Tissue-implant Interactions Research Articles

Biomechanical Properties and Corrosion Resistance of Plasma-Sprayed Fish Scale Hydroxyapatite (FsHA) and FsHA-Doped Yttria-Stabilized Zirconia Coatings on Ti–6Al–4V Alloy for Biomedical Applications

Hydroxyapatite (HA) coatings on metallic implants have been extensively used in orthopedic applications to improve tissue-implant interactions, enhance their biocompatibility, and enhance their functionality. However, the expensive synthetic HA is the most widely used bioceramic for implant coatings, leading to high implants costs. Hence, this research explored the potential of an inexpensive biogenic HA derived from fish scales and FsHA/yttria-stabilized zirconia (YSZ) bioceramic coatings on a Ti–6Al–4V alloy as an alternative to synthetic HA coatings. The FsHA/YSZ powders and the coatings were examined with X-ray diffraction (XRD) and scanning electron microscopy/energy dispersive X-ray (SEM/EDX), and the surface roughness, microhardness, corrosion resistance, bioactivity, and in vitro cytotoxicity of the coatings were also determined. The morphological powder analysis revealed particles with a slightly irregular morphology and a fine spherical morphology, while the coating microstructure analysis revealed a fine lamellar morphology, with partially melted and unmelted FsHA particles, and fine microcracks along with evenly dispersed ZrO2 particles. The surface roughness of the FsHA coating increased by 87.5% compared with the uncoated substrate, and the addition of YSZ significantly reduced this value. A 35.5% increase in hardness was obtained in the FsHA + 20 wt.% YSZ coating, and the FsHA coating showed a 43.2% reduction in the corrosion rate compared with the uncoated substrate; a further 73% reduction was observed with the addition of YSZ. The microstructure of the coatings after 14 days of immersion in simulated body fluid (SBF) revealed enlarged cracks and delaminated segments with well-grown apatite spherulite layers on the whole surface of the coatings, while in vitro cytotoxicity analysis showed a good cell viability of 95% at the highest concentration of the specimen.

The response of soft tissue cells to Ti implants is modulated by blood-implant interactions.

Titanium-based dental implants have been highly optimized to enhance osseointegration, but little attention has been given to the soft tissue-implant interface, despite being a major contributor to long term implant stability. This is strongly linked to a lack of model systems that enable the reliable evaluation of soft tissue-implant interactions. Current in vitro platforms to assess these interactions are very simplistic, thus suffering from limited biological relevance and sensitivity to varying implant surface properties. The aim of this study was to investigate how blood-implant interactions affect downstream responses of different soft tissue cells to implants in vitro, thus taking into account not only the early events of blood coagulation upon implantation, but also the multicellular nature of soft tissue. For this, three surfaces (smooth and hydrophobic; rough and hydrophobic; rough and hydrophilic with nanostructures), which reflect a wide range of implant surface properties, were used to study blood-material interactions as well as cell-material interactions in the presence and absence of blood. Rough surfaces stimulated denser fibrin network formation compared to smooth surfaces and hydrophilicity accelerated the rate of blood coagulation compared to hydrophobic surfaces. In the absence of blood, smooth surfaces supported enhanced attachment of human gingival fibroblasts and keratinocytes, but limited changes in gene expression and cytokine production were observed between surfaces. In the presence of blood, rough surfaces supported enhanced fibroblast attachment and stimulated a stronger anti-inflammatory response from macrophage-like cells than smooth surfaces, but only smooth surfaces were capable of supporting long-term keratinocyte attachment and formation of a layer of epithelial cells. These findings indicate that surface properties not only govern blood-implant interactions, but that this can in turn also significantly modulate subsequent soft tissue cell-implant interactions.

Microstructural and in-vitro characteristics of functional calcium silicate topcoat on hydroxyapatite coating for bio-implant applications.

