DMAEMA) were developed with two bioactive glasses (NbG and 45S5) in concentrations of 5, 10 and 20 (wt%). An experimental resin without glass and a commercial resin (Transbond XT) were used. Control of pH and ions release (calcium and phosphate) at different pH values (4 and 7) were evaluated in the time intervals of 24 h, 7 d, 14 d and 28 d. Microhardness, bioactivity (SEM, FTIR/ATR) and antibacterial activity of the resins were analyzed. Metal brackets were bonded to premolars (n = 10) with the resins to evaluate shear bond strength (SBS). ResultsThe experimental resins containing 45S5 were capable of raising the pH of the solution and showed high values of calcium and phosphate ions release. Resins containing NbG had a neutralizing potential. The NbG and Transbond resins released only phosphate ions. Transbond XT showed high microhardness values when compared with the experimental 45S5 resins (p < 0.05). Analysis by SEM showed precipitates and FTIR/ATR confirmed the presence of a calcium phosphate-based compound in the resins containing 45S5. There was no difference in SBS between the tested materials (p > 0,05). The resins with presence of bioactive particles showed antibacterial activity. ConclusionWithout compromising the shear bond strength, bioactive glasses showed the capacity to elevate pH, reduce the hardness of experimental resins when compared with Transbond XT and no filler experimental resin.

The use of bioactive particles and biomimetic analogues for increasing the longevity of resin-dentin interfaces: A literature review.

Protecting resin-dentin interfaces from hydrolytic and enzymatic degradation is critical for the longevity of adhesive restorations. In recent years, several strategies have been tested in vitro to induce apatite precipitation within interfibrillar and intrafibrillar collagen spaces, as well as in resin-sparse regions where the adhesive infiltration was incomplete. Also, the presence of calcium ions and other metallic ions has shown an inhibitory effect on enzymatic activity. Ion-releasing particles and biomimetic analogs have been studied for hybrid layer remineralization. Overall, remineralization strategy is dependent on the remaining mineral content. In partially demineralized dentin, residual apatite crystallites serve as nucleation sites for calcium and phosphate ions precipitation and crystal growth ("top-down" remineralization). In completely demineralized dentin where crystallites are absent (e.g., acid etched dentin) the use of mineral nano-precursors assisted by non-collagenous proteins analogs are necessary ("bottom-up" remineralization). This article reviews the approaches for hybrid layer remineralization and resin-dentin interface preservation.

Optimization of coenzyme Q10 encapsulation in liposomes using supercritical carbon dioxide

Coenzyme Q10 (CoQ10)-loaded liposomes were prepared with soy lecithin utilizing a single step supercritical carbon dioxide (SCCO2) method, which did not require the use of organic solvents, buffers or surfactants. The effects of pressure, temperature, pressurization rate and CoQ10-to-lecithin ratio on bioactive loading (BL), particle size (Ps) and polydispersity index (PdI) were investigated and modeled by response surface methodology (RSM). Pressure and concentration of CoQ10 had a great influence on the three responses. High pressures led to lower BLs, but also particles with smaller Ps and PdI. High concentrations of CoQ10 allowed obtaining higher BLs and lower PdI, but also higher Ps. High pressurization rates were needed to obtain high BLs, but, in contrast, it also led to higher PdIs. Temperature had a positive influence only on the PdI. The optimum conditions predicted by the model to simultaneously maximize the BL and minimize the Ps and PdI were 30 MPa, 40 °C, 6 MPa∙min−1 and 17 mol% CoQ10 (BL of 4.2 %, Ps of 177 nm and PdI of 0.313). Furthermore, encapsulation efficiencies between 87.6–99.7 % were achieved and semi-spherical stable particles (zeta potential ≈ −70 mV) were formed. Differential scanning calorimetry indicated a potential loss of crystallinity upon the encapsulation of CoQ10 into the liposomes. The findings reveal the great potential of this SCCO2 method for the encapsulation of CoQ10 in liposomes.

Poly(d,l-Lactic acid) Composite Foams Containing Phosphate Glass Particles Produced via Solid-State Foaming Using CO2 for Bone Tissue Engineering Applications.

