Department of Biomedical Engineering

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Computer–Aided Approaches To Discovery Of Novel Drugs Against The Human Hookworm Necator Americanus (Nematoda: Ancylostomatidae)
(University of Ghana, 2017-07) Agyapong, O.
There is a crucial need to develop novel anthelminthic drugs due to the mounting disease burden and increasing evidence of hookworm resistance to drugs such as albendazole and mebendazole, which for decades have been used to treat the infection. Consequently, it is exigent to develop alternative drugs with improved therapeutic efficacy. Natural products due to their unique active ingredients have been shown to possess exceptional structures with chemical diversity that is unmatched by any synthetic libraries. It is imperative to leverage natural products to augment hookworm drug discovery. Therefore, this study aimed to: (i) identify potential novel anthelminthic lead compounds by screening African natural product-derived ligands against beta tubulin of Necator americanus, a known hookworm receptor and (ii) develop support vector machine-based proteochemometric modelling (PCM) for bioactivity profiling of beta tubulins receptors. The 3D structure of the beta tubulin of hookworm with UniProt entry W2T758, was generated using homology modelling. The model was subjected to molecular dynamics simulations and active site interactions prediction. The first set of ligand libraries comprising 885 natural product compounds obtained from African medicinal plants database (AfroDb) combined with Dichapetalin A, were screened against the receptor. ZINC14760755 and ZINC28462577 compounds were found to be potential leads due to promising binding affinity, active site interactions and pharmacokinetic profiles. Additionally, a second set comprising 2297 compounds derived from Northern African Natural Product Database (NANPDB) were virtually screened. The compound S,5Z,8Z,11Z,13E,17Z-15-hydroxy-1-(2,4,6-trihydroxyphenyl)-15-methylicosa-5,8,11,13,17-pentaen-1-one exhibited plausible binding affinity, toxicity and pharmacokinetic profile. The aforementioned natural compounds are potential leads which can be experimentally characterised for possible pre-clinical trials. Support vector machine based proteochemometric modelling was also developed to predict the bioactivity relations between beta tubulin variants and small compounds using an interaction dataset retrieved from BindingDB. The model achieved reasonably good performance with a ROC-AUC of 87%, an MCC of 0.75 and a classification error of approximately 4%, although it was trained on a small dataset. The model allows the prediction of the likelihood of interactions between query datasets comprising ligands in SMILES format and protein sequences of beta tubulin targets. In future, larger bioactive datasets of beta tubulins originating from high throughput experiments can be utilised to possibly enhance the performance of the hookworm PCM model.
Investigating the Influence of Temperature on Kaolinite- Base Synthesis of Zeolite and Urease Immobilization For Potential Fabrication of Electrochemical Urea Biosensor
(University of Ghana, 2018-05) Anderson, D.E.
Temperature-dependent zeolite synthesis revealed unique surface morphology, surface area and pore size that influence morphology of zeolite synthesised from kaolin in the immobilization of urease on gold electrode support for biosensor fabrication. XRD characterization identified Zeolite X (Na) at all crystallization temperatures tested. However, Nitrogen adsorption and desorption results showed pore size and pore volume of Zeolite X (Na) 60 °C, Zeolite X (Na) 70 °C and Zeolite X (Na) 90 °C range from 1.92 nm – 2.45 nm and 0.012 cm3/g – 0.061 cm3/g respectively, with no significant differences. The specific surface area of Zeolite X (Na) at 60, 70 and 90 °C was 64 m2/g, 67 m2/g, and 113 m2/g respectively. The pore size, specific surface area and pore volumes of Zeolite X (Na) 80 °C and Zeolite X (Na) 100 °C were dramatically increased to 4.21 nm, 295 m2/g, 0.762 cm3/g and 4.92 nm, 389 m2/g, 0.837 cm3/g in that order. The analytical performance of the embedded urease in Zeolite X (Na) was also investigated using cyclic voltammetry measurements and the results showed distinct cathodic and anodic peaks by Zeolite X (Na) 80 °C and Zeolite X (Na) 100 °C. The molar conductance of the modified zeolite biosensors was measured as a function of urea concentration and gave an average exponential decay regression fit of 0.98. The findings in this study suggest crystallization temperature is a critical parameter for electrochemical analysis of zeolites synthesized from natural sources for various biomedical applications.
Investigation of In Vitro Loading and Release Kinetics of Hydroxyapatite/Cellulose Biocomposites
(University of Ghana, 2021) Gane, B.M.
