3D-Bioprinted Osteoblast-Laden Nanocomposite Hydrogel Constructs with Induced Microenvironments Promote Cell Viability, Differentiation, and Osteogenesis both In Vitro and In Vivo.

Xinyun Zhai,Changshun Ruan,Mingming Wu,Xiaoli Zhao,Yufei Ma,Wenguang Liu,William Weijia Lu,Haobo Pan,Delin Cheng

doi:10.1002/advs.201700550

Abstract

An osteoblast‐laden nanocomposite hydrogel construct, based on polyethylene glycol diacrylate (PEGDA)/laponite XLG nanoclay ([Mg5.34Li0.66Si8O20(OH)4]Na0.66, clay)/hyaluronic acid sodium salt (HA) bio‐inks, is developed by a two‐channel 3D bioprinting method. The novel biodegradable bio‐ink A, comprised of a poly(ethylene glycol) (PEG)–clay nanocomposite crosslinked hydrogel, is used to facilitate 3D‐bioprinting and enables the efficient delivery of oxygen and nutrients to growing cells. HA with encapsulated primary rat osteoblasts (ROBs) is applied as bio‐ink B with a view to improving cell viability, distribution uniformity, and deposition efficiency. The cell‐laden PEG–clay constructs not only encapsulated osteoblasts with more than 95% viability in the short term but also exhibited excellent osteogenic ability in the long term, due to the release of bioactive ions (magnesium ions, Mg2+ and silicon ions, Si4+), which induces the suitable microenvironment to promote the differentiation of the loaded exogenous ROBs, both in vitro and in vivo. This 3D‐bioprinting method holds much promise for bone tissue regeneration in terms of cell engraftment, survival, and ultimately long‐term function.

Highlights

We report on the development of a novel biodegradable bio-ink comprised of polyethylene glycol diacrylate (PEGDA) and laponite XLG nanoclay, which was photocrosslinked to form a stable gel (PEG–Clay) to support the printing process, facilitate optimal cell growth and function through the delivery of nutrients and oxygen, and promote osteogenesis due to the induced microenvironment forming by the released magnesium ions (Mg2+) and silicon ions (Si4+)
We successfully fabricated an osteoblast-laden nanocomposite hydrogel construct via a two-channel 3D-bioprinting method
The other channel guided the accurate delivery of cells into the 3D scaffolds, using rat osteoblasts (ROBs) encapsulated in 20% hyaluronic acid sodium salt (HA) solution

Summary

Introduction

The cell-laden PEG–clay constructs encapsulated osteoblasts with more than 95% viability in the short term and exhibited excellent osteogenic ability in the long term, due to the release of bioactive ions (magnesium ions, Mg2+ and silicon ions, Si4+), which induces the suitable microenvironment to promote the differentiation of the loaded exogenous ROBs, both in vitro and in vivo. This 3D-bioprinting method holds much promise for bone tissue regeneration in terms of cell engraftment, survival, and long-term function.

Results

Discussion

Conclusion