This study reports on the production and characterization of highly porous (up to 91%) composite foams for potential bone tissue engineering (BTE) applications. A calcium phosphate-based glass particulate (PGP) filler of the formulation 50P2O5-40CaO-10TiO2 mol.%, was incorporated into biodegradable poly(d,l-lactic acid) (PDLLA) at 5, 10, 20, and 30 vol.%. The composites were fabricated by melt compounding (extrusion) and compression molding, and converted into porous structures through solid-state foaming (SSF) using high-pressure gaseous carbon dioxide. The morphological and mechanical properties of neat PDLLA and composites in both nonporous and porous states were examined. Scanning electron microscopy micrographs showed that the PGPs were well dispersed throughout the matrices. The highly porous composite systems exhibited improved compressive strength and Young’s modulus (up to >2-fold) and well-interconnected macropores (up to ~78% open pores at 30 vol.% PGP) compared to those of the neat PDLLA foam. The pore size of the composite foams decreased with increasing PGPs content from an average of 920 µm for neat PDLLA foam to 190 µm for PDLLA-30PGP. Furthermore, the experimental data was in line with the Gibson and Ashby model, and effective microstructural changes were confirmed to occur upon 30 vol.% PGP incorporation. Interestingly, the SSF technique allowed for a high incorporation of bioactive particles (up to 30 vol.%—equivalent to ~46 wt.%) while maintaining the morphological and mechanical criteria required for BTE scaffolds. Based on the results, the SSF technique can offer more advantages and flexibility for designing composite foams with tunable characteristics compared to other methods used for the fabrication of BTE scaffolds.

Fluorine-Containing Bioactive Glass Spherical Particles Synthesized By Sol-Gel Route Assisted by Ultrasound Energy or Mechanical Mixing

Bioactive glasses (BG) are versatile materials for various biomedical applications due to their capacity to bond to hard and soft tissues. These materials can be produced with different nominal compositions, such that include fluoride ions. Fluorine-containing-BG (BGF) can be produced by the sol-gel method, and its properties can be changed by altering the synthesis parameters. Here, BGF particle size between 235 nm-390 nm were obtained through sol-gel method assisted by ultrasound energy (BGU) or through mechanical stirring (BGM). The BGM and BGU particles showed highly dispersed spherical shape, moreover BGM are mesoporous and BGU are dense structures, indicating mixing mode can alter mainly the material textural characteristics. All compositions have apatite forming ability, verified by DRX from 14 days in SBF. The results showed CaF2 on the surface of BGF particles, indicating that part of F ions was not incorporated in the material network. The samples did not show any cytotoxicity towards human cells in Cellular Metabolic Activity and Calcein assays. This study showed that mechanical agitation was more efficient to produce mesoporous particles to be applied as carrier of drugs and molecules to the biological environment, so BGM can be used as a more efficient biomaterial for such applications.

Modification of PMMA Cements for Cranioplasty with Bioactive Glass and Copper Doped Tricalcium Phosphate Particles.

Cranioplasty represents the surgical repair of bone defects or deformities in the cranium arising from traumatic skull bone fracture, cranial bone deformities, bone cancer, and infections. The actual gold standard in surgery procedures for cranioplasty involves the use of biocompatible materials, and repair or regeneration of large cranial defects is particularly challenging from both a functional and aesthetic point of view. PMMA-based bone cement are the most widely biomaterials adopted in the field, with at least four different surgical approaches. Modifications for improving biological and mechanical functions of PMMA-based bone cement have been suggested. To this aim, the inclusion of antibiotics to prevent infection has been shown to provide a reduction of mechanical properties in bending. Therefore, the development of novel antibacterial active agents to overcome issues related to mechanical properties and bacterial resistance to antibiotics is still encouraged. In this context, mechanical, biological, and antibacterial feature against P. aeruginosa and S. aureus bacterial strains of surgical PMMA cement modified with BG and recently developed Cu-TCP bioactive particles have been highlighted.

Evidence for Gender-Specific Bone Loss Mechanisms in Periprosthetic Osteolysis.

Osteolysis adjacent to total hip replacement (THR) prostheses is a major cause of their eventual failure. Periprosthetic osteolysis is associated with the production of bioactive particles, produced by the wear of articulating prosthesis surfaces. Wear particles invade the periprosthetic tissue, inducing inflammation and bone resorption. Previous studies have shown that osteocytes, the most numerous cell type in mineralised bone, can respond to wear particles of multiple orthopaedic material types. Osteocytes play important roles in bone resorption, regulating bone resorption by osteoclasts and directly through osteocytic osteolysis, also known as perilacunar remodelling. In this study, we perform a histological analysis of bone biopsies obtained from cohorts of male and female patients undergoing either primary THR surgery or revision THR surgery for aseptic loosening. The osteocyte lacunae area (Ot.Lac.Ar) and percentage lacunar area/bone area (%Ot.Lac.Ar/B.Ar) were significantly larger overall in revision THR bone than bone from similar sites in primary THR. Analysis by patient gender showed that increased Ot.Lac.Ar, indicative of increased perilacunar remodelling, was restricted to female revision samples. No significant differences in osteoclast parameters were detectable between the cohorts. These findings suggest previously unrecognised gender-specific mechanisms of bone loss in orthopaedic wear particle-induced osteolysis in humans.

