Calcium phosphate nanoclusters modify periodontium remodeling and minimize orthodontic relapse.

Orthodontic relapse is one of the most prevalent concerns of orthodontic therapy. Relapse results in patients' teeth reverting towards their pretreatment positions, which increases the susceptibility to functional problems, dental disease, and substantially increases the financial burden for retreatment. This phenomenon is thought to be induced by rapid remodeling of the periodontal ligament (PDL) in the early stages and poor bone quality in the later stages. Current therapies, including fixed or removable retainers and fiberotomies, have limitations with patient compliance and invasiveness. Approaches using biocompatible biomaterials, such as calcium phosphate polymer-induced liquid precursors (PILP), is an ideal translational approach for minimizing orthodontic relapse. Here, post-orthodontic relapse is reduced after a single injection of high concentration PILP (HC-PILP) nanoclusters by altering PDL remodeling in the early stage of relapse and improving trabecular bone quality in the later phase. HC-PILP nanoclusters are achieved by using high molecular weight poly aspartic acid (PASP, 14 kDa) and poly acrylic acid (PAA, 450 kDa), which resulted in a stable solution of high calcium and phosphate concentrations without premature precipitation. In vitro results show that HC-PILP nanoclusters prevented collagen type-I mineralization, which is essential for the tooth-periodontal ligament (PDL)-bone interphase. In vivo experiments show that the PILP nanoclusters minimize relapse and improve the trabecular bone quality in the late stages of relapse. Interestingly, PILP nanoclusters also altered the remodeling of the PDL collagen during the early stages of relapse. Further in vitro experiments showed that PILP nanoclusters alter the fibrillogenesis of collagen type-I by impacting the protein secondary structure. These findings propose a novel approach for treating orthodontic relapse and provide additional insight into the PILP nanocluster's structure and properties on collagenous structure repair.

The Effects of Presurgical Orthodontic Treatment on the Outcome of Secondary Bone Graft for Individuals With Cleft Lip and Palate.

BACKGROUND/OBJECTIVE: Alveolar bone graft (ABG) or repair has become a routine part of treatment protocols for individuals with cleft lip and/or palate. However, the necessity and potential benefits of presurgical orthodontic treatment in influencing the outcomes of secondary alveolar bone grafting remain inconclusive. This systematic review aimed to assess the impact of presurgical orthodontics on preparing patients for secondary alveolar bone grafts. STUDY DESIGN: The authors systematically searched for relevant articles in PubMed, Web of Science, and Embase databases spanning the period from January 1, 2000, to December 31, 2023, using keywords related to alveolar bone grafting and orthodontic treatment for patients with cleft lip and/or palate. The review encompassed various study designs, including prospective and retrospective studies, observational studies, cross-sectional studies, randomized and nonrandomized clinical trials, cohort studies, and case-control studies. The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the risk of bias was evaluated in studies selected for full-text review. RESULTS: The search strategy identified 809 publications. After initial screening and application of exclusion criteria, 11 studies were included for final review. Three were prospective studies, 8 were retrospective studies, and 3 were cross-sectional cohort studies. On the basis of ROBINS-I and RoB 2 risk assessment, 9 studies were found to be of moderate risk of bias, one study was categorized as of high risk of bias, and 1 study was categorized as low risk of bias. CONCLUSIONS: Drawing from the latest and most reliable studies, 7 out of 11 included studies provided compelling evidence that presurgical orthodontics preceding alveolar bone grafting (ABG) leads to significantly improved outcomes compared with cases without presurgical orthodontic intervention. Notably, individuals with specific conditions, such as severely collapsed upper arch and mispositioned upper incisors, appear to derive the greatest benefits from presurgical orthodontic treatment. However, a call for additional studies characterized by high methodological quality and with longer follow-up periods is emphasized to enhance the safety considerations for both practitioners and patients concerning the utilization of presurgical orthodontics in the treatment of individuals with cleft lip and palate.

Functional Biomaterials for Local Control of Orthodontic Tooth Movement.