The delayed tissue-implant interactions in metallic implants coated with hydroxyapatite (HA) paved the way for the development of alternative bioactive coatings. In this study, bi-layered functional gradient (HA-CS) coating was formulated by the atmospheric plasma spray (APS) process on Ti6Al4V alloy. The HA layer was applied at the metal interface to ensure long-term stability, while the calcium silicate (CS) outer layer was applied to achieve fast tissue-implant interactions. Moreover, single-layered HA and CS coating were also formulated for comparative analysis. The phase compositions, coating microstructure, chemical properties, microhardness, porosity, surface roughness, and in-vitro bioactivity were investigated. The CS top layer showed high porosity and surface roughness with respect to the inner HA layer, which constitutes an optimum microstructure to promote bioactivity. The microhardness of the outer CS layer of HA-CS was 520.3 ± 80.8 HV, while the corresponding value for the inner HA layer was 291.7 ± 45.7 HV. HA-CS and CS coatings demonstrated higher in-vitro bioactivity compared to HA coating. On the contrary, HA coating (3.76 mpy) displayed better corrosion resistance than the HA-CS (4.17 mpy) and CS coatings (4.34 mpy). The in-vitro results indicated that the HA-CS coating could promote the healthy development of osteoblast-like MG-63.

Dry vs. wet testing: quasi-static tensile experiment setup for polymer based biomaterials

Abstract Polymer materials can be manufactured with high reproducibility and do offer the potential for chemical modification. This enables matrix property modification and fine-tuning of several material characteristics, such as tissue-implant interaction, inflammatory potential or susceptibility to biofilm formation. Whereas manufacturing protocols are crucial for the resulting material properties, also the evaluation in terms of performance and safety has to be considered. Regarding this, both, temperature and composition of test medium may affect the physicochemical properties of implant materials. The present study addresses the influence of test medium compared to dry test conditions, each at two different temperatures, on the mechanical properties of elastomeric film and nonwoven materials.

Microstructure, mechanical properties, and in vitro behavior of biodegradable Zn-1Mg-0.1Ca and Zn-1Mg-0.5Ca.

In the present study, the microstructure, mechanical properties, corrosion behavior, wettability, haemocompatibility, and cytocompatibility of the as-cast and as-rolled biodegradable Zn-1Mg-0.1Ca and Zn-1Mg-0.5Ca have been systematically investigated to evaluate their feasibility as potential biodegradable materials. The results demonstrated that the Zn-1Mg-0.1Ca have significantly improved mechanical properties, with the yield strength (YS), ultimate tensile strength (UTS), and elongation of as-rolled Zn-1Mg-0.1Ca are (209.04 ± 28.31) MPa, (331.51 ± 40.06) MPa, and (35.43 ± 3.53)%, respectively. Wettability test results demonstrated that the Zn-1Mg-0.1Ca and Zn-1Mg-0.5Ca have hydrophilic surfaces that can enhance cell responses and tissue-implant interactions. The haemocompatibility evaluation showed that the hemolysis ratio of Zn-1Mg-0.1Ca have a low hemolysis ratio of 0.6%; the platelets remain sphere morphology and are not activated. High cell viability indicates the cytocompatibility of the as-rolled Zn-1Mg-0.1Ca alloy. The Zn-1Mg-0.1Ca alloy can be considered as new suitable biodegradable Zn-based alloys for further biomedical applications.

Influence of magnetized abutment on biological seal of the implant–soft tissue interface by reconstructed human gingiva (RHG) model

