109 Introduction Implant-associated infections represent an occasional but serious problem in orthopedic and dental surgery. Controlled release of antibacterial agents directly in the site of the metal implant may represent an effective approach to treat these chronic complications. In this work, polyacrylatebased hydrogel thin coatings were prepared on titanium (Ti) substrates by electrochemical polymerization (1) starting from poly(ethylene-glycol diacrylate) (PEGDA) and acrylic acid (AA). Copper (CuNPs) or silver (AgNPs) nanoparticles, synthesized both by electrochemical (2) and wet chemical methods (3), were immobilized on Ti implant surfaces exploiting the hydrogel coatings swelling capabilities. The antibacterial effect of CuNPsor AgNPs-modified hydrogel coatings was tested evaluating in vitro inhibition growth of methicillin-resistant Staphylococcus Aureus (MRSA). Preliminary results pointed out that both CuNPs and AgNPs-hydrogel coatings seem to be very promising as in situ antibacterial agent delivery systems.
Purpose Bioceramics are currently in use to cover bone defects in orthopedics and craniofacial surgery. But their compatibility and efficacy in cranium were not investigated in detail. The aims of this study were to produce, characterize, and assess the biocompatibility and osteointegration of Si-HA, Si-Sr-HA, HA-Wollastonite, and HA-Wollastonite-Frit bioceramics. Methods Bioceramics were implanted into the burr holes of 14 craniotomy patients who were followed up from three to 24 months. Radiologic and scintigraphic examinations were performed. Results Osteoblastic activity quantified by scintigraphy increased from 6.865 to 22.991±1.682 from four to eight months in the HA-Woll group. Adding fritt into HA-Woll decreased osteoblastic activity at 10 months. Si-Sr-HA displayed significantly higher osteoblastic activity when compared to the craniotomy site at 12 months. The scintigraphic ratio of the bioceramic implanted regions to the craniotomy sites varied between 1.10 and 1.57. Osteoblast formation and establishment of the trabecular pattern of bone was observed in the surroundings of bioceramics in two patients. Conclusion These bioceramics can be safely used to cover the burr holes of craniotomy patients, as well as to close the cranial bone defects.
Aim: Hyaluronic acid (HA) based dermal fillers (DF) in recent years aroused big interest in the area of cosmetic surgery for the rejuvenation of the dermis. There is not a ideal dermal filler for all applications and in commerce there are many types of DF that differ for their chemical-physical properties. The aim of this paper is to correlate the rheological and physical properties of different DF to their clinical effectiveness.Matherials and Methods: In this frame the samples have been subjected to oscillation dynamic rheological and steady shear measurements.Results: Our results demonstrate that the viscoelastic properties of different DF varie strongly also considering fillers of the same family. Furthermore it was found that the materials physical properties influence significantly the performance of dermal filler. In particular the clinical data appear to correlate with the concentration of the polymer and with the product between the concentration and the percent elasticity, so these should be crucial parameters for the clinical performance of DF.Conclusion: Rheological data can be a tool to have an indication on the efficacy and longevity of DF but it has to be considered that production technology, in-vivo-conditions, injector skills and experience also influence them significantly.
Purpose The aim of this study was to screen specific adherent matrix for endothelial progenitor cells (EPCs), which can be used for antibody capturing stents. Methods In this study, the adhesion of EPCs on different matrices containing three different antibodies, VEGFR-2, CD34, CD133, was observed under shear stress in a flow chamber. Nitric oxide (NO) release, cell proliferation and the retention rate of EPCs, were measured separately. Results The results demonstrated that shear stress within a certain range can promote proliferation and NO secretion of EPCs. Under the same shear stress, the EPCs showed stronger adhesion on matrix-containing CD133 antibody than on the other matrices. Conclusions CD133 antibody has the potential application for EPCs capture.
PurposeTo evaluate the biomechanical properties and biocompatibility of natural hydroxyapatite/chitosan (HA/CS) composites. MethodsThe natural HA/CS composites with a different proportion of HA and CS were prepared by the cross-linking method, and then the compressive strength, microstructure and pH values of extracts from these composites were measured by SEM and pH meter, respectively. Subsequently, the biocompatibility of the composites was evaluated by means of a series of biological tests, including MTT, acute systemic toxicity, heat source, and hemolysis tests in vitro. ResultsThe chitosan content in the composites had significantly influenced the mechanical properties and microstructure of the composites. The pH value of the composite extract was approximately 7.0, which was very close to that of human plasma. Furthermore, the natural HA/CS composites showed no cytotoxicity, irritation, teratogenicity, carcinogenicity and special pyrogen. ConclusionsThese results indicated that the natural HA/CS composite may be a potential bone repair material.
