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012, p = 0.012, respectively). In conclusion, progressive extramitral valve cardiac involvement (group 3 and group 4) was independently associated with all-cause mortality in patients with significant SMR.Obesity increases the risk of developing type 2 diabetes, hypertension, and hyperlipidemia. We sought to determine the impact of obesity maintenance, weight regain, weight loss maintenance, and magnitudes of weight loss on future risk and time to developing these cardiometabolic conditions. This was a retrospective cohort study of adults receiving primary care at Geisinger Health System between 2001 and 2017. Using electronic health records, patients with ≥3-weight measurements over a 2-year index period were identified and categorized. Obesity maintainers (OM) had obesity (body mass index ≥30 kg/m²) and maintained their weight within ±3% from baseline (reference group). Both weight loss rebounders (WLR) and weight loss maintainers (WLM) had obesity at baseline and lost >5% body weight in year 1; WLR regained ≥20% of weight loss by end of year 2 and WLM maintained ≥80% of weight loss. Incident type 2 diabetes, hypertension, and hyperlipidemia, and time-to-outcome were determined for each study group and by weight loss category for WLM. Of the 63,567 patients included, 67% were OM, 19% were WLR, and 14% were WLM. The mean duration of follow-up was 6.6 years (SD, 3.9). Time until the development of electronic health record-documented type 2 diabetes, hypertension, and hyperlipidemia was longest for WLM and shortest for OM (log-rank test p 15%) had a longer time to develop any of the outcomes compared with those with the least amount of weight loss ( less then 7%) (p less then 0.0001). In an integrated delivery network population, sustained weight loss was associated with a delayed onset of cardiometabolic diseases, particularly with a greater magnitude of weight loss.In this paper, a novel backstepping control law is investigated, which guarantees appointed-time convergence for a two-link manipulator. In contrast to other fixed-time controllers or predefined-time controllers, the practical convergence time can be precisely obtained instead of being estimated. By utilizing a novel appointed-time prescribed performance function, the trajectory tracking error of the manipulator can be previously constrained. Furthermore, the external disturbances have been suppressed by introducing a disturbance observer with the convergence time as a prior control parameter and a switching sliding mode control law. find more The stability of the controller is analyzed by the Lyapunov method. Various numerical simulation results are carried out to demonstrate the efficacy of the proposed control scheme.The current gold standard for auricular reconstruction after microtia or ear trauma is the autologous cartilage graft with an autologous skin flap overlay. Harvesting autologous cartilage requires an additional surgery that may result in donor area complications. In addition, autologous cartilage is limited and the auricular reconstruction requires complex sculpting, which requires excellent clinical skill and is very time consuming. This work explores the use of 3D printing technology to fabricate bioactive artificial auricular cartilage using chondrocyte-laden gelatin methacrylate (GelMA) and polylactic acid (PLA) for auricle reconstruction. In this study, chondrocytes were loaded within GelMA hydrogel and combined with the 3D-printed PLA scaffolds to biomimetic the biological mechanical properties and personalized shape. The printing accuracy personalized scaffolds, biomechanics and chondrocyte viability and biofunction of artificial auricle have been studied. It was found that chondrocytes were fixed in the PLA auricle scaffolds via GelMA hydrogels and exhibited good proliferative properties and cellular activity. In addition, new chondrocytes and chondrogenic matrix, as well as type II collagen were observed after 8 weeks of implantation. At the same time, the transplanted auricle complex kept full and delicate auricle shape. This study demonstrates the potential of using 3D printing technology to construct in vitro living auricle tissue. It shows a great prospect in the clinical application of auricle regeneration.Hydrogen sulfide (H2S) has been as an essential gasotransmitter and a potential therapeutic approach for several biomedical treatments such as cardiovascular disorders, hypertension, and other diseases. The endogenous and exogenous H2S also plays a crucial role in the bone anabolic process and a protective mechanism in cell signalling. In this study, we have utilized two types of polymers, polycaprolactone (PCL) and gelatin (Gel), for the fabrication of JK-2 (H2S donor) loaded nanofibrous scaffold via electrospinning process for bone healing and bone tissue engineering. Comparing the PCL/Gel and PCL/Gel-JK-2 scaffolds, the latter demonstrated enhanced cell adhesion and proliferation capabilities. Furthermore, both experimental scaffolds have been subjected to an in vivo experiment for 4 and 8 weeks in a bone-defect model of a rabbit to determine their biological responses under physiological conditions. There was an obvious increase in bone regeneration in the PCL/Gel-JK-2 group compared to the control and PCL/Gel groups. These results indicate the use of PCL/Gel scaffolds loaded with JK-2 should be considered for possible bone regeneration.Tissue-engineered skin equivalent (TESE) is an optimized alternative for the treatment of skin defects. Designing and fabricating biomaterials with desired properties to load cells is critical for the approach. In this study, we aim to develop a novel TESE with recombinant human collagen (rHC) hydrogel and fibroblasts to improve full-thickness skin defect repair. First, the bioactive effect of rHC on fibroblast proliferation, migration and phenotype was assayed. The