Background: osseointegration in implants have received a lot of attention. Recently, the focus has extended towards the development of abutment materials supporting gingival soft tissue attachment. The attachment of the soft tissue to the implant/abutment surface is necessary to form a biological seal that protects the pathogenic microbial colonization which can lead to periimplantitis and bone resorption culminating in dental implant failure. Aim/Hypothesis: To evaluate the Influence of magnetized abutment surface on biological seal of the implant–soft tissue interface that would enable junctional epithelium(JE) attachment to the abutment through an internal basal lamina and hemidesmosomes in order to prevent the JE from migrating too in depth. Materials and Methods: We developed novel magnetic nanoparticles (MNs) coated with chitosan(CS) (CS-MNs) for enhancing cellular migration using magnetic force. CS-MNs were characterized by XRD, UV, SEM. The CS-MNs where spherical shape with a diameter from 10 nm to 15 nm. The magnetized abutments surface was treated with CS-MNs. Influence of CS-MNs treated abutment on reconstructed human gingiva (RHG) model consisting of differentiated gingival epithelium cells was assessed in terms of Epithelial attachment, down-growth along the abutment surface, quantitative analysis by permeability and cell attachment tests. Phenotype via histomorphology, scanning electron microscopy, and immunohistochemistry 10 days after implantation. Results: Abutment values obtained from the intraexperiment replicates including measurement of the left and right side of the abutment (total of four measurements) were first averaged, and Differences were determined using one-way ANOVA followed by Dunnett's uncorrected multiple comparisons test. Differences were considered significant at P < 0.05. histomorphometric analyses showed epithelial growth near perpendicular to the surface of abutments. The magnification clearly showed individual keratinocytes spread and attached to abutment surfaces via filopodia extensions. Conclusions and Clinical Implications: The current RHG model shows the active migration of epithelial cells near perpendicularly along the magnetized abutment surface with higher gingival fibroblast attachment as compared with an untreated surface. This novel system is thought to be useful in the development of biological seal around the implant and cell-based strategies for the repair or replacement of tissue and other novel therapies. Keywords: Soft tissue-implant interactions, biological seal, tissue-engineered oral mucosa, three-dimensional in vitro model

Atomic layer deposition of nano-TiO2 thin films with enhanced biocompatibility and antimicrobial activity for orthopedic implants.

Titanium (Ti) and its alloys have been extensively used as implant materials in orthopedic applications. Nevertheless, implants may fail due to a lack of osseointegration and/or infection. The aim of this in vitro study was to endow an implant surface with favorable biological properties by the dual modification of surface chemistry and nanostructured topography. The application of a nanostructured titanium dioxide (TiO2) coating on Ti-based implants has been proposed as a potential way to enhance tissue-implant interactions while inhibiting bacterial colonization simultaneously due to its chemical stability, biocompatibility, and antimicrobial properties. In this paper, temperature-controlled atomic layer deposition (ALD) was introduced for the first time to provide unique nanostructured TiO2 coatings on Ti substrates. The effect of nano-TiO2 coatings with different morphology and structure on human osteoblast and fibroblast functions and bacterial activities was investigated. In vitro results indicated that the TiO2 coating stimulated osteoblast adhesion and proliferation while suppressing fibroblast adhesion and proliferation compared to uncoated materials. In addition, the introduction of nano-TiO2 coatings was shown to inhibit gram-positive bacteria (Staphylococcus aureus), gram-negative bacteria (Escherichia coli), and antibiotic-resistant bacteria (methicillin-resistant Staphylococcus aureus), all without resorting to the use of antibiotics. Our results suggest that the increase in nanoscale roughness and greater surface hydrophilicity (surface energy) together could contribute to increased protein adsorption selectively, which may affect the cellular and bacterial activities. It was found that ALD-grown TiO2-coated samples with a moderate surface energy at 38.79 mJ/m2 showed relatively promising antibacterial properties and desirable cellular functions. The ALD technique provides a novel and effective strategy to produce TiO2 coatings with delicate control of surface nanotopography and surface energy to enhance the interfacial biocompatibility and mitigate bacterial infection, and could potentially be used for improving numerous orthopedic implants.

Biomimetic implants for pelvic floor repair.

