Table 3.

Characteristics of the included studies.

First Author-Year	Study Type	Sample	Plasma System	Time of Exposure	Cell Type	Study Controls	Parameters Assessed	Evaluation Time	Outcome
Canullo 2020 [37]	In vitro	Grade 5 titanium discs with four different topographies (MAC, UTM, UTM-Y, XA)	Plasma reactor (Plasma R, Diener Electronic GmbH, Ebhausen, Germany) at 8 W and atmospheric pressure	6′	Normal Human Dermal Fibroblasts	UV treatment, no treatment	Cell culture, Cell morphology, Adhesion Test, Wettability, SEM	20′, 24 h, 72 h	Data showed potential biological benefits of treating implant abutment surfaces with the PoA in relation to early-stage cell adhesion.
Wang 2020 [38]	In vitro	Titanium grade 4 titanium disk	Atmospheric Pressure Plasma System model AS400 + PFW10, manufactured by Plasma Treat GmbH (Steinhagen, Germany)	90″	Osteoblast rat cells	No treatment	Surface Morphology, Surface Hydrophilicity, Surface Chemistry, Adhesion and Spreading, OCN Assay	12 h for the osteoblast morphology, 24 h for actin (spreading behavior and cytoskeletal arrangement), 7 and 14 days for OCN	Osteoblast cells’ adhesion, proliferation, and mineralization were all significantly improved. The low-temperature PoA treatment could be a potentially effective approach to activate titanium-based dental implants for improved performance.
Guo 2019 [39]	In vitro	Titanium grade 4 discs, tetragonal zirconia polycrystal discs and PEEK discs	NTP reactor (generator frequency 100 kHz, input power 24 W, system pressure 1 mbar, gas flow rate 1.25 sccm, and gas purity >99.5% Diener Electronic GmbH, Ebhausen, Germany).	12′	L929 murine fibroblast cells and human gingiva fibroblast cells	UV treatment, no treatment	Cell culture, Cell Attachment and Morphology, Viability Assay, Cytotoxicity Assay	2 h, 24 h, 48 h	Oxygen plasma treatment may improve the attachment, proliferation and viability of soft tissue cells. PoA treatment showed only minor effects on the cytocompatibility of soft tissue cells.
González-Blanco 2019 [40]	In vitro	Grade 4 and 5 SLA titanium discs	V15-G plasma reactor produced by Plasma Finish (PINK GmbH Thermosysteme, Wertheim, Germany), placed into an ISO 7 clean room (Lesatec, Opera Milan, Italy), pressure 20 Pa.	15′	Osteoblast MG-63 cell line	No treatment	Cell Culture, Cell Viability Analysis, Morphological Analysis and Mitochondrial Energy Balance	6 h, 24 h, 48 h	The use of argon plasma as an intervention for decontaminating the surfaces of titanium implants may lead to an improvement in the growth, cell size, spreading and mitochondrial activity of the MG-63 cells that cover them.
Pistilli 2018 [41]	In vitro	Grade 4 titanium discs	Plasma reactor (Plasma R, Sweden & Martina), 10 W, 1 bar	12′	Murine preosteoblasts (MC3T3-E1)	No treatment	SEM, Surface roughness analysis, Cell Adhesion (CA), Protein Adsorption (PA), Bacterial Biofilm Evaluation (BE)	20 min for CA, 30 min for PA, 24 h for BE)	PoA treatment significantly increased the protein adsorption level. Rough implant surfaces benefited the most from the PoA treatment.
Canullo 2017 [14]	In vitro	Grade 4 titanium discs with different surface modifications (MAC, TPS and ZRT)	APDBD treatment (8 W at atmospheric pressure) using a nonthermal dielectric barrier discharge (Plasma Beam Mini, Diener Electronic).	2′	Preosteoblastic murine cell line MC3T3-E1	No treatment	Contact angle, Bacterial Adhesion, Protein Adsorption (PA), Cell culture, Cell Adhesion Assay (CA), Cell Morphology (CM), Viability Assay (VA)	30′ for PA; 12′ for CA; 30′ and 8 h for CM; 24 h, 48 h, 72 h for VA	Argon atmospheric pressure dielectric barrier discharge showed the ability to enhance osteoblast attachment and spreading as well as bacterial decontamination.
Henningsen 2018 [42]	In vitro	Sandblasted and acid-etched grade 4 titanium discs	Yocto III NTP plasma reactor (Diener Electronic GmbH, Ebhausen, Germany). 24 W -0.5 mbar	12′	Murine osteoblast-like cells MC3T3-E1	UV treatment, no treatment	SEM, Surface Roughness Measurements, Wettability, Cell Culture, Cell Attachment and Morphology (CAM), Cell Proliferation (CP), Cytotoxicity, XPS Analysis, Viability	2 h, 24 h, 72 h for CAM; 52 h for Viability; 24 h, 48 h, 72 h for CP and Cytotoxicity	NTP and UV treatments result in an optimized cell environment on titanium disks compared to the non-treated control without conducting any topographical or roughness changes under laboratory conditions.
