Characterization of early myocardial inflammation in ischemia-reperfusion injury.

Background: Myocardial injury may be caused by myocardial ischemia-reperfusion (IR), and salvaging such an injury is still a great challenge in clinical practice. This study comprehensively characterized the physiopathologic changes of myocardial injury after IR to explore the underlying mechanism in the early reperfusion phase with particular emphasis on early myocardial inflammation. Methods and Results: The experimental IR model was obtained by the left anterior descending artery's transient ligation of C57BL/6 mice. T2W signals of all mice showed increased signal at different IR stages. It was positively correlated with inflammatory cytokines and cells. T2W imaging by 7.0 T MRI surprisingly detected signal enhancement, but histopathology and flow cytometry did not reveal any inflammatory cells infiltration within 3 h after IR. Cardiomyocyte swelling and increased vascular permeability were observed by WGA staining and ultrastructural analysis, respectively. The 3 h IR group showed that the cardiomyocytes were severely affected with disintegrating myofilaments and mitochondria. Both VEGF and phosphorylated Src protein were markedly expressed in the 3 h IR group in comparison with the sham group, and TUNEL staining displayed little positive cells. Cleaved caspase-3 apoptin also has similar expression levels with that of the sham group. Resident macrophages had notably become M1 phenotype. The T2W signal was still elevated, and we observed that collagen deposition occurred from 1 to 7 days. Conclusions: The inflammation response during the first week after reperfusion injury gradually increase 3 h later, but the main manifestation before that was edema. This study indicated that the first 3 h may be crucial to the early rescue process for reperfusion-induced myocardial injury due to inflammatory cell infiltration absence and apoptosis.

Surface modification of the Ti surface with nanoscale bio-MOF-1 for improving biocompatibility and osteointegration in vitro and in vivo.

Biocompatibility and osteointegration of implants are highly desired in orthopedic and dentistry applications. The synthesis of a coating with ideal biocompatibility and osteogenic effect carries practical significance for improving the bio-inertness of pure Ti implants. Metal-organic frameworks (MOFs) are effective surface modification agents in bone regeneration applications. Bio-MOF-1, a classic type of biofriendly MOF with a bio-derived constitution, possesses biocompatibility and osteogenic potential resulting from its Zn core and adenine ligand. In this study, bio-MOF-1 coatings at multiple concentrations were synthesized on alkali-heat treated Ti, and their cytocompatibility and osteogenic properties were systematically examined both in vitro and in vivo. Coatings were characterized to confirm the successful synthesis of bio-MOF-1 coatings. These coatings exhibited advanced thermostability, excellent biocompatibility, and stable Zn2+ release, which up-regulated the expression of osteogenesis-related genes and proteins. Furthermore, bio-MOF-1 coating of Ti implants enhanced early osseointegration at the bone-implant interface. This study demonstrates the promising potential of bio-MOF-1 coatings with the osteogenic effect for surface modification in bone tissue engineering.

Lactoferrin/Calcium Phosphate-Modified Porous Ti by Biomimetic Mineralization: Effective Infection Prevention and Excellent Osteoinduction.

The surface modification of titanium (Ti) can enhance the osseointegration and antibacterial properties of implants. In this study, we modified porous Ti discs with calcium phosphate (CaP) and different concentrations of Lactoferrin (LF) by biomimetic mineralization and examined their antibacterial effects and osteogenic bioactivity. Firstly, scanning electron microscopy (SEM), the fluorescent tracing method, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and the releasing kinetics of LF were utilized to characterize the modified Ti surface. Then, the antibacterial properties against S. sanguis and S. aureus were investigated. Finally, in vitro cytological examination was performed, including evaluations of cell adhesion, cell differentiation, extracellular matrix mineralization, and cytotoxicity. The results showed that the porous Ti discs were successfully modified with CaP and LF, and that the LF-M group (200 µg/mL LF in simulated body fluid) could mildly release LF under control. Further, the LF-M group could effectively inhibit the adhesion and proliferation of S. sanguis and S. aureus and enhance the osteogenic differentiation in vitro with a good biocompatibility. Consequently, LF-M-modified Ti may have potential applications in the field of dental implants to promote osseointegration and prevent the occurrence of peri-implantitis.

