Teresa Russo

Magnetic poly(ε-caprolactone)/iron-doped hydroxyapatite nanocomposite substrates for advanced bone tissue engineering

In biomedicine, magnetic nanoparticles provide some attractive possibilities because they possess peculiar physical properties that permit their use in a wide range of applications. The concept of magnetic guidance basically spans from drug delivery and hyperthermia treatment of tumours, to tissue engineering, such as magneto-mechanical stimulation/activation of cell constructs and mechanosensitive ion channels, magnetic cell-seeding procedures, and controlled cell proliferation and differentiation. Accordingly, the aim of this study was to develop fully biodegradable and magnetic nanocomposite substrates for bone tissue engineering by embedding iron-doped hydroxyapatite (FeHA) nanoparticles in a poly(ε-caprolactone) (PCL) matrix. X-ray diffraction analyses enabled the demonstration that the phase composition and crystallinity of the magnetic FeHA were not affected by the process used to develop the nanocomposite substrates. The mechanical characterization performed through small punch tests has evidenced that inclusion of 10 per cent by weight of FeHA would represent an effective reinforcement. The inclusion of nanoparticles also improves the hydrophilicity of the substrates as evidenced by the lower values of water contact angle in comparison with those of neat PCL. The results from magnetic measurements confirmed the superparamagnetic character of the nanocomposite substrates, indicated by a very low coercive field, a saturation magnetization strictly proportional to the FeHA content and a strong history dependence in temperature sweeps. Regarding the biological performances, confocal laser scanning microscopy and AlamarBlue assay have provided qualitative and quantitative information on human mesenchymal stem cell adhesion and viability/proliferation, respectively, whereas the obtained ALP/DNA values have shown the ability of the nanocomposite substrates to support osteogenic differentiation.

PLDLA/PCL-T Scaffold for Meniscus Tissue Engineering

Abstract The inability of the avascular region of the meniscus to regenerate has led to the use of tissue engineering to treat meniscal injuries. The aim of this study was to evaluate the ability of fibrochondrocytes preseeded on PLDLA/PCL-T [poly(L-co-D,L-lactic acid)/poly(caprolactone-triol)] scaffolds to stimulate regeneration of the whole meniscus. Porous PLDLA/PCL-T (90/10) scaffolds were obtained by solvent casting and particulate leaching. Compressive modulus of 9.5±1.0 MPa and maximum stress of 4.7±0.9 MPa were evaluated. Fibrochondrocytes from rabbit menisci were isolated, seeded directly on the scaffolds, and cultured for 21 days. New Zealand rabbits underwent total meniscectomy, after which implants consisting of cell-free scaffolds or cell-seeded scaffolds were introduced into the medial knee meniscus; the negative control group consisted of rabbits that received no implant. Macroscopic and histological evaluations of the neomeniscus were performed 12 and 24 weeks after implantation. The polymer scaffold implants adapted well to surrounding tissues, without apparent rejection, infection, or chronic inflammatory response. Fibrocartilaginous tissue with mature collagen fibers was observed predominantly in implants with seeded scaffolds compared to cell-free implants after 24 weeks. Similar results were not observed in the control group. Articular cartilage was preserved in the polymeric implants and showed higher chondrocyte cell number than the control group. These findings show that the PLDLA/PCL-T 90/10 scaffold has potential for orthopedic applications since this material allowed the formation of fibrocartilaginous tissue, a structure of crucial importance for repairing injuries to joints, including replacement of the meniscus and the protection of articular cartilage from degeneration.

