Microporous methacrylated glycol chitosan-montmorillonite nanocomposite hydrogel for bone tissue engineering

TLDR

Injectable hydrogels can fill irregular defects and promote in situ tissue regrowth, yet directing stem cell differentiation in 3D microenvironments for bone regeneration remains challenging. The study nanoengineers a microporous, photocrosslinkable chitosan hydrogel by incorporating intercalated nanoclay particles to create an interconnected network. The authors fabricated the hydrogel via photocrosslinking of chitosan with intercalated nanoclay and evaluated its in vivo performance in a critical‑size mouse calvarial defect model. The reinforced hydrogels exhibit higher stiffness, slower degradation, support MSC proliferation, attachment, differentiation, and in vivo recruit native cells to heal critical‑size calvarial defects without added therapeutics.

Abstract

Injectable hydrogels can fill irregular defects and promote in situ tissue regrowth and regeneration. The ability of directing stem cell differentiation in a three-dimensional microenvironment for bone regeneration remains a challenge. In this study, we successfully nanoengineer an interconnected microporous networked photocrosslinkable chitosan in situ-forming hydrogel by introducing two-dimensional nanoclay particles with intercalation chemistry. The presence of the nanosilicates increases the Young's modulus and stalls the degradation rate of the resulting hydrogels. We demonstrate that the reinforced hydrogels promote the proliferation as well as the attachment and induced the differentiation of encapsulated mesenchymal stem cells in vitro. Furthermore, we explore the effects of nanoengineered hydrogels in vivo with the critical-sized mouse calvarial defect model. Our results confirm that chitosan-montmorillonite hydrogels are able to recruit native cells and promote calvarial healing without delivery of additional therapeutic agents or stem cells, indicating their tissue engineering potential.