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Postoperative pain relief is crucial for full recovery. With the ongoing opioid epidemic and the insufficient effect of acetaminophen on severe pain; non-steroidal anti-inflammatory drugs (NSAIDs) are heavily used to alleviate this pain. However, NSAIDs are known to inhibit postoperative healing of connective tissues by inhibiting prostaglandin signaling. Pain intensity, inflammatory mediators associated with wound healing and the pharmacological action of NSAIDs vary throughout the day due to the circadian rhythm regulated by the clock genes. According to this rhythm, most of wound healing mediators and connective tissue formation occurs during the resting phase, while pain, inflammation and tissue resorption occur during the active period of the day. Here we show, in a murine tibia fracture surgical model, that NSAIDs are most effective in managing postoperative pain, healing and recovery when drug administration is limited to the active phase of the circadian rhythm. Limiting NSAID treatment to the active phase of the circadian rhythm resulted in overexpression of circadian clock genes, such as Period 2 (Per2) at the healing callus, and increased serum levels of anti-inflammatory cytokines interleukin-13 (IL-13), interleukin-4 (IL-4) and vascular endothelial growth factor. By contrast, NSAID administration during the resting phase resulted in severe bone healing impairment.

Therapies using human mesenchymal stem cells (MSCs) combined with three-dimensional (3D) printed scaffolds are a promising strategy for bone grafting. But the harvest of MSCs still remains invasive for patients. Human synovial fluid MSCs (hSF-MSCs), which can be obtained by a minimally invasive needle-aspiration procedure, have been used for cartilage repair. However, little is known of hSF-MSCs in bone regeneration. Polyetherketoneketone (PEKK) is an attractive bone scaffold due to its mechanical properties comparable to bone. In this study, 3D-printed PEKK scaffolds were fabricated using laser sintering technique. hSF-MSCs were characterized and cultured on PEKK to evaluate their cell attachment, proliferation, and osteogenic potential. Rabbit calvarial critical-sized bone defects were created to test the bone regenerative effect of PEKK with hSF-MSCs. In vitro results showed that hSF-MSCs attached, proliferated, and were osteogenic on PEKK. In vivo results indicated that PEKK seeded with hSF-MSCs regenerated twice the amount of newly formed bone when compared to PEKK seeded with osteogenically-induced hSF-MSCs or PEKK scaffolds alone. These results suggested that there was no need to induce hSF-MSCs into osteoblasts prior to their transplantations in vivo. In conclusion, the combined use of PEKK and hSF-MSCs was effective in regenerating critical-sized bone defects.

Data Sources: Pubmed, Embase, Sciences Citation Index, Cochrane Central Register of Controlled Trials (CENTRAL) and grey literature database of SIGLE were searched from January 1, 1990 to August 20, 2011 with no language restrictions., Study Selection: Randomised controlled trials (RCTs) or quasi-RCTs in which the participants were healthy and received additional interventions to conventional orthodontic treatment for accelerating tooth movements were included. Subjects with defects in oral and maxillofacial regions (ie, cleft lip/palate), dental pathologies and medical conditions were excluded., Data Extraction and Synthesis: Studies were selected by two independent reviewers and disagreements were resolved by discussion with a third reviewer. The primary outcomes included accumulative moved distance (AMD) or movement rate (MR) and time required to move the tooth to its destination. Secondary outcomes were pain improvement, anchorage loss, periodontal health, orthodontic caries, pulp vitality and root resorption. The reviewers performed statistical pooling, where possible, according to a priori criteria on the basis of comparability of patient type, treatments and outcomes measured and risk of bias. The reviewers tested for heterogeneity, publication bias and sensitivity. A quality assessment test was conducted to evaluate the method used to measure AMD., Results: The authors selected seven RCTs and two quasi-RCTs, which included a total of 101 patients with an age range of 12-26.3 years. Eight studies compared four intervention methods to no intervention group (control group). From them, four studies assessed low laser therapy (LLL), two evaluated corticotomy (CC), one assessed electrical current therapy (EC) and one evaluated pulsed electromagnetic field (PEF). Another study compared dentoalveolar distraction (DAD) vs periodontal distraction (PDD).Quality assessment scores showed that only two studies were of high quality, five studies were of medium quality, while two studies were of low quality. All studies, except one, compared left and right sides of the same participant (split mouth design), and measured the AMD.The method for measuring AMD was reliable in three studies, relatively reliable in one study and unreliable in four studies. The authors only performed pooled AMD mean meta-analysis for the LLL studies. The meta-analysis showed pooled mean AMD of 0.32 (95% confidence interval (CI), 20.04, 0.68), 0.76 (95% CI, 20.14, 1.65), and 0.73 (95% CI, 20.68, 2.14) for one month, two months and three months, respectively. Two LLL studies showed no differences regarding periodontal health and two LLL studies showed no differences in root resorption between LLL intervention and control groups. Compared to control group, one study reported that CS had significantly higher MR and another study showed that CS exhibited larger AMD for one month, two months, three months and four months. Two studies revealed that CS did not show any difference in the periodontal health status. One study reported the EC showed significantly larger AMD for one month, whereas another study reported that PEF induced larger AMD for five + 0.6 months. DAD showed faster MR and less anchorage loss compared to PDD. Teeth remained vital in both DAD and PDD interventions and one out of six cases presented root resorption in the PDD group., Conclusions: Among the five interventions corticotomy is effective and safe to accelerate orthodontic tooth movement, low-level laser therapy was unable to accelerate orthodontic tooth movement. The level of evidence does not support whether electrical current and pulsed electromagnetic fields are effective in accelerating orthodontic tooth movement and dentoalveolar or periodontal distraction is promising in accelerating orthodontic tooth movement.