Non-Gaussian anomalous diffusion of optical vortices.

Anomalous diffusion of different particlelike entities, the deviation from typical Brownian motion, is ubiquitous in complex physical and biological systems. While optical vortices move randomly in evolving speckle fields, optical vortices have only been observed to exhibit pure Brownian motion in random speckle fields. Here we present direct experimental evidence of the anomalous diffusion of optical vortices in temporally varying speckle patterns from multiple-scattering viscoelastic media. Moreover, we observe two characteristic features, i.e., the self-similarity and the antipersistent correlation of the optical vortex motion, indicating that the mechanism of the observed subdiffusion of optical vortices can only be attributed to fractional Brownian motion (FBM). We further demonstrate that the vortex displacements exhibit a non-Gaussian heavy-tailed distribution. Additionally, we modulate the extent of subdiffusion, such as diffusive scaling exponents, and the non-Gaussianity of optical vortices by altering the viscoelasticity of samples. The discovery of the complex FBM but non-Gaussian subdiffusion of optical vortices may not only offer insight into certain fundamental physics, including the anomalous diffusion of vortices in fluids and the decoupling between Brownianity and Gaussianity, but also suggest a strong potential for utilizing optical vortices as tracers in microrheology instead of the introduced exogenous probe particles in particle tracking microrheology.

DLP printed hDPSC-loaded GelMA microsphere regenerates dental pulp and repairs spinal cord.

Dental pulp regeneration is ideal for irreversible pulp or periapical lesions, and in situ stem cell therapy is one of the most effective therapies for pulp regeneration. In this study, we provided an atlas of the non-cultured and monolayer cultured dental pulp cells with single-cell RNA sequencing and analysis. Monolayer cultured dental pulp cells cluster more closely together than non-cultured dental pulp cells, suggesting a lower heterogeneous population with relatively consistent clusters and similar cellular composition. We successfully fabricated hDPSC-loaded microspheres by layer-by-layer photocuring with a digital light processing (DLP) printer. These hDPSC-loaded microspheres have improved stemness and higher multi-directional differentiation potential, including angiogenic, neurogenic, and odontogenic differentiation. The hDPSC-loaded microspheres could promote spinal cord regeneration in rat spinal cord injury models. Moreover, in heterotopic implantation tests on nude mice, CD31, MAP2, and DSPP immunofluorescence signals were observed, implying the formation of vascular, neural, and odontogenetic tissues. In situ experiments in minipigs demonstrated highly vascularized dental pulp and uniformly arranged odontoblast-like cells in root canals of incisors. In short, hDPSC-loaded microspheres can promote full-length dental pulp regeneration at the root canals' coronal, middle, and apical sections, particularly for blood vessels and nerve formation, which is a promising therapeutic strategy for necrotic pulp.

Application progress of alveolar ridge preservation in patients with tooth extracted due to periodontitis / 口腔医学

@#Alveolar ridge preservation (ARP) has developed rapidly as a method for preserving the alveolar socket's bone volume after tooth extraction. ARP can create conditions for implant restoration, and reduce operation difficulties by decreasing alveolar ridge absorption. There are certain difficulties of ARP applicationin patients with tooth extracted due to periodontitis. This paper mainly introduces the characteristics of ARP, compares the similarities and differences among ARP, guided tissue regeneration, guided bone regeneration and immediate implant, and then summarizes their advantages and disadvantages. The paper focuses on the specificity of ARP and the progress of ARP application in patients with tooth extracted due to periodontitis, in order to offer direction for clinical application and future research on ARP.

Digital light processing (DLP) in tissue engineering: from promise to reality, and perspectives.

Tissue engineering technology provides a revolutionary strategy to completely restore the structure and function of damaged tissues or organs. Digital light processing (DLP), as a kind of three-dimensional (3D) printing technology, has great advantages in printing resolution and efficiency, with low requirements for bioinks. This review introduces DLP-based printing and its development, as well as the manufacturing processes and printable materials. We also focus on tissue engineering products such as bone, tooth, cartilage, nerve, blood vessel, and so on. This review expounds on the difficulties and shortcomings of DLP printing technology in tissue engineering today. Perspectives are given on the current outlook on DLP-based 3D printing tissue engineering.

Evaluation of Blood Coagulation by Optical Vortex Tracking.

