A Poroelastic Mixture Model of Mechanobiological Processes in Biomass Growth: Theory and Application to Tissue Engineering

In this article we propose a novel mathematical description of biomass growth that combines poroelastic theory of mixtures and cellular population models. The formulation, potentially applicable to general mechanobiological processes, is here used to study the engineered cultivation in bioreactors of articular chondrocytes, a process of Regenerative Medicine characterized by a complex interaction among spatial scales (from nanometers to centimeters), temporal scales (from seconds to weeks) and biophysical phenomena (fluid-controlled nutrient transport, delivery and consumption; mechanical deformation of a multiphase porous medium). The principal contribution of this research is the inclusion of the concept of cellular \u201cforce isotropy\u201d as one of the main factors influencing cellular activity. In this description, the induced cytoskeletal tensional states trigger signalling transduction cascades regulating functional cell behavior. This mechanims is modeled by a parameter which estimates the influence of local force isotropy by the norm of the deviatoric part of the total stress tensor. According to the value of the estimator, isotropic mechanical conditions are assumed to be the promoting factor of extracellular matrix production whereas anisotropic conditions are assumed to promote cell proliferation. The resulting mathematical formulation is a coupled system of nonlinear partial differential equations comprising: conservation laws for mass and linear momentum of the growing biomass; advection\u2013diffusion\u2013reaction laws for nutrient (oxygen) transport, delivery and consumption; and kinetic laws for cellular population dynamics. To develop a reliable computational tool for the simulation of the engineered tissue growth process the nonlinear differential problem is numerically solved by: (1) temporal semidiscretization; (2) linearization via a fixed-point map; and (3) finite element spatial approximation. The biophysical accuracy of the mechanobiological model is assessed in the analysis of a simplified 1D geometrical setting. Simulation results show that: (1) isotropic/anisotropic conditions are strongly influenced by both maximum cell specific growth rate and mechanical boundary conditions enforced at the interface between the biomass construct and the interstitial fluid; (2) experimentally measured features of cultivated articular chondrocytes, such as the early proliferation phase and the delayed extracellular matrix production, are well described by the computed spatial and temporal evolutions of cellular populations

Scaling-Up Techniques for the Nanofabrication of Cell Culture Substrates via Two-Photo Polymerization for Industrial-Scale Expansion of Stem Cells

Stem-cell-based therapies require a high number (106–109) of cells, therefore in vitro expansion is needed because of the initially low amount of stem cells obtainable from human tissues. Standard protocols for stem cell expansion are currently based on chemically-defined culture media and animal-derived feeder-cell layers, which expose cells to additives and to xenogeneic compounds, resulting in potential issues when used in clinics. The two-photon laser polymerization technique enables three-dimensional micro-structures to be fabricated, which we named synthetic nichoids. Here we review our activity on the technological improvements in manufacturing biomimetic synthetic nichoids and, in particular on the optimization of the laser-material interaction to increase the patterned area and the percentage of cell culture surface covered by such synthetic nichoids, from a low initial value of 10% up to 88% with an optimized micromachining time. These results establish two-photon laser polymerization as a promising tool to fabricate substrates for stem cell expansion, without any chemical supplement and in feeder-free conditions for potential therapeutic uses

Review of recent progress in nanoscratch testing

Nanoscratch testing, as an important technique for the assessment of the mechanical failure behaviour and adhesion strength of ceramic coatings and a simulation tool of single asperity contact in tribological experiments, is increasingly becoming an established nanomechanical characterisation method. This paper reviews recent work in nanoscratch testing in different engineering applications including thin ceramic films, automotive organic coatings, chemical- mechanical polishing and biomaterials. In the main part of the paper, nanoscratch results from experiments performed using NanoTest systems fitted with tangential force sensors and spherical indenters as scratch probes are presented and discussed. The types of nanoscratch tests described include constant load nanoscratches, ramped load nanoscratch tests and multipass repetitive unidirectional constant load nanoscratch tests (nanowear). The results are discussed in terms of critical load sensitivity to intrinsic and extrinsic factors, impact of scan speed and loading rate, influence of probe radius and geometry, estimation of tip contact pressure, influence of surface roughness and film stress and thickness, and finally role of ploughing on friction evolution

Selective laser melting–enabled electrospinning: Introducing complexity within electrospun membranes

Additive manufacturing technologies enable the creation of very precise and well-defined structures that can mimic hierarchical features of natural tissues. In this article, we describe the development of a manufacturing technology platform to produce innovative biodegradable membranes that are enhanced with controlled microenvironments produced via a combination of selective laser melting techniques and conventional electrospinning. This work underpins the manufacture of a new generation of biomaterial devices that have significant potential for use as both basic research tools and components of therapeutic implants. The membranes were successfully manufactured and a total of three microenvironment designs (niches) were chosen for thorough characterisation. Scanning electron microscopy analysis demonstrated differences in fibre diameters within different areas of the niche structures as well as differences in fibre density. We also showed the potential of using the microfabricated membranes for supporting mesenchymal stromal cell culture and proliferation. We demonstrated that mesenchymal stromal cells grow and populate the membranes penetrating within the niche-like structures. These findings demonstrate the creation of a very versatile tool that can be used in a variety of tissue regeneration applications including bone healing

Management of cryptorchidism: a survey of clinical practice in Italy

<p>Abstract</p> <p>Background</p> <p>An evidence-based Consensus on the treatment of undescended testis (UT) was recently published, recommending to perform orchidopexy between 6 and 12 months of age, or upon diagnosis and to avoid the use of hormones. In Italy, current practices on UT management are little known. Our aim was to describe the current management of UT in a cohort of Italian children in comparison with the Consensus guidelines. As management of retractile testis (RT) differs, RT cases were described separately.</p> <p>Methods</p> <p>Ours is a retrospective, multicenter descriptive study. An online questionnaire was filled in by 140 Italian Family Paediatricians (FP) from <it>Associazione Culturale Pediatri </it>(ACP), a national professional association of FP. The questionnaire requested information on all children with cryptorchidism born between 1/01/2004 and 1/01/2006. Data on 169 children were obtained. Analyses were descriptive.</p> <p>Results</p> <p>Overall 24% of children were diagnosed with RT, 76% with UT. Among the latter, cryptorchidism resolved spontaneously in 10% of cases at a mean age of 21.6 months. Overall 70% of UT cases underwent orchidopexy at a mean age of 22.8 months (SD 10.8, range 1.2-56.4), 13% of whom before 1 year. The intervention was performed by a paediatric surgeon in 90% of cases, with a success rate of 91%. Orchidopexy was the first line treatment in 82% of cases, while preceded by hormonal treatment in the remaining 18%. Hormonal treatment was used as first line therapy in 23% of UT cases with a reported success rate of 25%. Overall, 13 children did not undergo any intervention (mean age at last follow up 39.6 months). We analyzed the data from the 5 Italian Regions with the largest number of children enrolled and found a statistically significant regional difference in the use of hormonal therapy, and in the use of and age at orchidopexy.</p> <p>Conclusions</p> <p>Our study showed an important delay in orchidopexy. A quarter of children with cryptorchidism was treated with hormonal therapy. In line with the Consensus guidelines, surgery was carried out by a paediatric surgeon in the majority of cases, with a high success rate.</p