The use of biomaterials in dentistry is more widespread than in any other medical field in terms of both amount and variety. Most of them were not originally designed for dental applications but for other medical applications or, sometimes, for no medical purposes. Among these materials, biodegradable materials play an important role, especially in bone regeneration and in periodontal surgery. This paper briefly reviews some degradable polymers developed as tools for the treatment of periodontal and bone diseases. We discuss materials previously applied in other industrials contexts, such as polyesters, methylcellulose, and chitosan and we provide perspectives for their use in periodontal regeneration.
Background There is mounting evidence to suggest the involvement of the immune system by means of activation by metal ions released via biocorrosion, in the pathophysiologic mechanisms of aseptic loosening of orthopedic implants. However, the detailed mechanisms of how metal ions become antigenic and are presented to T-lymphocytes, in addition to how the local inflammatory response is driven, remain to be investigated. Methods Human T-lymphocytes were cultured in the presence of a variety of metal ions before investigating functional and phenotypic changes using flow cytometric analysis. Additionally, human monocyte-derived dendritic cells (mDC) loaded with metal ions were used as antigen-presenting cells and incubated with naive T-lymphocytes with the aim of generating titanium-specific T-lymphocytes. Results Using an autologous in vitro model, with mDC treated with Titanium (IV), we were able to induce Titanium (IV)-specific T-lymphocytes. These T-lymphocytes responded in a dose-related manner to Titanium (IV), while they did not cross-react with Titanium (III) or other metal ions, indicating that the new antigenic peptide complexes formed by Titanium (IV) are highly specific. Conclusion This study showed that mDC exposed to Titanium (IV) are able to induce the generation of Titanium (IV)-specific T-lymphocytes, demonstrating the strong and specific antigenicity of Titanium (IV) ions released by biocorrosion.
Purpose. Experimental tests have played a major role in the assessment of fatigue endurance of orthopedic prostheses; however, cyclic tests on devices entail high costs. Here, a multiaxial fatigue criterion coupled with computational simulations and material properties measurements has been employed to predict fatigue life of the tibial component of a polymeric PMMA spacer. The ultimate aim is to obtain valid information on fatigue behavior avoiding fatigue tests on the device.Methods. First, an accurate measurement of the static and fatigue properties of PMMA samples is performed. Then, numeric simulations of the fatigue behavior of the PMMA spacer reproducing the experimental test conditions according to ISO 14879-1 were carried out in order to calculate the stress field throughout the device. Finally, a Risk Index was calculated by using a proper multiaxial fatigue criterion for brittle materials (Kakuno-Kawada) for the assessment of the device fatigue behavior by predicting the F-N curves.Results. The numeric results were validated by comparing the predictions against experimental data already published by our group. The multiaxial fatigue criterion was able to predict the most critical point on the spacer upper surface and the fatigue behavior of the device that nicely matched the experimental curves.Conclusions. This approach represents a valuable tool to investigate the mechanical reliability of implantable devices; nevertheless, the use of advanced and specific failure criteria coupled with accurate data of the device's material is mandatory to represent a real alternative to the experimental approach in fatigue life prediction.
Purpose. Since bacterial pollution is more troublesome than other nonbiologic air pollutants, the need to control airborne micro-organisms has led to renewed interest in filter media for air filtration in indoor environments. Although mechanical filtration of aerosols by HEPA systems is the most common method for particle removal, these filters characterized by high efficiency usually reveal a higher drop in pressure and noise and are very expensive. On this basis, we aimed to develop novel, very effective air filters for removal of airborne bacteria from confined environments.Methods. Parallelepiped filters surrounded by a cardboard frame were manufactured by aligning strips of corrugated cardboard and were assessed in terms of airflow rate reduction. Cardboard filters were soaked in isopropanol or used untreated in in vitro experiments for assessment of their antibacterial effect against E. coli and in a testing chamber for assessment of airborne bacterial removal. The surface morphology of cardboard specimens was also investigated by scanning electron microscopy.Results. Cardboard filters determined a very low decrease in airflow rate. Although specimens showed no antimicrobial behavior, untreated filters showed a maximum of 77% abatement of the airborne bacteria and the alcohol treatment of filters further increased their effectiveness by 14% probably because of their more convoluted surface.Conclusions. This work disclosed corrugated cardboard-based filters as promising tools for the air treatment of indoor environments because of their excellent microbial abatement properties. Moreover, cardboard is lightweight, inexpensive, and eco-friendly material, and corrugated cardboard-based air filters are very simple in shaping, mounting, and replacing existing ventilation systems.
