Materials in Implant Applications and Regenerative Medicine

Low-pressure cold spray (LPCS) technology has attracted interest for the deposition of ceramic coatings due to the thermo-kinetic conditions experienced by the sprayed particles. Unlike conventional thermal spray techniques, the spraying conditions in LPCS can be controlled to avoid the formation of undesired phases. However, ceramics deposition through this process is still challenging. The present study includes a finite element analysis and simulation study of the kinetic conditions of ceramic particles in the LPCS process based on experimental data. The analysis seeks to discuss the effect of nozzle geometry on the kinetic and thermal energy of the sprayed particles at impact and elucidate how the particle travels within the high-velocity jet to be deposited onto a metallic surface. This work examines the behavior of hydroxyapatite particles as a function of particle size and nozzle geometry during LPCS deposition. Interestingly, the results from this research suggest that particle size and nozzle geometry have an influence on the deposition of hydroxyapatite particles. Inertia of large particles proved to be beneficial in keeping their trajectories, allowing them to contribute to the formation of the coatings. Nozzle geometry modifications produced changes in the jet profile and affected the homogeneity of the coatings obtained. This finding contributes to a better understanding of the deposition of hydroxyapatite particles by cold spraying. Full article

Background: Although the influence of titanium implants’ micro-surface properties on titanium discs has been extensively investigated, the research has not taken into consideration their whole-body effect, which may be considered possible using a combinatorial approach. Methods: Five titanium dental implants with a similar moderate roughness and different surface textures were thoroughly characterized. The cell adhesion and proliferation were assessed after adipose-tissue-derived stem cells (ADSCs) were seeded on whole-body implants. The implants’ inductive properties were assessed by evaluating the osteoblastic gene expression. Results: The surface micro-topography was analyzed, showing that hydroxyapatite (HA)-blasted and bland acid etching implants had the highest roughness and a lower number of surface particles. Cell adhesion was observed after 24 h on all the implants, with the highest score registered for the HA-blasted and bland acid etching implants. Cell proliferation was observed only on the laser-treated and double-acid-etched surfaces. The ADSCs expressed collagen type I, osteonectin, and alkaline phosphatase on all the implant surfaces, with high levels on the HA-treated surfaces, which also triggered osteocalcin expression on day seven. Conclusions: The findings of this study show that the morphology and treatment of whole titanium dental implants, primarily HA-treated and bland acid etching implants, impact the adherence and activity of ADSCs in osteogenic differentiation in the absence of specific osteo-inductive signals. Full article

Mesoporous bioactive glass nanoparticles (MBGNs) are widely recognized for their ability to bond to hard tissue, while the ions released from the BG structure enhance specific cellular pathways. In this study, the SiO₂-P₂O₅-CaO-MgO-ZnO system was used to successfully synthesize MBGNs by a microemulsion-assisted sol-gel method. The MBGNs calcinated at 600 °C/3 h had a typical phosphosilicate structure together with a poorly crystalline hydroxyapatite (HAp). The addition of ZnO not only led to a higher degree of crystallinity of HAp but also induced a higher porosity of the particles. All MBGNs had a mesoporous structure with an interconnected network of slit shape pores. For each type of composition, two families of highly dispersed spherical nanoparticles could be identified. In vitro tests in simulated body fluid (SBF) proved that after only 3 days of immersion all the materials were covered with a layer of brushite whose degree of crystallinity decreases in the presence of Zn²⁺. The antibacterial assay revealed a strong inhibitory effect for all samples after 40 h of contact. Simultaneously, MBGNs did not increase the intracellular oxidative stress while it stimulated the cell proliferation process. Full article

