Development of in situ bioprinting: A mini review

Abstract

Bioprinting has rapidly progressed over the past decade. One branch of bioprinting known as in situ bioprinting has benefitted considerably from innovations in biofabrication. Unlike ex situ bioprinting, in situ bioprinting allows for biomaterials to be printed directly into or onto the target tissue/organ, eliminating the need to transfer pre-made three-dimensional constructs. In this mini-review, recent progress on in situ bioprinting, including bioink composition, in situ crosslinking strategies, and bioprinter functionality are examined. Future directions of in situ bioprinting are also discussed including the use of minimally invasive bioprinters to print tissues within the body.

Keywords: bedside mounted bioprinter; bioink; crosslinking; handheld bioprinter; in situ bioprinting; minimally invasive.

FIGURE 1

Examples of current in situ bioprinters with a focus on printers that show potential in minimally invasive repair (A) Traditional in situ bioprinter moving along x-y-z axes while depositing bioink onto chest wound according to a computer-aided design (CAD) model (B) Robotic arm-assisted bioprinter delivering bioink to cartilage injury from an advantageous position due to the high rotational freedom of the robot. (C) Magnetoactive soft nozzle printing a circular pattern onto tissue beneath the skin’s surface through magnetic actuation. (D) Photocrosslinking light-sensitive biopolymers that have been injected into the dermis by intravital 3D (i3D) bioprinting to form a final hydrogel structure. (E) Printing sheets of biomaterials onto dorsal full thickness skin wound by delivering hydrogel precursor solution and crosslinker solution concurrently to wound site using a handheld printer. (F) Delivering photopolymerizable bioink to muscle injury and crosslinking bioink with blue/purple light using a handheld device.

FIGURE 2

Examples of bioinks for in situ bioprinting (A) Fibrin-based bioink with mesenchymal stem cells (MSCs) crosslinked using thrombin to form a hydrogel in a skin wound bed. (B) Fibroblast-laden bioink composed of gelatin methacrylate (GelMA) and polyethylene oxide (PEO) photocrosslinked using UV light to create a porous scaffold. (C) GelMA and alginate bioink containing oxygen-producing microalgae to treat chronic wounds. (D) Growth factor-eluting bioink applied to muscle injury to promote functional muscle recovery. (E) Conductive hydrogel composed of hyaluronic acid and pluronic-F-127 printed onto liver.