Nanoscale Zeolitic Imidazolate Framework-8 Activator of Canonical MAPK Signaling for Bone Repair.

Zeolitic imidazolate framework-8 (ZIF-8) is an important type of metal organic framework and has found numerous applications in the biomedical field. Our previous studies have demonstrated that nano ZIF-8-based titanium implants could promote osseointegration; however, its osteogenic capacity and the related mechanisms in bone regeneration have not been fully clarified. Presented here is a nanoscale ZIF-8 that could drive rat bone mesenchymal stem cell (rBMSC) differentiation into osteoblasts both in vitro and in vivo, and interestingly, nano ZIF-8 exhibited a better osteogenic effect compared with ionic conditions of Zn at the same concentration of Zn2+. Moreover, the cellular uptake mechanisms of the nanoparticles were thoroughly clarified. Specifically, nano ZIF-8 could enter the rBMSC cytoplasm probably via caveolae-mediated endocytosis and macropinocytosis. The intracellular and extracellular Zn2+ released from nano ZIF-8 and the receptors involved in the endocytosis may play a role in inducing activation of key osteogenic pathways. Furthermore, through transcriptome sequencing, multiple osteogenic pathways were found to be upregulated, among which nano ZIF-8 primarily phosphorylated ERK, thus activating the canonical mitogen-activated protein kinase pathway and promoting the osteogenesis of rBMSCs. Taken together, this study helps to elucidate the mechanism by which nano ZIF-8 regulates osteogenesis and suggests it to be a potential biomaterial for constructing multifunctional composites in bone tissue engineering.

Accelerated Bone Regeneration by MOF Modified Multifunctional Membranes through Enhancement of Osteogenic and Angiogenic Performance.

Owing to the insufficient guidance of new bone formation in orthopedic and craniomaxillofacial surgery, construction of a guided bone regeneration membrane to support vascularized bone regeneration remains a challenge. Herein, an electrospun asymmetric double-layer polycaprolactone/collagen (PCL/Col) membrane modified by metal-organic framework (MOF) crystals is developed. The optimization of the PCL/Col weight ratio (1:1 and 1:1.5) enables the composite membrane with a balanced tensile strength (only fell by 49.9% in wet conditions) and a controlled degradation rate (completely degraded at 12 weeks). The MOF crystals can provide a pH-responsive release of Zn2+ ions. In vitro experiments indicate that the barrier layer functions to prevent the infiltration of fibrous connective tissue. The MOF crystal layer functions to enhance osteogenesis and angiogenesis in vitro. Using a rat calvarial defect model, the MOF crystals exhibit a sign of osteoinductivity along with blood vessel formation after 8 weeks post-surgery. Strikingly, when assessed in a chick chorioallantoic membrane model, the MOF modified membrane demonstrates a significant angiogenic response, which can be envisaged as its outstanding merits over the commercially Col membrane. Therefore, the MOF crystals represent an exciting biomaterial option, with neovascularization capacity for bone tissue engineering and regenerative medicine.

Zeolitic Imidazolate Framework-8 Encapsulating Risedronate Synergistically Enhances Osteogenic and Antiresorptive Properties for Bone Regeneration.

Bisphosphonates (BPs) are routinely administered for the treatment of turnover bone diseases. To avoid the undesirable adverse effects of long-term usage of bisphosphonates and improve their bioavailability in the bone microenvironment, we initially encapsulated risedronate (RIS) molecules inside nanoscale zeolitic imidazolate framework-8 particles (nZIF-8) by a one-step synthesis method to generate RIS@ZIF-8 nanoparticles. RIS@ZIF-8 nanoparticles displayed high loading encapsulation efficiency (64.21 ± 2.48%), good biocompatibility, controlled drug release capacity, and dual effects for bone regeneration. This work explored the potential of RIS@ZIF-8 nanoparticles, which could not only enhance ATP production, induce extracellular matrix (ECM) mineralization, and upregulate the expression levels of osteogenic genes but also effectively inhibit the formation of multinucleated giant osteocasts and decrease the Rankl/Opg ratio. Overall, RIS@ZIF-8 nanoparticles could be a very promising approach to synergistically enhance osteogenic and antiresorptive properties for bone regeneration, which could be utilized for the local treatment of bone defects.