Cellulose nanocrystal (CNC) and hydroxyapatite (HAP) offer numerous advantages in drug delivery. A significant challenge encountered is the occurrence of burst release when these materials are used as drug carriers. This renders drugs ineffective when used at sites that require a sustained release. In this work, CNC and HAP composites were synthesized and used as drug carriers to investigate the release behavior of a model drug (curcumin). Two synthesis techniques were used where one material serves as the base material and the other as a modifier in varying concentrations. The formulated composites were characterized by Fourier-transform infrared spectroscopy (FTIR) and X-Ray powder Diffraction (XRD). The drug was loaded onto the composites for 22 hours. Composites with HAP as base material demonstrated successful loading of curcumin whereas composites with CNC as base material did not exhibit drug uptake. There were no significant differences (p > 0.05) in terms of drug uptake between the formulated composites and the control (HAP). The release properties of the composites were evaluated in vitro for 6 hours at acidic (pH ≈ 6.2) and basic (pH ≈ 7.4) conditions. The percentage drug release in acidic medium was found to be higher than basic medium. One-way ANOVA revealed that there was no difference in the means of the release data between the composites and the control group at acidic pH (p > 0.05). However, at basic condition, the release data of the composites and the control group showed significant differences (p < 0.05). Significant differences (p < 0.01) were observed for all composites across groups, indicating that changes in pH had a significant effect on the drug release. All composites and control at both pH (6.2 and 7.4) were best described by the Korsmeyer-Peppas model. Cell viability studies showed that modified composites inhibited cell growth at all time points during the drug release as compared to HAP only. This shows that the combination of HAP and CNC serves as a better drug delivery system than HAP only.
Investigation Of The Cytotoxicity Of Cassava Microfiber-Gelatin Composite Scaffold
(University of Ghana, 2022-06) Plange, P.N.A
Cellulose fiber-reinforced composite scaffolds have recently become an interesting target for Biomedical Engineers and Biomaterials Researchers for Tissue Engineering (TE) applications. This has led to the exploration of cellulose from diverse sources such as tunicates, bacteria and especially from plants. Cassava bagasse, which is a fibrous solid residue obtained after the extraction of cassava and soluble sugars, has recently been explored as a potential source of cellulose, and has been successfully used to enhance the mechanical properties of gelatin scaffold for TE purposes. However, there is lack of knowledge on the biocompatibility of this fabricated scaffold, limiting its potential to be considered at the research level as a biomaterial for TE purposes. This study provided knowledge on the cytotoxicity of the scaffold by using HEK 293 and MDA MB 231 cell lines. The tests performed were according to ISO standards for checking in vitro cytotoxicity of medical devices- extraction and direct contact tests. Scaffold prepared with gelatin only, and cells cultured on well plates with no scaffold were used as the controls. Extracts obtained from the samples were exposed to the cells and analyzed after 24 h and 48 h of incubation, using optical and fluorescence microscopy. Additionally, cells were seeded directly on the samples and analyzed after day 1, 3 and 5 using tetrazolium-based colorimetric assay. Results obtained for HEK 293 cells demonstrated enhanced cell viability and little/no changes in cell morphology. However, there was a decline in cell viability and changes in cell morphology for MDA MB 231 cells. These results suggest that the presence of the fiber in gelatin is not cytotoxic to HEK 293 cells and can be considered for TE purposes when using normal cells. On the contrary, the presence of the fiber in gelatin is cytotoxic to MDA MB 231 cells and may not be considered for TE purposes such as 3D tumor cell studies that require the growth of cancer cells. However, further studies are required to explore the use of the cassava bagasse for its anti-cancer cell properties as demonstrated in this study.
Isolation And Characterization Of Cassava Fibre For Tissue Engineering Scaffold Application
(University of Ghana, 2017-07) Diabor, E.
