Electrospun polymer/ceramic composites have attracted considerable attention for bone tissue engineering, yet the influence of strontium (Sr) substitution in hydroxyapatite (HA) on the properties of fibrous composite systems remains insufficiently understood. In this study, electrospun poly(ε-caprolactone)/gelatin (PCL/Gel) scaffolds incorporating HA with controlled Sr substitution levels (HA, Sr50-HA, and Sr100-HA) were fabricated to elucidate composition–structure–property relationships under identical processing conditions. Morphological characterization confirmed the formation of continuous, bead-free fibers, with a progressive reduction in fiber diameter upon ceramic incorporation and increasing Sr content. The presence of the inorganic crystals influenced ion release behaviour, as Sr50-HA-PCL/Gel showed enhanced Ca2+ and Sr2+ release. All composite scaffolds displayed improved acellular in vitro bioactivity, promoting apatite formation in simulated body fluid compared with the polymeric control. Despite measurable ion release, Indirect cytocompatibility assays indicated no cytotoxic effects, with all samples maintaining MG-63 cell viability above 80%. Direct cell culture confirmed good cytocompatibility, with Sr-containing scaffolds exhibiting enhanced early metabolic activity. Mechanical testing revealed composition-dependent behaviour: HA-PCL/Gel and Sr100-HA-PCL/Gel exhibited higher stiffness, whereas Sr50-HA-PCL/Gel showed a reduced modulus, consistent with its distinct structural attributes. Overall, this work demonstrates that the degree of Sr substitution governs the interplay between crystallinity, ion release, mechanical performance, and cellular response, highlighting compositional tuning as an effective strategy for optimizing electrospun scaffolds for bone tissue engineering applications.
Nucleoamino acids and nucleopeptides represent an emerging class of hybrid biomolecular scaffolds with unique potential in medicinal chemistry, combining peptide-like structural versatility with nucleobase-mediated recognition and supramolecular organization. Herein, a detailed biophysical characterization of two tyrosine-based scaffolds functionalized with thymine nucleobase is reported. Specifically, the nucleoamino acid derivative TyrT and the nucleodipeptide TyrTyrT are investigated for self-assembling ability in a phosphate saline buffer using a combination of spectroscopic and microscopy-based techniques as well as in silico analyses. Both compounds exhibit marked, concentration-dependent self-assembling behaviour forming mainly spherical-shaped nanostructures, evidenced by scanning electron microscopy (SEM) and atomic force microscopy (AFM) analyses, having hydrodynamic diameter of about 400 nm at 100 and 50 μM concentration for TyrT and TyrTyrT, respectively, with good homogeneity and stability over time, in agreement with dynamic light scattering (DLS) data. Spectroscopic analyses reveal distinct aggregation regimes probably driven by π-π stacking, hydrogen bonding, and nucleobase interactions, with temperature-dependent arrangements distinguishing kinetically trapped from thermodynamically stabilized assemblies. Preliminary binding experiments demonstrate that the formed nanostructures can interact with a small, water-soluble metabolite such as 2′-deoxyadenosine 5′-monophosphate (dAMP), as well as with the hydrophobic and poor bioavailable drug curcumin enhancing its cytotoxic effects on a selected cancer cell line, probably because of the protecting effect of the nanosystems towards its degradation in aqueous environment. Collectively, these findings, together with the non-toxic profile of TyrT and TyrTyrT on healthy cells, indicate them as promising building blocks for potential drug delivery applications.
