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Biomimetic human tissue models and their application in disease pathology studies and therapeutic interventions

Adhikari, Bikram
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Abstract
The field of biomaterials is a multidisciplinary area of science that focuses on the development, design, and application of materials that interact with biological systems. Tissue engineering evolved from the field of biomaterials and refers to the practice of combining cells, scaffolds, and bioactive molecules into a functional tissue. It combines principles from biology, materials science, and engineering to design and produce models capable of replacing, repairing or augmenting malfunctioning human tissues. In general, any material engineered to interact with the body are biomaterials. This thesis focuses on efforts aimed at developing 3D tissue models using biomaterials. These models are capable of mimicking human tissues and directing cellular responses for therapeutic purposes. To study glaucoma, hydrogels and scaffold-based models were engineered to replicate the native trabecular meshwork, a filter like tissue responsible for maintaining eye pressure. Cellular behavior in those models was monitored in response to external stressors, both mechanical and biochemical. Genotypic and phenotypic differences were observed in normal vs glaucoma induced cells. Similarly, drug (short interfering RNA) loaded hydrogels were designed to direct stem cell differentiation behavior. These are applicable in prevention of unwanted bone formation after injuries to the growth plate, a cartilaginous region at the end of long bones. Mapk14 pathway silencing helped in preventing stem cells from expressing genes implicated in bone formation. Further studies with these hydrogels aim at employing novel cell directive motifs capable of circumventing limitations of the siRNA therapy.
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