Recent advances in additive manufacturing of patient-specific devices for dental and maxillofacial rehabilitation.

OBJECTIVES: Customization and the production of patient-specific devices, tailoring the unique anatomy of each patient's jaw and facial structures, are the new frontiers in dentistry and maxillofacial surgery. As a technological advancement, additive manufacturing has been applied to produce customized objects based on 3D computerized models. Therefore, this paper presents advances in additive manufacturing strategies for patient-specific devices in diverse dental specialties. METHODS: This paper overviews current 3D printing techniques to fabricate dental and maxillofacial devices. Then, the most recent literature (2018-2023) available in scientific databases reporting advances in 3D-printed patient-specific devices for dental and maxillofacial applications is critically discussed, focusing on the major outcomes, material-related details, and potential clinical advantages. RESULTS: The recent application of 3D-printed customized devices in oral prosthodontics, implantology and maxillofacial surgery, periodontics, orthodontics, and endodontics are presented. Moreover, the potential application of 4D printing as an advanced manufacturing technology and the challenges and future perspectives for additive manufacturing in the dental and maxillofacial area are reported. SIGNIFICANCE: Additive manufacturing techniques have been designed to benefit several areas of dentistry, and the technologies, materials, and devices continue to be optimized. Image-based and accurately printed patient-specific devices to replace, repair, and regenerate dental and maxillofacial structures hold significant potential to maximize the standard of care in dentistry.

The effect of micro-osteoperforation on root resorption, pulp vitality, and biological changes of teeth subjected to orthodontic tooth movement: A systematic review study.

Background: These days minimally invasive micro-osteoperforation (MOPs) has accelerated orthodontic tooth movement (OTM). However, there are some conflicting reports about their various impacts; hence, the present systematic review study aimed to evaluate the effect of MOP on root resorption, pulp vitality, and the biological changes of teeth subjected to OTM. Materials and Methods: Search in electronic databases of English literature including PubMed, Scopus, Web of sciences, Cochrane, and Google scholar as well as a manual search was performed from 2013 to 2022. Most of the studies included in this article were randomized controlled trials. Results: From the total number of 321 found articles, 31 duplicated and 268 irrelevant articles were excluded regarding the defined inclusion and exclusion criteria. Consequently, 22 articles were subjected to the quality assessment process, and finally, 18 articles were selected for the review phase. Root resorption during tooth movement using the MOP approach was reported only in one study. Besides, except for two animal studies, all of the relevant included articles showed that MOPs significantly increased the expression of some inflammatory biomarkers known to recruit osteoclast precursors and increase the number of osteoclast cells. On the other hand, two animal studies showed no differences in osteoclast counts by using MOPs in comparison to their control groups, which was consequently the result of biologic variability between animal and human and also probably the small sample sizes of these two studies. Conclusion: In this systematic review, according to the adverse effects of MOP on root resorption, one study showed higher levels of root resorption among patients undergoing MOP. However, this outcome was due to the different methods used to evaluate the effect of MOPs on root resorption. Moreover, a high certainty of evidence supports that MOP causes biological changes and an elevation in cytokines, chemokines, and other biomarkers that stimulates osteoclasts differentiation which in turn accelerate OTM. There was no change in pulp vitality status based on available evidence.

Antioxidant Materials in Oral and Maxillofacial Tissue Regeneration: A Narrative Review of the Literature.

Oral and maxillofacial tissue defects caused by trauma, tumor reactions, congenital anomalies, ischemic diseases, infectious diseases, surgical resection, and odontogenic cysts present a formidable challenge for reconstruction. Tissue regeneration using functional biomaterials and cell therapy strategies has raised great concerns in the treatment of damaged tissue during the past few decades. However, during biomaterials implantation and cell transplantation, the production of excessive reactive oxygen species (ROS) may hinder tissue repair as it commonly causes severe tissue injuries leading to the cell damage. These products exist in form of oxidant molecules such as hydrogen peroxide, superoxide ions, hydroxyl radicals, and nitrogen oxide. These days, many scientists have focused on the application of ROS-scavenging components in the body during the tissue regeneration process. One of these scavenging components is antioxidants, which are beneficial materials for the treatment of damaged tissues and keeping tissues safe against free radicals. Antioxidants are divided into natural and synthetic sources. In the current review article, different antioxidant sources and their mechanism of action are discussed. The applications of antioxidants in the regeneration of oral and maxillofacial tissues, including hard tissues of cranial, alveolar bone, dental tissue, oral soft tissue (dental pulp, periodontal soft tissue), facial nerve, and cartilage tissues, are also highlighted in the following parts.