Complete inclusion of bioactive molecules and particles in polydimethylsiloxane: a straightforward process under mild conditions

By applying a slow curing process, we show that biomolecules can be incorporated via a simple process as liquid stable phases inside a polydimethylsiloxane (PDMS) matrix. The process is carried out under mild conditions with regards to temperature, pH and relative humidity, and is thus suitable for application to biological entities. Fluorescence and enzymatic activity measurements show that the biochemical properties of the proteins and enzyme tested are preserved, without loss due to adsorption at the liquid-polymer interface. Protected from external stimuli by the PDMS matrix, these soft liquid composite materials are new tools of interest for robotics, microfluidics, diagnostics and chemical microreactors.

Bioactive glass-containing hydrogel delivery system for osteogenic differentiation of human dental pulp stem cells.

Osteoconductive hydrogels can be fabricated by incorporating necessary growth factors and bioactive particles or simply utilizing the ability of the hydrogel itself to induce bone regeneration. The osteogenic inductive potential of the bioactive glass microparticles (BG MPs) has been well-studied. However, the role of the hydrogel embedding the BG MPs on the osteogenic differentiation of the encapsulated stem cells has not been well established. Moreover, it has been reported that the dental pulp stem cell (DPSC) has the capability of regenerating the craniofacial bone tissue when receiving the necessary osteogenic signals from the microenvironment. In the current study, we have fabricated a composite hydrogel based on alginate and Matrigel containing BG MPs and evaluated the role of the BG MPs and Matrigel on osteogenic differentiation of the encapsulated DPSCs. Our results confirmed that presence of Matrigel enhances the osteogenic differentiation of the DPSCs regardless of the decrease in elasticity of the hydrogel in presence of the BG MPs. This strategy of modifying the microenvironment can be a promising approach for craniofacial bone tissue engineering.

Influence of Bioactive Particles on Properties of Resin Infiltrant

Dental caries is considered one of the most prevailing diseases affect humans. The avoidance of dental caries and the remineralization of demineralized surface lesions before restorative interference is the goal of modern dentistry [1]. Enamel demineralization is the first sign of dental caries which jeopardizes tooth health and esthetics. Remineralization of these lesions is capable to arrest and reverse the lesion to healthy enamel tissue.

Generation of Alkali Metal Iodide Aerosols with Glycerin for Inhalation

Abstract—The article describes a method of generating bioactive alkali metal iodide aerosol particles with glycerin for inhalation; the particles have a diameter of d ≈ 0.03–3 µm and a mass productivity of m = 10–200 µg/s. A delivery device has been created.

Superior biological performance and osteoinductive activity of Si-containing bioactive bone regeneration particles for alveolar bone reconstruction

Bone grafting materials for repair of alveolar bone deficits have improved markedly in recent years, increasing the applicability and success of oral implantology. The long-term success rate of dental implant surgery is strongly dependent on the quality and stability of residual bone tissue. Therefore, reconstruction of resorbed alveolar bone is a challenge for clinicians. In the present study, we have developed bioactive bone regeneration particles (BRPs) using amorphous calcium phosphate and 58S bioglass as raw materials. The structural characteristics, biocompatibility, and osteoinductivity of these BRPs were compared to commercially available bovine spongy bone (BSB) without organic components. X-ray diffractometry (XRD) and scanning electron microscopy (SEM) showed that BRPs were composed of β-tricalcium phosphate (β-TCP) and calcium silicate in the form of hexagonal crystals, while BSB was mainly hydroxyapatite (HA) arranged in orderly nano-sized crystals. The viability of human bone marrow mesenchymal stem cells (hBMSCs) cultured in BRP-containing medium was roughly equal to that of hBMSCs in control medium. Moreover, hBMSCs in BRP medium exhibited greater proliferation rates, substrate attachment, alkaline phosphatase (ALP) activity, alizarin red staining intensity, and expression levels of osteogenic-related genes (COL-I, OCN, Runx-2, ALP, BSP) than hBMSCs in BSB medium, indicating the superior osteoinductivity of BRPs. Silicon ions released from BRPs during cell culture were crucial for these enhanced biological properties. BRPs also demonstrated superior osteoconduction and osteoinduction properties for bone defect repair, suggesting promise for alveolar bone repair surgery.

