Improved efficacy of bio-mineralization of human mesenchymal stem cells on modified PLLA nanofibers coated with bioactive materials via enhanced expression of integrin α2β1

被引:3
作者
Andalib, Nazanin [1 ]
Kehtari, Mousa [2 ]
Seyedjafari, Ehsan [3 ]
Motamed, Nassrin [4 ]
Matin, Maryam M. [1 ,5 ,6 ]
机构
[1] Ferdowsi Univ Mashhad, Fac Sci, Dept Biol, Mashhad, Razavi Khorasan, Iran
[2] Stem Cell Technol Res Ctr, Dept Stem Cell Biol, Tehran, Iran
[3] Univ Tehran, Coll Sci, Dept Biotechnol, Tehran, Iran
[4] Univ Tehran, Coll Sci, Dept Cell & Mal Biol Sch Biol, Tehran, Iran
[5] Ferdowsi Univ Mashhad, Inst Biotechnol, Novel Diagnost & Therapeut Res Grp, Mashhad, Razavi Khorasan, Iran
[6] Iranian Acad Ctr Educ Culture & Res ACECR, Khorasan Razavi Branch, Stem Cell & Regenerat Med Res Grp, Mashhad, Razavi Khorasan, Iran
关键词
bone tissue engineering; human bone marrow mesenchymal stem cells; integrin alpha 2 beta 1; nanofibrous scaffold; osteogenic differentiation; topography; OSTEOGENIC DIFFERENTIATION; BONE REGENERATION; HIERARCHICAL STRUCTURE; COMPOSITE SCAFFOLD; NANOCOMPOSITES; ANGIOGENESIS; GROWTH; GLASS; CUES;
D O I
10.1002/pat.4952
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
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.
引用
收藏
页码:2325 / 2338
页数:14
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