Author ORCID Identifier

0000-0002-7295-540X

Date of Award

17-8-2025

Document Type

Thesis

School

School of Chemical & Biotechnology

Programme

Ph.D.-Doctoral of Philosophy

First Advisor

Prof.S.Swaminathan

Keywords

Bioprinting, Cardiac Tissue Engineering, Nanofiber, Health Care, Medical Innovation

Abstract

Tissue-engineered three-dimensional (3D) myocardial patches offer superior and innovative treatment strategy for myocardial infarction (MI). Among the various scaffold fabrication techniques, electrospinning and 3D bioprinting have received great attention due to their ability to recreate native cardiac tissue mimetic characteristics. Despite several advantages, electrospun nanofibers have limitations in cell delivery due to random cell seeding, while bioprinting faces challenges in creating hydrogel constructs with ideal mechanical properties capable of supporting cardiac contraction/relaxation cycle. Hence in this work, hybrid myocardial patches were developed by converging electrospinning and bioprinting techniques.

Electrospinning of PLCL:PEOz (B73, 7:3 blend of poly-L-lactide-co-ε-caprolactone (PLCL) and polyethyl oxazoline (PEOz)) produced a hydrophilic, axially aligned and cardiac mimetic ECM having heterogeneous fiber distribution. In vitro evaluation using primary neonatal rat ventricular cardiomyocytes (NRVCMs) showed enhanced viability, contractility, and maturity indicating the compatibility of B73 nanofiber for cardiac tissue engineering applications.

Further, two different bioprinting strategies such as laser-assisted bioprinting (LAB) and extrusion bioprinting were explored by developing specific bioinks for the fabrication of cardiac patch using B73 as support matrix. LAB confirmed high-resolution printing using sodium alginate /gelatin bioink, however it was found not suitable to create 3D hydrogel constructs with high cell density. Hence, extrusion bioprinting was preferred to fabricate a hybrid cardiac patch. Two different thermoresponsive bioink compositions such as carboxymethyl cellulose/agarose/gelatin (CAG) and sodium alginate/gelatin/PEOz (AGP) were prepared and found to have excellent printability. However, CAG bioink failed to achieve high-resolution strand deposition.

Hence, AGP bioink along with dual crosslinking (100 mM CaCl2 and 2.5% (w/v)) TG (microbial transglutaminase) was optimized for hybrid cardiac patch fabrication. Bioprinted AGP cardiac constructs had improved NRVCMs viability, orientation, contractility and maturity. Hybrid cardiac patch (AGP-B73) was found to have a significant improvement in mechanical properties, along with improved shape fidelity and handleability compared to AGP constructs. The results confirm the potential of AGP-B73 cardiac patch to maintain NRVCMs viability and functional maturation. This study serves as a proof of concept in demonstrating the successful development of AGP-B73 cardiac patch for targeting MI and other drug testing studies in the future.

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