Polycaprolactone-collagen nanofibers loaded with dexamethasone and simvastatin as an osteoinductive and immunocompatible scaffold for bone regeneration applications

• Published in: Biomaterials and biosystems Vol. 8; p. 100064
• Main Authors: Rather, Hilal Ahmad, Varghese, Johnna Francis, Dhimmar, Bindiya, Yadav, Umesh C.S., Vasita, Rajesh
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2022; Elsevier
• Subjects: Anti-inflammatory; Bone regeneration; Dual drug delivery; Macrophage; Mesenchymal stromal cells; Osteogenesis; Dual drug delivery; Mesenchymal stromal cells; Bone regeneration; Anti-inflammatory; Osteogenesis; Macrophage
• ISSN: 2666-5344; 2666-5344
• DOI: 10.1016/j.bbiosy.2022.100064

•Development of dual drug loaded nanofibrous scaffold with the immunomodulatory and osteoinductive properties.•The scaffold maintained structural integrity to support as osteoconductive platform for osteogenic differentiation of mesenchyme stem cells (MSCs) by enhancing mineral deposition and gene expression.•Dual drug-loaded fibrous scaffold promotes anti-inflammatory phenotype and gene expression in human monocytes (U937 cells). Physiological inflammation has been shown to promote bone regeneration; however, prolonged inflammation impedes the osteogenesis and bone repair process. To overcome the latter we aimed to develop a dual drug delivering nanofibrous scaffold to promote osteogenic differentiation of mesenchymal stromal cells (MSCs) and modulate the pro-inflammatory response of macrophages. The polycaprolactone (PCL)-collagen nanofibrous delivery system incorporating dexamethasone and simvastatin was fabricated by electrospinning process. The morphological analysis and mRNA, as well as protein expression of proinflammatory and anti-inflammatory cytokines in human monocytes (U937 cells), demonstrated the immunocompatibility effect of dual drug-releasing nanofibrous scaffolds. Nitric oxide estimation also demonstrated the anti-inflammatory effect of dual drug releasing scaffolds. The scaffolds demonstrated the osteogenic differentiation of adipose-derived MSCs by enhancing the alkaline phosphatase (ALP) activity and mineral deposition after 17 days of cell culture. The increased expression of Runt-related transcription factor-2 (RUNX-2) and osteocalcin at mRNA and protein levels supported the osteogenic potential of dual drug-loaded fibrous scaffolds. Hence, the results indicate that our fabricated nanofibrous scaffolds exhibit immunomodulatory properties and could be employed for bone regeneration applications after further in-vivo validation.