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.