Neue Wege für die Nanomedizin | NanoMed


Funding period:May 1, 2024 to Dec. 31, 2024
Agency: SMWK

Acknowledgements

We acknowledge funding by the SMWK project "Neue Wege für die Nanomedizin" (NanoMed)


Description

Exploring Nanostructured Physical Supports for Stem Cell Culture: Understanding the Role of Mechanical Properties in Cellular Differentiation

Our aim is to explore the utilization of a nanostructured physical support for in vitro stem cell culture, where we intend to meticulously control and characterize both the nanometrical topography and mechanical properties. We will design nanopatterned substrates aimed at closely replicating the in vivo microenvironment where stem cells proliferate and differentiate, as we believe that mimicking the natural niche equilibrium is pivotal in determining cellular fate. Furthermore, we plan to delve into understanding the role of substrate mechanical properties in comparison to other factors such as substrate composition and geometry. To further control the differentiation of embryonic stem cells (ESCs), we envisage manipulating the physical parameters of the substrates. However, we acknowledge that this approach will necessitate a deeper understanding of the cell-substrate interaction. To this end, we anticipate studying the behaviour of cellular type precursors on various artificial (organic and/or inorganic) substrates, employing a combination of atomic force microscopy, scanning electron microscopy, and single-cell force spectroscopy measurements. This research will enable us to appreciate the significance of physical parameters in regulating cellular differentiation and will provide new guidelines for future applications in regenerative medicine.

Exploring Nanostructured Surfaces for Antibacterial Applications:
The global research challenge of microbial contamination on surfaces has become particularly significant due to the emergence of multi-drug resistant bacterial strains. In this context, nanomaterials characterized by high aspect ratio topographical features often exhibit notable surface properties, such as high hydrophobicity and significant cellular-level biological activity. Indeed, nanopatterned surfaces with high aspect ratios generate a mechanical bactericidal effect, irrespective of their chemical composition. Our objective is to evaluate the antibacterial efficacy of nanostructured surfaces with various geometries. Initially, these surfaces will be characterized using atomic force microscopy (AFM) and scanning electron microscopy (SEM). Subsequently, different bacterial strains (both gram-positive and gram- negative) will be inoculated onto the nanostructured surfaces, and the morphological alterations of bacterial cells will be assessed through SEM, AFM, and force scanning analysis. Our aim is to deepen the understanding of the antibacterial effect induced by the contact of the bacterial membrane with ordered nanostructures, an aspect still not fully understood by the scientific community. Furthermore, to date, only a few studies have been conducted on cytomechanics of the bacterial envelope, underscoring the importance and novelty of our research.

Exploring the Role of Particle Elasticity in Cellular Drug Uptake: Synthesis and Characterization of Hydrogel Nanocarriers

Pharmacological research is focused on developing new therapeutic strategies, with particular attention to cellular drug uptake, which represents one of the most significant challenges. The use of nanoscale drug delivery systems offers the possibility to improve the pharmacokinetic and pharmacodynamic profiles of drugs by increasing the concentration of the active ingredient internalized at specific sites. In this context, hydrogel nanocarriers, characterized by high biocompatibility and biodegradability, represent a promising therapeutic strategy. Therapeutic agents can be encapsulated within the polymeric matrix or adsorbed/conjugated onto the surface of these particles, thus providing precise control over drug release. Despite parameters such as size, shape, and surface chemistry having been extensively studied, the understanding of the mechanisms underlying the influence of particle elasticity on cellular uptake remains partially unexplored. Therefore, the aim of our study is to synthesize polymer micelles of hydrogel with defined size, shape, and surface charge, as well as variable elasticity, in order to investigate the impact of this parameter on the rate of cellular uptake. The characterization of the elasticity of the nano-micelles will be conducted through force scanning microscopy, and the data will be correlated with real-time measurements obtained in the laboratories of the University of Salento. At the same time, we will evaluate the degree of cellular uptake through colocalization experiments in confocal microscopy, using specific fluorochromes to load the micelles. We expect that this study will provide important insights into the role of elasticity as a key parameter in the design of nanosystems to improve drug delivery efficiency, thus contributing to the optimization of therapeutic strategies in disease treatment.

