Although neurophysiological and psychophysical proof of osseoperception is accumulating, histomorphometric evidence for the neural mechanisms of functional compensation following immediate and delayed implant loading is still lacking. For this randomized split-mouth study, six mongrel dogs randomly received one of four treatment protocols at 36 implant-recipient sites over 16 weeks （third maxillary incisor, third and fourth mandibular premolar）： immediate implant placement and immediate loading （liP＋ IL）; delayed implant placement and delayed loading （DIP＋DL）; delayed implant placement and immediate loading （DIP＋IL）; and natural extraction socket healing （control）. Histomorphometry was performed in the peri-implant bone and soft tissues within 300 pm around the implants. Immunocytochemistry and transmission electron microscopy were used to confirm the presence of neural structures and to reveal their ultrastructural characteristics, respectively. Myelinated nerve fibres densely populated the peri-implant crestal gingival and apical regions, although they were also identified in the woven bone and in the osteons near the implant threads. Compared with the control group in the mandible, the group that received IIP＋IL showed a higher innervation （in N.mm^-2, 5.94±1.12 vs. 3.15±0.63, P〈0.001） and smaller fibre diameter （in pm, 1.37±0.05 vs. 1.64±0.13, P=0.016）, smaller axon diameter （in pm, 0.89±0.05 vs. 1.24±0,10, P=0.009） and g-ratio （0.64±0.04 vs. 0.76±0.05, P〈0.001） in the middle region around the implants. Compared with DIP＋IL in the mandible, IIP＋IL had a higher nerve density （in N.mm^-2, 13.23±2.54 vs. 9.64±1.86, P=0.027）, greater fibre diameter （in pm, 1.32±0.02 vs. 1.20±0.04, P=0.021）, greater axon diameter （in μm, 0.92±0.01 vs. 0.89±0.03, P=-0.035） and lower g-ratio （0.69±0.01 vs. 0.74±0.01, P=-0.033） in the apical region around the implants. It may be assumed that the treatment protocol with liP＋ IL is the preferred me
Yan HuangJeroen van DesselWendy MartensIvo LambrichtsWei-Jian ZhongGuo-Wu MaDan LinXin LiangReinhilde Jacobs
