Abstract
The potential of mesenchymal stem cells (MSCs) for implantology and cell-based therapy represents one of the major ongoing research subjects within the last decades. In bone regeneration applications, the various environmental factors including bioactive compounds such as growth factors, chemicals and physical characteristics of biointerfaces are the key factors in controlling and regulating osteogenic differentiation from MSCs. In our study, we have investigated the influence of Lactoferrin (Lf) and Hydroxyapatite (HA) embedded within a biodegradable PEG-PCL copolymer on the osteogenic fate of MSCs, previous studies revealing an anti-inflammatory potential of the coating and osteogenic differentiation of murine pre-osteoblast cells. The copolymer matrix was obtained by the Matrix Assisted Pulsed Laser Evaporation technique (MAPLE) and the composite layers containing the bioactive compounds (Lf, HA, and Lf-HA) were characterised by Scanning Electron Microscopy and Atomic Force Microscopy. Energy-dispersive X-ray spectroscopy contact angle and surface energy of the analysed coatings were also measured. The characteristics of the composite surfaces were correlated with the viability, proliferation, and morphology of human MSCs (hMSCs) cultured on the developed coatings. All surfaces were found not to exhibit toxicity, as confirmed by the LIVE/DEAD assay. The Lf-HA composite exhibited an increase in osteogenic differentiation of hMSCs, results supported by alkaline phosphatase and mineralisation assays. This is the first report of the capacity of biodegradable composite layers containing Lf to induce osteogenic differentiation from hMSCs, a property revealing its potential for application in bone regeneration.
Highlights
The behaviour of cells mediated by bioresponsive substrates and interfaces represents an important and ever-growing area in tissue engineering
As surface characteristics are strongly correlated to cell response and behaviour, the Lf-based composite coatings characteristics were investigated in order to correlate those properties with the effect on the mesenchymal stem cells (MSCs)
The contents of Ca composite coatings characteristics were investigated in order to correlate those properties with the effect on the mesenchymal stem cells (MSCs)
Summary
The behaviour of cells mediated by bioresponsive substrates and interfaces represents an important and ever-growing area in tissue engineering. The approaches used are based on either injecting bioactive compounds (i.e., natural protein) in a direct manner or attaching them to a biomaterial surface. Materials 2019, 12, 3414 functionalising and addressing/controlling the locally attached proteins over the injecting approach is related to avoiding a rapid clearance of the interest biocompound from the body and side effects. Different formulations or constructs containing Lf were designed and tested in vitro and in vivo for bone tissue regeneration enhancement. These included Lf incorporation into the collagen membrane [10], hydrogels [11], nanofiber loading [12], or into microspheres [13], or coupled with compounds [14], in order to improve the effectiveness of biomaterials used in bone regeneration
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