A Systematic Review and Meta-Analysis on the Effect of Flavonoids on Insulin-like Growth Factor and Insulin-like Growth Factor Binding Protein and Incidence of Breast Cancer.

BACKGROUND: Insulin-like growth factor (IGF-1) is associated with breast cancer in menopausal women. Naturally occurring biomolecules found in common dietary protocols, such as flavonoids, play a key role in the inhibition and treatment of cancer. In-vitro/in-vivo studies showed that treatment involving flavonoids led to a reduced risk of breast cancer due to the decrease of IGF-1 level in addition to an increased insulin-like growth factor binding protein (IGFBP)-3. However, clinical studies did not show conclusive results in this regard because they are contradictory. OBJECTIVE: The aim of the present study was to find the effect of flavonoids on IGF-1 and IGFBP-3 and the incidence of breast cancer. METHODS: This systematic review was performed using PubMed, Scopus, ISI Web of Science, and EMBASE databases to collect results about the clinical use of flavonoids and their effects on breast cancer. After eliminating duplicate articles, the title and abstract of the remaining articles were examined in thematic communication, and related clinical articles were selected and studied based on inclusion criteria. The data were extracted from each article, and then statistical analysis was subsequently carried out by Comprehensive Meta-Analysis. RESULTS: The results showed that the effect of flavonoids on changes in IGF1 and IGFBP-3 was not statistically significant. No significant heterogeneity was detected across the studies. Pooled effect size also indicated that the mean change was not statistically significant. No significant heterogeneity was detected across the studies. There was no evidence of publication bias for IGF1 and IGFBP-3. CONCLUSION: This meta-analysis study suggests that flavonoid supplementations have no significant effect on IGF-1 and IGFBP-3, and a high soy diet has beneficial effects on IGF system components, which might be useful in breast cancer.

Acceleration of Wound Healing in Rats by Modified Lignocellulose Based Sponge Containing Pentoxifylline Loaded Lecithin/Chitosan Nanoparticles.

Dressing wounds accelerates the re-epithelialization process and changes the inflammatory environment towards healing. In the current study, a lignocellulose sponge containing pentoxifylline (PTX)-loaded lecithin/chitosan nanoparticles (LCNs) was developed to enhance the wound healing rate. Lecithin/chitosan nanoparticles were obtained by the solvent-injection method and characterized in terms of morphology, particle size distribution, and zeta potential. The lignocellulose hydrogels were functionalized through oxidation/amination and freeze-dried to obtain sponges. The prepared sponge was then loaded with LCNs/PTX to control drug release. The nanoparticle containing sponges were characterized using FTIR and SEM analysis. The drug release study from both nanoparticles and sponges was performed in PBS at 37 °C at different time points. The results demonstrated that PTX has sustained release from lignocellulose hydrogels. The wound healing was examined using a standard rat model. The results exhibited that PTX loaded hydrogels could achieve significantly accelerated and enhanced healing compared to the drug free hydrogels and the normal saline treatment. Histological examination of the healed skin confirmed the visual observations. Overall speaking, the in vivo assessment of the developed sponge asserts its suitability as wound dressing for treatment of chronic skin wounds.

Effect of bassorin (derived from gum tragacanth) and halloysite nanotubes on physicochemical properties and the osteoconductivity of methylcellulose-based injectable hydrogels.