Although laser irradiation and implantoplasty (IP) are both treatment options for peri-implantitis, no studies have yet combined these two treatment solutions. The aim of this study was to identify the effect of an Er, Cr: YSGG laser on the IP surface. In experiment 1, TiUnite anodized surface implants were treated with an Er, Cr: YSGG laser at 0.5 to 2 W on the panel energy setting and 20 Hz under water irrigation. In experiment 2, all implant surfaces were treated with the IP procedure first, then irradiated with the Er, Cr: YSGG laser. All samples were analyzed by stereomicroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and surface topography. Stereomicroscopy and SEM revealed no obvious surface change at any energy setting once the surface was polished with the IP procedure, whereas damage was caused to the TiUnite original implant surface when the Er, Cr: YSGG laser panel energy was set at 1 W or higher. EDS showed no significant difference in element composition once the surface was polished with the IP procedure, while a compositional change was detected when the Er, Cr: YSGG laser panel energy was set to 0.5 W or higher to irradiate the original TiUnite surface. Surface roughness may be related to laser irradiation energy, but no significant changes occurred following IP. These results indicated that the Er, Cr: YSGG laser may have little effect on the post-IP surface compared with the virgin TiUnite surface. Full article

Polyetheretherketone (PEEK) has become an alternative material for orthopaedics and dental implants. However, bio-inertness is an important limitation in this material. In the present study, a hydroxyapatite (HA)–titanium nitride (TiN) coating was fabricated via pulsed DC magnetron sputtering and treated with hydrothermal treatment to improve the bioactive property of PEEK. The dissolution behavior of the coating was studied in simulated body fluid solution (SBF) at 1, 3, 5, 7, 14, 21, 28, and 56 days. The coating surface was analyzed before and after the immersion process by X-ray photoelectron spectroscopy (XPS), atomic force microscope (AFM), and scanning electron microscope (SEM). The calcium and phosphorus concentration alteration in SBF was quantified by an inductively coupled plasma-optical emission spectrometer (ICP-OES). Coating dissolution and the precipitation of calcium phosphate complex from SBF were observed as occurring suddenly and continuously throughout the immersion times. These processes resulted in an alteration in both physical and chemical coating properties. After 56 days, the coating remained on PEEK surfaces and the Ca/P ratio was 1.16. These results indicate that HA-TiN coating via pulsed DC magnetron sputtering followed by hydrothermal treatment improved the bioactivity of materials and provided a potential benefit to orthopedics and dental applications. Full article

Nanotechnology has become an emerging research field with numerous biomedical scientific applications. Silver possesses bactericidal activities that have been harnessed for centuries; however, there is a concern about the toxic effects of silver nanoparticles. This paper aims to provide an overview of silver-treated dental implants and discuss their potential to reduce the prevalence of peri-implant diseases. An electronic search was performed using PubMed. After screening, data extraction was performed on the 45 remaining articles using inclusion and exclusion criteria. Most of the articles demonstrated that silver nanoparticles embedded in a coating layer and/or on surface-treated titanium exhibit sound antibacterial effects and biocompatibility. Most of the reviewed studies revealed that silver nanoparticles on dental implant surfaces reduced cytotoxicity but provided a prolonged antibacterial effect. The cytotoxicity and antibacterial effect are closely linked to how the silver nanoparticles are released from the titanium surfaces, where a slower release increases cell viability and proliferation. However, to improve the clinical translation, there is still a need for more studies, especially evaluating the long-term systemic effects and studies recreating the conditions in the oral cavity. Full article

Conductive polypyrrole (PPy) has excellent biocompatibility and structural stability. It is an ideal electroactive biomaterial that can apply exogenous electrical stimulation to promote osteoblast differentiation. However, PPy is a kind of bio-inert material, which does not have osteoinductive capacity. Therefore, we have introduced a kind of bioactive material, hydroxyapatite (HA), to construct PPy/HA composite to enhance bioactivity and osteoinduction. In addition, micron-topological morphology of scattered grid pattern has been designed and introduced to the PPy/HA coatings, which can further enhance the regulation ability of the coatings to the adhesion, proliferation and differentiation of MC3T3-E1 cells. In vitro simulated body fluids (SBFs) immersion test results have demonstrated that the fabricated micropatterned PPy/HA composite coatings perform bioactivity well and can promote the mineral deposition of HA on the surface. Moreover, it can also benefit the proliferation and osteognetic differentiation of MC3T3-E1 cells, when accompanied by external electrical stimulation (ES). In this study, we have successfully constructed electroactive and bioactive coatings, the method of which can potentially be applied to the surface functional modification of traditional bone repair metals. Full article