Collagen-low molecular weight hyaluronic acid semi-interpenetrating network loaded with gelatin microspheres for cell and growth factor delivery for nucleus pulposus regeneration

Intervertebral disc (IVD) degeneration is one of the main causes of low back pain. Current surgical treatments are complex and generally do not fully restore spine mobility. Development of injectable extracellular matrix-based hydrogels offers an opportunity for minimally invasive treatment of IVD degeneration. Here we analyze a specific formulation of collagen-low molecular weight hyaluronic acid (LMW HA) semi-interpenetrating network (semi-IPN) loaded with gelatin microspheres as a potential material for tissue engineering of the inner part of the IVD, the nucleus pulposus (NP). The material displayed a gel-like behavior, it was easily injectable as demonstrated by suitable tests and did not induce cytotoxicity or inflammation. Importantly, it supported the growth and chondrogenic differentiation potential of mesenchymal stem cells (MSC) and nasal chondrocytes (NC) in vitro and in vivo. These properties of the hydrogel were successfully combined with TGF-β3 delivery by gelatin microspheres, which promoted the chondrogenic phenotype. Altogether, collagen-LMW HA loaded with gelatin microspheres represents a good candidate material for NP tissue engineering as it combines important rheological, functional and biological features.

3d fiber deposition technique to make multifunctional and tailor-made scaffolds for tissue engineering applications

Tissue engineering represents an interesting approach which aims to create tissues and organs de novo. In designing scaffolds for tissue engineering applications, the principal goal is to mimic the function of the natural extracellular matrix, providing a temporary template for the growth of target tissues. For this reason, scaffolds should possess suitable mechanical properties and architecture to play their specific role. In this paper, limitations of conventional scaffold fabrication methods will be briefly introduced, and rapid prototyping techniques will be described as advanced processing methods to realize customized scaffolds with controlled internal microarchitecture. Among the rapid prototyping techniques, the potential and challenges of 3D fiber deposition to create multifunctional and tailor-made scaffolds will be reviewed.

Technical features and criteria in designing fiber-reinforced composite materials: from the aerospace and aeronautical field to biomedical applications.

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.

Multidisciplinary perspectives for Alzheimer's and Parkinson's diseases: hydrogels for protein delivery and cell-based drug delivery as therapeutic strategies

This review presents two intriguing multidisciplinary strategies that might make the difference in the treatment of neurodegenerative disorders such as Alzheimers and Parkinsons diseases. The first proposed strategy is based on the controlled delivery of recombinant proteins known to play a key role in these neurodegenerative disorders that are released in situ by optimized polymer-based systems. The second strategy is the use of engineered cells, encapsulated and delivered in situ by suitable polymer-based systems, that act as drug reservoirs and allow the delivery of selected molecules to be used in the treatment of Alzheimers and Parkinsons diseases. In both these scenarios, the design and development of optimized polymer-based drug delivery and cell housing systems for central nervous system applications represent a key requirement. Materials science provides suitable hydrogel-based tools to be optimized together with suitably designed recombinant proteins or drug delivering-cells that, once in situ, can provide an effective treatment for these neurodegenerative disorders. In this scenario, only interdisciplinary research that fully integrates biology, biochemistry, medicine and materials science can provide a springboard for the development of suitable therapeutic tools, not only for the treatment of Alzheimers and Parkinsons diseases but also, prospectively, for a wide range of severe neurodegenerative disorders.

Nanocomposites for neurodegenerative diseases: hydrogel-nanoparticle combinations for a challenging drug delivery

Neurodegenerative disorders are expected to strike social and health care systems of developed countries heavily in the coming decades. Alzheimers and Parkinsons diseases (AD/PD) are the most prevalent neurodegenerative pathologies, and currently their available therapy is only symptomatic. However, innovative potential drugs are actively under development, though their efficacy is sometimes limited by poor brain bioavailability and/or sustained peripheral degradation. To partly overcome these constraints, the development of drug delivery devices made by biocompatible and easily administrable materials might be a great adjuvant. In particular, materials science can provide a powerful tool to design hydrogels and nanoparticles as basic components of more complex nanocomposites that might ameliorate drug or cell delivery in AD/PD. This kind of approach is particularly promising for intranasal delivery, which might increase brain targeting of neuroprotective molecules or proteins. Here we review these issues, with a focus on nanoparticles as nanocomponents able to carry and tune drug release in the central nervous system, without ignoring warnings concerning their potential toxicity.

