Wiesemcdaniel7841

Acute toxicity studies of the cationic polymer showed no toxicity at a dose equivalent to 10 mg/kg based on the hematological, biochemical, and histopathological examination.Delayed wound healing in heavily irradiated areas is a serious clinical complication that makes widespread therapeutic use of radiation difficult. Efficient treatment strategies are urgently required for addressing radiation-induced wound failure. Herein, we applied liquid-type nonthermal atmospheric plasma (LTP) to a silk-fibrin (SF) composite gel to investigate whether controlled release of LTP from SF hydrogel not only induced favorable cellular events in an irradiated wound bed but also modulated the SF hydrogel microstructure itself, eventually facilitating the development of a regenerative microenvironment. Scanning electron microscopy and Fourier-transform infrared spectroscopy revealed that LTP modulated the microstructures and chemical bindings of the SF gel. Improved cell viability, morphology, and extracellular matrix depositions by the LTP-treated SF hydrogel were identified with wound-healing assays and immunofluorescence staining. An irradiated random-pattern skin-flap animal model was established in six-week-old C57/BL6 mice. Full-thickness skin was flapped from the dorsum and SF hydrogel was placed underneath the raised skin flap. Postoperative histological analysis of the irradiated random-pattern skin-flap mice model suggested that LTP-treated SF hydrogel much improved wound regeneration and the inflammatory response compared to the SF hydrogel- and sham-treated groups. These results support that LTP-treated SF hydrogel significantly enhanced irradiated wound healing. Liproxstatin-1 clinical trial Cellular and tissue reactions to released LTP from the SF hydrogel were favorable for the regenerative process of the wound; furthermore, mechanochemical properties of the SF gel were improved by LTP.Macrophages, the primary effector cells in the immune response, respond rapidly to the physical or chemical properties of biomaterial implants. Balanced macrophage polarization, phagocytosis, and migration would be beneficial for implant success and tissue regeneration. Here, we investigated macrophage phenotypic changes, phagocytosis, and migration in response to RGD functionalized surfaces and changes in stiffness of gellan gum hydrogels. We also inhibited the RhoA pathway. The compressive moduli ranged from ~5 to 30 kPa. Cell population and cell spreading area of classically activated macrophages (M(LPS)) and alternatively activated macrophages (M(IL-4)) are promoted on RGD modified hydrogel. ROCK inhibitor induced the opposite effect on the cell spreading of both M(LPS) and M(IL-4) macrophages on RGD modified hydrogels. Macrophage polarization was found to be stiffness-driven and regulated by the RGD motif and blocked by the RhoA pathway. RGD functionalized hydrogel shifted M(IL-4) cells toward a more pro-inflammatory phenotype, while ROCK inhibition shifted M(LPS) cells to a more anti-inflammatory phenotype. Both M(LPS) and M(IL-4) cells on untreated hydrogels shifted to a more pro-inflammatory phenotype in the presence of aminated-PS particles. The RGD motif had a significant impact on cellular uptake, whereas cellular uptake was stiffness driven on untreated hydrogels. Cell migration of M(LPS) and M(IL-4) cells had ROCK-dependent migration. The stiffness of gellan gum hydrogels had no influence on macrophage migration rate. Collectively, our results showed that gellan gum hydrogels can be used to direct immune response, macrophage infiltration, and phagocytosis.Localized delivery of chemotherapeutic agents allows extended drug exposure at the target site, thereby reducing systemic toxicity. We report the development of functionalized polymeric patch with unidirectional drug release to treat gastric cancer. The oxaliplatin-loaded patch was prepared by incorporating sodium carboxymethyl cellulose, hydroxypropyl cellulose and polyvinylpyrrolidone. The patch was functionalized by coating with transferrin-poly(lactic-co-glycolic acid) conjugate on one side of the patch for cancer targeting. The other side of the patch was coated with ethylcellulose (EC) to restrict the release of oxaliplatin. The physical and mechanical properties of oxaliplatin-loaded patches were characterized. Mucoadhesion studies using excised rat stomach tissue have shown that the functionalized side of the patch has significantly (p less then 0.05) greater mucoadhesion strength compared with EC coated side of the patch. The in vitro and ex vivo (stomach sac and open-membrane model) studies revealed greater permeation of oxaliplatin across the stomach tissue when adhered to the functionalized and non-functionalized side of the patch compared with EC coated side. It was found that the growth inhibition with oxaliplatin solution was not significantly greater compared with corresponding concentrations of oxaliplatin-loaded patch in AGS and Caco-2 cell models. The in vivo studies were performed in mice, where indocyanine green-loaded patch encapsulated in a gelatin capsule was orally administered. link2 The near-infrared (NIR) optical imaging revealed adherence of the patch on the mucosal side of the stomach tissue for up to 6 h. In conclusion, the functionalized polymeric patch loaded with oxaliplatin can be a potential localized delivery system to target gastric cancer.Intimal hyperplasia, thrombosis formation, and delayed endothelium regeneration are the main causes that restrict the clinical applications of PTFE small-diameter vascular grafts (inner diameter less then 6 mm). An ideal strategy to solve such problems is to facilitate in situ endothelialization. Since the natural vascular endothelium adheres onto the basement membrane, which is a specialized form of