Tommaso Casalini

Bio: Tommaso Casalini is an academic researcher from ETH Zurich. The author has contributed to research in topics: Self-healing hydrogels & Drug delivery. The author has an hindex of 15, co-authored 46 publications receiving 708 citations. Previous affiliations of Tommaso Casalini include SUPSI & Polytechnic University of Milan.

A Perspective on Polylactic Acid-Based Polymers Use for Nanoparticles Synthesis and Applications.

Abstract: Polylactic acid (PLA)-based polymers are ubiquitous in the biomedical field thanks to their combination of attractive peculiarities: biocompatibility (degradation products do not elicit critical responses and are easily metabolized by the body), hydrolytic degradation in situ, tailorable properties, and well-established processing technologies. This led to the development of several applications, such as bone fixation screws, bioresorbable suture threads, and stent coating, just to name a few. Nanomedicine could not be unconcerned by PLA-based materials as well, where their use for the synthesis of nanocarriers for the targeted delivery of hydrophobic drugs emerged as a new promising application. The purpose of the here presented review is two-fold: on one side, it aims at providing a broad overview of PLA-based materials and their properties, which allow them gaining a leading role in the biomedical field; on the other side, it offers a specific focus on their recent use in nanomedicine, highlighting opportunities and perspectives.

Diffusion and Aggregation of Sodium Fluorescein in Aqueous Solutions

Abstract: The diffusion and aggregation of sodium fluorescein in aqueous solutions was investigated adopting density functional theory (DFT) and molecular dynamics (MD) simulations. First, DFT calculations in implicit water were used to determine minimum energy structure and atomic charges of the solute, which were then used as input for explicit water MD simulations. The self-diffusion coefficient of sodium fluorescein was calculated using the Einstein equation, computing the mean square displacement from 24 ns trajectories. The calculated diffusion coefficient, 0.42 · 10(-5) cm(2) s(-1), is in good agreement with literature experimental data. The simulations confirmed the tendency of fluorescein to form dimers. In order to achieve a deeper understanding of aggregation phenomena, the dimer geometry was investigated through DFT calculations both in vacuo and in implicit water using different functionals and solvation theories. The results showed that dimerization does not occur in vacuo, as charge repulsion dominates, and that the minimum energy dimer structure is symmetric and stabilized by edge-to-face π-π interactions. The interaction energy was computed both at the DFT level and through MD simulations using Umbrella Sampling. The free interaction energy calculated with the WHAM and Umbrella Integration protocol, -1.3 kcal/mol, is in good agreement with experimental data, while the value determined using DFT calculations is significantly smaller and depends largely from the chosen functional and the computational methodology used to determine the solute-solvent boundary surface.

Mathematical modeling of PLGA microparticles: from polymer degradation to drug release.

Abstract: The present work is focused on the development and the validation of a mechanistic model describing the degradation of drug-loaded polylactic-co-glycolic acid microparticles and the drug release process from such devices. Microparticles’ degradation is described through mass conservation equations; the application of population balances allows a detailed description of the hydrolysis kinetics, which also takes into account the autocatalytic behavior that characterizes bulk eroding polymers. Drug release considers both drug dissolution and the diffusion of dissolved active principle through the polymeric matrix. The diffusion of oligomers, water, and drug is assumed to follow Fickian behavior; the use of effective diffusion coefficients takes into account the diffusivity increase due to polymer hydrolysis. The model leads to a system of partial differential equations, solved by means of the method of lines. The model predictions satisfactorily match with different sets of literature data, indicating that t...