Osteoconductive silk fibroin (SF) binders were fabricated for the bone repair of an alveolar cleft defect. Binders were prefigureared by mixing different ratios of a mixture of random coils and SF aggregation with SF fibrils: 100:0 (SFB100), 75:25 (SFB75), 50:50 (SFB50), 25:75 (SFB25), and 0:100 (SFB0). The gelation, molecular organization, structures, topography, and morphology of the binders were characterized and observed. Their physical, mechanical, and biological properties were tested. The SF binders showed gelation via self-assembly of SF aggregation and fibrillation. SFB75, SFB50, and SFB25 had molecular formation via the amide groups and showed more structural stability than SFB100. The morphology of SFB0 demonstrated the largest pore size. SFB0 showed a lowest hydrophilicity. SFB100 showed the highest SF release. SFB25 had the highest maximum load. SFB50 exhibited the lowest elongation at break. Binders with SF fibrils showed more cell viability and higher cell proliferation, ALP activity, calcium deposition, and protein synthesis than without SF fibrils. Finally, the results were deduced: SFB25 demonstrated suitable performance that is promising for the bone repair of an alveolar cleft defect. Full article

The process of foaming poly(caprolactone)-based composite materials using supercritical carbon dioxide was analyzed, especially in terms of the biocompatibility of the resultant materials. The influence of foaming process conditions and composite material properties on the functional properties of polymer solid foams, intended for artificial scaffolds for bone cell culture, was investigated. The relationship between wettability (contact angle) and water absorption rate as a result of the application of variable conditions for the production of porous structures was presented. For the evaluation of potential cytotoxicity, the MTT and PrestoBlue tests were carried out, and animal cells (mouse fibroblasts) were cultured on the materials for nine days. There was no toxic effect of composite materials made of poly(caprolactone) containing porogen particles: hydroxyapatite, crystalline nanocellulose, and graphene oxide on cells. The desired effect of the porogens used in the foaming process on the affinity of cells to the resultant material was demonstrated. The tested materials have been shown to be biocompatible and suitable for applications in biomedical engineering. Full article

Over the last decade, pedicle fixation systems have evolved and modifications in spinal fusion techniques have been developed to increase fusion rates and improve clinical outcomes after lumbar interbody fusion (LIF). Regarding materials used for screw and rod manufacturing, metals, especially titanium alloys, are the most popular resources. In the case of pedicle screws, that biomaterial can be also doped with hydroxyapatite, CaP, ECM, or tantalum. Other materials used for rod fabrication include cobalt–chromium alloys and nitinol (nickel–titanium alloy). In terms of mechanical properties, the ideal implant used in LIF should have high tensile and fatigue strength, Young’s modulus similar to that of the bone, and should be 100% resistant to corrosion to avoid mechanical failures. On the other hand, a comprehensive understanding of cellular and molecular pathways is essential to identify preferable characteristics of implanted biomaterial to obtain fusion and avoid implant loosening. Implanted material elicits a biological response driven by immune cells at the site of insertion. These reactions are subdivided into innate (primary cellular response with no previous exposure) and adaptive (a specific type of reaction induced after earlier exposure to the antigen) and are responsible for wound healing, fusion, and also adverse reactions, i.e., hypersensitivity. The main purposes of this literature review are to summarize the physical and mechanical properties of metal alloys used for spinal instrumentation in LIF which include fatigue strength, Young’s modulus, and corrosion resistance. Moreover, we also focused on describing biological response after their implantation into the human body. Our review paper is mainly focused on titanium, cobalt–chromium, nickel–titanium (nitinol), and stainless steel alloys. Full article