extracellular matrix (ECM) secreted by endothelial cells (ECs) and smooth muscle cells (SMCs), functionalizing PTFE with an ECM coating was proposed. However, besides ECs, the ECM-modified PTFE improved SMC growth as well, thereby increasing the risk of intimal hyperplasia. In the present study, heparin was immobilized on the ECM coating at different densities (4.89 ± 1.02 μg/cm2, 7.24 ± 1.56 μg/cm2, 15.63 ± 2.45 μg/cm2, and 26.59 ± 3.48 μg/cm2), aiming to develop a bio-favorable environment that possessed excellent hemocompatibility and selectively inhibited SMC growth while promoting endothelialization. The results indicated that a low heparin density (4.89 ± 1.02 μg/cm2) was not enough to restrict platelet adhesion, whereas a high heparin density (26.59 ± 3.48 μg/cm2) resulted in decreased EC growth and enhanced SMC proliferation. Therefore, a heparin density at 7.24 ± 1.56 μg/cm2 was the optimal level in terms of antithrombogenicity, endothelialization, and SMC inhibition. Collectively, this study proposed a heparin-immobilized ECM coating to modify PTFE, offering a promising means to functionalize biomaterials for developing small-diameter vascular grafts.The present experimental study aims to extend know-how on resorbable polycaprolactone/hydroxyapatite (PCL/HA, 70/30 wt%) scaffolds, produced by Laser Powder Bed Fusion (LPBF) technology, to geometrically complex lattice structures and micro porous struts. Using optimized LPBF printing parameters, micro- and macro-porous scaffolds for bone tissue regeneration were produced by regularly repeating in space Diamond (DO) and Rhombic Dodecahedron (RD) elementary unit cells. After production, scaffolds were submitted to structural, mechanical, and biological characterization. The interaction of scaffolds with human Mesenchymal Stem Cells (hMSCs) allowed studying the degradative processes of the PCL matrix. Biomechanical performances and biodegradation of scaffolds were compared to literature results and bone tissue data. Mechanical compression test, biological viability up to 4 days of incubation and degradation rate evidenced strong dependence of scaffold behavior on unit cell geometry as well as on global geometrical features.A novel airflow shearing method was introduced to prepare microspheres efficiently with precisely control of microsphere size and homogeneity. The effects of technical parameters in the formation of the microspheres, such as solution concentration, nozzle size and airflow strength, were investigated. By optimizing the technical parameters (8% PLGA concentration, 27-32 G nozzle size, 6-8 l/min airflow strength), nano-hydroxyapatite and poly(lactide-co-glycolide) nanocomposite (nHA/PLGA) microspheres with a diameter around 250 μm and up to 40 wt% nHA content was prepared successfully. Especially, the microspheres possessed revealed great homogeneity and unique "acorn" appearance with two sides A hard smooth side as well as a crumpled rough side, generated in the preparation process. Furthermore, the nHA/PLGA microspheres' potential application in bone tissue engineering was studied. In vitro, enhanced proliferation and osteogenic differentiation of the MC3T3-E1 cells was observed on as-prepared nHA/PLGA microspheres with high nHA content. In vivo, the BV/TV value of the microspheres with 20 wt% nHA was up to 75% and similar to the clinical products' performance. link3 Moreover, beside high nHA content, the rough porous surface leads to bone ingrowth, which plays an important role in accelerating bone repair. Therefore, airflow shearing method could be an effective approach to fabricate biocompatible microsphere, and the as-prepared microspheres showed unique surface state and bone repair ability and making them as potential candidates for bone tissue engineering and bone implantation clinical applications.Guided Bone Regeneration (GBR) is a widely used process for the treatment of periodontal defects to prevent the formation of surrounding soft tissue at the periodontal defect and to provide hard tissue regeneration. Recently GBR designs have focused on the development of resorbable natural polymer-based barrier membranes due to their biodegradability and excellent biocompatibility. The aim of this study is to fabricate a novel bilayer nanocomposite membrane with microporous sublayer composed of chitosan and Si doped nanohydroxyapatite particles (Si-nHap) and chitosan/PEO nanofiber upper layer. Bilayer membrane was designed to prevent epithelial and fibroblastic cell migration and growth impeding bone formation with its upper layer and to support osteogenic cell bioactivity at the defect site with its sublayer. Microporous and nanofiber layers were fabricated by using freeze-drying and electrospinning techniques respectively. The effect of Si-nHap content on the morphological, mechanical and physical properties of the composites were investigated using SEM, AFM, micro-Ct, compression test, water uptake capacity and enzymatic degradation study. Antimicrobial properties of nanocomposite membranes were investigated with tube dilution and disk diffusion methods. In vitro cytotoxicity of bilayer membranes was evaluated. Saos-2 and NIH/3T3 proliferation studies were carried out on each layer. In vitro bioactivity of Saos-2 and NIH/3T3 cells were evaluated with ALP activity and hydroxyproline content respectively. Results showed that Si-nHap incorporation enhanced the mechanical and physical properties as well as controlling biodegradability of the polymer matrix. Besides, Si-nHap loading induced the bioactivity of Saos-2 cells by enhancing cell attachment, spreading and biomineralization on the material surface. Thus, results supported that designed bilayer nanocomposite membranes can be used as a potential biomaterial for guided bone regeneration in periodontal applications.