Date of Award

6-11-2024

Document Type

Thesis

School

School of Chemical & Biotechnology

Programme

Ph.D.-Doctoral of Philosophy

First Advisor

Prof.S.Swaminathan

Keywords

Bioprinting, Tissue Engineering, Muscle Regeneration, Volumetric Muscle Loss, Bioinks

Abstract

Myocardial infarction (MI) and volumetric muscle loss (VML) are debilitating conditions that severely affect patient quality of life and challenge healthcare systems, particularly in diagnosis and treatment. Conventional therapies often result in long recovery periods with limited functional restoration. Advances in regenerative medicine, especially extrusion-based 3D bioprinting, offer promising potential to improve the regeneration of complex tissues by precisely depositing cells and biomaterials layer-by-layer to create tailored tissue constructs.

A critical challenge in muscle tissue regeneration is developing protein-polysaccharide bioinks that closely mimic the native muscle tissue microenvironment. In this study, two protein-inpolysaccharide bioinks (alginate-fibrinogen and methylcellulose-gelatin-alginate) were developed to replicate the extracellular matrix of muscle tissues and evaluated for their ability to support muscle cell viability and functionality. Although the alginatefibrinogen bioink maintained cardiomyocyte viability, it failed to restore functionality.

To address the limitations of the Alg/fib bioink, a methylcellulose-gelatin-alginate bioink was developed, offering improved handleability, enhanced cell-cell and cellmaterial interactions, and maintained cardiomyocyte viability. However, it still failed to restore cardiomyocyte functionality. Alternatively, the methylcellulose-gelatinalginate bioink was tested for skeletal muscle regeneration by incorporating muscle cells and evaluating myotube formation and muscle-specific markers in vitro.

In vivo studies in mouse VML models demonstrated that bioprinted muscle tissue constructs (BMTCs) promoted functional recovery, enhancing vascularization and innervation. These results suggested that BMTCs held significant potential for treating VML injuries, with outcomes comparable to autologous minced muscle.

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