Ladefogedfarrell9743

We found that application of ultrasound in combination with a subtherapeutic dosage of PLPs resulted in increased clot density and stiffness, improved fibroblast migration in vitro and increased epidermal thickness and angiogenesis in vivo, indicating that this combination therapy has potential to facilitate multiphase pro-healing outcomes. Additionally, while these particular studies focus on the role of ultrasound in enhancing specific interactions between fibrin-binding synthetic PLPs embedded within fibrin networks, these studies have wide applicability in understanding the role of ultrasound stimulation in enhancing multi-scale colloidal interactions within fibrillar matrices.Biodegradable cardiac patch is desirable to possess mechanical properties mimicking native myocardium for heart infarction treatment. We fabricated a series of anisotropic and biodegradable polyurethane porous scaffolds via thermally induced phase separation (TIPS) and tailored their mechanical properties by using various polyurethanes with different soft segments and varying polymer concentrations. The uniaxial mechanical properties, suture retention strength, ball-burst strength, and biaxial mechanical properties of the anisotropic porous scaffolds were optimized to mechanically match native myocardium. The optimal anisotropic scaffold had a ball burst strength (20.7 ± 1.5 N) comparable to that of native porcine myocardium (20.4 ± 6.0 N) and showed anisotropic behavior close to biaxial stretching behavior of the native porcine myocardium. Furthermore, the optimized porous scaffold was combined with a porcine myocardium-derived hydrogel to form a biohybrid scaffold. The biohybrid scaffold showed morphologies similar to the decellularized porcine myocardial matrix. This combination did not affect the mechanical properties of the synthetic scaffold alone. After in vivo rat subcutaneous implantation, the biohybrid scaffolds showed minimal immune response and exhibited higher cell penetration than the polyurethane scaffold alone. This biohybrid scaffold with biomimetic mechanics and good tissue compatibility would have great potential to be applied as a biodegradable acellular cardiac patch for myocardial infarction treatment.Mammalian teeth primarily consist of two distinct calcified tissues, enamel and dentin, that are intricately integrated by a complex and critical structure, the dentin-enamel junction (DEJ). see more Loss of enamel exposes the underlying dentin, increasing the risk of several irreversible dental diseases. This paper highlights the significance of utilizing the functional domains of a major enamel matrix protein, amelogenin, intrinsic to tooth enamel and the DEJ interface, to rationally design smaller bioinspired peptides for regeneration of tooth microstructures. Using this strategy, we designed a synthetic peptide, P26, that demonstrates a remarkable dual mineralization potential to restore incipient enamel decay and mineralization defects localized in peripheral dentin below the DEJ. As a proof of principle, we demonstrate that interaction between P26 and collagen prompts peptide self-assembly, followed by mineralization of collagen fibrils in vitro. P26-mediated nucleation of hydroxyapatite (HAP) crystals on demineralized dentin in situ significantly facilitates the recovery of mineral density and effectively restores the biomechanical properties of dentin to near-native levels, suggesting that P26-based therapy has promising applications for treating diverse mineralized tissue defects in the tooth.Enhancing materials with the qualities of living systems, including sensing, computation, and adaptation, is an important challenge in designing next-generation technologies. Living materials address this challenge by incorporating live cells as actuating components that control material function. For abiotic materials, this requires new methods that couple genetic and metabolic processes to material properties. Toward this goal, we demonstrate that extracellular electron transfer (EET) from Shewanella oneidensis can be leveraged to control radical cross-linking of a methacrylate-functionalized hyaluronic acid hydrogel. Cross-linking rates and hydrogel mechanics, specifically storage modulus, were dependent on various chemical and biological factors, including S. oneidensis genotype. Bacteria remained viable and metabolically active in the networks for a least 1 week, while cell tracking revealed that EET genes also encode control over hydrogel microstructure. Moreover, construction of an inducible gene circuit allowed transcriptional control of storage modulus and cross-linking rate via the tailored expression of a key electron transfer protein, MtrC. Finally, we quantitatively modeled hydrogel stiffness as a function of steady-state mtrC expression and generalized this result by demonstrating the strong relationship between relative gene expression and material properties. This general mechanism for radical cross-linking provides a foundation for programming the form and function of synthetic materials through genetic control over extracellular electron transfer.Despite the success of vaccines in preventing many infectious diseases, effective vaccines against pathogens with ongoing challenges - such as HIV, malaria, and tuberculosis - remain unavailable. The emergence of new pathogen variants, the continued prevalence of existing pathogens, and the resurgence of yet other infectious agents motivate the need for new, interdisciplinary approaches to direct immune responses. Many current and candidate vaccines, for example, are poorly immunogenic, provide only transient protection, or create risks of regaining pathogenicity in certain immune-compromised conditions. Recent advances in biomaterials research are creating new potential to overcome these challenges through improved formulation, delivery, and control of immune signaling. At the same time, many of these