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.

Dental 3D-Printing: Transferring Art from the Laboratories to the Clinics.

The rise of three-dimensional (3D) printing technology has changed the face of dentistry over the past decade. 3D printing is a versatile technique that allows the fabrication of fully automated, tailor-made treatment plans, thereby delivering personalized dental devices and aids to the patients. It is highly efficient, reproducible, and provides fast and accurate results in an affordable manner. With persistent efforts among dentists for refining their practice, dental clinics are now acclimatizing from conventional treatment methods to a fully digital workflow to treat their patients. Apart from its clinical success, 3D printing techniques are now employed in developing haptic simulators, precise models for dental education, including patient awareness. In this narrative review, we discuss the evolution and current trends in 3D printing applications among various areas of dentistry. We aim to focus on the process of the digital workflow used in the clinical diagnosis of different dental conditions and how they are transferred from laboratories to clinics. A brief outlook on the most recent manufacturing methods of 3D printed objects and their current and future implications are also discussed.

Biomimetic Aspects of Oral and Dentofacial Regeneration.

Biomimetic materials for hard and soft tissues have advanced in the fields of tissue engineering and regenerative medicine in dentistry. To examine these recent advances, we searched Medline (OVID) with the key terms "biomimetics", "biomaterials", and "biomimicry" combined with MeSH terms for "dentistry" and limited the date of publication between 2010-2020. Over 500 articles were obtained under clinical trials, randomized clinical trials, metanalysis, and systematic reviews developed in the past 10 years in three major areas of dentistry: restorative, orofacial surgery, and periodontics. Clinical studies and systematic reviews along with hand-searched preclinical studies as potential therapies have been included. They support the proof-of-concept that novel treatments are in the pipeline towards ground-breaking clinical therapies for orofacial bone regeneration, tooth regeneration, repair of the oral mucosa, periodontal tissue engineering, and dental implants. Biomimicry enhances the clinical outcomes and calls for an interdisciplinary approach integrating medicine, bioengineering, biotechnology, and computational sciences to advance the current research to clinics. We conclude that dentistry has come a long way apropos of regenerative medicine; still, there are vast avenues to endeavour, seeking inspiration from other facets in biomedical research.

Structures of a dimodular nonribosomal peptide synthetase reveal conformational flexibility.

Nonribosomal peptide synthetases (NRPSs) are biosynthetic enzymes that synthesize natural product therapeutics using a modular synthetic logic, whereby each module adds one aminoacyl substrate to the nascent peptide. We have determined five x-ray crystal structures of large constructs of the NRPS linear gramicidin synthetase, including a structure of a full core dimodule in conformations organized for the condensation reaction and intermodular peptidyl substrate delivery. The structures reveal differences in the relative positions of adjacent modules, which are not strictly coupled to the catalytic cycle and are consistent with small-angle x-ray scattering data. The structures and covariation analysis of homologs allowed us to create mutants that improve the yield of a peptide from a module-swapped dimodular NRPS.

Structural Insight into a Novel Formyltransferase and Evolution to a Nonribosomal Peptide Synthetase Tailoring Domain.

Nonribosomal peptide synthetases (NRPSs) increase the chemical diversity of their products by acquiring tailoring domains. Linear gramicidin synthetase starts with a tailoring formylation (F) domain, which likely originated from a sugar formyltransferase (FT) gene. Here, we present studies on an Anoxybacillus kamchatkensis sugar FT representative of the prehorizontal gene transfer FT. Gene cluster analysis reveals that this FT acts on a UDP-sugar in a novel pathway for synthesis of a 7-formamido derivative of CMP-pseudaminic acid. We recapitulate the pathway up to and including the formylation step in vitro, experimentally demonstrating the role of the FT. We also present X-ray crystal structures of the FT alone and with ligands, which unveil contrasts with other structurally characterized sugar FTs and show close structural similarity with the F domain. The structures reveal insights into the adaptations that were needed to co-opt and evolve a sugar FT into a functional and useful NRPS domain.