Hybrid microscaffold-based 3D bioprinting of multi-cellular constructs with high compressive strength: A new biofabrication strategy.

Yu Jun Tan,Shu Beng Tor,Wai Yee Yeong,Xipeng Tan

doi:10.1038/srep39140

Abstract

A hybrid 3D bioprinting approach using porous microscaffolds and extrusion-based printing method is presented. Bioink constitutes of cell-laden poly(D,L-lactic-co-glycolic acid) (PLGA) porous microspheres with thin encapsulation of agarose-collagen composite hydrogel (AC hydrogel). Highly porous microspheres enable cells to adhere and proliferate before printing. Meanwhile, AC hydrogel allows a smooth delivery of cell-laden microspheres (CLMs), with immediate gelation of construct upon printing on cold build platform. Collagen fibrils were formed in the AC hydrogel during culture at body temperature, improving the cell affinity and spreading compared to pure agarose hydrogel. Cells were proven to proliferate in the bioink and the bioprinted construct. High cell viability up to 14 days was observed. The compressive strength of the bioink is more than 100 times superior to those of pure AC hydrogel. A potential alternative in tissue engineering of tissue replacements and biological models is made possible by combining the advantages of the conventional solid scaffolds with the new 3D bioprinting technology.

Highlights

It was thought that the solid scaffold-based TE methods and the solid scaffold-free bioprinting approaches cannot be integrated[5,16]
Examples of bioprinting approaches utilizing solid scaffolds as support would take reference from recent studies presented by Kang et al.[17] and Jung et al.18. 3D printing of solid polycaprolactone (PCL) scaffolds was accomplished simultaneously with the cell-laden hydrogels
The cells seeded on the microspheres will be expanded in stirred or perfused culture, and form cell-laden microspheres (CLMs) without further passaging

Summary

Introduction

It was thought that the solid scaffold-based TE methods and the solid scaffold-free bioprinting approaches cannot be integrated[5,16]. A very high initial cell number is needed for the fabrication of scaffold-free tissue spheroids/strands in the large tissues’ bioprinting. Considering what is feasible for 3D bioprinting nowadays, in this work, we are presenting a micropipette extrusion-based bioprinting method using cell-laden microscaffold-based bioinks. Polymer microcarriers such as microspheres are commonly utilized as injectable biomaterials for clinically relevant applications[22,23]. The highly porous microscaffolds provide high specific surface areas so that they allow the anchorage-dependent cells to attach, infiltrate and grow before extrusion-based printing By exploiting this property, the cells seeded on the microspheres will be expanded in stirred or perfused culture, and form cell-laden microspheres (CLMs) without further passaging. Micropipette[26] was used in the printing in order to achieve tightly packed constructs

Methods

Results

Discussion

Conclusion