Roberto De Santis

Polymer-based composite scaffolds for tissue engineering

Tissue engineering may be defined as the application of biological, chemical and engineering principles toward the repair, restoration or regeneration of living tissue using biomaterials, cells and biologically active molecules alone or in combinations. The rapid restoration of tissue biomechanical function represents a great challenge, highlighting the need to mimic tissue structure and mechanical behavior through scaffold designs. For this reason, several biodegradable and bioresorbable materials, as well as technologies and scaffold designs, have been widely investigated from an experimental and/or clinical point of view. Accordingly, this review aims at stressing the importance of polymer-based composite materials to make multifunctional scaffolds for tissue engineering, with a special focus on bone, ligaments, meniscus and cartilage. Moreover, polymer-based nanocomposites will also be briefly introduced as an interesting strategy to improve the biological and mechanical performances of polymer scaffolds, especially for bone tissue engineering.

A multi-component fiber-reinforced PHEMA-based hydrogel/HAPEX™ device for customized intervertebral disc prosthesis.

Spinal disease due to intervertebral disc degeneration represents a serious medical problem which affects many people worldwide. Disc arthroplasty may be considered the future ‘‘gold standard’’ of back pain treatment, even if problems related to available disc prostheses are considered. Hence, the aim of the present study was to improve the artificial disc technology by proposing the engineering of a pilot-scale device production process for a total multi-component intervertebral disc prosthesis. The device is made up of a poly(2-hydroxyethyl methacrylate)/poly(methyl methacrylate) (PHEMA/PMMA) (80/20 w/w) semi-interpenetrating polymer network (s-IPN) composite hydrogel reinforced with poly(ethylene terephthalate) (PET) fibers as annulus/nucleus substitute, and two hydroxyapatite-reinforced polyethylene composite (HAPEX TM) endplates in order to anchor the multi-component device to the vertebral bodies. Static and dynamic—mechanical characterization show appropriate mechanical behavior. An example of engineering of a suitable pilot-scale device production process is also proposed in order to manufacture custom made implants.

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.

Hyperthermia Induced in Magnetic Scaffolds for Bone Tissue Engineering

The design and fabrication of advanced biocompatible and bioresorbable materials able to mimic the natural tissues present in the human body constitutes an important challenge in regenerative medicine. The size-dependent properties that materials exhibit at the nanoscale as a consequence of their higher surface-to-volume ratio have opened a wide range of opportunities for applications in almost every imaginable field. In this regard, the incorporation of magnetic nanoparticles (MNPs) into biocompatible scaffold formulations provides final materials with additional multifunctionality and reinforced mechanical properties for bone tissue engineering applications. In addition to the biological implications due to their magnetic character (i.e., magnetic stimuli that favor the cell adhesion/proliferation, guiding of growth factors loaded magnetic nanocarriers, etc.), the ability of superparamagnetic scaffolds to simultaneously show magnetic hyperthermia when a dynamic external magnetic field is applied become promising to treat critical bone defects caused by malignant bone cancer through a combined therapy consisting of on demand temperature increase and thermally activated drug delivery. In this paper, we will comment on several different approaches to construct magnetic scaffolds with hyperthermia properties for bone tissue engineering. Experimental details about the design, fabrication and physicochemical characterization of a representative set of magnetic scaffolds have been described, focusing on their hyperthermia properties. The following synthesis procedures to magnetize biocompatible scaffolds reported in this paper covers dip coating of biocompatible gelatin-based scaffolds in aqueous MNPs dispersions, iron doping of the hydroxyapatite (HA) crystal structure, and incorporation of magnetic bioresorbable HA nanoparticles into poly-ε-caprolactone-based polymeric matrices.

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.

Galactose grafting on poly(ε-caprolactone) substrates for tissue engineering: a preliminary study

The grafting of galactose units onto poly(ε-caprolactone) (PCL) substrates by a wet chemistry two-step procedure is proposed. Even though a reduction of hardness from 0.58-0.31 GPa to 0.12-0.05 GPa is achieved, the chemical functionalization does not negatively affect the tensile modulus (332.2±31.3 MPa and 328.5±34.7 MPa for unmodified and surface-modified PCL, respectively) and strength (15.1±1.3 MPa and 14.8±1.5 MPa as assessed before and after the surface modification, respectively), as well as the mechanical behaviour evaluated through small punch test. XPS and enzyme-linked lectin assay (ELLA) demonstrate the presence, and also the correct exposition of the saccharidic epitope on PCL substrates. The introduction of carbohydrate moieties on the PCL surfaces clearly enhances the hydrophilicity of the substrate, as the water contact angle decreases from 82.1±5.8° to 62.1±4.2°. Furthermore, preliminary biological analysis shows human mesenchymal stem cell viability over time and an improvement of cell adhesion and spreading.

Further Theoretical Insight into the Mechanical Properties of Polycaprolactone Loaded with Organic–Inorganic Hybrid Fillers

Experimental/theoretical analyses have already been performed on poly(ε-caprolactone) (PCL) loaded with organic–inorganic fillers (PCL/TiO2 and PCL/ZrO2) to find a correlation between the results from the small punch test and Young’s modulus of the materials. PCL loaded with Ti2 (PCL = 12, TiO2 = 88 wt %) and Zr2 (PCL = 12, ZrO2 = 88 wt %) hybrid fillers showed better performances than those obtained for the other particle composition. In this context, the aim of current research is to provide further insight into the mechanical properties of PCL loaded with sol–gel-synthesized organic–inorganic hybrid fillers for bone tissue engineering. For this reason, theoretical analyses were performed by the finite element method. The results from the small punch test and Young’s modulus of the materials were newly correlated. The obtained values of Young’s modulus (193 MPa for PCL, 378 MPa for PCL/Ti2 and 415 MPa for PCL/Zr2) were higher than those obtained from a previous theoretical modelling (144 MPa for PCL, 282 MPa for PCL/Ti2 and 310 MPa for PCL/Zr2). This correlation will be an important step for the evaluation of Young’s modulus, starting from the small punch test data.

Effect of light curing and dark reaction phases on the thermomechanical properties of a Bis-GMA based dental restorative material

PURPOSE The effects of light curing units (LCU) and energy doses on the chemical and physical properties of a dental composite were investigated. METHODS The effects on the chemical and physical properties of a bisphenol A diglycidylether methacrylate (Bis-GMA) based dental restorative material were evaluated through photospectrometry, differential scanning calorimetry, and mechanical measurements. RESULTS The light curing conditions associated with direct and indirect restorations were replicated in vitro using optical investigation techniques. A slight attenuation resulted independently of the LCU and a strong attenuation was measured for the cement luting a thick inlay, as well as for the deepest layer of a composite filling increment. Calorimetric measurements indicated that the curing degree is very sensitive to the light energy dose rather than to the LCU. Mechanical testing showed a transient phase during which properties increased. The delay of the composite in reaching adequate properties is strongly dependent on the energy dose. CONCLUSIONS It is recommended that composites subject to unfavorable light curing conditions undergo a prolonged light curing process.