Organ printing: Tissue spheroids as building blocks

Abstract

Organ printing can be defined as layer-by-layer additive robotic biofabrication of three-dimensional functional living macrotissues and organ constructs using tissue spheroids as building blocks. The microtissues and tissue spheroids are living materials with certain measurable, evolving and potentially controllable composition, material and biological properties. Closely placed tissue spheroids undergo tissue fusion — a process that represents a fundamental biological and biophysical principle of developmental biology-inspired directed tissue self-assembly. It is possible to engineer small segments of an intraorgan branched vascular tree by using solid and lumenized vascular tissue spheroids. Organ printing could dramatically enhance and transform the field of tissue engineering by enabling large-scale industrial robotic biofabrication of living human organ constructs with “built-in” perfusable intraorgan branched vascular tree. Thus, organ printing is a new emerging enabling technology paradigm which represents a developmental biology-inspired alternative to classic biodegradable solid scaffold-based approaches in tissue engineering.

Introduction

The ultimate goal of tissue engineering is to design and fabricate natural-like functional human tissues and organs suitable for regeneration, repair and replacement of damaged, injured or lost human organs [1], [2], [3], [4]. The engineered tissues and organs are technically “artificial” or “man-made” based on methods of their generation, but at the same time they are also “natural-like” living tissues and organs. At least theoretically, an ideal tissue engineered human organ must eliminate, dramatically reduce, or more realistically reinvent the problem of biocompatibility [5], which is a critically important issue for any biomaterial-based approach for creating artificial organs, devices or prostheses. Without tissue engineering, living functional human organs can be produced only during natural embryonic development. How close tissue engineers can recapitulate and capture the most essential structure–function features of normal natural human tissues and organs, and how far they must try to imitate developmental histogenesis, morphogenesis and organogenesis, are still open for debate. Because of economic constraints and the intrinsic limitations of producing living tissues and organs, it is reasonable to assume that biofabrication technology will probably not allow one to create a 100% authentic copy of functional living human organs. Rather, engineering of natural-like functional vascularized tissue engineered organ constructs capable of restoring essential function is a more realistic technological goal and represent a great accomplishment if successful. Developmental processes already serve as a positive control or reference point and provide powerful insights into tissue engineering [6], [7]. Furthermore, the integration of developmental biology and tissue engineering, or the so-called biomimetic approach, is not wishful thinking but rather work in progress [8]. It is interesting that one initially suggested term for the tissue engineering field was “chimeric neomorphogenesis” [9]. Thus, it is safe to predict that deep understanding, biomimicking and employing developmental mechanisms of embryonic histogenesis and organogenesis can be very beneficial for tissue engineering. The goal of this paper is to introduce and discuss a novel, rapidly emerging developmental biology-inspired paradigm of solid biodegradable scaffold-free minitissue-based biomimetic approach, or more specifically, organ printing using self-assembled tissue spheroids as a possible alternative to classic solid biodegradable scaffold-based approach in the field of tissue engineering.