Early molecular assessment of osseointegration in humans

• Published in: Clinical oral implants research Vol. 25; no. 11; pp. 1273 - 1285
• Main Authors: Thalji, Ghadeer N., Nares, Salvador, Cooper, Lyndon F.
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.11.2014; Wiley Subscription Services, Inc
• Subjects: Adherent cells; Aged; Amino Acid Transport Systems, Neutral - genetics; Angiogenesis; Antigens, CD20 - genetics; Biological activity; Biomarkers - analysis; biomaterials; Biomechanics; bone implant interactions; Bone implants; Bone-Implant Interface - anatomy & histology; CCL18 protein; Chemokines, CC - genetics; Collagen; Collagen - genetics; Dental Implants; Dental Materials - chemistry; Dental Prosthesis Design; DNA microarrays; Extracellular matrix; Extracellular Matrix - genetics; Female; Fibrillogenesis; Gene expression; Gene Expression Profiling - methods; Gene regulation; Genomes; Humans; Immune response; Immune system; Immunomodulation; Implantation; Inflammation; Macrophage Activation - genetics; Macrophages; Male; Membrane Proteins - genetics; Middle Aged; Neovascularization, Physiologic - genetics; Nerve Tissue Proteins - genetics; Osseointegration; Osseointegration - genetics; Physical properties; Receptors, Immunologic - genetics; Ribonucleic acid; RNA; Scavenger Receptors, Class A - genetics; Surface Properties; Surgical implants; Titanium - chemistry; Topography; Topology; Transcription; Transcription, Genetic - genetics; wound healing; wound healing; bone implant interactions; biomaterials
• ISSN: 0905-7161; 1600-0501; 1600-0501
• DOI: 10.1111/clr.12266

Objective To determine the early temporal‐wide genome transcription regulation by the surface topography at the bone–implant interface of implants bearing microroughened or superimposed nanosurface topology. Materials and methods Four commercially pure titanium implants (2.2 × 5.0 mm) with either a moderately roughened surface (TiOblast) or super‐imposed nanoscale topography (Osseospeed) were placed (n = 2/surface) in edentulous sites of eleven systemically healthy subjects and subsequently removed after 3 and 7 days. Total RNA was isolated from cells adherent to retrieved implants. A whole‐genome microarray using the Affymetrix Human gene 1.1 ST Array was used to describe the gene expression profiles that were differentially regulated by the implant surfaces. Results There were no significant differences when comparing the two implant surfaces at each time point. However, the microarray identified several genes that were differentially regulated at day 7 vs. day 3 for both implant surfaces. Functionally relevant categories related to the extracellular matrix (ECM), collagen fibril organization, and angiogenesis were upregulated at both surfaces (day7 vs. day3). Abundant upregulation of several differential markers of alternative activated macrophages was observed (e.g., MRC1, MSR1, MS4A4A, SLC38A6, and CCL18). The biological processes involved with the inflammatory/immune response gene expression were concomitantly downregulated. Conclusions Gene regulation implicating collagen fibrillogenesis and ECM organization as well as the inflammatory/immune responses involving the alternative activated pathway are observed in implant adherent cells at early (3–7 days) after implantation. These gene expression events may indicate a pivotal role of collagen fibrillogenesis as well as immunomodulation in altering bone accrual and biomechanical physical properties of the implant–bone interface.