Orthodontic tooth movement (OTM) occurs with the application of a controlled mechanical force and results in coordinated tissue resorption and formation in the surrounding bone and periodontal ligament. The turnover processes of the periodontal and bone tissue are associated with specific signaling factors, such as Receptor Activator of Nuclear factor Kappa-ß Ligand (RANKL), osteoprotegerin, runt-related transcription factor 2 (RUNX2), etc., which can be regulated by different biomaterials, promoting or inhibiting bone remodeling during OTM. Different bone substitutes or bone regeneration materials have also been applied to repair alveolar bone defects followed by orthodontic treatment. Those bioengineered bone graft materials also change the local environment that may or may not affect OTM. This article aims to review functional biomaterials that were applied locally to accelerate OTM for a shorter duration of orthodontic treatment or impede OTM for retention purposes, as well as various alveolar bone graft materials which may affect OTM. This review article summarizes various types of biomaterials that can be locally applied to affect the process of OTM, along with their potential mechanisms of action and side effects. The functionalization of biomaterials can improve the solubility or intake of biomolecules, leading to better outcomes in terms of increasing or decreasing the speed of OTM. The ideal timing for initiating OTM is generally considered to be 8 weeks post-grafting. However, more evidence is needed from human studies to fully understand the effects of these biomaterials, including any potential adverse effects.

Quantitative Assessment of Fat Levels in Caenorhabditis elegans Using Dark Field Microscopy.

The roundworm Caenorhabditis elegans is widely used as a model for studying conserved pathways for fat storage, aging, and metabolism. The most broadly used methods for imaging fat in C. elegans require fixing and staining the animal. Here, we show that dark field images acquired through an ordinary light microscope can be used to estimate fat levels in worms. We define a metric based on the amount of light scattered per area, and show that this light scattering metric is strongly correlated with worm fat levels as measured by Oil Red O (ORO) staining across a wide variety of genetic backgrounds and feeding conditions. Dark field imaging requires no exogenous agents or chemical fixation, making it compatible with live worm imaging. Using our method, we track fat storage with high temporal resolution in developing larvae, and show that fat storage in the intestine increases in at least one burst during development.

mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation.

Mesenchymal stem cells (MSCs) are promising candidates for cell-based therapy to treat several diseases and are compelling to consider as vehicles for delivery of biological agents. However, MSCs appear to act through a seemingly limited "hit-and-run" mode to quickly exert their therapeutic impact, mediated by several mechanisms, including a potent immunomodulatory secretome. Furthermore, MSC immunomodulatory properties are highly variable and the secretome composition following infusion is uncertain. To determine whether a transiently controlled antiinflammatory MSC secretome could be achieved at target sites of inflammation, we harnessed mRNA transfection to generate MSCs that simultaneously express functional rolling machinery (P-selectin glycoprotein ligand-1 [PSGL-1] and Sialyl-Lewis(x) [SLeX]) to rapidly target inflamed tissues and that express the potent immunosuppressive cytokine interleukin-10 (IL-10), which is not inherently produced by MSCs. Indeed, triple-transfected PSGL-1/SLeX/IL-10 MSCs transiently increased levels of IL-10 in the inflamed ear and showed a superior antiinflammatory effect in vivo, significantly reducing local inflammation following systemic administration. This was dependent on rapid localization of MSCs to the inflamed site. Overall, this study demonstrates that despite the rapid clearance of MSCs in vivo, engineered MSCs can be harnessed via a "hit-and-run" action for the targeted delivery of potent immunomodulatory factors to treat distant sites of inflammation.

Cell-surface sensors: lighting the cellular environment.

Cell-surface sensors are powerful tools to elucidate cell functions including cell signaling, metabolism, and cell-to-cell communication. These sensors not only facilitate our understanding in basic biology but also advance the development of effective therapeutics and diagnostics. While genetically encoded fluorescent protein/peptide sensors have been most popular, emerging cell surface sensor systems including polymer-, nanoparticle-, and nucleic acid aptamer-based sensors have largely expanded our toolkits to interrogate complex cellular signaling and micro- or nano-environments. In particular, cell-surface sensors that interrogate in vivo cellular microenvironments represent an emerging trend in the development of next generation tools which biologists may routinely apply to elucidate cell biology in vivo and to develop new therapeutics and diagnostics. This review focuses on the most recent development in areas of cell-surface sensors. We will first discuss some recently reported genetically encoded sensors that were used for monitoring cellular metabolites, proteins, and neurotransmitters. We will then focus on the emerging cell surface sensor systems with emphasis on the use of DNA aptamer sensors for probing cell signaling and cell-to-cell communication.