Neue Wege für die Nanomedizin | NanoMed


Funding period:May 1, 2024 to Dec. 31, 2024
Agency: SMWK

Acknowledgements

We acknowledge funding by the SMWK project "Neue Wege für die Nanomedizin" (NanoMed)


Description

Exploring Nanostructured Physical Supports for Stem Cell Culture: Understanding the Role of Mechanical Properties in Cellular Differentiation

Our aim is to explore the utilization of a nanostructured physical support for in vitro stem cell culture, where we intend to meticulously control and characterize both the nanometrical topography and mechanical properties. We will design nanopatterned substrates aimed at closely replicating the in vivo microenvironment where stem cells proliferate and differentiate, as we believe that mimicking the natural niche equilibrium is pivotal in determining cellular fate. Furthermore, we plan to delve into understanding the role of substrate mechanical properties in comparison to other factors such as substrate composition and geometry. To further control the differentiation of embryonic stem cells (ESCs), we envisage manipulating the physical parameters of the substrates. However, we acknowledge that this approach will necessitate a deeper understanding of the cell-substrate interaction. To this end, we anticipate studying the behaviour of cellular type precursors on various artificial (organic and/or inorganic) substrates, employing a combination of atomic force microscopy, scanning electron microscopy, and single-cell force spectroscopy measurements. This research will enable us to appreciate the significance of physical parameters in regulating cellular differentiation and will provide new guidelines for future applications in regenerative medicine.

Exploring Nanostructured Surfaces for Antibacterial Applications:
The global research challenge of microbial contamination on surfaces has become particularly significant due to the emergence of multi-drug resistant bacterial strains. In this context, nanomaterials characterized by high aspect ratio topographical features often exhibit notable surface properties, such as high hydrophobicity and significant cellular-level biological activity. Indeed, nanopatterned surfaces with high aspect ratios generate a mechanical bactericidal effect, irrespective of their chemical composition. Our objective is to evaluate the antibacterial efficacy of nanostructured surfaces with various geometries. Initially, these surfaces will be characterized using atomic force microscopy (AFM) and scanning electron microscopy (SEM). Subsequently, different bacterial strains (both gram-positive and gram- negative) will be inoculated onto the nanostructured surfaces, and the morphological alterations of bacterial cells will be assessed through SEM, AFM, and force scanning analysis. Our aim is to deepen the understanding of the antibacterial effect induced by the contact of the bacterial membrane with ordered nanostructures, an aspect still not fully understood by the scientific community. Furthermore, to date, only a few studies have been conducted on cytomechanics of the bacterial envelope, underscoring the importance and novelty of our research.

Exploring the Role of Particle Elasticity in Cellular Drug Uptake: Synthesis and Characterization of Hydrogel Nanocarriers

Pharmacological research is focused on developing new therapeutic strategies, with particular attention to cellular drug uptake, which represents one of the most significant challenges. The use of nanoscale drug delivery systems offers the possibility to improve the pharmacokinetic and pharmacodynamic profiles of drugs by increasing the concentration of the active ingredient internalized at specific sites. In this context, hydrogel nanocarriers, characterized by high biocompatibility and biodegradability, represent a promising therapeutic strategy. Therapeutic agents can be encapsulated within the polymeric matrix or adsorbed/conjugated onto the surface of these particles, thus providing precise control over drug release. Despite parameters such as size, shape, and surface chemistry having been extensively studied, the understanding of the mechanisms underlying the influence of particle elasticity on cellular uptake remains partially unexplored. Therefore, the aim of our study is to synthesize polymer micelles of hydrogel with defined size, shape, and surface charge, as well as variable elasticity, in order to investigate the impact of this parameter on the rate of cellular uptake. The characterization of the elasticity of the nano-micelles will be conducted through force scanning microscopy, and the data will be correlated with real-time measurements obtained in the laboratories of the University of Salento. At the same time, we will evaluate the degree of cellular uptake through colocalization experiments in confocal microscopy, using specific fluorochromes to load the micelles. We expect that this study will provide important insights into the role of elasticity as a key parameter in the design of nanosystems to improve drug delivery efficiency, thus contributing to the optimization of therapeutic strategies in disease treatment.