Platelet-rich plasma for regeneration of neural feedback pathways around dental implants: a concise review and outlook on future possibilities

Along with the development of new materials, advanced medical imaging and surgical techniques, osseointegrated dental implants are considered a successful and constantly evolving treatment modality for the replacement of missing teeth in patients with complete or partial edentulism. The importance of restoring the peripheral neural feedback pathway and thus repairing the lack of periodontal rnechanoreceptors after tooth extraction has been highlighted in the literature. Nevertheless, regenerating the nerve fibers and reconstructing the neural feedback pathways around osseointegrated implants remain a challenge. Recent studies have provided evidence that platelet-rich plasma （PRP） therapy is a promising treatment for musculoskeletal injuries. Because of its high biological safety, convenience and usability, PRP therapy has gradually gained popularity in the clinical field Although much remains to be learned, the growth factors from PRP might play key roles in peripheral nerve repair mechanisms. This review presents known growth factors contributing to the biological efficacy of PRP and illustrates basic and （pre-）clinical evidence regarding the use of PRP and its relevant products in peripheral nerve regeneration. In addition, the potential of local application of PRP for structural and functional recovery of iniured peripheral nerves around dental implants is discussed.

Sensory innervation around immediately vs. delayed loaded implants: a pilot study

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 method to allow optimized peri-implant re-innervation, but further functional measurements are still required.

Validation of a novel imaging approach using multi-slice CT and cone-beam CT to follow-up on condylar remodeling after bimaxillary surgery

The main goal of this study was to introduce a novel three-dimensional procedure to objectively quantify both inner and outer condylar remodelling on preoperative multi-slice computed tomography （MSCT） and postoperative cone-beam computed tomography （CBCT） images. Second, the reliability and accuracy of this condylar volume quantification method was assessed. The mandibles of 20 patients （11 female and 9 male） who underwent bimaxillary surgery were semi-automatically extracted from MSCT/CBCT scans and rendered in 3D. The resulting condyles were spatially matched by using an anatomical landmark-based registration procedure. A standardized sphere was created around each condyle, and the condylar bone volume within this selected region of interest was automatically calculated. To investigate the reproducibility of the method, inter- and intra-observer reliability was calculated for assessments made by two experienced radiologists twice five months apart in a set of ten randomly selected patients. To test the accuracy of the bone segmentation, the inner and outer bone structures of one dry mandible, scanned according to the clinical set-up, were compared with the gold standard, micro-CT. Thirty-eight condyles showed a significant （P〈O.05） mean bone volume decrease of 26.4%_ 11.4% （502.9 mm3＋ 268.1 mm3）. No significant effects of side, sex or age were found. Good to excellent （ICC〉 0.6） intra- and inter-observer reliability was observed for both MSCT and CBCT. Moreover, the bone segmentation accuracy was less than one voxel （0.4 mm） for MSCT （0.3 mm __. 0.2 mm） and CBCT （0.4 mm _ 0.3 mm）, thus indicating the clinical potential of this method for objective follow-up in pathological condylar resorption.

Validating cone-beam computed tomography for peri-implant bone morphometric analysis

Cone-beam computed tomography （CBCT） has been recently used to analyse trabecular bone structure around dental implants. To validate the use of CBCT for three-dimensional （3D） peri-implant trabecular bone morphometry by comparing it to two-dimensional （2D） histology, 36 alveolar bone samples （with implants n=27 vs. without implants n=9） from six mongrel dogs, were scanned ex vivo using a high-resolution （80 ~m） CBCT. After scanning, all samples were decalcified and then sectioned into thin histological sections （-6 jim） to obtain high contrast 2D images. By using CTAn imaging software, bone morphometric parameters including trabecular number （Tb.N）, thickness （Tb.Th）, separation （Tb.Sp） and bone volume fraction （BV/TV） were examined on both CBCT and corresponding histological images. Higher Tb.Th and Tb.Sp, lower BV/TV and Tb.N were found on CBCT images （P〈0.001）. Both measurements on the peri-implant trabecular bone structure showed moderate to high correlation （r=0.65-0.85）. The Bland-Altman plots showed strongest agreement for Tb.Th followed by Tb.Sp, Tb.N and BV/TV, regardless of the presence of implants. The current findings support the assumption that peri-implant trabecular bone structures based on high-resolution CBCT measurements are representative for the underlying histological bone characteristics, indicating a potential clinical diagnostic use of CBCT-based peri-implant bone morphometric characterisation.

Neuropathic pain after bilateral sagittal split osteotomy:management and prevention

Neuropathic pain is characterized by spontaneous and provoked pain and other signs reflecting neural damage.Aberrant regeneration following peripheral nerve lesions leaves neurons unusually sensitive and prone to spontaneous pathological activity,abnormal excitability and heightened sensitivity to stimuli.This review covers the current understanding of neuropathic pain after bilateral sagittal split osteotomy(BSSO)of the lower jaw.The reported incidence of neuropathic pain after mandibular osteotomies is less than 1%,while the incidence in patients with iatrogenic inferior alveolar nerve(IAN)injuries during BSSO can be as high as 45%.The factors which modulate the healing process toward neuropathic pain during or after nerve damage have not yet been elucidated.Patients at highest risk for developing post-BSSO neuropathic pain are older than 45 years and have undergone procedures involving IAN compression,partial severance,or complete discontinuity of the lingual nerve with a proximal stump neuroma,patients with nerve injury repair delayed longer than 12 months and patients with chronic illnesses that compromise healing or increase risk for peripheral neuropathy.Although neuropathic pain tends to be long-lasting,some patients can recover completely.Preventive measures include risk assessment prior to surgery,prevention of nerve damage during surgery,and early repair of nerve injury.