Periodontitis is one of the most common dental diseases. Compared with healthy periodontal tissues, the immune microenvironment plays the key role in periodontitis by allowing the invasion of pathogens. It is possible that modulating the immune microenvironment can supplement traditional treatments and may even promote periodontal regeneration by using stem cells, bacteria, etc. New anti-inflammatory therapies can enhance the generation of a viable local immune microenvironment and promote cell homing and tissue formation, thereby achieving higher levels of immune regulation and tissue repair. We screened recent studies to summarize the advances of the immunomodulatory treatments for periodontitis in the aspects of drug therapy, microbial therapy, stem cell therapy, gene therapy and other therapies. In addition, we included the changes of immune cells and cytokines in the immune microenvironment of periodontitis in the section of drug therapy so as to make it clearer how the treatments took effects accordingly. In the future, more research needs to be done to improve immunotherapy methods and understand the risks and long-term efficacy of these methods in periodontitis.

Immediate loading of dental implants has gained widespread popularity because of its advantages in shortening treatment duration and improving esthetics and patient acceptance. However, whether immediate loading can achieve clinical outcomes comparable with those of early or conventional delayed loading is still unclear. The purpose of this systematic review and meta-analysis was to compare the efficacy of immediate loading versus early or conventional loading implants in patients rehabilitated with fixed prostheses. Electronic searches of CENTRAL, EMBASE, and MEDLINE were supplemented by manual searches up to October 2018. Only human randomized controlled trials (RCTs) comparing immediate with early or conventional loading dental implants were included. Quality assessment was performed by using the Cochrane Collaboration tool. For the meta-analysis, the dichotomous and continuous variables were pooled and analyzed by using risk ratios (RRs) and weighted mean differences (WMDs), with 95% confidence intervals (95% CIs). The outcomes assessed included survival rate, marginal bone level changes, peri-implant gingival level, probing depth, and implant stability. The subgroup analyses included healing methods, implant time, occlusal contact, number of missing teeth, and tooth position. Thirty-nine trials (49 articles) were included from the initial 763 references evaluated. When compared with conventional loading, with implants regarded as a statistical unit, a statistically significant lower survival rate was observed in the immediate loading dental implant (RR=0.974; 95% CI, 0.954, 0.994; P=.012). Regarding other outcomes, including marginal bone level changes, peri-implant gingival level, probing depth, and implant stability, no statistically significant differences were observed when comparing immediate versus early or conventional loading (P>.05). Compared with early loading, immediate loading could achieve comparable implant survival rates and marginal bone level changes. Compared with conventional loading, immediate loading was associated with a higher incidence of implant failure.

The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.