In Vitro Activation of Human Peripheral Blood Mononuclear Cells Induced by Human Biologic Meshes1

Orenstein, Sean; Qiao, Yi; Kaur, Manjot; Klueh, Ulrike; Kreutzer, Don; Novitsky, Yuri

doi:10.1016/j.jss.2009.05.033

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Volume 158, Issue 1 , Pages 10-14, January 2010

In Vitro Activation of Human Peripheral Blood Mononuclear Cells Induced by Human Biologic Meshes¹

Sean Orenstein, M.D.
- Connecticut Comprehensive Center for Hernia Repair, Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut
Yi Qiao, M.D.
- Center for Molecular Tissue Engineering, Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut
Manjot Kaur, B.S.
- Center for Molecular Tissue Engineering, Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut
Ulrike Klueh, Ph.D.
- Connecticut Comprehensive Center for Hernia Repair, Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut
- Center for Molecular Tissue Engineering, Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut
Don Kreutzer, Ph.D.
- Connecticut Comprehensive Center for Hernia Repair, Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut
- Center for Molecular Tissue Engineering, Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut
Yuri Novitsky, M.D.
- Connecticut Comprehensive Center for Hernia Repair, Department of Surgery, University of Connecticut Health Center, Farmington, Connecticut
- To whom correspondence and reprint requests should be addressed at Department of Surgery, University of Connecticut Health Center, 263 Farmington Avenue–MC 3955, Farmington, Connecticut 06030.

published online 19 June 2009.

Background

Inflammation and wound healing play critical roles in the integration of biologic meshes (BMs) at sites of hernia repair. Monocytes/macrophages (M/MQs) are key cells involved in mesh integration. Interleukin-1β (IL-1β) is one of the major M/MQ-derived cytokines, and its expression is a reflection of the degree of M/MQ activation. We hypothesized that BMs induce M/MQ activation in vitro and that IL-1β expression by M/MQ varies among various BMs.

Materials and Methods

Acellular human dermis-derived BM samples (AlloDerm, AlloMax, FlexHD) were placed in 48-well plates and cultured with peripheral blood mononuclear cells (PBMCs) from three healthy human subjects for 7 d. The resulting supernatants were assayed for IL-1β levels by enzyme-linked immunosorbent assay (ELISA), and the BMs were evaluated histologically.

Results

IL-1β expression varied among donors as well as the BMs [AlloDerm (2.11–38.25pg/10⁶ PBMCs); AlloMax (13.12–715.40pg/10⁶ PBMCs); and FlexHD (116.69–665.40pg/10⁶ PBMCs)]. Analysis of this data indicated that AlloMax and FlexHD induced significantly more M/MQ activation compared with AlloDerm (P<0.05). Histologic evaluation of the BMs indicated adherence of M/MQs on BM surface, however no degradation was detected.

Conclusion

For the first time, we have demonstrated that M/MQs are activated to varying levels by human BMs in vitro. These differences may be related to BM processing technologies and/or the biologic variation between donors. Our results raise the possibility that these differences in M/MQ activation could result in varying intensity of inflammation and wound healing that control the integration of BMs at sites of hernia repair.

Key Words: biologic mesh, human, dermal matrix, mononuclear cells, monocyte, macrophage, cytokine, Interleukin-1β, in vitro