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Table 3 Summary of findings from the included studies ( n= 4)

From: Genomic analyses of early peri-implant bone healing in humans: a systematic review

Study Ivanovski et al. [ 34 ] Donos et al. [ 35 ] Bryington et al. [ 36 ] Thalji et al. [ 37 ]
Design 9 patients; 9 implants placed 18 patients; 18 implants placed 10 patients; 60 implants placed 11 patients; 44 implants placed
Total RNA extracted from peri-implant tissue (trephine) 16 samples analyzed 42 samples analyzed Total RNA extracted from implant adherent cells (reverse thread)
  Total RNA extracted from peri-implant tissue (trephine) Total RNA extracted from implant adherent cells (reverse thread)  
Surface SLActive SLA vs. SLActive TiOBlast vs. Osseospeed TiOBlast vs. Osseospeed
GE day 3/4 Upregulated Upregulated on SLA Upregulated on both surfaces No significant differences between surfaces at any time point (P > 0.05)
 CKs (TNF-a, IL-6, IL-2)  Neurogenesis  Osteogenesis (Runx2, Osx, BMP6, OPN) Results presented as GE at day 7 vs. day 3 for each surface
 Immune-inflammatory cells (LC, MP)  Collagen organization  Inflammatory CKs (IL-1A,B, TNF)  
 Inflammatory NF-kB p/w Upregulated on SLActive  MP activity
   Ras protein p/w Upregulated on Osseospeed
 Collagen organization  Chemotaxis (CCL18, CXCL10, CXCL14)
 CK response  Anti-inflammatory CKs (TOLLIP, IL9, IL22)
GE day 7 Upregulated Upregulated on both surfaces Upregulated on both surfaces Upregulated on both surfaces
   MSC genes (HOX, Sp3)  Inflammatory CKs (IL1, IL2, IL6, TNFS)  Osteogenesis (Runx2, Osx*, OCN*, OPN, BMP6, BSP)  ECM (Coll, GPs, PGs)
 GF (TGF-B receptor)  Neurogenesis  [* Osseo > TiOB; P < 0.05]  Collagen organization (PLODs, LOX, PCOLCE)
 VEGF sig. (vs. day 14)  Upregulated on SLActive    Angiogenesis/VEGF sig. (ANXA, EPAS1)
 Wnt p/w  Neurogenesis (BDNF, NTF3)  Ossification
Downregulated  ECM (OPN)  Remodeling (MMPs, TIMPs)
 Inflammatory NF-kB p/w (vs. day 4)  BMP p/w (BMP4, BMP2K)  Osteoclastic (CTSK, ACP5)
   MAPK sig.  Chemotaxis (CKs, MP activity)
 Mineralization  Anti-inflammatory CKs (CCL22, CCL18)
 Focal adhesion (integrins) Downregulated on both surfaces
 Angiogenesis (VEGF sig., P13-Akt p/w)  Inflammatory CKs (IL1A, IL1B)
Downregulated on SLActive  
 Inflammatory cells (LC)
GE day 14 Upregulated Upregulated on both surfaces -
 ECM (Coll, OC, ON, ALP)  BMP p/w (BMP4, BMP2K)  
 TFs (Osx, Dlx5, Twist1, Smad6) Downregulated on both surfaces  
 Remodeling (MMP, CTSK)  Inflammatory cells (LC)  
 GFs (BMP, GDF)   
 Angiogenesis (VEGF sig.)  
 Neurogenesis  
 TGF-b/BMP, Notch p/w  
 Ras protein p/w  
 Wnt-receptor genes  
 Notch genes (up/down)  
Downregulated  
 Inflammatory response (vs. day 7)  
  1. GE, gene expression; CKs, cytokines; p/w, pathway; MSC, mesenchymal stem cells; GF, growth factors; sig., signaling; ECM, extracellular matrix; TFs, transcription factors; MP, macrophage; LC, lymphocytes; GPs, glycoproteins; PGs, proteoglycans.