Scaffold architecture plays a significant role in regulating cellular and microbial interactions in tissue engineering applications. This study evaluates the performance of 3D-printed poly (lactic acid) (PLA) scaffolds with varying porosity levels (20%, 40%, 60%, 80%, and 100%) in mechanical strength, supporting human skin fibroblast (HSF) viability and reducing bacterial colonization of Gram-positive bacteria (Staphylococcus epidermidis, Staphylococcus aureus), and Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli). The maximum tensile strength (28 MPa) was achieved in the 100% dense scaffold. Increasing porosity drastically decreased tensile strength, where 80% PLA scaffold possessed 16 MPa strength. At greater levels of porosity (60% and 40%), tensile strengths greatly decrease (8 MPa and 4 MPa), while ductility increases, especially at high porosity levels. HSF viability, assessed using the AlamarBlue assay, showed a time-dependent increase in cell proliferation, with the highest viability observed on scaffolds with 60% and 80% porosity. SEM imaging confirmed strong cell adhesion on the 80% porous scaffold, indicating that intermediate-to-high porosity enhances cell attachment and metabolic activity. In contrast, bacterial adhesion showed species-specific responses to scaffold porosity. S. epidermidis and E. coli exhibited a progressive increase in adherence with porosity, peaking at 100%. P. aeruginosa showed maximum adhesion at 80%, suggesting a porosity “sweet spot” that favors its colonization. S. aureus adhered most strongly to scaffolds with intermediate porosities (40–60%) and significantly less at 100% porosity. The current study provides insights into scaffold design considerations, emphasizing the need for optimized scaffold architecture that balances regenerative potential with infection control in tissue engineering applications.

Background/Objectives: Children with autism spectrum disorder (ASD) frequently experience poor compliance with oral medication due to bitterness, unpleasant taste, and unsuitable dosage forms such as large tablets or capsules. Risperidone, a widely prescribed antipsychotic for managing ASD symptoms, is particularly challenging in this regard. The present study aimed to develop a novel sucrose-based microfiber drug delivery system to improve the palatability, acceptance, and bioavailability of risperidone in pediatric patients with ASD. Methods: Risperidone was incorporated into sucrose microfibers using centrifugal spinning technology. Fiber morphology was characterized by scanning electron microscopy (SEM). Drug loading (DL), encapsulation efficiency (EE%), and disintegration time were measured. In vitro drug release and cytotoxicity assays were performed using human foreskin fibroblast cells (HFF-1). An in vivo palatability and preference study was conducted in male BALB/c mice to evaluate the acceptability of the formulation compared with a commercial risperidone oral solution. Results: SEM analysis revealed smooth, bead-free, non-porous fibers with uniform morphology and size distribution. The formulation showed a rapid disintegration time of ~3 s, DL of 30 ± 5 µg/mg, and EE% of 60 ± 10%. Approximately 50% of risperidone was released within 15 min. Cytotoxicity testing confirmed that concentrations ≤ 125 µg/mL maintained high cell metabolic activity, indicating biocompatibility. In vivo, the microfiber solution demonstrated a strong preference (93%) compared with the commercial oral solution (30%). Conclusions: Risperidone-loaded sucrose microfibers represent a promising fast-dissolving oral delivery system for children with ASD. This child-friendly formulation improves palatability and compliance while maintaining safety and drug release performance.