In Vitro Evaluation of Bioactive PCL/Alginate Hierarchical Fibers with Controlled Liposomal Silymarin Release for Enhanced Tissue Engineering: Breaking Barriers in MSC Transplantation

Purpose : The clinical application of mesenchymal stem cells (MSCs) in tissue engineering is hindered by critical challenges, including low cell survival rates, poor retention at injury sites, and the lack of bioactive scaffolds that mimic the native tissue microenvironment. To address these limitations, this study developed a multifunctional platform using liposomal silymarin (Lip-Sil)-enriched polycaprolactone/alginate (PCL/Alg) hierarchical fibers to enhance the delivery, adhesion, and functionality of adipose-derived MSCs (AMSCs) for tissue regeneration. Methods : Lip-Sil was synthesized using the remote loading method and characterized for particle size, zeta potential, encapsulation efficiency, and dissolution behavior. PCL/Alg hierarchical fibers were fabricated via electrospinning and evaluated for mechanical properties, morphology, hydrophilicity, degradation rate, , and surface chemistry using attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. The biological performance of the scaffolds was assessed through in vitro studies, including cell viability, adhesion, and proliferation of AMSCs using MTT assay, DAPI staining, and FE-SEM imaging. Results : The Lip-Sil formulation exhibited a particle size of 94.7 nm, a zeta potential of -29 mV, and an encapsulation efficiency of 73%. The cumulative dissolution profile showed a sustained release, reaching 65% after 2 weeks. The PCL/Alg fibers demonstrated a significant reduction in diameter (157.7 ± 42.8 nm) compared to pure PCL fibers (323.3 ± 122.8 nm). Mechanical testing revealed that the PCL and PCL/Alg scaffolds had a tensile strength of 10 ± 1.3 and 2.7 ± 0.17 MPa and a strain at break of 67.4 ± 2.41% and 55.1 ± 2.9%, respectively. The addition of alginate improved hydrophilicity (water contact angle: 31.8 ± 4.1° vs. 126.9 ± 9.6° for PCL) and degradation rate. The water uptake rate of PCL/Alg scaffolds reached 80.7 ± 5.3% within 18 hours, significantly higher than that of PCL scaffolds (18.6 ± 0.88%) and these ratios for both samples remained constant until 28 hours. AMSCs cultured on PCL/Alg/Lip-Sil scaffolds showed an excellent increase in cell proliferation compared to control groups (p<0.01) after 7 days of incubation. DAPI staining revealed a mean cell adhesion index of 1.6 ± 0.1 for the composite scaffold. FE-SEM imaging confirmed enhanced cell spreading and expansion on the composite scaffolds. Conclusion : The developed PCL/Alg/Lip-Sil scaffold represents a promising platform for tissue engineering, offering controlled drug release, improved cell adhesion, and enhanced AMSC proliferation. This multifunctional system addresses key challenges in stem cell delivery and tissue regeneration, providing a robust foundation for future clinical applications.