Polypropylene implants are used for the reconstructive surgery of urogynaecological disorders like pelvic organ prolapse, but severe complications associated with their use have been reported. There is evidence that surface properties and a difference in mechanical stiffness between the implant and the host tissue contribute to these adverse events. Electrospinning is an innovative engineering alternative that provides a biomimetic microstructure for implants, resulting in a different mechano-biological performance. The main objective of this review is to inform about the potential of electrospun matrices as an alternative modality for pelvic floor repair. Publications with the following studies of electrospun matrices were reviewed: (i) the technique; (ii) in vitro use for soft tissue engineering; (iii) in vivo use for reconstruction of soft tissues in animals; and (iv) clinical use in humans. Electrospun matrices provide a synthetic mimic of natural extracellular matrix (ECM), favoring cellular attachment, proliferation and matrix deposition, through which a proper, low-inflammatory tissue-implant interaction can be established. Electrospun sheets can also be created with sufficient mechanical strength and stiffness for usage in prolapse surgery. Electrospun matrices mimic the structural topography of the extracellular matrix and can be functionalized for better biological performance. As such, they have great potential for the next generation of urogynecological implants. However, their long-term safety and efficacy must still be established in vivo.

Nanotextured titanium surfaces stimulate spreading, migration, and growth of rat mast cells.

Titanium is a biomaterial widely used in dental and orthopedic implants. Since tissue-implant interactions occur at the nanoscale level, nanotextured titanium surfaces may affect cellular activity and modulate the tissue response that occurs at the tissue-implant interface. Therefore, the characterization of diverse cell types in response to titanium surfaces with nanotopography is important for the rational design of implants. Mast cells are multifunctional cells of the immune system that release a range of chemical mediators involved in the inflammatory response that occurs at the tissue-implant interface. Therefore, the aim of this study was to investigate the effects of the nanotopography of titanium surfaces on the physiology of mast cells. The results show that the nanotopography of titanium surfaces promoted the spreading of mast cells, which was accompanied by the reorganization of the cytoskeleton. Also, the nanotopography of titanium surfaces enhanced cell migration and cell growth, but did not alter the number of adherent cells in first hours of culture or affect focal adhesions and mediator release. Thus, the results show that nanotopography of titanium surfaces can affect mast cell physiology, and represents an improved strategy for the rational production of surfaces that stimulate tissue integration with the titanium implants. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2150-2161, 2017.

Biomaterials and host versus graft response: a short review.

Biomaterials and biotechnology are increasing becoming an important area in modern medicine. The main aim in this area is the development of materials, which are biocompatible to normal tissue. Tissue-implant interactions with molecular, biological and cellular characteristics at the implant-tissue interface are important for the use and development of implants. Implantation may cause an inflammatory and immune response in tissue, foreign body reaction, systemic toxicity and imminent infection. Tissue-implant interactions determine the implant life-period. The aims of the study are to consider the biological response to implants. Biomaterials and host reactions to implants and their mechanisms are also briefly discussed.

Yrjö Tapio Konttinen 1952–2014

Yrjö Tapio Konttinen 1952–2014

Prevention of pin tract infection with titanium‐copper alloys

The most frequent complication in external fixation is pin tract infection. To reduce the incidence of implant-associated infection, many published reports have looked at preventing bacterial adhesion by treating the pin surface. This study aimed to evaluate the antibacterial activity of a Titanium-Copper (Ti-Cu) alloy on implant infection, and to determine the potential use of the Ti-Cu alloy as a biomaterial. Two forms of Ti-Cu alloys were synthesized: one with 1% Cu and the other with 5% Cu. For analyzing infectious behavior, the implants were exposed to Staphylococcus aureus and Escherichia coli. The reaction of pathogens to the Ti-Cu alloys was compared with their reaction to stainless steel and pure titanium as controls. Both Ti-Cu alloys evidently inhibited colonization by both bacteria. Conversely, cytocompatibility studies were performed using fibroblasts and colony formation on the metals was assessed by counting the number of colonies. Ti-1% Cu alloy showed no difference in the number of colonies compared with the control. External fixator pins made of Ti-Cu alloys were evaluated in a rabbit model. The tissue-implant interactions were analyzed for the presence of infection, inflammatory changes and osteoid-formation. Ti-1% Cu alloy significantly inhibited inflammation and infection, and had excellent osteoid-formation. Copper blood levels were measured before surgery and at 14 days postoperatively. Preoperative and postoperative blood copper values were not statistically different. Overall, it was concluded that Ti-Cu alloys have antimicrobial activity and substantially reduce the incidence of pin tract infection. Ti-1% Cu alloy shows particular promise as a biomaterial.

