Abstract

New strategies in regenerative medicine include the implantation of stem cells cultured in bio-resorbable polymeric scaffolds to restore the tissue function and be absorbed by the body after wound healing. This requires the development of appropriate micro-technologies for manufacturing of functional scaffolds with controlled surface properties to induce a specific cell behavior. The present report focuses on the effect of substrate topography on the behavior of human mesenchymal stem cells (MSCs) before and after co-differentiation into adipocytes and osteoblasts. Picosecond laser micromachining technology (PLM) was applied on poly (L-lactide) (PLLA), to generate different microstructures (microgrooves and microcavities) for investigating cell shape, orientation, and MSCs co-differentiation. Under certain surface topographical conditions, MSCs modify their shape to anchor at specific groove locations. Upon MSCs differentiation, adipocytes respond to changes in substrate height and depth by adapting the intracellular distribution of their lipid vacuoles to the imposed physical constraints. In addition, topography alone seems to produce a modest, but significant, increase of stem cell differentiation to osteoblasts. These findings show that PLM can be applied as a high-efficient technology to directly and precisely manufacture 3D microstructures that guide cell shape, control adipocyte morphology, and induce osteogenesis without the need of specific biochemical functionalization.

Highlights

  • Adult stem cells are the main source for developing new strategies in regenerative medicine, such as cell-based therapy [1], genetic therapy [2] and tissue engineering [3]

  • Our finding reveals that surface surface topography alone can control adipocyte morphology

  • It is likely that, according according to the results presented in our study, surface topography could the expression to the results presented in our study, surface topography could affectalso theaffect expression of these of these factors as it influences adipocyte morphology

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Summary

Introduction

Adult stem cells are the main source for developing new strategies in regenerative medicine, such as cell-based therapy [1], genetic therapy [2] and tissue engineering [3]. Proliferation and differentiation of stem cells in vivo are regulated by their microenvironment, known as niche, which comprises both cellular components and interacting signals between them [4,5,6] These niches, in addition to other functions, provide stem cells with physical anchors (by means of adhesion molecules) and regulate the molecular factors that control cell number and fate [5]. Some of these factors are influenced by cell shape, cytoskeletal tension, and contractility [7,8]. Surface microstructuring technologies play a significant role in the manufacturing of 3D scaffolds with modified surfaces, to improve the biocompatibility and performance of these devices to induce tissue regeneration

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