RT Journal Article T1 Chitosan-aloe vera scaffolds with tuned extracellular vesicles and histatin-5 display osteogenic and anti-biofilm activities A1 García García, Patricia A1 Évora, Carmen A1 Delgado, Araceli A1 Díaz Rodríguez, Patricia K1 Aloe vera K1 Bacteria biofilm K1 Chitosan scaffolds K1 Extracellular vesicles K1 Histatin 5 AB The use of extracellular vesicles (EVs) has garnered significant attention as an alternative to cell-based therapies due to their stability and biocompatibility. In this study, we stimulated mesenchymal stem cells (MSCs) with therapeutic agents affecting the bone regenerative cascade, including bone morphogenetic protein 2 (BMP-2), stromal-derived factor (SDF-1), interleukin 4 (IL-4), alendronate (ALD) and osteogenic differentiation media to obtain osteogenic EVs. The tuned EVs were tested on MSCs and fibroblasts, selecting EVs-BMP-2 as suitable systems. Chitosan-aloe vera (AV) scaffolds were designed to allow for the loading and release of these EVs while leveraging the antibacterial and anti-inflammatory properties of AV. To enhance the dual effect on regeneration and antibacterial activity, poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating Histatin 5 (Hist-5) were incorporated to the scaffolds. Hist-5 encapsulation was successful, and effectively prevented Staphylococcus aureus biofilm formation on the scaffolds surface. The optimized chitosan-AV scaffolds loaded with EVs-BMP-2 promoted MSCs adhesion and proliferation and exhibited a 2-fold increase in osteogenic differentiation compared to chitosan scaffolds. This study demonstrates the successful combination of bioengineered EVs and Hist-5-loaded microspheres within a chitosan-AV scaffold, providing a promising dual approach for enhancing bone regeneration while reducing the risk of infection. These systems show potential as effective implants for bone fractures, offering both antibacterial and regenerative capabilities. PB Elsevier SN 0378-5173 YR 2025 FD 2025-05-15 LK https://hdl.handle.net/10347/43066 UL https://hdl.handle.net/10347/43066 LA eng NO García-García P, Évora C, Delgado A, Diaz-Rodriguez P. Chitosan-aloe vera scaffolds with tuned extracellular vesicles and histatin-5 display osteogenic and anti-biofilm activities. Int J Pharm. 2025 May 15;676:125592. doi: 10.1016/j.ijpharm.2025.125592. Epub 2025 Apr 12. PMID: 40228611. NO This work was funded by ACIISI and FEDER “Canarias avanza con Europa” (ProID2020010086). P García-García acknowledges University of La Laguna for the action: “Recualificación de personal Universitario: Margarita Salas para la formación de jóvenes doctores”. DS Minerva RD 4 may 2026