Canullo 2017 [43]	In vitro	Grade 4 titanium discs with different surface modifications (MAC, TPS and ZRT)	Plasma reactor (Plasma R, Sweden & Martina), 10 W, 1 bar	12′	Preosteoblastic murine cell line MC3T3-E1	No treatment	FESEM, Contact Angle, Cell Culture, Cell Morphology	2 h, 8 h, 24 h for cell morphology	Morphologic changes in adherent osteoblasts could be detected, supporting the efficacy of cold PoA treatment, for all the implant surfaces evaluated.
Garcia 2017 [30]	In vivo	Titanium abutment, 30 patients	Plasma reactor (Diener Electronic GmbH, Jettingen, Germany), 75 W, −10 Mpa	12′	Fibroblast	No treatment	Abutment Surface Analysis, Histological Analysis	2 weeks after a second surgery	PoA may promote cell adhesion and positively influence collagen fiber orientation.
Canullo 2016 [28]	In vitro	Grade 4 titanium disks with different surface modifications (MAC, TPS and ZRT)	Plasma reactor (Plasma R; Sweden & Martina), 10 W, 1 bar	12′	Preosteoblastic murine cell line MC3T3-E1 and human osteoblastic cell line MG-63	UV treatment, no treatment	Topography and Surface Analyses, Protein Adsorption (PA), Cell culture, Cell Adhesion assay (CA)	30′ for PA, 15′ for CA	The present study highlights the potential benefits of treating implant surfaces with PoA (12 min) or UV (3 h)
Canullo 2014 [32]	In vivo	Titanium abutments, 18 patients	Plasma reactor (Diener Electronic GmbH, Jettingen, Germany), 75 W, −10 Mpa	12′	Fibroblast	No treatment, laboratory customization and cleaning by steam	Percentage of the Total Area Occupied by Cells, Presence or Absence of Cells, Aspect of the Adhered Cells and the Presence of Contaminants	One week after a second surgery	Results suggest a better adhesion of soft tissue cells to titanium abutments cleaned by PoA than to those inserted as they come from the industry or cleaned by steam after laboratory customization.
Canullo 2013 [29]	In vitro	Machined grade 5 titanium disks	Plasma reactor (Colibri, Gambetti Company), 10 W, 1 bar	6′	Murine fibroblastic cells (L929)	No treatment	Cell Adhesion, Process of Adhesion and Colonization of the Surfaces	2 h, 8 h, 48 h	PoA treatment on titanium disks immediately before exposure to a suspension of L929 murine fibroblastic cells significantly increased the speed of cellular adhesion compared to untreated control disks.
Duske 2012 [23]	In vitro	Grade IV Titanium disks with different topographies	Atmospheric pressure plasma jet (INP Greifswald, Greifswald, Germany), with a frequency of applied voltage of 1.82 MHz with an input power of 2–3 W	30″, 60″, 120″	Human osteoblastic cells (MG-63, ATCC, CRL-1427)	Machined (M), sandblast-etched (SLA) and discs with a hydrophilic SLActive® surface (ACT)	Contact Angle Measurement, Cell Culture, Spreading, Metabolic Activity and SEM of Human Osteoblastic Cells (MG-63)	30′, 60′ and 24 h	Results suggest that a PoA with a small oxygen admixture was effective for surface modifications resulting in favourable cell responses.
Stanford 1994 [44]	In vitro	Commercially pure Titanium samples	Plasma discharge chamber (model PDC-32G Plasma Cleaner, Harrick Scientific Corporation, Ossining, NY), 100 W, 0.07 Mpa	5′	Rat calvarial osteoblast-like cells	UV light, autoclave, ethylene oxide gas	Cell culture, Osteocalcin RIA, Collagen Expression, Alkaline Phosphatase Enzyme Activity, Alizarin Red Calcium Assay	4, 6, 8, 10, 12 days	Osteocalcin and alkaline phosphatase, but not collagen expression, were significantly affected by surface roughness when these surfaces were altered by PoA-cleaning. In general, PoA-cleaned cpTi surfaces demonstrated an inverse relationship between surface roughness and phenotypic markers for a bone-like response
Michaels 1991 [45]	In vitro	Commercially pure Titanium disks	Harrick plasma-cleaning device (Harrick Scientific, Ossininf, NY 10562, USA)	1′, 5′	Rat periodontal ligament fibroblast-like cells	UV light, autoclave, ethylene oxide gas	Cell Attachment Assay, SEM Evaluation of Cellular Spreading	15′, 30′, 60′, 120′	PoA-cleaning for up to five min did not appear to enhance cell attachment, but it benefited spreading.
Swart 1992 [27]	In vitro	Commercially pure Titanium disks	Harrick PDC-32G plasma cleaning device (Harrick Scientific Corp., Ossining, NY, USA), Ar 100 W, 0.15 atm	1′, 5′, 10′	Osteoblast like cells	No treatment	Cell Attachment Assays, SEM, X-ray Photoelectron Spectroscopy, Auger Electron Spectroscopy, Contact Angle	15′, 30′, 60′, 120′	Short-term PoA-cleaning treatments may produce a relatively contaminant-free, highly wettable surface that favors early in vitro osteoblast-like cellular attachment and morphological integration.