Design and Development of Printable and Injectable Bio-Hybrid Inks for Tissue Engineering and Regeneration

Abstract

Regenerative medicine is the branch of medicine that develops methods to regrow, repair or replace damaged or diseased cells, tissues or organs. It includes genic therapy, genomic editing, cell therapy and tissue engineering. Among those, tissue engineering is attracting more and more attentions due to its potential. It applies the principles of life sciences and engineering towards the development of biological substitutes to restore, maintain, or improve tissue and organs functions. It consists in the development of engineered scaffolds, loaded or not with cells and drugs, operating within the organism as closed or open systems. The design of a tissue engineering device requires multiple steps. Applying the principle of biomimicry, meaning look at, learn from and mimic the strategies found in Nature to face and solve some of the outstanding problems humans are dealing with is certainly the first and main to take. Then, it has to be considered the device will have to work within a living organism, consequently it will have to be biocompatible. Towards this purpose, material election, functionalization, biodegradation, crosslinking and process technology have to be thoroughly thought. Within this work we applied the principles of biomimicry to target the regeneration of three different tissues, chondral tissue, bone tissue and neural tissue. Starting by the same natural biopolymer, gelatine, derived by hydrolysis of collagen, the main constituent of the extracellular matrix (ECM) in the human body, we exploited different process technologies, functionalization, and crosslinking techniques to develop devices suitable for the targeted tissues engineering. More specifically, we performed a comparison among two process technology, 3D printing and mould casting, for the realization of three-dimensional scaffolds potentially suitable for chondral regeneration. We developed a nano-hydroxyapatite (nano-HA) functionalized bioink embedding human bone marrow stem cells (hBMSCs) and possible to crosslink with visible (VIS) light employable in bone regeneration and we designed and realized an in-vivo injectable and in-situ crosslinkable conductive ink with potential applicability in neural regeneration. An all-round characterization of the crucial aspects for each device was thoroughly performed, highlighting the main achievements and the aspects possible to be further improved for each of them.