TABLE 1.

Summary of publications included in this systematic review

	Galeotti et al. (2013)	Malkoc et al. (2012)	Kim et al. (2008)	Markhoff et al. (2017)	Chander et al. (2017)	Mostardi et al. (2010)	Dalal et al. (2012)	Evans (1994)
Test Materials	Stainless Steel Grade IV Ti‐6Al‐4 V	Stainless Steel Ti‐6Al‐4 V	Grade 2 Ti‐6Al‐4 V	Ti‐6Al‐4 V Ti‐6Al‐4 V additive manufactured NiTi NiTi DLC	Grade 1 Ti‐6Al‐4 V	Cp‐Ti Cp‐Ta Ti‐6Al‐4 V Co‐Cr‐A Co‐Cr‐B	Ti‐6Al‐4 V Co‐Cr‐Mo Zr‐oxide Zr‐alloy	Ti Ti‐6Al‐4 V Co‐Cr‐Mo
Size	Whole implant	Whole implant	Discs 5 mmx 3 mm	Disks 10 mm x 2 mm	Disks 8 mm x 5 mm	Particle (Size not reported)	Particle 0.1 to 1 μm	Particle Max 45 μm
Fibroblast origin	Human gingival fibroblasts	Human gingival fibroblasts	Mouse fibroblasts 3 T3	Fibroblasts human skin biopsies, osteoblasts, macrophages	Human gingival fibroblasts	Human synovial fibroblasts	Human fibroblasts (origin not specified)	Fibroblasts ‐ rat skin)
Culture methods	Cell culture in implant eluates	Cell culture in implant eluates	Days 2 + 5 proliferation 16 hrs adhesion	96 Hours	48 and 72 hours	5 days	48 hours	2,4,6 days
Variable	Test material, pH and time	Test material and time	Time	Alloy, cell time	Time different solutions	Particle concentration	Particle concentration	Direct/indirect contact
Analysis	MTT metabolic activity assay	xCELLigence cell survival	MTT Proliferation assay Adhesion	WST‐1 Inflammatory cytokine assay	MTT Proliferation assay	Trypan blue cell count	ATP chemiluminescence Proliferation LDH assay Inflammatory cytokine assay	Cells counted
Findings	Ti‐6Al‐4 V eluates (pH 4) resulted in significant (p < 0.01) cytotoxicity	Ti‐6Al‐4 V whole implant is not cytotoxic	Vanadium ion effects proliferation	Ti‐6Al‐4 V increase MMP‐1	Ti‐6Al‐4 V reduced cell viability	Reduced cell number (large patient variation	Decreased proliferation, upregulated inflammatory marker of fibroblasts in a dose dependant manner	Reduced cell number