Nanotopographical cues of electrospun PLLA efficiently modulate non-coding RNA network to osteogenic differentiation of mesenchymal stem cells during BMP signaling pathway

Physical cues from the extracellular microenvironment play an important role in regulating cell behavior, such as adhesion, migration, and differentiation. Many studies have shown that different physical parameters (eg, stiffness and topography) could modulate the in vitro differentiation of mesenchymal stem cells (MSCs), which had multilineage differentiation potential and could be easily isolated from various tissues such as bone marrow, adipose tissue, and the umbilical cord. However, the underlying mechanism of the topographical influence on MSCs and the detailed cell‐substrate interaction remain unclear. Here, we present oriented elliptical inverse opal structures for regulating the morphology and alignment of bone marrow‐derived MSCs. The inverse opal structures were made through a convenient bottom‐up approach of self‐assembly, which is facile and cost effective. MSCs cultured on the oriented structures were highly aligned and extended highly oriented thick lamellipodia. Moreover, the oriented substrates cracked along the lateral boundary of the cells, suggesting that a strong cell‐substrate interaction was induced by the response of MSCs to the oriented topography. These features of the oriented elliptical topography indicated their promising value in stem cell research and tissue engineering.

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Microtopography based on inverse opal structures regulates the behavior of bone marrow‐derived mesenchymal stem cells

Xiao

Zhang

Zheng

et al. 2019

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

Andalib

Kehtari

Seyedjafari

et al. 2020

Self Cite

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 α2β1 as well as the osteogenic genes BGLAP, COL1A1, and RUNX2. Following use of integrin α2β1 blocker antibody, the protein level of integrin α2β1 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 α2β1/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 α2β1/ERK axis, and thus it might be applicable in bone tissue engineering.

Different osteoconductivity of PLLA/PHB composite nanofibers prepared by one‐ and two‐nozzle electrospinning

Sabouri

Rezaie²,

Enderami

et al. 2021

Electrospinning is a method that has a high potential for use in tissue engineering due to its simplicity, cheapness, versatility, and high applicability for preparing of composite nanofibrous scaffolds. In this study, nanofibrous scaffolds were made of poly‐l‐lactic acid (PLLA) and Polyhydroxybutyrate (PHB) polymers by electrospinning single‐nozzle (combined polymers: C‐PLLA/PHB) and two‐nozzle (separated polymers: S‐PLLA/PHB). Constructed scaffolds were characterized using SEM, in vitro degradation, cell attachment, protein adsorption, and nontoxicity assays. Then, scaffolds osteoconductive capacity was investigated by culturing adipose‐derived stem cells (ADSCs) and by evaluating common osteogenic markers. Obtained results displayed that fibers diameter, scaffold degradation, and biocompatibility of S‐PLLA/PHB nanofibrous scaffold were increased compared to the C‐PLLA/PHB nanofibers. In addition, significantly increased alkaline phosphatase (ALP) activity, calcium content, and osteogenic‐related gene expression were also observed in the ADSCs cultured on S‐PLLA/PHB nanofibrous scaffold compared to the cultured cells on C‐PLLA/PHB nanofibrous scaffold. Overall, this study shows that using two‐nozzle electrospinning to constructing PLLA/PHB nanofibrous scaffold can improve its osteoconductive capacity, and also its combination with ADSCs can be a promising candidate to use in bone tissue engineering.