Herein, a nanocomposite hydrogel was produced using laponite and polyethylene-glycol diacrylate (PEGDA), with or without Irgacure (IG), for application in bone tissue regeneration. The nanocomposites were characterized by X-ray diffraction (XRD), Fourier-Transform infrared spectroscopy (FTIR), and thermal analysis (TG/DTG). The XRD results showed that the crystallographic structure of laponite was preserved in the nanocomposite hydrogels after the incorporation of PEGDA and IG. The FTIR results indicated that PEGDA polymer chains were entangled on laponite in hydrogels. The TG/DTG found that the presence of laponite (Lap) improved the thermal stability of nanocomposite hydrogel. The toxicity tests by Artemia salina indicated that the nanocomposite hydrogels were not toxic, because the amount of live nauplii was 80.0%. In addition, in vivo tests demonstrated that the hydrogels had the ability to regenerate bone in a bone defect model of the tibiae of osteopenic rats. For the nanocomposite hydrogel (PEGDA + Lap nanocomposites + UV light), the formation of intramembranous bone in the soft callus was more intense in 66.7% of the animals. Thus, the results presented in this study evidence that nanocomposite hydrogels obtained from laponite and PEGDA have the potential for use in bone regeneration. Full article

Corneal blindness is a common phenomenon, and corneal transplantation is an effective treatment for corneal defects. However, there is usually a mismatch between the corneal repair material and the degree of the patient’s corneal defect. Therefore, patients with different corneal defects need suitable corneal repair materials with a specific microstructure for personalized treatment. In this research, collagen films with bionic structures were fabricated through ethanol evaporation technique by regulating the volume ratios of collagen solution: ethanol = 10:0(Col)/9:1(CC91)/8:2(CC82)/CC73(CC73). Under various preparation conditions, the obtained collagen films contain layered structures of different density. SEM photos show that the CC73 film with a dense layer arrangement has a microstructure similar to that of the corneal epithelial layer, whereas the Col film has a loose layered structure similar to that of the corneal stroma layer. Four kinds of collagen films showed different optical properties and water absorption ability. A more ordered arrangement of internal layer structure leads to better mechanical properties of the collagen film. In view of this, we think that these collagen films with different microstructures and different interlayer spacing may have huge potential applications for personalized corneal repair. Full article

To prevent endocochlear insertion trauma, the development of drug delivery coatings in the field of CI electrodes has become an increasing focus of research. However, so far, the effect of a polymer coating of PLLA on the mechanical properties, such as the insertion pressure and friction of an electrode array, has not been investigated. In this study, the insertion pressure of a PLLA-coated, 31.5-mm long standard electrode array was examined during placement in a linear cochlear model. Additionally, the friction coefficients between a PLLA-coated electrode array and a tissue simulating the endocochlear lining were acquired. All data were obtained at different insertion speeds (0.1, 0.5, 1.0, 1.5, and 2.0 mm/s) and compared with those of an uncoated electrode array. It was shown that both the maximum insertion pressure generated in the linear model and the friction coefficient of the PLLA-coated electrode did not depend on the insertion speed. At higher insertion speeds above 1.0 mm/s, the insertion pressure (1.268 ± 0.032 mmHg) and the friction coefficient (0.40 ± 0.15) of the coated electrode array were similar to those of an uncoated array (1.252 ± 0.034 mmHg and 0.36 ± 0.15). The present study reveals that a PLLA coating on cochlear electrode arrays has a negligible effect on the electrode array insertion pressure and the friction when higher insertion speeds are used compared with an uncoated electrode array. Therefore, PLLA is a suitable material to be used as a coating for CI electrode arrays and can be considered for a potential drug delivery system. Full article

It is necessary to study the design method and molding techniques of selective laser melting (SLM) tibial implants to improve the success rate of knee implant surgery and the quality of life of patients. In this study, the three-dimensional (3D) reconstruction of tibial implants was completed using the reverse combined with forward methods, optimization design was carried out on the constructed tibial implant model by adopting the parametric finite element method (FEM), and the SLM device was employed for the direct manufacture of tibial implants and to study its molding techniques. The results indicated that the tibial implant model completed using reverse and forward methods combined with FEM displayed favorable modeling effects, with more homogeneous stress distribution. After optimizing the molding techniques of SLM molding tibial implants, excellent molding effects could be achieved, with high tibial implant surface finish but no buckling deformation or obvious adhering slag. Studying the above modeling and molding methods can provide important foundation for the individualized design and direct manufacture of tibial implant. Full article