PURPOSETo assess both the in vitro and in vivo biological response of a laser modified surface in an integrated manner. A combined innovative approach applies lasers to macrostructure as well as to oxidize the surface of titanium alloy implants.MATERIALS AND METHODSA Nd:YAG marking and ArF excimer lasers were used for macrostructuring and UV-oxidizing the surface of Ti6Al4V discs, respectively. Human fetal osteoblastic cell culture and a sheep tibia model were used to assess the cell response and the osseogeneration capability of as-machined, laser macrostructured and laser macrostructured and oxidized surfaces.RESULTSIn vitro: Laser macrostructuration alone did not promote cell response. Cellular proliferation was enhanced by the additional UV laser oxidation. In vivo: A greater significant percentage of bone-implant contact was obtained for both laser treated surfaces compared to machine-turned control samples, three months after implantation, in spite of the low cellular response for macrostructured samples. The use of sheep model for six months appears to be less adequate for a comparison because of the high level of bone integration in all samples. In spite of the often reported positive effect of titanium oxidation on the triggering of faster osseointegration, in this experiment the additional UV laser oxidation did not lead to a significant in vivo improvement.CONCLUSIONSLaser macrostructuration of titanium alloy surfaces appears to promote bone apposition and may therefore constitute a promising surface modification strategy. In animal models, the natural process of titanium surface oxidation, because of physiologic fluids, alters properties observed in vitro with cells.
A complete morphologic characterization of porous scaffolds for tissue engineering application is fundamental, as the architectural parameters, in particular porosity, strongly affect the mechanical and biological performance of the structures. Therefore, appropriate techniques for this purpose need to be selected. Several techniques for the assessment of scaffold porosity have been proposed, including scanning electron microscopy observation, mercury and liquid extrusion porosimetry, gas pycnometry, and capillary flow porometry. Each of these techniques has several drawbacks and, a combination of different techniques is often required so as to achieve an in depth study of the morphologic properties of the scaffold. A single technique is often limited and suitable only for the assessment of a specific parameter. To overcome this limit, the most attractive option would be a single nondestructive technique, yet capable of providing a comprehensive set of data. It appears that micro-computed tomography (micro-CT) can potentially fulfill this role. Initially developed to characterize the 3D trabecular microarchitecture of bone, its use has been recently exploited by researchers for the morphologic characterization of porous biomaterials, as it enables obtaining a full assessment of the porous structures both in terms of pore size and interconnected porosity. This review aims to explore the use of micro-CT in scaffold characterization, comparing it with other previously developed techniques; we also focus on the contribution of this innovative tool to the development of scaffold-based tissue engineering application.
PURPOSE:The aim of this work is to develop a 3D finite elements model to study the nanomechanical behavior of mineralized collagen microfibrils, which consists of three phases, (i) collagen phase formed by five tropocollagen (TC) molecules linked together with cross-links, (ii) a mineral phase (Hydroxyapatite), and (iii) impure mineral phase, and to investigate the important role of individual properties of every constituent.METHODS:The mechanical and geometric properties (TC molecule diameter) of both tropocollagen and mineral were taken into consideration as well as cross-links, which was represented by spring elements with adjusted properties based on experimental data. In this paper an equivalent homogenized model was developed to assess the whole microfibril mechanical properties (Young's modulus and Poisson's ratio) under varying mechanical properties of each phase.RESULTS:In this study, both equivalent Young's modulus and Poisson's ratio, which were expressed as functions of Young's modulus of each phase, were obtained under tensile load with symmetric and periodic boundary conditions.