A review of in vivo animal studies in retinal prosthesis research

The development of a functional retinal prosthesis for acquired blindness is a great challenge. Rapid progress in the field over the last 15 years would not have been possible without extensive animal experimentation pertaining to device design and fabrication, biocompatibility, stimulation parameters and functional responses. This paper presents an overview of in vivo animal research related to retinal prosthetics, and aims to summarize the relevant studies. A Pubmed search of the English language literature was performed. The key search terms were: retinal implant, retinal prosthesis, artificial vision, rat, rabbit, cat, dog, sheep, pig, minipig. In addition a manual search was performed based on references quoted in the articles retrieved through Pubmed. We identified 50 articles relevant to in vivo animal experimentation directly related to the development of a retinal implant. The highest number of publications related to the cat (n = 18). The contribution of animal models to the development of retinal prosthetic devices has been enormous, and has led to human feasibility studies. Grey areas remain regarding long-term tissue-implant interactions, biomaterials, prosthesis design and neural adaptation. Animals will continue to play a key role in this rapidly evolving field.

Cell type-specific aspects in biocompatibility testing: the intercellular contact in vitro as an indicator for endothelial cell compatibility

Endothelial cells cover the inner surface of blood vessels and form the interface between the blood and the tissues. Endothelial cells are involved in regulating barrier function, which is maintained by the interendothelial cell contacts. These interendothelial cell contacts are established by the interaction of different molecules. The maintenance of the barrier requires an appropriate signalling between these molecules. Thus, a number of different signalling pathways are integrated within interendothelial contacts. Since endothelial cells are important in tissue-implant interactions (especially for stent materials) this study examines the expression pattern of different interendothelial contact molecules to determine the usefulness in the analysis of biocompatibility in vitro. The effects of different pro-inflammatory and toxic stimuli and contact of human microvascular endothelial cells to metallic surfaces were examined for their impact on the pattern of interendothelial contact molecules. Striking modifications in the arrangement of these molecules were induced and the mode of modification was dependent on the tested compound. Thus, examining the pattern of expression of specific interendothelial contact molecules in vitro may be useful for testing the endothelial cell compatibility of biomaterials and their corrosion products.

Connective‐tissue responses to defined biomaterial surfaces. I. Growth of rat fibroblast and bone marrow cell colonies on microgrooved substrates

Surface microgeometry plays a role in tissue-implant surface interactions, but our understanding of its effects is incomplete. Substrate microgrooves strongly influence cells in vitro, as evidenced by contact guidance and cell alignment. We studied "dot" colonies of primary fibroblasts and bone marrow cells that were grown on titanium-coated, microgrooved polystyrene surfaces that we designed and produced. Rat tendon fibroblast and rat bone marrow colony growth and migration varied (p < 0.01) by microgroove dimension and slightly by cell type. We observed profoundly altered morphologies, reduced growth rates, and directional growth in colonies grown on microgrooved substrates, when compared with colonies grown on flat, control surfaces (p < 0.01). The cells in our colonies grown on microgrooved surfaces were well aligned and elongated in the direction parallel to the grooves and colonies. Our "dot" colony is an easily reproduced, easily measured and artificial explant model of tissue-implant interactions that better approximates in vivo implant responses than culturing isolated cells on biomaterials. Our results correlate well with in vivo studies of titanium dioxide-coated polystyrene, titanium, and titanium alloy implants with controlled microgeometries. Microgrooves and other surface features appear to directionally or spatially organize cells and matrix molecules in ways that contribute to improved stabilization and osseointegration of implants.