Wolf's post-herpetic isotopic response: Infections, tumors, and immune disorders arising on the site of healed herpetic infection

Herpes simplex viruses (HSV-1/HSV-2) and varicella-zoster virus (VZV) have several characteristics in common. Both are epidermoneurotropic, cause skin eruptions accompanied by sensory symptoms (itch, pain), damage peripheral sensory nerve fibers and cutaneous nerve endings, and interfere with neuromediator release, which can alter local mechanisms of immune control. For this reason, herpes-infected areas may become a preferential location for the subsequent onset of immunity-related skin disorders (infections, tumors, and dysimmune reactions), an event first reported by a neurologist and focused on by two brothers, a dermatologist and a pediatrician. The phenomenon therefore named Wolfs post-herpetic isotopic response (PHIR) refers to the occurrence of a new skin disorder at the site of a previous and already healed herpetic eruption (herpes zoster in most cases). Until now, we have been able to gather 189 well-documented cases of PHIR (all reported in the reference section), but our list is far from being complete. Some of the most emblematic cases are briefly described here. In some circumstances, the opposite of PHIR occurs, with diffuse skin disorders or eruptions that selectively spare herpes-infected areas (Wolfs post-herpetic isotopic nonresponse). Experimental investigations with patch testing have been performed in seven patients who were sensitized to nickel and had had herpes zoster in the past years. The tests were carried out bilaterally on the affected dermatomes and on the unaffected contralateral ones. The uneven immune responses we obtained have shown that the immune behavior of an herpes zoster-affected dermatome can be different from that of the corresponding contralateral dermatome, thus supporting the existence of immune dysregulation in herpes-infected areas.

Calorimetric and Thermomechanical Properties of Titanium-Based Orthodontic Wires: DSC–DMA Relationship to Predict the Elastic Modulus

Orthodontic treatment is strongly dependent on the loads developed by metal wires, and the choice of an orthodontic archwire should be based on its mechanical performance. The desire of both orthodontists and engineers would be to predict the mechanical behavior of archwires. To this aim, Gum Metal (Toyota Central R&L Labs., Inc.), TMA (ORMCO), 35°C Copper NiTi (SDS ORMCO), Thermalloy Plus (Rocky Mountain), Nitinol SE (3M Unitek), and NiTi (SDS ORMCO) were tested according to dynamic mechanical analysis and differential scanning calorimetry. A model was also developed to predict the elastic modulus of superelastic wires. Results from experimental tests have highlighted that superelastic wires are very sensitive to temperature variations occurring in the oral environment, while the proposed model seems to be reliable to predict the Young’s modulus allowing to correlate calorimetric and mechanical data. Furthermore, Gum Metal wire behaves as an elastic material with a very low Young’s modulus, and it can be particularly useful for the initial stage of orthodontic treatments.

Ruocco's immunocompromised cutaneous district

The concept of ‘locus minoris resistentiae’ (lmr) is an old but still effective way of thinking in Medicine. In Dermatology, there are many reports of privileged localization of cutaneous diseases on injured skin, which therefore represents a typical condition of lmr. Lately the innovative concept of immunocompromised cutaneous district (ICD) has been introduced to explain why a previously injured cutaneous site may become in time a privileged location for the outbreak of opportunistic infections, tumors, and immune reactions. An ample documentation of multifarious disorders (infectious, neoplastic, immune) appearing in ICDs was delineated by Ruocco et al. in 2009. These cases were grouped according to the clinical settings responsible for the local immune imbalance: regional chronic lymphedema; herpes‐infected sites, which feature the well‐known Wolfs isotopic response; and otherwise damaged areas, comprising sites of vaccination, ionizing or UV radiation, thermal burns, and traumas. In the following five years, what was a “novel” pathogenic concept has been extended to an enlarging variety of clinical conditions. This paper focuses on ICD and the expanding spectrum of this now established pathogenic concept.