Injectable hydrogels have been known as promising materials for the regeneration of irregular shape tissue defects. In this study, novel thermosensitive methylcellulose (MC) hydrogels containing bassorin (Ba) and halloysite nanotubes (HNTs) have been developed for application in bone tissue engineering. Bassorin isolated from gum tragacanth (GT) with the concentration of 0.25-1.5 w/v% was blended with MC. The best MC/Ba gel (containing 0.5% bassorin) was chosen based on the results of injectability and rheological tests. HNTs (1-7%) were added to this formulation and tested for the physicochemical, mechanical, rheological, degradation, swelling, and biological properties. In vitro biological evaluations including cell proliferation (by MTT assay), cell attachment (by SEM), osteogenic activity (by Alizarin Red staining and alkaline phosphatase assay), and osteogenic gene expression (by quantitative real-time polymerase chain reaction) were done using MG-63 cells. Results showed that bassorin led to the increased gel-forming ability (at a lower temperature) and mechanical properties of MC hydrogel. The presence of HNTs and bassorin affected the degradation rate and swelling degree of MC-based hydrogel. Results showed significant enhancement in cell proliferation, differentiation, and mineralization, as well as higher bone-specific gene expression of the cell on bassorin and HNTs incorporated MC compared to pure MC hydrogel.

Recent progress in extrusion 3D bioprinting of hydrogel biomaterials for tissue regeneration: a comprehensive review with focus on advanced fabrication techniques.

Over the last decade, 3D bioprinting has received immense attention from research communities for developing functional tissues. Thanks to the complexity of tissues, various bioprinting methods have been exploited to figure out the challenges of tissue fabrication, in which hydrogels are widely adopted as a bioink in cell printing technologies based on the extrusion principle. Thus far, there is a wealth of literature proposing the crucial parameters of extrusion-based bioprinting of hydrogel biomaterials (e.g., hydrogel properties, printing conditions, and tissue scaffold design) toward enhancing performance. Despite the growing research in this field, numerous challenges that hinder advanced applications still exist. Herein, the most recently reported hydrogel-based bioprinted scaffolds, i.e., skin, bone, cartilage, vascular, neural, and muscular (including skeletal, cardiac, and smooth) scaffolds, are systematically discussed with an emphasis on the advanced fabrication techniques from the tissue engineering perspective. The methods covered include multiple-dispenser, coaxial, and hybrid 3D bioprinting. The present work is a unique study to figure out the opportunities of the novel techniques to fabricate complicated constructs with structural and functional heterogeneity. Finally, the principal challenges of current studies and a vision of future research are presented.

Injectable gellan gum/lignocellulose nanofibrils hydrogels enriched with melatonin loaded forsterite nanoparticles for cartilage tissue engineering: Fabrication, characterization and cell culture studies.

Injectable hydrogels based on natural polysaccharides have attracted considerable attention in cartilage tissue engineering, especially those reinforced with mineral nanofilers carrying drug molecules. Here, a novel injectable hydrogel based on gellan gum (GG)/lignocellulose nanofibrils (LGNF) composite enriched with melatonin (MEL) loaded forsterite (FS) nanoparticles (FS-MEL) was developed to yield enhanced mechanical and biological properties of the hydrogels. Gelation time and temperature were determined for different hydrogel formulation containing 1-5 w/v% LGNF and 0.1-0.3 w/v% FS-MEL. The injectability test proved the ease of injection of the developed hydrogels. Degradation rate and swelling degree of developed hydrogel were evaluated to determine the effect of LGNF and FS on hydrogel behaviour. Results of mechanical characterization showed that the compressive modulus and strength of GG hydrogels were improved by incorporation of LGNF and FS. The results of MEL release study in PBS revealed that MEL showed more sustained release from the hydrogel compared to FS nanoparticles. Cell-hydrogels interaction was evaluated by culturing chondrocyte cells. Results exhibited higher cell adhesion, proliferation and gene expression on GG/LGNF/FS-MEL hydrogel compared to GG/LGNF and GG/LGNF/FS, which can be attributed to the synergic effect of FS and MEL. Overall results demonstrated that the developed GG/LGNF/FS-MEL hydrogels can be offered as promising materials for cartilage regeneration applications.

RGD peptide grafted polybutylene adipate-co-terephthalate/gelatin electrospun nanofibers loaded with a matrix metalloproteinase inhibitor drug for alleviating of wounds: an in vitro/in vivo study.

