The Cocktail Effect of BMP-2 and TGF-β1 Loaded in Visible Light-Cured Glycol Chitosan Hydrogels for the Enhancement of Bone Formation in a Rat Tibial Defect Model.

Sun-Jung Yoon,Dae Yang,Sang Nam,Youngbum Yoo,So Kim,Sewook Um,Hoon Hyun,Sung Hong,Sung Hong,Heung Chun,Deok-Won Lee

doi:10.3390/md16100351

Abstract

Bone tissue engineering scaffolds offer the merits of minimal invasion as well as localized and controlled biomolecule release to targeted sites. In this study, we prepared injectable hydrogel systems based on visible light-cured glycol chitosan (GC) hydrogels containing bone morphogenetic protein-2 (BMP-2) and/or transforming growth factor-beta1 (TGF-β1) as scaffolds for bone formation in vitro and in vivo. The hydrogels were characterized by storage modulus, scanning electron microscopy (SEM) and swelling ratio analyses. The developed hydrogel systems showed controlled releases of growth factors in a sustained manner for 30 days. In vitro and in vivo studies revealed that growth factor-loaded GC hydrogels have no cytotoxicity against MC3T3-E1 osteoblast cell line, improved mRNA expressions of alkaline phosphatase (ALP), type I collagen (COL 1) and osteocalcin (OCN), and increased bone volume (BV) and bone mineral density (BMD) in tibia defect sites. Moreover, GC hydrogel containing BMP-2 (10 ng) and TGF-β1 (10 ng) (GC/BMP-2/TGF-β1-10 ng) showed greater bone formation abilities than that containing BMP-2 (5 ng) and TGF-β1 (5 ng) (GC/BMP-2/TGF-β1-5 ng) in vitro and in vivo. Consequently, the injectable GC/BMP-2/TGF-β1-10 ng hydrogel may have clinical potential for dental or orthopedic applications.

Highlights

Various forms of biomaterials, such as hydrogels, films, sponges, fiber sheets, etc., have received extensive attention as tissue-engineered scaffolds due to their good biocompatibility and biodegradability as well as their simple processability [1]
The results demonstrated that the storage moduli at 100 rad/s are power- and time-dependent, which had 41.1 Pa, 50.2 Pa and 61.7 Pa in the powers, and 37.9 Pa, 61.7 Pa and 114.2 Pa in the times, respectively
The hydrogel precursor solution irradiated with visible light for 300 s lost its injectable capacity due to increased elasticity; the irradiation conditions of 9 W and 200 s was chosen for the rapid procedure required for the animal test

Summary

Introduction

Various forms of biomaterials, such as hydrogels, films, sponges, fiber sheets, etc., have received extensive attention as tissue-engineered scaffolds due to their good biocompatibility and biodegradability as well as their simple processability [1]. Hydrogels allow for appropriate structures that facilitate the migration, adhesion, proliferation, and differentiation of osteoprogenitor cells into osteoblasts by the efficient delivery of nutrients and growth factors [3,4]. Such hydrogel systems prolong the half-life of growth factors, and maintain its stability and activation when incorporated [5]. Injectable hydrogel is of interest to scientists or clinicians engaged in tissue engineering applications due to their advantages, such as no biological damage of the irradiation, the controlled release of biomolecules by readily modulating cross-linking density, and the water solubility, biocompatibility and biodegradability of GC [6,7]. These remarkable characteristics give them clinical potential as bone tissue engineering scaffolds

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Conclusion