Blood coagulation is a complicated dynamic process that maintains the blood's fluid state and prevents uncontrollable bleeding. The real-time monitoring of coagulation dynamics is critical for blood transfusion guidance, emergency management of trauma-induced coagulopathy, perioperative bleeding, and targeted hemostatic therapy. Here, we utilize optical vortex dynamics to detect the blood coagulation dynamic process in a rapid and non-contact manner. To characterize the temporal changes in viscoelastic properties of blood during coagulation, we track the stochastic motion of optical vortices in the time-varying speckles reflected from 100 blood samples with varied coagulation profiles. The mean square displacement (MSD) of the vortices increases nonlinearly with time lag during blood coagulation reminiscent of the particles in viscoelastic fluids. The MSD curves with coagulation time are similar to the tracings of thromboelastography (TEG) during the blood coagulation. The retrieved coagulation parameters, such as reaction time and activated clotting time measured using the optical vortex method, exhibit a close correlation to those parameters acquired from TEG. These results demonstrate the feasibility of the optical vortex method for monitoring blood coagulation at the point of care. Our method is also applicable to measuring the viscoelasticity of complex fluids and turbid soft matters.

A Smartphone-Enabled Portable Digital Light Processing 3D Printer.

3D printing has emerged as an enabling approach in a variety of different fields. However, the bulk volume of printing systems limits the expansion of their applications. In this study, a portable 3D Digital Light Processing (DLP) printer is built based on a smartphone-powered projector and a custom-written smartphone-operated app. Constructs with detailed surface architectures, porous features, or hollow structures, as well as sophisticated tissue analogs, are successfully printed using this platform, by utilizing commercial resins as well as a range of hydrogel-based inks, including poly(ethylene glycol)-diacrylate, gelatin methacryloyl, or allylated gelatin. Moreover, due to the portability of the unique DLP printer, medical implants can be fabricated for point-of-care usage, and cell-laden tissues can be produced in situ, achieving a new milestone for mobile-health technologies. Additionally, the all-in-one printing system described herein enables the integration of the 3D scanning smartphone app to obtain object-derived 3D digital models for subsequent printing. Along with further developments, this portable, modular, and easy-to-use smartphone-enabled DLP printer is anticipated to secure exciting opportunities for applications in resource-limited and point-of-care settings not only in biomedicine but also for home and educational purposes.

Iroquois Homeobox 5 Negatively Regulated by miRNA-147 Promotes the Proliferation, Metastasis, and Invasion by Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common tumors worldwide and has one of the highest mortalities. The progression of OSCC is accompanied by changes in the levels of many genes. Iroquois homeobox 5 (IRX5), a novel protein involved in several embryonic developmental processes, has been found in recent years to play a significant role in regulating the growth of malignant tumors. However, its role and mechanism in OSCC are still unclear. In this study, we used nano-PCR to examine the levels of IRX5 in OSCC tissues. Through overexpression and knockdown experiments, we researched the role of IRX5 in regulating OSCC cell multiplication, metastasis, and epithelial-mesenchymal transition (EMT). The results demonstrated that IRX5 expression is higher in OSCC tissues in contrast to adjacent tissues. Overexpression of IRX5 promotes the multiplication, metastasis, invasion, and EMT of OSCC cells. Additional bioinformatics analysis showed that miRNA-147 can target the 3'UTR end of IRX5 and negatively regulate its expression, and overexpression of miRNA-147 can weaken the cancer-promoting effect of IRX5. In conclusion, this study found that IRX5 plays a role in promoting cancer in OSCC, and IRX5 is also negatively regulated by miRNA-147.

Early bone formation in mini-lateral window sinus floor elevation with simultaneous implant placement: An in vivo experimental study.

OBJECTIVE: To investigate the early bone formation in beagles with mini-lateral window sinus floor elevation and simultaneous implant placement. MATERIAL AND METHODS: Six beagles were selected for the split-mouth design procedures. In each animal, one maxillary recess received a 5 mm-diameter mini-round lateral osteotomy (test group), and the contralateral maxillary recess received a large rectangular osteotomy (10 mm long and 8 mm wide), (control group). Simultaneous implant installation was executed on bilateral maxillary recesses. Tetracycline and calcein dyes were administered on the 14th, 13th days and the 4th, 3rd days prior to sacrifice, respectively. After 8 weeks of healing, the beagles were euthanized for fluorescent labeling and histomorphometric analyses. RESULTS: In both groups, new bone formation initiated from the circumferential native bone of the maxillary recesses and extended toward the central sub-recess cavities. The maxillary recesses with the mini-window procedures exhibited superior mineral apposition rate, bone formation rate, and the percentage of new bone area to those of the group exposed to large osteotomy procedure (p < .05). While there was no significant difference in the value of bone-to-implant contact, the mini-window group displayed a tendency for an increase in this aspect (p > .05). Bone formation rate and new bone amount were not statistically correlated with bone-to-implant contact (p > .05). CONCLUSION: The hypothesis that mini-lateral window sinus floor elevation with simultaneous implant placement would improve early new bone formation in augmented sinus compared with large lateral window procedure is accepted.

