Donor Sex and Passage Conditions Influence MSC Osteogenic Response in Mineralized Collagen Scaffolds

Abstract Contemporary tissue engineering efforts often seek to use mesenchymal stem cells (MSCs) due to their multi‐potent potential and ability to generate a pro‐regenerative secretome. While many have reported the influence of matrix environment on MSC osteogenic response, few have investigated the effects of donor and sex. Here, a well‐defined mineralized collagen scaffold is used to study the influence of passage number and donor‐reported sex on MSC proliferation and osteogenic potential. A library of bone marrow and adipose tissue‐derived stem cells from eight donors to examine donor viability in osteogenic capacity in mineralized collagen scaffolds is obtained. MSCs displayed reduced proliferative capacity as a function of passage duration. Further, MSCs showed significant sex‐associated variability in osteogenic capacity. Notably, MSCs from male donors displayed significantly higher cell proliferation while MSCs from female donors displayed significantly higher osteogenic response via increased alkaline phosphate activity, osteoprotegerin release, and mineral formation in vitro. The study highlights the essentiality of including donor‐reported sex as an experimental variable and reporting culture expansion in future studies of biomaterial regenerative potential.