The advancement achieved in Tissue Engineering is based on a careful and in-depth study of cell–tissue interactions. The choice of a specific biomaterial in Tissue Engineering is fundamental, as it represents an interface for adherent cells in the creation of a microenvironment suitable for cell growth and differentiation. The knowledge of the biochemical and biophysical properties of the extracellular matrix is a useful tool for the optimization of polymeric scaffolds. This review aims to analyse the chemical, physical, and biological parameters on which are possible to act in Tissue Engineering for the optimization of polymeric scaffolds and the most recent progress presented in this field, including the novelty in the modification of the scaffolds’ bulk and surface from a chemical and physical point of view to improve cell–biomaterial interaction. Moreover, we underline how understanding the impact of scaffolds on cell fate is of paramount importance for the successful advancement of Tissue Engineering. Finally, we conclude by reporting the future perspectives in this field in continuous development.

The advancements achieved in Tissue Engineering are based on a careful and in-depth study of cell-tissue interaction. The choice of a certain biomaterial in Tissue Engineering is fundamental as it represents an interface for adherent cells in the creation of a microenvironment suitable for cell growth and differentiation. The knowledge of the biochemical and biophysical properties of the extracellular matrix is a useful tool for the optimization of polymeric scaffolds. The aim of this re-view is to analyse the chemical, physical and biological parameters on which it is possible to act in Tissue Engineering for the optimization of polymeric scaffolds. Understanding the scaffold impact on cell fate is of paramount importance for the successful advancement of Tissue Engineering.

The inherent hydrophilicity of biopolymers presents significant limitations to their implementation, particularly in coating and packaging applications. Concerns regarding the toxicity, cost, and environmental impact of conventional chemical strategies for hydrophobization have prompted researchers to pursue more sustainable and eco‐friendlier approaches. This study centers on a solvent‐free, green, transesterification reaction (TER) to chemically graft fatty acid ethyl esters derived from diverse vegetable oils onto ethyl cellulose (EC), yielding enhancements in hydrophobicity, flexibility, and barrier performance without synthetic reagents. Successful TER of EC was verified through Fourier transform infrared spectroscopy. Among the tested oils, sunflower oil exhibited the highest TER efficiency (> 25%), attributable to high polyunsaturated fatty acid content. Atomic force microscopy confirmed a homogeneous surface morphology for TER‐modified EC, while mechanical analysis revealed a threefold enhancement in elongation at break compared to unmodified EC. Moreover, oxygen and water vapor transmission rates were reduced by ~50%, signifying improved barrier properties. TER enhanced optical transparency (~82%) and surface hydrophobicity (~97°) for EC, as well as displayed better performance as a coating on substrates like wood. Integrating renewable feedstock into the TER protocol provides a potent pathway for sustainable chemical modification of EC while minimizing environmental impact by adhering to green chemistry principles.

Nanomedicine has reshaped healthcare, especially in targeted drug delivery systems (DDSs) and diagnostics, addressing the limitations of traditional cancer therapies. Integration of photodynamic therapy (PDT) with nanoparticle‐based DDSs has significantly improved the targeted accumulation and pharmacokinetic properties of photosensitizers within tumor cells, enabling selective tumor cell death while sparing healthy tissues. This study developed chitosan‐sericin polyelectrolyte nanoparticles (CSSN NPs) via the Flash nanocomplexation (FNC) technique to enhance the 5‐aminolevulinic acid (5‐ALA) delivery, a precursor of protoporphyrin IX (PpIX), and evaluated their potential in PDT against the MCF‐7 breast cancer cell line. The 5‐ALA‐loaded CSSN NPs exhibited a hydrodynamic diameter ≤100 nm, a positive surface charge, and an encapsulation efficiency of ∼92% with a controlled release profile in acidic environments. In vitro assays demonstrated a ∼40% reduction in cell viability compared with free 5‐ALA, further confirmed by elevated red fluorescence observed in the Calcein/Propidium iodide assay. Confocal microscopy revealed strong PpIX red fluorescence and increased perinuclear accumulation, indicating effective cellular uptake. PpIX phototoxicity was validated by reactive oxygen species induction upon irradiation. These innovative biopolymer‐based DDSs demonstrate considerable potential in enhancing the therapeutic efficacy of 5‐ALA and improving PDT outcomes, setting the stage for future advancements in targeted cancer therapies.