Biodegradable intramedullary nail (BIN) with high-strength bioceramics for bone fracture.

About 10 million fractures occur worldwide each year, of which more than 60% are long bone fractures. It is generally agreed that intramedullary nails have significant advantages in rigid fracture fixation. Metal intramedullary nails (INs) can provide strong support but a stress shielding effect can occur that results in nonunion healing in clinic. Nondegradable metals also need to be removed by a second operation. Could INs be biodegradable and used to overcome this issue? As current degradable biomaterials always suffer from low strength and cannot be used in Ins, herein, we report a novel device consisting of biodegradable IN (BIN) made for the first time with bioceramics. These BINs have an extremely high bending strength and stable internal and external structure. Experiments show that the BINs could not only fix and support the tibial fracture model, but also promote osteogenesis and affect the microenvironment of the bone marrow cavity. Therefore, they could be expected to replace traditional metal IN and become a more effective treatment option for tibial fractures.

Complexation-induced resolution enhancement of 3D-printed hydrogel constructs.

Three-dimensional (3D) hydrogel printing enables production of volumetric architectures containing desired structures using programmed automation processes. Our study reports a unique method of resolution enhancement purely relying on post-printing treatment of hydrogel constructs. By immersing a 3D-printed patterned hydrogel consisting of a hydrophilic polyionic polymer network in a solution of polyions of the opposite net charge, shrinking can rapidly occur resulting in various degrees of reduced dimensions comparing to the original pattern. This phenomenon, caused by complex coacervation and water expulsion, enables us to reduce linear dimensions of printed constructs while maintaining cytocompatible conditions in a cell type-dependent manner. We anticipate our shrinking printing technology to find widespread applications in promoting the current 3D printing capacities for generating higher-resolution hydrogel-based structures without necessarily having to involve complex hardware upgrades or other printing parameter alterations.

Chiral geometry regulates stem cell fate and activity.

Geometry sensing of cells inevitably involves cytoskeletal remodeling and the activation of biochemical signaling, which control multiple aspects of cell behaviors, such as proliferation, differentiation and migration. A variety of size-, shape- and geometry-dependent cell behaviors have been revealed, but the role of geometric chirality in regulating cellular behaviors and the underlying biophysical mechanisms remain elusive. Here, we report an intriguing mechanotransduction of stem cells on chiral geometries that human mesenchymal stem cells (hMSCs) prefer to migrate towards dextral geometry with nearly 30% relative advantage in migration speed, referred to as "chirotaxis". We also found that cell adhesion, proliferation, and differentiation of hMSCs are greatly enhanced for cells cultured on dextral geometry than those on sinistral geometry, by triggering transcription factor AP-1 complex through p38/MAPK signaling that regulates hMSCs fate and activity. We demonstrated that the cytoskeletal network consisting of transverse and radial stress fibers exhibits a strengthening/offsetting effect on dextral/sinistral geometry through focal adhesion sites, and consequently, cell's cytoskeletal contractility on the dextral geometry is nearly 80% higher. These findings highlight the importance of geometric chirality as an extracellular cue in regulating stem cell's behaviors through cell-material interactions.

Surface Modification by Divalent Main-Group-Elemental Ions for Improved Bone Remodeling To Instruct Implant Biofabrication.

Divalent main-group-elemental ions are widely used to improve osteogenic capacity of implants biofabricated from Ti and its alloys. However, the conclusions regarding their osseointegration and immunogenicity are always inconsistent because of the multiple bone remodeling processes as well as the distinct material surface features arising from processing. Here we successfully manufactured the porous micro/nanostructured surface topography with divalent main-group-elemental ions (Mg2+, Ca2+, Sr2+, Ba2+) on substrates through hydrothermal treatment and comprehensively evaluated the complex bone remodeling processes, including osseointegration, immunogenicity, and fibrosis of substrates and implants. We found that Sr-modified implants not only upregulated the adhesion and proliferation of mesenchymal stem cells but also the differentiation of osteogenic markers compared with those modified by other divalent main-group-elemental ions (Mg2+, Ca2+, Ba2+). More importantly, the osteoclastogenesis, immunogenicity, and fibrosis of Sr-modified implants were also significantly downregulated. In vivo, evaluations of new bone formation and histological morphology at the interface of implant and host as well as the removal torque similarly indicated the improved osseointegration of Sr-modified implants as well as the absence of immunogenicity, fibrosis, or necrosis. Our results suggested that among various divalent main-group-elemental ions, Sr2+ might be a promising one for enhancing bone remodeling, which can be used to instruct functionalization of the surfaces of biofabricated Ti-based orthopedic and dental implants in the future.