The success of osseointegration depends on many factors. With temperatures beyond a 47 °C threshold over 1 min, bone survival may be impaired. The purpose of the study was to evaluate, in fresh human cadaver tibiae, the temperature changes during osteotomy preparations using two straight and two tapered implant systems’ drills, external irrigation, and varying revolutions per minute (RPM). The tibiae from a fresh female cadaver were harvested bilaterally. Two tapered and two straight design drills were assessed. Two-hundred and forty osteotomies were prepared at 6 mm depth following the drill sequence of the manufacturers’ protocol for each drilling speed. Difference in temperature (ΔΤ) was calculated by subtracting the baseline from the maximum temperature (ΔT = T_max − T_base). Drill design and drill diameter, as independent variables or synergistically, had a significant effect on ΔΤ. Tapered drills: As the drill diameter increased, ΔΤ increased at all RPM. Straight drills: As the drill diameter increased, ΔΤ remained constant or slightly decreased at all RPM. Drill diameter and design had a significant effect on ΔΤ in human tibiae, which never exceeded the critical threshold of 47 °C. Tapered drills caused significantly greater heat production compared to straight drills. Full article

Nanotechnology has transformed engineering designs across a wide spectrum of materials and applications. Mesoporous Silica Nanoparticles (MSNs) are one of the new fabrications of nanostructures as medication delivery systems. MSNs have pore sizes varying from 2 to 50 nm, making them ideal for a variety of biological applications. They offer unique characteristics such as a tunable surface area, well-defined surface properties, and the ability to improve drug pharmacokinetic characteristics. Moreover, they have the potential to reduce adverse effects by delivering a precise dose of medications to a specific spot rather than the more frequent systemic delivery, which diffuses across tissues and organs. In addition, the vast number of pores allow drug incorporation and transportation of drugs to various sites making MSNs a feasible platform for orally administered drugs. Though the oral route is the most suitable and convenient platform for drug delivery, conventional oral drug delivery systems are associated with several limitations. Surpassing gastrointestinal barriers and the low oral bioavailability of poorly soluble medicines pose a major challenge in the pharmaceutical industry. This review provides insights into the role of MSNs and its mechanism as an oral drug delivery system. Full article

The laser micro-machining was carried out on a station equipped with a TruMicro 5325c laser emitting ultraviolet radiation (343 nm wavelength) in picosecond pulses. On the surface of the Ti6Al7Nb alloy, dimple texturing with a constant diameter of ~200 μm, different depths (from ~5 to ~78 μm) and density (from 10% to 50%) were produced. The value of surface free energy was determined with the Owens–Wendt method using two measuring liquids: distilled water and diodomethane. The Staphylococcus epidermidis strain was used to test the adhesion of bacteria. It was found that the surface free energy value is influenced by both of the texture parameters (density, depth). The density also affects the potential for biofilm formation. Based on the analysis, it was shown that with an increase in surface free energy, the number of adhering microorganisms increases exponentially. Moreover, the study shows that there is a correlation between the number of adhering microorganisms and surface free energy. Full article