results showed that rHC had good biocompatibility and could stimulate fibroblasts migration and secrete various growth factors. Then, rHC was cross-linked with transglutaminase (TG) to prepare rHC hydrogel. Rheometer tests indicated that 10% rHC/TG hydrogel could reach a oscillate stress of 251 Pa and remained stable. Fibroblasts were seeded into rHC/TG hydrogel to prepare TESE. Confocal microscope and scanning electronic microscope observation showed that seeded fibroblasts survived well in the hydrogel. Finally, the therapeutic effect of the newly prepared TESE was tested in a mouse full-thickness skin defect model. The results demonstrated that TESE could significantly improve skin defect repair in vivo. Conclusively, TESE prepared from rHC and fibroblasts in this study exhibits great potential for clinical application in the future.The high near infrared (NIR) absorption displayed by reduced graphene oxide (rGO) nanostructures renders them a great potential for application in cancer photothermal therapy. However, the production of this material often relies on the use of hydrazine as a reductant, leading to poor biocompatibility and environmental-related issues. In addition, to improve rGO colloidal stability, this material has been functionalized with poly(ethylene glycol). However, recent studies have reported the immunogenicity of poly(ethylene glycol)-based coatings. In this work, the production of rGO, by using dopamine as the reducing agent, was optimized considering the size distribution and NIR absorption of the attained materials. The obtained results unveiled that the rGO produced by using a 15 graphene oxidedopamine weight ratio and a reaction time of 4 h (termed as DOPA-rGO) displayed the highest NIR absorption while retaining its nanometric size distribution. Subsequently, the DOPA-rGO was functionalized with thiol-terminated poly(2-ethyl-2-oxazoline) (P-DOPA-rGO), revealing suitable physicochemical features, colloidal stability and cytocompatibility. When irradiated with NIR light, the P-DOPA-rGO could produce a temperature increase (ΔT) of 36 °C (75 μg/mL; 808 nm, 1.7 W/cm2, 5 min). The photothermal therapy mediated by P-DOPA-rGO was capable of ablating breast cancer cells monolayers (viability less then 3%) and could reduce heterotypic breast cancer spheroids' viability to just 30%. Overall, P-DOPA-rGO holds a great potential for application in breast cancer photothermal therapy.Titanium-based implants are the leading material for orthopaedic surgery, due to their strength, versatility, fabrication via additive manufacturing and invoked biological response. However, the interface between the implant and the host tissue requires improvement to better integrate the implant material and mitigate foreign body response. The interface can be manipulated by changing the surface energy, chemistry, and topography of the Titanium-based implant. Recently, polycrystalline diamond (PCD) has emerged as an exciting coating material for 3D printed titanium scaffolds showing enhanced mammalian cell functions while inhibiting bacterial attachment in vitro. In this study, we performed in-depth characterisation of PCD coatings investigating the surface topography, thickness, surface energy, and compared its foreign body response in vivo with uncoated titanium scaffold. Coating PCD onto titanium scaffolds resulted in a similar microscale surface roughness (RMS(PCD-coated) = 24 μm; RMS(SLM-Ti) = 28 μm), increased nanoscale roughness (RMS(PCD-coated) = 35 nm; RMS(SLM-Ti) = 66 nm) and a considerable decrease in surface free energy (E(PCD-coated) = 4 mN m-1; E(SLM-Ti) = 16 mN m-1). These surface property changes were supported by X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy as corresponding to observed surface chemistry changes induced by the coating. The underlying mechanism of how the diamond coatings chemical and physical properties changes the wettability of implants was examined. In vivo, the coated scaffolds induced similar level of fibrous encapsulation with uncoated scaffolds. This study thus provides further insight into the physicochemical characteristics of PCD coatings, adding evidence to the promising potential of PCD-coatings of medical implants.To induce bone regeneration there is a complex cascade of growth factors. Growth factors such as recombinant BMP-2, BMP-7, and PDGF are FDA-approved therapies in bone regeneration. Although, BMP shows promising results as being an alternative to autograft, it also has its own downfalls. BMP-2 has many adverse effects such as inflammatory complications such as massive soft-tissue swelling that can compromise a patient's airway, ectopic bone formation, and tumor formation. BMP-2 may also be advantageous for patients not willing to give up smoking as it shows bone regeneration success with smokers. BMP-7 is no longer an option for bone regeneration as it has withdrawn off the market. PDGF-BB grafts in studies have shown PDGF had similar fusion rates to autologous grafts and fewer adverse effects. There is also an FDA-approved bioactive molecule for bone regeneration, a peptide P-15. P-15 was found to be effective, safe, and have similar outcomes to autograft at 2 years post-op for cervical radiculopathy due to cervical degenerative disc disease. Growth factors and bioactive molecules show some promising results in bone regeneration, although more research is needed to avoid their adverse effects and learn about the long-term effects of these therapies. There is a need of a bone regeneration method of similar quality of an autograft that is osteoconductive, osteoinductive, and osteogenic. This review covers all FDA-approved bone regeneration therapies such as the "gold standard" autografts, allografts, synthetic bone grafts, and the newer growth factors/bioactive molecules. It also covers international bone grafts not yet approved in the United States and upcoming technologies in bone grafts.