Let's Talk About Sex-Biological Sex Is Underreported in Biomaterial Studies

Abstract

Precision medicine aims to better individualize healthcare. It requires that biomaterials be designed for the physiological characteristics of a specific patient. To make this a reality, biomaterials research and development must address differences of biological sex. More specifically, biomaterials should be designed with properties optimized and appropriate for male and female patients. In analyzing research articles from seven prominent biomaterials journals, sex as a biological variable is missing from an overwhelming majority of in vitro biomaterial studies. From the survey, the reporting of the sex of primary cell cultures happened only 10.3% of the time. Contributing to this trend is that commercial vendors bias cell lines toward one sex or another by not disclosing information of cell line sex at the time of purchase; researchers do not communicate this pertinent information in published studies; and many journal policies have little to no requirements for reporting cell line characteristics. Omitting this valuable information leads to a gap in the understanding of sex-specific cell-biomaterial interactions and it creates a bias in research findings towards one sex or another. To curb this concerning trend and make precision biomaterials a reality will require the biomaterials field to "talk about sex" by reporting cell sex more broadly.

Keywords: cell-material interactions; hormones; patient-specific; precision biomaterials; sex differences.

Figure 1.

Breakdown of cell sex for all the cell cultures reported (A); for all primary cells isolated or harvested “in-house” (B); and for all primary cells purchased from commercial vendors (C). For our survey, we recorded whether the cells used were reported as male, female, or if the sex was unreported.

Figure 2.

The comparison of the number of male and female primary cell lines (A) HUVEC = Human Umbilical Vein Endothelial Cell; (B) HAEC = Human Aortic Endothelial Cell; and (C) HAoSMC = Human Aortic Smooth Muscle Cells available from two commercial vendors for three vascular-derived cell types. LCT = Lifeline Cell Technologies. CA = Cell Applications. This is a snapshot from August 2019.

Figure 3.

Comparison of the number of male and female primary cell lines (A) HUVEC = Human Umbilical Vein Endothelial Cell; and (B) HAoSMC = Human Aortic Smooth Muscle Cells available from Cell Applications at two separate times of year.

Figure 4.

Comparison of the number of male and female immortalized/established/transformed cell lines derived from sex-specific tissue (female breasts, ovaries, gonads, cervix, male prostates etc.) and non-specific tissue (all other tissue).

Figure 5.

Comparison of the number of male and female transformed/immortalized/established cell lines reported in the 303 journal articles that described in vitro cell culture experiments from 7 prominent biomaterials journals (See Table 1). Cell lines have been separated by non-specific tissue for those cell lines derived from (A) humans and (B) mice.

Figure 6.

Breakdown of cell sex for all the cell cultures recorded for each journal surveyed for articles published in December 2019.