The effects of submicron-textured surface topography on antibiotic efficacy against biofilms.

Submicron-textured surfaces have been a promising approach to mitigate biofilm development and control microbial infection. However, the use of the single surface texturing approach is still far from ideal for achieving complete control of microbial infections on implanted biomedical devices. The use of a surface topographic modification that might improve the utility of standard antibiotic therapy could alleviate the complications of biofilms on devices. In this study, we characterized the biofilms of Staphylococcus aureus and Pseudomonas aeruginosa on smooth and submicron-textured polyurethane surfaces after 1, 2, 3, and 7 days, and measured the efficacy of common antibiotics against these biofilms. Results show that the submicron-textured surfaces significantly reduced biofilm formation and growth, and that the efficacy of antibiotics against biofilms grown on textured surfaces was improved compared with smooth surfaces. The antibiotic efficacy appears to be related to the degree of biofilm development. At early time points in biofilm formation, antibiotic treatment reveals reasonably good antibiotic efficacy against biofilms on both smooth and textured surfaces, but as biofilms mature, the efficacy of antibiotics drops dramatically on smooth surfaces, with lesser decreases seen for the textured surfaces. The results demonstrate that surface texturing with submicron patterns is able to improve the use of standard antibiotic therapy to treat device-centered biofilms by slowing the development of the biofilm, thereby offering less resistance to antibiotic delivery to the bacteria within the biofilm community.

In Vitro and In Vivo Assessment of the Infection Resistance and Biocompatibility of Small-Molecule-Modified Polyurethane Biomaterials.

Bacterial intracellular nucleotide second messenger signaling is involved in biofilm formation and regulates biofilm development. Interference with the bacterial nucleotide second messenger signaling provides a novel approach to control biofilm formation and limit microbial infection in medical devices. In this study, we tethered small-molecule derivatives of 4-arylazo-3,5-diamino-1H-pyrazole on polyurethane biomaterial surfaces and measured the biofilm resistance and initial biocompatibility of modified biomaterials in in vitro and in vivo settings. Results showed that small-molecule-modified surfaces significantly reduced the Staphylococcal epidermidis biofilm formation compared to unmodified surfaces and decreased the nucleotide levels of c-di-AMP in biofilm cells, suggesting that the tethered small molecules interfere with intracellular nucleotide signaling and inhibit biofilm formation. The hemocompatibility assay showed that the modified polyurethane films did not induce platelet activation or red blood cell hemolysis but significantly reduced plasma coagulation and platelet adhesion. The cytocompatibility assay with fibroblast cells showed that small-molecule-modified surfaces were noncytotoxic and cells appeared to be proliferating and growing on modified surfaces. In a 7-day subcutaneous infection rat model, the polymer samples were implanted in Wistar rats and inoculated with bacteria or PBS. Results show that modified polyurethane significantly reduced bacteria by ∼2.5 log units over unmodified films, and the modified polymers did not lead to additional irritation/toxicity to the animal tissues. Taken together, the results demonstrated that small molecules tethered on polymer surfaces remain active, and the modified polymers are biocompatible and resistant to microbial infection in vitro and in vivo.

Frequency of cd44 expression in diagnosed cases of oral Epithelial dysplasia and squamous cell carcinoma.

Background: Oral cavity cancer is one of the most widespread head and neck cancers in the world. 90 percent of oral cavity cancers are squamous cell carcinoma (SCC). Oral Potentially Malignant Disorder (OPMD), are well known to develop into squamous cell carcinoma. CD44 is a glycoprotein present on the cell surface and plays a vital role in cancer cell invasion, migration, metastasis of cancers and prognosis. The present study aims to detect the frequency of CD44 immunomarker expression in epithelial dysplasia and squamous cell carcinoma samples and correlates the expression with histologic grades of this lesion. Methods: Cross sectional study at the Department of Pathology, BMSI, JPMC, Karachi between 01-01-2018 to 31-12-2021. 95 patients diagnosed on morphological characterization of the lesion as squamous cell carcinoma/dysplasia were selected by using non-probability purposive sampling technique, among them 41 were diagnosed as epithelial dysplasia and 54 as SCC and were subjected to immunohistochemistry. Results: A total of 95 cases were selected. The mean age was 49.32 years. The majority of cases were seen in 4th and 5th decades. 69 (72.6%) were males and 26 (27.4%) were females with male to female ratio 2.65:1. The closest site was buccal mucosa 75(78.9%). Among 41 cases of dysplasia, 36 showed membranous positivity for CD44 (87.8%), and 45 showed positive membranous CD44 immunoreactivity (83.3%) among 54 cases of squamous cell carcinoma. Conclusion: Increased frequency of CD44 expression was found with increasing grades of dysplasia and squamous cell carcinoma, which may be a possible indicator of malignant transformation and can serve as a prognostic biomarker for oral SCC.