Differential regulation of osteogenic differentiation of stem cells on surface roughness gradients

Tissue engineering using scaffold-cell constructs holds the potential to develop functional strategies to regenerate bone. The interface of orthopedic implants with the host tissues is of great importance for its later performance. Thus, the optimization of the implant surface in a way that could stimulate osteogenic differentiation of mesenchymal stem cells (MSCs) is of significant therapeutic interest. The effect of surface roughness of polycaprolactone (PCL) on the osteogenic differentiation of human bone-marrow MSCs was investigated. We prepared surface roughness gradients of average roughness (Ra) varying from the sub-micron to the micrometer range (~0.5e4.7 mm), and mean distance between peaks (RSm) gradually varying from ~214 mm to 33 mm. We analyzed the degree of cytoskeleton spreading, expression of alkaline phosphatase, collagen type 1 and mineralization. The response of cells to roughness divided the gradient into three groups of elicited stem cell behavior: 1) faster osteogenic commitment and strongest osteogenic expression; 2) slower osteogenic commitment but strong osteogenic expression, and 3) similar or inferior osteogenic potential in comparison to the control material. The stem-cell modulation by specific PCL roughness surfaces highlights the potential for creating effective solutions for orthopedic applications featuring a clinically relevant biodegradable material.This work was supported by the Portuguese Foundation for Science and Technology for the PhD grant of Faia-Torres AB (SFRH/BD136476/2007) We are also grateful to the Competence Center for Materials Science and Technology (CCMX) and the Swiss National Science Foundation (SNF) grant PA00P3_142120/1 for providing funds to MC