Aim In this work, we report the use of plasticized polyvinyl chloride (PVC) as a potential antifouling coating material. The materials contain a variety of sebacic and succinic acid-derived plasticizers providing a variation in molecular shape and structure; diethyl succinate (DESn), di-(2-ethylhexyl sebacate) (DEHS), dibutyl sebacate (DBS), and diethyl sebacate (DES). Each plasticizer from the sebacate group possessed the same basic C10H16O4 moiety with varied dialkyl terminated groups, affording a different range of homologous series plasticizers. This work investigates whether branching of the side substituted alkyl chains on each plasticizer molecule affects microorganism attachment and subsequent fouling. Materials and Methods The plasticized polymers are spin coated to create thin films for testing. In order to determine the antifouling capacity of the materials, the polymer coatings underwent a series of analyses for biomass determination, glycocalyx production, and protein and carbohydrate adsorption. Topological and morphological characterization was performed using scanning electron microscopy and atomic force microscopy. Results After a 7 day laboratory biofouling study it was found that the plasticizers with increased alkyl branching, DESN, and DEHS revealed the greatest degree of prevention of microorganism colonization and attachment thus significantly reducing the initial formation of biofilms by up to 65% in some biofouling assays when compared to the unplasticized PVC blank.
Regenerative medicine is a critical frontier in biomedical and clinical research. The major progresses in the last few years were driven by a strong clinical need which could benefit from regenerative medicine outcomes for the treatment of a large number of conditions including birth defects, degenerative and neoplastic diseases, and traumatic injuries. Regenerative medicine applies the principles of engineering and life sciences to enhance the comprehension of the fundamental biological mechanisms underlying the structure-function relationships in physiologic and pathologic tissues and to accomplish alternative strategies for developing in vitro biological substitutes which are able to restore, maintain, or improve tissue, and organ function. This paper reviews selected approaches currently being investigated at Politecnico di Milano in the field of regenerative medicine. Specific tissue-oriented topics are divided in three sections according to each developmental stage: in vitro study, pre-clinical study, and clinical application. In vitro studies investigate the basic phenomena related to gene delivery, stem cell behavior, tissue regeneration, and to explore dynamic culture potentiality in different applications: cardiac and skeletal muscle, cartilage, hematopoietic system, peripheral nerve, and gene delivery. Specific fields of regenerative medicine, i.e., bone, blood vessels, and ligaments engineering have already reached the preclinical stage providing promising insights for further research towards clinical applications. The translation of the results obtained during in vitro and preclinical steps into clinical organ replacement is a very challenging issue, which can offer a valid alternative to fight morbidity, organ shortage, and ethical-social problems associated with allotransplantation as shown in the clinical case reported in this review.
Genomics is the study of an organism's genome aimed at the functional specification of the different parts of the sequence that comprise the blueprint of the living cell to unveil the mechanisms of the physiology of the cell and its basic, developmental, and tissue-specific processes.Proteomics is the comprehensive study of the executive molecules of the cell coded by the genome, further raising the level of complexity, because of the large amplification in the number, going from genes to proteins, and to the sophisticated structural and functional characterization of protein products, which confer specific biochemical properties.While continuous progress in technology provides new experimental solutions to study and measure the behavior of genes and proteins in the cell, the analysis and the management of biological data cannot be uncoupled from the use of mathematics, statistics, and informatics disciplines that play a key role in modern molecular biology.Together, genomics and proteomics, meant as complementary approaches, delineate the framework of modern molecular medicine, where the knowledge of the functional mechanisms on a subcellular scale, both under physiologic and pathologic conditions, may lead to an improvement in diagnosis, therapy, and drug development.
Purpose The purpose of this study was to explore the effects of implant angulation and its possible influence on prosthetic connection as regards implant/tooth strains in a combined implant and natural tooth abutment fixed partial denture. Methods A natural tooth was embedded between vertically-aligned and 17° angulated implants in a polymethyl methacrylate acrylic resin model. Three designs (Group 1: tooth and vertically-aligned implant; Group 2: tooth and 17° angulated implant, Group 3: tooth and vertically-aligned implant having a different prosthetic connection to Group 1) of tooth-implant supported prostheses (n=4) were fabricated. Strain gauges were bonded on the prostheses and on the approximal sides of the natural tooth abutment and implants. Once the test fixed partial dentures were seated, a static load of 150 N was applied to each prosthesis. During testing, strain-gauge signals were digitalized by a data acquisition system and this signal was stored and assessed with corresponding software at a sample rate of 10 KHz. Results The data were then evaluated using Mann-Whitney U and Kruskal Wallis tests at 95% confidence level. Mesiodistal tilting of implants increased peri-implant strains in implant-tooth supported prostheses during torque-tightening and under load. The mode of prosthesis connection may affect strains within the prosthesis and natural tooth abutments, although its impact under static loading conditions seems negligible. Conclusions This investigation suggests that mesiodistal tilting of implants may have a biomechanical effect in tooth-implant supported prostheses.