3D printing of metal-organic framework incorporated porous scaffolds to promote osteogenic differentiation and bone regeneration.

Bone substitute biomaterials, whose compositions and structures both play vital roles in bone defect healing, hold promising prospects in the clinical treatment of bone defects. Three-dimensional (3D) printed porous scaffolds incorporating osteoinductive components are considered as ideal bone grafts, because of the accurate control of structure parameters and the capacity to enhance bone tissue regeneration. Our previous studies demonstrated that nanoscale zeolitic imidazolate framework-8 (nanoZIF-8), a subclass of metal organic frameworks (MOFs), presented minimal cytotoxicity, inhibited bacterial activities, and promoted osteogenesis both in vitro and in vivo. However, the application of nanoZIF-8 in the 3D printed scaffold system remains unknown. In this study, nanoZIF-8 was incorporated into composite scaffolds composed of polycaprolactone (PCL) and dicalcium phosphate dihydrate (DCPD) via extrusion-based 3D printing technology. The results revealed that the composite scaffolds possessed increased mechanical strength and exhibited homogeneous structure with highly interconnected macropores. In vitro studies indicated that scaffolds showed biocompatibility to bone mesenchymal stem cells (BMSCs), significantly up-regulated the expression of osteogenesis-related genes and proteins, and facilitated the extracellular matrix mineralization. In vivo results showed that 3D printed porous scaffolds promoted new bone formation and enhanced micro-architecture at the critical defect sites (Φ10 mm) in rabbits, compared with the blank control group. Moreover, composite scaffolds significantly improved calvarial defect healing in comparison with scaffolds without nanoZIF-8 incorporation. In summary, nanoZIF-8 modified 3D printed porous composite scaffolds demonstrated great potential in the treatment of critical-sized bone defects, proving the effectiveness of MOF incorporation in 3D printed composite scaffolds to promote osteogenesis in the field of bone tissue engineering.

Tazarotene Released from Aligned Electrospun Membrane Facilitates Cutaneous Wound Healing by Promoting Angiogenesis.

Wound treatment is a long-lasting clinical issue. Poor angiogenesis leading to delayed wound closure causes huge challenges for healing. Functional electrospun membranes have been established as an efficient strategy to promote wound recovery by protecting and improving vascular regeneration. Here, we aimed to investigate the effect of tazarotene, an active drug for angiogenesis, loaded in aligned electrospun nanofibrous barrier on a soft tissue wound. This aligned membrane was arranged in a single direction, and tazarotene could be released from its nanofibers sustainably. The in vitro study demonstrated that compared with the random drug-loaded or other control groups, the aligned tazarotene-loaded membranes [poly-caprolactone (PCL)/AT] could stimulate proliferation, migration, angiogenesis, and vascular endothelial growth factor secretion and its gene expression of human umbilical vein endothelial cells. Furthermore, the in vivo model showed that the prepared tazarotene-loaded aligned membrane significantly accelerated the speed of healing, improved the neovascularization and re-epithelialization, and inhibited the inflammatory reaction in the wound area. All these results above indicated that the PCL/AT nanofibrous dressing, which could promote angiogenesis because of both stimulation of structure and chemical signals, is a promising wound-caring material.

Effect of toothpaste containing arginine on dental plaque-A randomized controlled in situ study.