Optimized beagle model for maxillary sinus floor augmentation via a mini-lateral window with simultaneous implant placement.

OBJECTIVE: This study was performed to establish an optimized beagle model for maxillary sinus floor augmentation via a mini-lateral window with simultaneous implant placement. METHODS: Twelve beagles underwent maxillary sinus floor augmentation via a mini-lateral window with simultaneous implant placement through sites selected by analyzing preoperative cone beam computed tomography (CBCT) images. During the experiment, no maxillary teeth were extracted and the infraorbital nerve was not severed. The osteotomy was only 5 mm in diameter. The implant stability quotient was measured, and postoperative CBCT was used to detect the condition of the sinus membrane and bone augmentation. RESULTS: The site corresponding to the tip of the highest dental cusp of the maxillary fourth premolar was suitable for the procedure, and the implant site was on the palatal bone plate. All implants achieved good primary stability. Postoperative CBCT showed no sinus membrane perforation, and the implants penetrated into the sinus cavity surrounded by bone substitute. CONCLUSION: The herein-described optimized model with mini-lateral osteotomy and without extraction or severing of the infraorbital nerve was minimally invasive, retained more lateral bone of the sinus, and achieved good sinus floor-lifting results. This model is highly reproducible and merits wider application.

Surface Atomic Structure Directs the Fate of Human Mesenchymal Stem Cells.

Stem cells in contact with materials are able to sense their surface features, integrate extracellular matrix (ECM) protein cues through a signal transduction pathway, and ultimately direct cell fate decisions. However, discovering the interdisciplinary mechanisms of how stem cells respond to inherent material surface features still remains a challenge due to the complex, multicomponent signaling milieu present in the ECM environment. Here, we demonstrate that the fate of human mesenchymal stem cells (hMSCs) can be regulated by the inherent physical cue of the material surface down to atomic-scale features. hMSCs on a TiO-terminated SrTiO3 {110} substrate tend to differentiate into specific lineage cells (osteoblast, chondrocyte, adipocyte), whereas on a TiO2-terminated SrTiO3 {100} substrate they are prone to maintain pluripotency. The experimental observations and molecular dynamics simulations indicate that the distinct conformations of the initially adsorbed serum albumin and fibronectin proteins activate the integrin-focal adhesion cytoskeleton actin transduction pathway and, subsequently, direct the gene and protein expressions of hMSCs. Moreover, we demonstrate that the initial protein adsorption behaviors are dependent on the distinct hydroxyl groups originating from different surface atomic structures as well as the work functions. This work, therefore, provides new insights into the fundamental understanding of cell-material interactions and will have a profound impact on further designing materials to direct the stem cell fate.

Surface hydroxyl groups regulate the osteogenic differentiation of mesenchymal stem cells on titanium and tantalum metals.

Titanium (Ti) and tantalum (Ta) metals have been widely used as implants for their favorable mechanical features and good biocompatibility. However, the results on their osteogenic capacity have been conflicting due to the synergistic effects of complex and multiple material surface features (such as topography, surface chemistries etc.) on cellular behaviors. Here, we directly compare the osteogenic response of mesenchymal stem cells (MSCs) to Ti and Ta metal surfaces with alterable surface hydroxyl groups. Although no difference was found on both surface topographies, cellular adhesion, proliferation, and the expression of osteogenic-related markers were upregulated with the increasing amount of surface hydroxyl groups (-OH) after ultraviolet (UV) light treatment. Moreover, Ti showed better effects in promoting osteogenic differentiation of MSCs than Ta before UV light treatment, but demonstrated the opposite after UV light treatment. These results might be attributed to the comparative quantity of the distinct type of surface hydroxyl groups (bridging-OH and terminal-OH), which regulated the conformation of the initial protein adsorption and subsequent cellular behaviors. Our results demonstrate the central role of the surface hydroxyl groups in mediating cell-material interactions and implicate this interface as helping in optimizing osteointegration of Ti and Ta based orthopaedic and dental implants.