A study protocol for a systematic qualitative literature review was developed based on recommended methods [29]. The focused question was ‘what biological processes are reflected by gene expression analyses in peri-implant tissues of humans during the early stages (up to 4 weeks) of healing?’

All studies, controlled (using different implants) or uncontrolled, reporting gene expression analyses of peri-implant tissues harvested from ≥5 human patients at ≥2 time points during the first 4 weeks of healing, were eligible for inclusion. Studies reporting the use of either ‘experimental’ (micro) or standard implants with clear description of implant surface properties, placed in the maxilla or mandible and retrieved at a later time point, were eligible for inclusion. Studies reporting (1) analyses of peri-implant mucosa or sulcular fluid or peri-implant tissues of failing or infected implants (peri-implantitis), (2) only histological or immunohistochemical analyses without gene expression of harvested tissues, and (3) in vitro and preclinical in vivo studies were excluded. Primary outcome of interest was the biological process (or processes) reflected by gene expression at a particular time point of peri-implant tissue healing.

Electronic databases of MEDLINE (via PubMed) and EMBASE were searched by one author (SS) for relevant English-language literature up to and including June 2014. The search strategy used for MEDLINE was ((((("gene expression" OR transcriptome OR transcriptional OR molecular OR microarray))) AND ((osseointegration OR healing OR "peri implant"))) AND implants) AND ((human OR humans OR patients OR subjects)). Unpublished literature was searched via the Google and Google Scholar search engines. Additionally, the bibliographies of all relevant studies and review articles were searched.

Titles and abstracts of the search identified studies were screened by two authors (SS and VS) based on the inclusion criteria, and full texts of all eligible studies were obtained. Differences in assessment of eligibility were resolved by discussion with the third author (AS). Full texts were independently reviewed by both reviewers, and final inclusion was based on the aforementioned inclusion criteria.