The present article reviews on different research lines, namely: drug and gene delivery, surface modification/modeling, design of advanced materials (shape memory polymers and biodegradable stents), presently developed at Politecnico di Milano, Italy.For gene delivery, non-viral polycationic-branched polyethylenimine (b-PEI) polyplexes are coated with pectin, an anionic polysaccharide, to enhance the polyplex stability and decrease b-PEI cytotoxicity. Perfluorinated materials, specifically perfluoroether, and perfluoro-polyether fluids are proposed as ultrasound contrast agents and smart agents for drug delivery.Non-fouling, self-assembled PEG-based monolayers are developed on titanium surfaces with the aim of drastically reducing cariogenic bacteria adhesion on dental implants. Femtosecond laser microfabrication is used for selectively and spatially tuning the wettability of polymeric biomaterials and the effects of femtosecond laser ablation on the surface properties of polymethylmethacrylate are studied. Innovative functionally graded Alumina-Ti coatings for wear resistant articulating surfaces are deposited with PLD and characterized by means of a combined experimental and computational approach. Protein adsorption on biomaterials surfaces with an unlike wettability and surface-modification induced by pre-adsorbed proteins are studied by atomistic computer simulations.A study was performed on the fabrication of porous Shape Memory Polymeric structures and on the assessment of their potential application in minimally invasive surgical procedures. A model of magnesium (alloys) degradation, in a finite element framework analysis, and a bottom-up multiscale analysis for modeling the degradation mechanism of PLA matrices was developed, with the aim of providing valuable tools for the design of bioresorbable stents.
Purpose: The present paper is focused on the effects of in vitro induced nonenzymatic glycation of bone collagen on stiffness and fracture of demineralized bone matrix in unconfined compression were investigated.Material and Methods: Regular specimens from mid-shaft of bovine femur were grouped in pairs. One sample (R) from each pair was incubated in ribose solution, control samples (C) were incubated in a buffer solution. Samples were then demineralized in formic acid. Demineralized samples were axially compressed to failure (0.033/s). Direction of compression was along the longitudinal axis of femur (L) or perpendicular (transverse) to that (T). Mechanical behavior of demineralized samples was characterized in terms of secant modulus, stress, and strain at fracture and work to failure. The development of damage was examined in terms of acoustic emission (AE) signal recorded during loading.Results: In L direction, strain at fracture following glycation was lower than in the controls (p=0.038); secant modulus and ultimate stress were not significantly different in R and C. In the transverse direction, strain at fracture in R was higher than in C (p=0.053), as well as work to failure (p=0.020). Anisotropy of bone matrix, defined in terms of a ratio of the parameters in two perpendicular directions, decreased markedly in ribosylated samples. Both the number of AE events and cumulative AE energy during deformation were significantly higher in ribosylated samples than in the control for both directions of compression.Conclusion: The study demonstrated that nonenzymatic glycation plays a significant role in modifying organic matrix properties in cortical bone.
Polymer-based composite materials are ideal for applications where high stiffness-to-weight and strength-to-weight ratios are required. From aerospace and aeronautical field to biomedical applications, fiber-reinforced polymers have replaced metals, thus emerging as an interesting alternative. As widely reported, the mechanical behavior of the composite materials involves investigation on micro- and macro-scale, taking into consideration micromechanics, macromechanics and lamination theory. Clinical situations often require repairing connective tissues and the use of composite materials may be suitable for these applications because of the possibility to design tissue substitutes or implants with the required mechanical properties. Accordingly, this review aims at stressing the importance of fiber-reinforced composite materials to make advanced and biomimetic prostheses with tailored mechanical properties, starting from the basic principle design, technologies, and a brief overview of composites applications in several fields. Fiber-reinforced composite materials for artificial tendons, ligaments, and intervertebral discs, as well as for hip stems and mandible models will be reviewed, highlighting the possibility to mimic the mechanical properties of the soft and hard tissues that they replace.