materials systems - such as polymers, lipids, and self-assembly technologies - may achieve this goal while maintaining favorable safety profiles. This review highlights ways in which biomaterials can advance existing vaccines to safer, more efficacious technologies, and support new vaccines for pathogens that do not yet have vaccines. Biomaterials that have not yet been applied to vaccines for infectious disease are also discussed, and their potential in this area is highlighted.Hydrogel systems are an appealing class of therapeutic delivery vehicles, though it can be challenging to design hydrogels that maintain desired spatiotemporal presentation of therapeutic cargo. In this work, we propose a different approach in which computational tools are developed that creates a theoretical representation of the hydrogel polymer network to design hydrogels with predefined mesh properties critical for controlling therapeutic delivery. We postulated and confirmed that the computational model could incorporate properties of alginate polymers, including polymer content, monomer composition and polymer chain radius, to accurately predict cross-link density and mesh size for a wide range of alginate hydrogels. Additionally, the simulations provided a robust strategy to determine the mesh size distribution and identified properties to control the mesh size of alginate hydrogels. Furthermore, the model was validated for additional hydrogel systems and provided a high degree of correlation (R2 > 0.95) to the mesh sizes determined for both fibrin and polyethylene glycol (PEG) hydrogels. Finally, a full factorial and Box-Behnken design of experiments (DOE) approach utilized in combination with the computational model predicted that the mesh size of hydrogels could be varied from approximately 5 nm to 5 μm through controlling properties of the polymer network. Overall, this computational model of the hydrogel polymer network provides a rapid and accessible strategy to predict hydrogel mesh properties and ultimately design hydrogel systems with desired mesh properties for potential therapeutic applications.Hydrogels have recently been attractive in various drug delivery and tissue engineering applications because of their structural similarities to the natural extracellular matrix. Despite enormous advances in the application of hydrogels, poor mechanical properties and lack of control for the release of drugs and biomolecules act as major barriers for widespread clinical applications. To overcome these challenges, we developed both physically and covalently conjugated nanocage-laden hydrogels between the surface of the nanocage and a gelatin methacryloyl (GelMA) hydrogel matrix. Ferritin and its empty-core equivalent apoferritin were used as nanocages that could be easily incorporated into a GelMA hydrogel via physical bonding. To fabricate covalently conjugated nanocage-laden GelMA hydrogels, ferritin and apoferritin were chemically modified to present the methacryloyl groups, ferritin methacryloyl (FerMA) and apoferritin methacryloyl (ApoMA), respectively. The covalently conjugated FerMA- and ApoMA-GelMA hydrogels offered a better ability to tune mechanical properties compared with those prepared by direct dispersion of ferritin and apoferritin into GelMA hydrogels with physical bonding, without affecting their porosity or cell growth. Furthermore, the ability of the nanocage to release small chemical compounds was confirmed by performing a cumulative release test on fluorescein isothiocyanate (FITC) encapsulated apoferritin and ApoMA incorporated GelMA hydrogels by pH stimulus. Thus, the nanocage incorporated hydrogels have emerged as excellent materials for drug delivery and tissue engineering applications.National data indicate that 50% of assistant professors leave a School of Medicine (SOM) within eight years of hire. At-risk for attrition in some studies are women, racial/ethnic underrepresented minorities (URM), and clinical faculty. Retention of faculty is not adequately studied in the Southwestern US, where at-risk faculty constitute the majority group. The study hypothesized that at-risk faculty have lower retention rates than those not at-risk. Identification of factors predicting retention of at-risk faculty may help institutions devise novel and targeted retention strategies. Prospective time to event analyses studied assistant professors hired at the University of New Mexico's (UNM) SOM from 2008-2019. Eight factors, measured at the time of hire, included rank, race/ethnicity, gender, MD degree, academic track, department type, salary, and fiscal year of hire. Univariate analyses included graphical analysis of Kaplan-Meier analysis and Cox proportional hazard ratios with years to departure measuringus the existing diversity and faculty development programs at UNM SOM.In this study, we examined the clinical significance and molecular mechanisms of a long non-coding RNA (lncRNA), double homeobox A pseudogene 8 (DUXAP8) in hepatocellular carcinoma (HCC). DUXAP8 expression was compared using quantitative real-time PCR in HCC versus adjacent tissues and in HCC cell lines versus normal hepatic epithelial cells. The correlations between DUXAP8 level and clinicopathological features were analyzed. Assays including MTT, colony-forming analysis, Transwell assay, western blot, xenograft formation, experimental metastasis, luciferase assay, RNA pull-down, and RNA immunoprecipitation were used to examine DUXAP8-induced malignant phenotypes, its regulation on forkhead box protein M1 (FOXM1), and the importance of FOXM1 in mediating DUXAP8 phenotypes. Our results showed that DUXAP8 was significantly upregulated in HCC tissues or cell lines associated with tumors of advanced grades, tumors that were positive for lymph node metastasis, and patients with poor overall survival. DUAXP8 was essential in maintaining multiple malignant phenotypes (including resistance to olaparib) both in vitro and in vivo.