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    Improved efficacy of bio-mineralization of human mesenchymal stem cells on modified PLLA nanofibers coated with bioactive materials via enhanced expression of integrin alpha 2 beta 1

    Year: 2020

    Journal: Polym. Adv. Technol., Volume 31, OCT, page 2325–2338

    Authors: Andalib, Nazanin; Kehtari, Mousa; Seyedjafari, Ehsan; Motamed, Nassrin; Matin, Maryam M.

    Organizations: Ferdowsi University of Mashhad [48816]

    Keywords: bone tissue engineering; human bone marrow mesenchymal stem cells; integrin alpha 2 beta 1; nanofibrous scaffold; osteogenic differentiation; topography

    Current therapeutic interventions in bone defects are mainly focused on finding the best bioactive materials for inducing bone regeneration via activating the related intracellular signaling pathways. Integrins are trans-membrane receptors that facilitate cell-extracellular matrix (ECM) interactions and activate signal transduction. To develop a suitable platform for supporting human bone marrow mesenchymal stem cells (hBM-MSCs) differentiation into bone tissue, electrospun poly L-lactide (PLLA) nanofiber scaffolds were coated with nano-hydroxyapatite (PLLA/nHa group), gelatin nanoparticles (PLLA/Gel group), and nHa/Gel nanoparticles (PLLA/nHa/Gel group) and their impacts on cell proliferation, expression of osteoblastic biomarkers, and bone differentiation were examined and compared. MTT data showed that proliferation of hBM-MSCs on PLLA/nHa/Gel scaffolds was significantly higher than other groups (P < .05). Alkaline phosphatase activity was also more increased in hBM-MSCs cultured under osteogenic media on PLLA/nHa/Gel scaffolds compared to others. Gene expression evaluation confirmed up-regulation of integrin alpha 2 beta 1 as well as the osteogenic genes BGLAP, COL1A1, and RUNX2. Following use of integrin alpha 2 beta 1 blocker antibody, the protein level of integrin alpha 2 beta 1 in cells seeded on PLLA/nHa/Gel scaffolds was decreased compared to control, which confirmed that most of the integrin receptors were bound to gelatin molecules on scaffolds and could activate the integrin alpha 2 beta 1/ERK axis. Collectively, PLLA/nHa/Gel scaffold is a suitable platform for hBM-MSCs adhesion, proliferation, and osteogenic differentiation in less time via activating integrin alpha 2 beta 1/ERK axis, and thus it might be applicable in bone tissue engineering.
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