The objective of the present study was the fabrication of a wound dressing membrane based on RGD modified polybutylene adipate-co-terephthalate (PBAT)/gelatin nanofibrous structures loaded with doxycycline (DOX). This type of nanofiber for wound healing has not been reported so far and is quite novel. PBAT and gelatin nanofibers were separately electrospun using double needles electrospinning setup. Electrospinning variables were optimized to obtain bead-free thin nanofibers. The amount of drug loaded and release were measured in different concentrations of DOX and PBAT. MMPs inhibition was studied by polyacrylamide gel-zymography. Then, surface of the nanofibers was modified with RGD peptide, and their antimicrobial effect was investigated on Staphylococcus aureus and Pseudomonas aeruginosa. Effect of developed nanofibrous membranes on L929 fibroblast cells proliferation, adhesion and closure of excised wounds in rat were also studied. PBAT/gelatin nanofibrous structures with average fiber diameter of 75-529 nm were developed successfully. Drug release study revealed that about 65% of DOX was released from the optimized formulation (P17D1.6) after 20 h. The developed DOX loaded membrane inhibited the MMPs activity and showed no cytotoxicity. RGD surface-modified PBAT/gelatin nanofibers significantly improved the wound closure and histopathological results (re-epithelialization, collagen deposition, and angiogenesis) in rats compared to the control groups. Overall, RGD immobilized PBAT/gelatin nanofibrous membrane may have a potential application for wound healing.

Poly (3-hydroxybutyrate-co-3-hydroxyvalerate)/fibrinogen/bredigite nanofibrous membranes and their integration with osteoblasts for guided bone regeneration.

Guided bone regeneration (GBR) has been established to be an effective method for the repair of defective tissues, which is based on isolating bone defects with a barrier membrane for faster tissue reconstruction. The aim of the present study is to develop poly (hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/fibrinogen (FG)/bredigite (BR) membranes with applicability in GBR. BR nanoparticles were synthesized through a sol-gel method and characterized using transmission electron microscopy and X-ray diffractometer. PHBV, PHBV/FG, and PHBV/FG/BR membranes were fabricated using electrospinning and characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, contact angle, pore size, thermogravimetric analysis and tensile strength. The electrospun PHBV, PHBV/FG, and PHBV/FG/BR nanofibers were successfully obtained with the mean diameter ranging 240-410 nm. The results showed that Young's modulus and ultimate strength of the PHBV membrane reduced upon blending with FG and increased by further incorporation of BR nanoparticles, Moreover hydrophilicity of the PHBV membrane improved on addition of FG and BR. The in vitro degradation assay demonstrated that incorporation of FG and BR into PHBV matrix increased its hydrolytic degradation. Cell-membrane interactions were studied by culturing human fetal osteoblast cells on the fabricated membrane. According to the obtained results, osteoblasts seeded on PHBV/FG/BR displayed higher cell adhesion and proliferation compared to PHBV and PHBV/FG membrane. Furthermore, alkaline phosphatase activity and alizarin red-s staining indicated enhanced osteogenic differentiation and mineralization of cells on PHBV/FG/BR membranes. The results demonstrated that developed electrospun PHBV/FG/BR nanofibrous mats have desired potential as a barrier membrane for guided bone tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1154-1165, 2019.

GPTMS-Modified Bredigite/PHBV Nanofibrous Bone Scaffolds with Enhanced Mechanical and Biological Properties.

Bioceramic nanoparticles with high specific surface area often tend to agglomerate in the polymer matrix, which results in undesirable mechanical properties of the composites and poor cell spreading and attachment. In the present work, bredigite (BR) nanoparticles were modified with an organosilane coupling agent, 3-glycidoxypropyltrimethoxysilane (GPTMS), to enhance its dispersibility in the polymer matrix. The polyhydroxybutyrate-co-hydroxyvaletare (PHBV) nanofibrous scaffolds containing either bredigite or GPTMS-modified bredigite (G-BR) nanoparticles were fabricated using electrospinning technique and characterized using scanning electron microscopy, transmission electron microscopy, and tensile strength. Results demonstrated that modification of bredigite was effective in enhancing nanoparticle dispersion in the PHBV matrix. PHBV/G-BR scaffold showed improved mechanical properties compared to PHBV and PHBV/BR, especially at the higher concentration of nanoparticles. In vitro bioactivity assay performed in the simulated body fluid (SBF) indicated that composite PHBV scaffolds were able to induce the formation of apatite deposits after incubation in SBF. From the results of in vitro biological assay, it is concluded that the synergetic effect of BR and GPTMS provided an enhanced hFob cells attachment and proliferation. The developed PHBV/G-BR nanofibrous scaffolds may be considered for application in bone tissue engineering.