Cassava bagasse and its extracted cellulose fibres have seen frequent application mostly in the packaging industry as reinforcement material in plastic composites development. However, the material properties such as the mechanical properties of the single elementary cassava cellulose fibres have not been examined and reviewed literature does not show its potential use in the development of tissue engineering scaffolds for cell culture. The study, therefore, characterized the mechanical properties, physicochemical, morphological and microstructural characteristics and thermal degradation profiles of single elementary cellulose fibre as well as the central vascular fibre (“thick-core fibre) isolated from three genotypes of cassava (tagged in this study as ID4, ID6 and AF). Additionally, the study examined the effect of incorporating cassava cellulose microfibres as reinforcement on the mechanical properties and microstructure characteristics of three-dimensional gelatin scaffolds. Non-treated isolated cassava fibres were tested according to ASTM C1557. Three-dimensional cassava microfibre/gelatin scaffolds with different fibre weight fractions were fabricated using phase separation and freeze-drying methods. Tensile test results showed that there was no significant difference (p > 0.05) in mechanical properties recorded between the single elementary fibre and vascular fibre (thick-core) for the three cassava genotypes. Different genotypes of cassava fibre showed significant differences (p < 0.05) in tensile strength and Young’s modulus, with ID4 fibre recording the highest average tensile strength of 7.567 ± 3.844 MPa and highest elastic modulus of 336.485 ±130.803 MPa. XRD analysis showed similar diffraction pattern with minimal variation in signal intensities for both single and thick-core fibres for all cassava genotypes suggesting nonsignificant differences in crystalline structure between them. TGA analysis showed that cassava fibre is thermally stable between the temperatures of 100 °C – 200 °C. The cassava cellulose microfibre/gelatin scaffolds fabricated showed rough surfaces compared to pure gelatin scaffolds and were highly porous with surface porosity ranging between 84 and 90%, and had interconnected pores of average size 36 ±12 μm. Gelatin scaffolds containing up to 7% cassava cellulose microfibre load recorded a maximum compressive strength of 0.29±0.02 MPa, about eight (8) times higher than that for the pure gelatin scaffolds and average Young’s modulus of 1.31 ±0.03 MPa, about four times higher than pure gelatin scaffolds. Preliminary theoretical modelling using Halpin-Tsai model could accurately explain the variabilities in the compression modulus of the gelatin composite scaffolds. In all, the results showed that cassava fibre has considerable mechanical strength and stiffness and can be used as reinforcement filler to improve the mechanical integrity of tissue engineering polymer scaffolds. The cassava fibre/gelatin scaffolds showed surface architecture that could improve cell–matrix adhesion and efficient cell seeding and diffusion of nutrients during cell culture.
The Effect of High-Flux Dialyzer Size And Dialysate Flow Rate on Hemodialysis Adequacy in Accra, Ghana
(University of Ghana, 2021) Aboagye, A.
Hemodialysis is associated with high morbidity and mortality due to inefficiency of dialysis. Dialysis adequacy is based on numerous factors, such as dialysate flow rate and dialyzer size. These parameters are normally adjusted per the patient's clinical needs in countries such as the United Kingdom and the United States of America. In the Ghanaian context, dialysate flow rate adjustment, dialyzer (filter) size selection, and the use of KT/V estimated by the dialysis machine (HD-KT/V), which are used to determine dialysis adequacy are not used in our hospitals. This study was therefore designed to assess the effect of High-flux Dialyzer size and Dialysate flow rate on Dialysis Adequacy in hemodialysis patients in Accra, Ghana. Twenty-five patients were considered for a Cross-Over Clinical Trial. The experiment was divided into four stages which comprised the pairing of dialysate flow rate (500 and 800 ml/min) and High-Flux dialyzer size (1.8 and 2.1 m2 ). Urea Reduction Ratio (URR) and KT/Vurea were calculated from the experimental data and HD-KT/V was recorded from the dialysis machine after the dialysis treatment. Paired sample t-test was used to assess the effect of each of the dialyzer sizes and dialysate flow rate on dialysis adequacy and a repeated ANOVA was used to assess the relationship between the experimental results and KT/V estimated from the dialysis machine. The effect of dialysate flow rate on dialysis adequacy was analysed and found out that 800 ml/min gave a better dialysis adequacy than 500 ml/min when both 1.8 m2 and 2.1 m2 were used. It was observed that for dialyzer with 2.1 m2 , KT/Vurea did not record dialysis inadequacy but observed a 38% increase from moderate adequacy to total dialysis adequacy; for URR, total dialysis adequacy was increased by 38.4%, and all the 53.8% who had dialysis inadequacy when dialyzed with 500 ml/min either achieved moderate or adequate dialysis. The effect of dialyzer size on dialysis adequacy was also analysed and the results indicates that 2.1 m2 gave a better dialysis adequacy than 1.8 m2 when a dialysate flow rate of 800 ml/min was used, however, 500 ml/min yielded no difference in the means. It was observed that for dialysate flow of 800 ml/min; none of the participants got dialysis inadequacy (KT/Vurea) and dialysis inadequacy for URR was reduced by 15.3%; total dialysis adequacy was therefore increased in both cases (URR, 30.7%; KT/Vurea, 23%). It was finally determined that HD-KT/V cannot be used to predict KT/Vurea values for 500 ml/min when 1.8 m2 and 2.1 m2 were used, but can be used to predict KT/Vurea values for 800 ml/min when both 1.8 and 2.1 m2 were used. The out-come and findings if adequately implemented in our hospitals may improve dialysis adequacy; thereby reducing mortality and morbidity in hemodialysis patients