OBJECTIVES: To evaluate the effects of 8% arginine-containing toothpaste on the dental plaque of no caries (NC) and high caries (HC) individuals in situ. METHODS: 6 no caries (DMFT=0) and 6 high caries (DMFT≥6) individuals wearing a self-developed in situ dental plaque acquisition device were involved in a randomized double-blinded crossover study for 6 weeks: including lead-in (1 week), arginine-free (2 weeks), washout (1 week) and arginine-active (2 weeks) stages. The in situ plaque samples were collected at the endpoint of arginine-free and arginine-active stages and subjected to lactic acid production, metabolic activity, live/dead bacteria ratio and total biofilm biomass detections. RESULTS: The arginine-containing dentifrice reduced lactic acid production significantly in both the NC and HC groups, while the inhibitory abilities in the HC group were stronger than that in the NC group. In addition, the arginine-containing dentifrice didn't significantly decrease the metabolic activity, live/dead bacteria ratio and total biofilm biomass in either the NC or the HC group. CONCLUSIONS: Arginine-containing toothpaste can significantly reduce the lactic acid production from the in situ plaques to a low level without changing the metabolic activity, live/dead bacteria ratio and total biofilm biomass through a critical clinical randomized double-blinded crossover study. CLINICAL SIGNIFICANCE: Arginine is a potential ecological prevention and control agent for dental caries. Meanwhile, the in situ model is an easy and pragmatic way to evaluate oral hygiene products (clinical trial registration: ChiCTR-INR-16010226).

A systematic review of the survival and complication rates of inlay-retained fixed dental prostheses.

OBJECTIVES: The aim of this systematic review was to investigate the survival and complication rates of inlay-retainer fixed dental prostheses (IRFDPs). DATA/SOURCES: A systematic search was conducted in the PubMed, EMBASE, and Cochrane Library databases in English and time filters (articles published from 1960) were used. STUDY SELECTION: Randomized controlled trails (RCTs), controlled clinical trials (CCTs) and prospective cohort studies on IRFDPs with a mean follow-up period of at least 2 years were included. Among 501 screened articles, one RCT and ten prospective cohort studies were included in this study. Of the included studies, information on failure and complications was independently extracted by two reviewers in duplicate. The failure and complication rates of IRFDPs were pooled with a random effect model and Poisson regression was applied to further investigate the influence of framework materials. The estimated 3- and 5-year survival rates of IRFDPs were 92.6% (95% CI: 85.8-97.6%) and 87.9% (95% CI: 77.4-96.1%), respectively. Debonding, fracture, dentine hypersensitivity and secondary caries were primary complications. The estimated 5-year rates of debonding, veneer fracture and secondary caries were 5.3%, 15.2% and 2.7%, respectively. Additionally, fiber-reinforced composite IRFDPs exhibited a lower incidence of debonding and caries with a higher rate of veneer fracture compared with metal-based and all-ceramic IRFDPs (p<0.05). CONCLUSIONS: Compared with conventional fixed dental prostheses (FDPs) and implant-supported single crowns (ISCs), IRFDPs exhibited an acceptable 3-year survival rate but higher complication rates of debonding and veneer fracture. CLINICAL SIGNIFICANCE: IRFDPs can be recommended as viable short- or middle-term minimally invasive alternatives to short-span conventional FDPs and ISCs, while the clinical outcome of IRFDPs as long-term definitive restorations still calls for further research. The indications of IRFDPs should be strictly controlled and monitored.

Evaluation of tooth root surface area using a three-dimensional scanning technique and cone beam computed tomographic reconstruction in vitro.

OBJECTIVE: To study the feasibility of measuring root surface area (RSA) by 3D scanning technique and cone beam computed tomography (CBCT) reconstruction in vitro. DESIGN: Twenty extracted teeth (10 single-rooted teeth and 10 multi-rooted teeth) were collected in this study. The RSA of the extracted teeth was measured by the membrane technique, 3D scanning technique, and CBCT reconstruction. A standard part was also designed to check the accuracy of each method. All statistical analyses were performed using the SPSS software. RESULTS: According to the results of one-way ANOVA, there was no significant difference among the values of RSA measured by the three techniques (p>0.05). The results of Wilcoxon matched-pairs signed-rank test further demonstrated that there was no significant difference among the values of RSA in both single- and multi-rooted teeth measured by the three techniques (p>0.05). CONCLUSIONS: The membrane technique, the 3D scanning technique, and CBCT reconstruction are novel reliable techniques for measuring the RSA in both single- and multi-rooted teeth, which will provide wide clinical applications in the future.