3D-printed polycaprolactone/tricalcium silicate scaffolds modified with decellularized bone ECM-oxidized alginate for bone tissue engineering.

The treatment of large craniofacial bone defects requires more advanced and effective strategies than bone grafts since such defects are challenging and cannot heal without intervention. In this regard, 3D printing offers promising solutions through the fabrication of scaffolds with the required shape, porosity, and various biomaterials suitable for specific tissues. In this study, 3D-printed polycaprolactone (PCL)-based scaffolds containing up to 30 % tricalcium silicate (TCS) were fabricated and then modified by incorporation of decellularized bone matrix- oxidized sodium alginate (DBM-OA). The results showed that the addition of 20 % TCS increased compressive modulus by 4.5-fold, yield strength by 12-fold, and toughness by 15-fold compared to pure PCL. In addition, the samples containing TCS revealed the formation of crystalline phases with a Ca/P ratio near that of hydroxyapatite (1.67). Cellular experiment results demonstrated that TCS have improved the biocompatibility of PCL-based scaffolds. On day 7, the scaffolds modified with DBM and 20 % TCS exhibited 8-fold enhancement of ALP activity of placenta-derived mesenchymal stem/stromal cells (P-MSCs) compared to pure PCL scaffolds. The present study's results suggest that the incorporation of TCS and DBM-OA into the PCL-based scaffold improves its mechanical behavior, bioactivity, biocompatibility, and promotes mineralization and early osteogenic activity.

Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer.

Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells. The nanoformulation was first optimized (based on size, polydispersity index, and entrapment efficiency); then, we characterized the morphology, stability, and release behavior of the nanoparticles. Epirubicin release from the HA-coated system (Epi-Nio-HA) showed a 21% (acidic buffer) and 20% (neutral buffer) reduction in comparison with the non-coated group (Epi-Nio). The cytotoxicity and apoptosis results of 4T1 and SkBr3 cells showed an approximately 2-fold increase in the Epi-Nio-HA system over Epi-Nio and free epirubicin, which confirms the superiority of the engineered nanocarriers. Moreover, real-time PCR data demonstrated the down-regulation of the MMP-2, MMP-9, cyclin D, and cyclin E genes expression while caspase-3 and caspase-9 gene expression were up-regulated. Confocal microscopy and flow cytometry studies uncovered the cellular uptake mechanism of the Epi-Nio-HA system, which was CD44-mediated. Furthermore, in vivo studies indicated Epi-Nio-HA decreased mice breast tumor volume by 28% (compared to epirubicin) without side effects on the liver and kidney. Conclusively, our results indicated that the HA-functionalized niosomes provide a promising nanoplatform for efficient and targeted delivery of epirubicin to potentially treat breast cancer.

Enhanced Antibacterial Activity of Echinacea angustifolia Extract against Multidrug-Resistant Klebsiella pneumoniae through Niosome Encapsulation.

With the increased occurrence of antibiotic-resistant bacteria, alternatives to classical antibiotics are urgently needed for treatment of various infectious diseases. Medicinal plant extracts are among the promising candidates due to their bioactive components. The aim of this study was to prepare niosome-encapsulated Echinacea angustifolia extract and study its efficacy against multidrug-resistant Klebsiella pneumoniae strains. Encapsulation was first optimized by Design of Experiments, followed by the empirical study. The obtained niosomes were further characterized for the size and morphology using dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Spherical niosomes had a diameter of 142.3 ± 5.1 nm, as measured by DLS. The entrapment efficiency (EE%) of E. angustifolia extract reached up to 77.1% ± 0.3%. The prepared niosomes showed a controlled drug release within the tested 72 h and a storage stability of at least 2 months at both 4 and 25 °C. The encapsulated E. angustifolia displayed up to 16-fold higher antibacterial activity against multidrug-resistant K.pneumoniae strains, compared to the free extract. Additionally, the niosome exhibited negligible cytotoxicity against human foreskin fibroblasts. We anticipate that the results presented herein could contribute to the preparation of other plant extracts with improved stability and antibacterial activity, and will help reduce the overuse of antibiotics by controlled release of natural-derived drugs.