Effects Bone Regeneration Using Nanotechnology – Calcium Silicate Nano-Composites.

Calcium phosphate ceramics are rapidly degraded faster than the rate of tissue formation, which makes no Scaffolding enough strength and makes it unsuitable for applications that are bearing the load. Therefore, Bio-Ceramic a new generation of ceramics, with calcium silicate (Ca-Si) attention attracted to. Methodology: One way to improve the biochemical properties of these metal ions into their structure is Bio- Ceramic Add. Nowadays, along with approaching the normal structure of bones and making use of the properties of nanotechnology researchers to build Nano-composite scaffolds were driven. Results: The results of powder X-ray diffraction is shown in Figure 1. The pattern observed in this figure shows the corresponding Hardystonite reference card. Hardystonite powder pattern of tetragonal structure with a=7.8287 and c=5.0140 angstrom fixed network specifies. In addition, sharp peaks indicating the crystalline structure Hardystonite after heat treatment. Conclusion: Bioactive particles in the inner and outer composite is increased bioactivity. By placing the samples in a solution of calcium and phosphate ions in the SBF solution and those other elements on the surface sediment samples from the MAP images visible.

Magnesium-Based Bioactive Composites Processed at Room Temperature.

Hydroxyapatite and bioactive glass particles were added to pure magnesium and an AZ91 magnesium alloy and then consolidated into disc-shaped samples at room temperature using high-pressure torsion (HPT). The bioactive particles appeared well-dispersed in the metal matrix after multiple turns of HPT. Full consolidation was attained using pure magnesium, but the center of the AZ91 disc failed to fully consolidate even after 50 turns. The magnesium-hydroxyapatite composite displayed an ultimate tensile strength above 150 MPa, high cell viability, and a decreasing rate of corrosion during immersion in Hank’s solution. The composites produced with bioactive glass particles exhibited the formation of calcium phosphate after 2 h of immersion in Hank’s solution and there was rapid corrosion in these materials.

Remineralization of early enamel caries lesions induced by bioactive particles: An in vitro speckle analysis.

This study aimed at evaluating the remineralization effect promoted by different bioactive fillers on simulated early caries lesions in enamel (ECLE). Forty sound bovine incisors were used to prepare buccal enamel specimens (6 × 6 × 2 mm). The specimens were divided into two areas (3 × 3 mm²): control (CTR) and experimental (EXP). All the enamel specimens were then submitted to a specific protocol for a period of 48 h to induce simulated caries lesions. Subsequently, the specimens were treated for 7 days (2 min, twice a day) with a slurry pastes containing different bioactive particles (P/L ratio: 1 g/mL). All the specimens were analyzed by laser speckle before and after treatments. The results showed after the first analysis that the ECLE had very low average intensity (back-scattered light). Conversely, after application of the bioactive pastes, higher average intensity was always detected; this was comparable to CTR sound specimens. In conclusion, innovative pastes/gels developed for enamel remineralization should contain bioactive particles that when applied daily on early caries lesions may "boost" the remineralization process to reestablish a sound enamel.

Spheroidization on Fructus Mori polysaccharides to enhance bioavailability and bioactivity by anti-solvent precipitation method

The natural bioactive polysaccharide was regarded as the effective nanocarrier for delivery of active ingredients for its biocompatibility and biodegradability. Moreover, the Fructus Mori polysaccharide has been proved to have good antioxidant and hypoglycemic activities. In this study, the Fructus Mori polysaccharide particles were prepared using antisolvent precipitation method. The bioactive polysaccharide particles exhibited smaller and rounder as the increase of the ethanol/water ratio. The average size, polydispersity index (PDI) and ξ-potential of the bioactive polysaccharide particles were 396.06 nm, 0.38 and −21.23 mV at ethanol/water ratio of 20:1. After spheroidization, the polysaccharide particles exhibited more stable when exposed to heat, increased ionic strength and alkaline conditions. Furthermore, the bioactive polysaccharide particle with the smallest size had the strongest protein adsorption capacity and bioavailability. Especially, the MFP-NP3 showed the ORAC value of 917.06 ± 34.13 μmol TE/g, and the α-glucosidase inhibitory activity of 56.98 ± 1.19% at 0.5 mg/mL. In addition, compared to the native Fructus Mori polysaccharide, the spheroidization enhanced the antioxidant ability and hypoglycemic activity.