Large bone defects requiring invasive surgical procedures have long been a problem for orthopedic surgeons. Despite the use of autologous bone grafting, satisfactory results are often not achieved due to associated limitations. Biomaterials are viable alternatives and have lately been used in association with Stromal Vascular Fraction (SVF), stem cells, and signaling factors for bone tissue engineering (BTE). The objective of the current study was to assess the biocompatibility of Silicon Hydroxyapatite (Si-HA) and to improve osteogenic potential by using autologous adipose-derived SVF with Si-HA in a rabbit bone defect model. Si-HA granules synthesized using a wet precipitation method were used. They were characterized using scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). A hemolysis assay was used to assess the hemolytic effects of Si-HA, while cell viability was assessed through Alamar Blue assay using MC3T3 mouse osteoblasts. The osteogenic potential of Si-HA both alone and with enzymatically/non-enzymatically-derived SVF (modified) was performed by implantation in a rabbit tibia model followed by histomorphometric analysis and SEM of dissected bone after six weeks. The results showed that Si-HA granules were microporous and phase pure and that the addition of Silicon did not influence Si-HA phase composition. Si-HA granules were found to be non-hemolytic on the hemolysis assay and non-toxic to MC3T3 mouse osteoblasts on the Alamar Blue assay. Six weeks following implantation Si-HA showed high biocompatibility, with increased bone formation in all groups compared to control. Histologically more mature bone was formed in the Si-HA implanted along with non-enzymatically-derived modified SVF. Bone formation was observed on and around Si-HA, reflecting osseointegration. In conclusion, Si-HA is osteoconductive and promotes osteogenesis, and its use with SVF enhances osteogenesis. Full article

In this study, we report results of the interaction of titanium (Ti) with human synovial fluids. A wide palette of electrochemical techniques was used, including open circuit potential, potentiodynamic methods, and electrochemical impedance. After the electrochemical testing, selected surfaces were analyzed using Auger Electron Spectroscopy to provide laterally resolved information on surface chemistry. For comparison purposes, similar tests were conducted in a series of simulated body fluids. This study shows that compared to the tested simulated body fluids, synovial liquids show a large patient variability up to one order of magnitude for some crucial electrochemical parameters such as corrosion current density. The electrochemical behavior of Ti exposed to human synovial fluids seems to be controlled by the interaction with organic molecules rather than with reactive oxygen species. Full article

Disc herniation is one of the most ubiquitous healthcare problems in modern cities—severe patients eventually require surgical intervention. However, the existing operations—spinal fusion and artificial disc replacement—alter the biomechanics of the spine, leaving much room for improvement. The appropriateness of polyvinyl alcohol (PVA) for biomedical applications has been recognised due to its high water content, excellent biocompatibility, and versatile mechanical properties. In this study, a newly-designed PVA–bacterial cellulose (PVA-BC) composite was assembled to mimic both the biomechanics and annular structure of natural intervertebral discs (IVDs). PVA-BC composites of various concentrations were fabricated and tested under unconfined compression and compressive creep in order to acquire the values of the normalised compressive stiffness and whole normalised deformation. The normalised compressive stiffness increased considerably with an increasing PVA concentration, spanning from 1.82 (±0.18) to 3.50 (±0.14) MPa, and the whole normalised deformation decreased from 0.25 to 0.13. Formulations of 40% PVA provided the most accurate mimicry of natural human IVDs in normalised whole deformation, and demonstrated higher dimensional stability. The biocompatible results further confirmed that the materials had excellent biocompatibility. The novel bionic structure and formulations of the PVA-BC materials mimicked the biomechanics and structure of natural IVDs, and ensured dimensional stability under prolonged compression, reducing the risk of impingement on the surrounding tissue. The PVA-BC composite is a promising material for third-generation artificial IVDs with integrated construction. Full article

The process of foaming poly(caprolactone)-based composites using supercritical carbon dioxide was analyzed. The impact of the conditions of the solid-foam production process on the process efficiency and properties of porous structures was investigated. The novel application of various types of porogens—hydroxyapatite, nanocellulose, carboxymethylcellulose, and graphene oxide—was tested in order to modify the properties and improve the quality of solid foams, increasing their usefulness in specialized practical applications. The study showed a significant influence of the foaming process conditions on the properties of solid foams. The optimal process parameters were determined to be pressure 18 MPa, temperature 70 °C, and time 1 h in order to obtain structures with appropriate properties for applications in biomedical engineering, and the most promising material for their production was selected: a composite containing 5% hydroxyapatite or 0.2% graphene oxide. Full article