In Situ 3D Printing: Opportunities with Silk Inks

Abstract

In situ 3D printing is an emerging technique designed for patient-specific needs and performed directly in the patient's tissues in the operating room. While this technology has progressed rapidly, several improvements are needed to push it forward for widespread utility, including ink formulations and optimization for in situ context. Silk fibroin inks emerge as a viable option due to the diverse range of formulations, aqueous processability, robust and tunable mechanical properties, and self-assembly via biophysical adsorption to avoid exogenous chemical or photochemical sensitizer additives, among other features. In this review, we focus on this new frontier of 3D in situ printing for tissue regeneration, where silk is proposed as candidate biomaterial ink due to the unique and useful properties of this protein polymer.

Keywords: in situ 3D printing; ink; silk.

Figure 1, Key Figure.. In situ 3D printing with silk.

Silk fibroin extracted from Bombyx mori exhibits several advantages for in situ 3D applications including many modes of gelation to fabricate inks. In a surgical setting, based on patient-specific data, the ink is directly printed in vivo to reproduce 3D reconstructions of the defect site and to monitor the printing process, remotely controlled by the surgeon.

Figure 2. General requirements for inks for 3D printing.

Ink formulations require suitable rheological (shear-thinning, storage modulus, viscosity) and mechanical properties. In addition, biodegradability, biocompatibility, and permeability to oxygen and nutrients and for in situ 3D printing, in situ rapid gelation and shape integrity after printing are requirements.

Figure 3.. Silk fibroin composition and sol gel-transition.

Silk fibroin is composed of heavy and light chains, covalently bound by a disulfide bond. The heavy chain is composed of hexapeptide repeated sequence made of GAGAGX where X can be valine, serine, or glycine, interspersed into amorphic spacers (3a). During the sol-gel transition phase, from a random coil conformation, silk fibroin structure folds into β-sheets antiparallel domains, through hydrogen bond formation both inter- and intra-chain, forming insoluble structures, thermodynamically stable (3b).