Characterization and in vivo evaluation of sol–gel derived hydroxyapatite coatings on Ti6Al4V substrates

Hydroxyapatite (HAP) based coatings on titanium alloy Ti6Al4V were attempted by sol-gel process. Precursor sol was dip-coated onto the substrates and the formation of HAP as the main phase was ensured after the sintering of coatings at 900 degrees C, as confirmed by the characterization studies involving XRD, FT-IR, Raman, and SEM-EDXS analysis. The biocompatibility of HAP-based coated titanium implants was tested by implantation studies in rabbit's tibia for a period of 8 weeks. Bone remodelling and inflammatory responses of the implants were studied during the implantation period. The better tissue-implant interaction of the coated implants with respect to the uncoated implants was observed after a defect healing period of 8 weeks. A coated implant with no evidence of rejection is a further advantage of the sol-gel derived HAP coating.

Morphometric Evaluation of Tissue-Implant Reaction Associated With ALCAP and TCP Bioceramics In Vivo

The purpose of this investigation was to correlate the thickness of the fibrous capsule and the various histological components surrounding aluminum-calcium phosphate (ALCAP) and tricalcium phosphate (TCP) bioceramics at the subcutaneous (sc) and intraperitoneal (ip) implantation sites. The rational of conducting this investigation is to further elucidate the mechanisms of tissue-implant interaction. Thirteen Sprague-Dawley adult male albino rats were randomly divided into three groups. Animals in groups I and II (n = 5/group) were implanted at both ip and sc implantation sites with either ALCAP or TCP ceramics, respectively. Animals in group III (n

Biocompatibility of silver-coated polyurethane catheters and silvercoated Dacron ® material

The local effects of silver-coated polyurethane catheters and Dacron ® material were compared to uncoated polyurethane catheters and Dacron ® material in a long-term implantation test using rabbits. The tissue-implant interaction was analysed by investigating the type and number of inflammatory cells, capillaries, fat tissue, the extent of fibrosis, thickness of the fibrous capsule, number and distribution of silver particles, and the size of giant cells. Silver-coated and uncoated materials displayed comparable signs of inflammation and tissue reaction. Biomaterials (1994) 15, (10) 753–758

Dental implant materials. I. Some effects of preparative procedures on surface topography.

The effect of different treatments for preparing implant materials was examined by scanning electron microscopy and by contact angle measurements. The materials examined were Ti6A14V alloy, Co-Cr-Mo alloy, A12O3, and synthetic hydroxyapatite. Samples were prepared with solid or porous surfaces of these materials. These were detergent-cleaned and then either autoclaved (steam sterilization), radiation-sterilized, nitric acid-etched, or plasma-cleaned. The results of wettability studies indicated marked changes in surface energy corresponding to the different preparation methods, and differences in surface morphology were also observed. These differences could have significant consequences on in vivo implant behaviour as mediated by tissue-implant interactions.

Fibroblast stimulation by monocytes cultured on protein adsorbed biomedical polymers. I. Biomer and polydimethylsiloxane

The studies presented in this paper evaluate the modulatory role of protein pre-adsorbed polydimethylsiloxane (PDMS) and Biomer on the secretion of fibroblast stimulating growth factors from human monocytes/macrophages. The results of these studies show that Biomer and PDMS selectively activate human monocytes to produce fibroblast "progression-like" and to a lesser extent "competence-like" stimulating growth factors. Polydimethylsiloxane stimulated the monocytes/macrophages to produce more "progression-like" fibro-blast stimulating growth factors than Biomer. The induction of "competence-like" fibroblast stimulating activity from the monocytes was enhanced by preadsorption of PDMS with human derived fibrinogen, fibronectin, IgG, hemoglobin, or albumin. This phenomenon was not observed with protein pre-adsorbed Biomer. These studies support the hypothesis that protein pre-adsorbed polymers will selectively modulate monocyte/macrophage activation and induction of growth factors which have the potential to participate in tissue-implant interactions in vivo.