Engineered local delivery of extracellular vesicles loaded with si-TNF-α, via a core-sheath 3D-bio-printed scaffold as an effective wound dressing

• Published in: Journal of drug delivery science and technology 2024-11, Vol.101, p.106189, Article 106189
• Main Authors: Vakilian, Saeid, Jamshidi-adegani, Fatemeh, Al-Fahdi, Fahad, Mirsanei, Zahra, Al-kindi, Juhaina, Al-Riyami, Khamis, Alwahaibi, Nasar, Shalaby, Asem, Al-Harrasi, Ahmed, Al-Sharabi, Niyaz, Mustafa, Kamal, Al-Hashmi, Sulaiman
• Format: Article
• Language: English
• Subjects: 3D-bioprinting; Core-sheath; Electroporation; Extracellular vesicles; Fast degradable; Inflammation; Si-TNF-α; Wound
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2024.106189

The management of chronic wounds remains a clinical challenge despite advancements in wound care. Excessive secretion of TNF-α can hinder the healing process, making TNF-α a potential therapeutic target. Short interfering RNA (si-TNF-α) has shown promise in suppressing TNF-α expression in chronic wounds. Extracellular vesicles (EVs) have emerged as effective carriers for delivering siRNAs in novel wound dressings. This study isolated EVs from NIH/3T3 cells and confirmed their identity through morphological and molecular characterization. Si-TNF-α was loaded into EVs via electroporation, and the functionality of si-TNF-α loading on M2 macrophage polarization was confirmed. These si-TNF-α-loaded EVs (si-TNF-α-EVs) were incorporated into a core-sheath 3D-bioprinted scaffold, utilizing alginate as the core and a sheath formed by combining carboxymethyl cellulose with alginate lyase. In vitro experiments demonstrated controlled fast release of si-TNF-α-containing EVs from the 3D-bioprinted scaffold, exhibiting the desired morphology and core-sheath structure. In vivo studies showed that the core-sheath scaffold loaded with si-TNF-α-EVs outperformed scaffolds loaded with bare EVs and the negative control. This study suggests that a rapidly-degrading scaffold mimicking the extracellular matrix, capable of delivering functional si-TNF-α-EVs, holds promise as an effective wound dressing. Overall, the core-sheath 3D-bioprinted scaffold incorporating si-TNF-α-EVs presents an innovative approach to efficient wound healing. [Display omitted]