Multi-level customized 3D printing for autogenous implants in skull tissue engineering

Three-dimensional (3D) printing of decellularized extracellular matrix (ECM) has been achieved to ensure real physiological environments for tissue engineering. However, the limited source, biocompatibility, and biosafety of decellularized ECM are deficiencies in its large clinical use. Autogenous ECM is biocompatible, bioactive, and biosafe, making it an optimal choice for future clinical applications of 3D printing. Here, we developed a multi-level customized 3D printing (MLC-3DP) strategy applying autogenous bone matrix (Auto-BM). This MLC-3DP includes shape specificity (shape), material specificity (Auto-BM), and cell specificity (autogenous cells) for true patient-specific repairs. Auto-BM (skull flaps) is readily accessible for specific patients after craniectomy, providing sufficient autogenous materials for MLC-3DP. Under mild conditions of this strategy, human-scale 3D printed samples can be fabricated using bioactive micron-sized Auto-BM particles. Multi-level customized autogenous bones (MLC-Auto-Bones) are finally obtained by combining autogenous bone marrow-derived mesenchymal stem cells (Auto-BMSCs). With autogenous materials and cells, MLC-Auto-Bones are inherently biocompatible and biosafe, providing good bioactivity for osteogenesis. In this implant, Auto-BMSCs can spontaneously differentiate into osteoblasts in vitro without additional osteogenic factors. In critical-sized skull defect models in vivo (3 months), implants integrate tightly to the defects’ margin, facilitate mineralization, and generate vascularized mature bone. This work provides not only feasibility for patient-specific implants for skull defects, but also potential patient-specific solutions for other similar clinical requirements.

Facile one-step bioinspired mineralization by chitosan functionalized with graphene oxide to activate bone endogenous regeneration

Facilitated endogenous tissue engineering is emerging as a convenient and easy strategy for bone repair. However, the substitution with satisfactory bioactivity and osteoinductivity which can activate endogenous stem cells responds and in situ recruit them homing towards to damaged area remains a challenge. To stimulate the biomineralization process of inorganic nanoparticles in natural bone, bioactive nano hydroxyapatite particles (nHAP) were in situ crystallized into the graphene oxide/chitosan/nHAP (GO/CS/nHAP) scaffold via effective regulation of CS functionalized with GO network matrix and presented a uniform dispersion with nanometer-scale. As-prepared scaffold exhibited better physicochemical properties, such as three-dimensional (3D) porous bone-like hierarchical structure, proper mechanical property, biodegradation as well as suitable water uptake and retention ratio. The biomimetic mineralization and cell culture experiments demonstrated that hybrid scaffold possessed superior bioactivity and cell proliferation ability in vitro. In addition, the rat calvarial defect repair models and tissue pathological characterization further proved that the hybrid scaffold had excellent biocompatibility and capacity of in situ inducing bone regeneration. Herein, the prepared scaffold might be an excellent candidate for endogenous bone repair.

Achieving High-Yield Production of Functional AAV5 Gene Delivery Vectors via Fedbatch in an Insect Cell-One Baculovirus System

Despite numerous advancements in production protocols, manufacturing AAV to meet exceptionally high demand (1016–1017 viral genomes [VGs]) in late clinical stages and for eventual systemic delivery poses significant challenges. Here, we report an efficient, simple, scalable, robust AAV5 production process utilizing the most recent modification of the OneBac platform. An increase in volumetric yield of genomic particles by ∼6-fold and functional particles by ∼20-fold was achieved by operating a high-cell-density process in shake flasks and bioreactors that involves an Sf9-based rep/cap stable cell line grown at a density of about 10 million cells/mL infected with a single baculovirus. The overall volumetric yields of genomic (VG) and bioactive particles (enhanced transducing units [ETUs]) in representative fedbatch bioreactor runs ranged from 2.5 to 3.5 × 1014 VG/L and from 1 to 2 × 1011 ETU/L. Analytical ultracentrifugation analyses of affinity-purified AAV vector samples from side-by-side batch and fedbatch production runs showed vector preparations with a full and empty particle distribution of 20%–30% genomic and 70%–80% empty particles. Moreover, the stoichiometric analysis of capsid proteins from fedbatch production in shake flask and bioreactor run samples demonstrated the incorporation of higher VP1 subunits, resulting in better functionality.