Gelatin/GelMA Composite Bioink for Improved Biocompatibility and Mechanical Stability of 3D Printed Tissue-like Structures

Tissue engineering is the design and fabrication of artificial tissue constructs for medical treatment or pharmaceutical research and development.1 In tissue engineering, biomaterials are combined with cells, growth factors, biologics, and co-factors to build functional tissues.1 The shortage of donor tissues for transplantation along with a need for a three-dimensionally accurate tissue microenvironment for drug development, has led to the recent use of 3D bioprinting.1 3D bioprinting is an emerging biofabrication technology that has the potential to advance medicine, pharmaceutical research, and drug delivery by rapidly developing complex structures to mimic native tissue.2,3 Models from computerized tomography (CT) or magnetic resonance imaging (MRI) scans can be used as a template for computer-aided models to deliver patient-specific biomaterial treatments.2 Cell-laden biomaterials called bio-inks are deposited layer-by-layer into predetermined structures from stereolithography files produced by computer-aided design (CAD).2,3 This method of biofabrication has the potential to produce complex patient-specific biological structures with even cell distribution, tunable mechanical properties, biocompatible materials, various tissue architectures, and improved vasculature for cell growth and proliferation.1 Gelatin is a thermally responsive natural biopolymer with excellent biocompatibility, rapid biodegradability, non-immunogenicity, and printability.5 It has been used extensively in tissue engineering and is often used to encapsulate growth factors, cells, or other bioactive agents. However, gelatin alone does not have significant mechanical strength and stability to maintain complex 3D structures in physiological conditions.5 To date, finding a printable bio-ink that displays both excellent biocompatibility and mechanical strength remains a challenge. We propose the design of a composite bio-ink with enhanced mechanical strength and biocompatibility by forming an interpenetrating network (IPN) between naturally occurring biopolymers gelatin, GelMA, and alginate