Scaffolds as Structural Tools for Bone-Targeted Drug Delivery

Abstract: Although bone has a high potential to regenerate itself after damage and injury, the efficacious repair of large bone defects resulting from resection, trauma or non-union fractures still requires the implantation of bone grafts. Materials science, in conjunction with biotechnology, can satisfy these needs by developing artificial bones, synthetic substitutes and organ implants. In particular, recent advances in materials science have provided several innovations, underlying the increasing importance of biomaterials in this field. To address the increasing need for improved bone substitutes, tissue engineering seeks to create synthetic, three-dimensional scaffolds made from organic or inorganic materials, incorporating drugs and growth factors, to induce new bone tissue formation. This review emphasizes recent progress in materials science that allows reliable scaffolds to be synthesized for targeted drug delivery in bone regeneration, also with respect to past directions no longer considered promising. A general overview concerning modeling approaches suitable for the discussed systems is also provided.

Self-assembling peptide and protein amyloids: from structure to tailored function in nanotechnology

Abstract: Self-assembled peptide and protein amyloid nanostructures have traditionally been considered only as pathological aggregates implicated in human neurodegenerative diseases. In more recent times, these nanostructures have found interesting applications as advanced materials in biomedicine, tissue engineering, renewable energy, environmental science, nanotechnology and material science, to name only a few fields. In all these applications, the final function depends on: (i) the specific mechanisms of protein aggregation, (ii) the hierarchical structure of the protein and peptide amyloids from the atomistic to mesoscopic length scales and (iii) the physical properties of the amyloids in the context of their surrounding environment (biological or artificial). In this review, we will discuss recent progress made in the field of functional and artificial amyloids and highlight connections between protein/peptide folding, unfolding and aggregation mechanisms, with the resulting amyloid structure and functionality. We also highlight current advances in the design and synthesis of amyloid-based biological and functional materials and identify new potential fields in which amyloid-based structures promise new breakthroughs.

Combinatorial Development of Biomaterials for Clonal Growth of Human Pluripotent Stem Cells

Abstract: Structure–property relationships between material properties and stem cell behaviour are investigated using high-throughput methods. The data identify the optimal substrates within a range of different polymeric surfaces to support the growth and self-renewal of human embryonic stem cells from fully dissociated single cells.

Synthetic alternatives to Matrigel.

Abstract: Matrigel, a basement-membrane matrix extracted from Engelbreth–Holm–Swarm mouse sarcomas, has been used for more than four decades for a myriad of cell-culture applications. However, Matrigel is limited in its applicability to cellular biology, therapeutic-cell manufacturing and drug discovery, owing to its complex, ill-defined and variable composition. Variations in the mechanical and biochemical properties within a single batch of Matrigel — and between batches — have led to uncertainty in cell-culture experiments and a lack of reproducibility. Moreover, Matrigel is not conducive to physical or biochemical manipulation, making it difficult to fine-tune the matrix to promote intended cell behaviours and achieve specific biological outcomes. Recent advances in synthetic scaffolds have led to the development of xenogenic-free, chemically defined, highly tunable and reproducible alternatives. In this Review, we assess the applications of Matrigel in cell culture, regenerative medicine and organoid assembly, detailing the limitations of Matrigel and highlighting synthetic-scaffold alternatives that have shown equivalent or superior results. Additionally, we discuss the hurdles that are limiting a full transition from Matrigel to synthetic scaffolds and provide a brief perspective on the future directions of synthetic scaffolds for cell-culture applications. Matrigel is widely used for cell culture. However, its ill-defined composition, batch-to-batch variability and animal-derived nature lead to experimental uncertainty and a lack of reproducibility. In this Review, we discuss the limitations of Matrigel and highlight synthetic alternatives for stem-cell culture, regenerative medicine and organoid assembly.

Plasma Surface Modification of Biodegradable Polymers: A Review

Abstract: Besides their use as packaging materials, biodegradable polymers can play a major role in tissue engineering as three-dimensional porous structures (scaffolds). The success of these biodegradable scaffolds is, however, determined by the response it elicits from the surrounding biological environment and this response is governed, to a large extent, by the surface characteristics of the scaffold. Multiple approaches have been developed to obtain the desired surface properties, however, in the past decade, the use of non-thermal plasmas for selective surface modification has been a rapidly growing research field. This paper therefore presents a critical overview on recent advances in plasma-assisted surface modification of biodegradable polymers.