Injectable cell‐free template for bone‐tissue formation

Abstract

Here we present a novel injectable hydrogel which forms a template for de novo formation of bone tissue. Hydrogel formation takes place in situ in less than 1 min by the cross-linking of multifunctional hyaluronic acid and polyvinyl alcohol derivatives. Endogenous cells are recruited in vivo by incorporating bone morphogenetic protein-2 (BMP-2), a powerful promoter for osteogenic differentiation. The hydrogel was evaluated in vitro by performing a cell viability test and a release study and in vivo by a rat ectopic model. Examination by X-ray, microcomputed tomography, and histology revealed a significant bone formation at the target site for gels containing BMP-2, and a complete degradation was observed for gels without BMP-2 four weeks after injection. There were no signs of inflammation or foreign body response in either group and we believe that this system has the potential as an off-the-shelf injectable to be used where bone tissue is needed.

Evaluation of Alginate and Hyaluronic Acid for Their Use in Bone Tissue Engineering

“…Previous studies have demonstrated that modified alginate and hyaluronic acid hydrogels induce bone formation in vitro [8,14,15,17,26,36,37] and in vivo [15,17,19,27]. Here, we demonstrate that unmodified hydrogels also support osteoblast differentiation, though alginate hydrogels induced a higher degree of differentiation than the high molecular weight hyaluronic acid hydrogels used in the present study.…”

“…Moreover, when containing bFGF, HA hydrogels enhance calcium deposition, osteopontin and BSP expression and decrease alkaline phosphatase in rat bone marrow stromal cells [26]. In vivo, HA hydrogels containing BMP-2 showed increased bone formation [19,27].…”

“…HA is a natural linear polysaccharide consisting of repeating D-glucuronic acid-b-1,3-N-acetyl-D-glucosamine-b-1,4 units [13,19]. HA is one of the main components of the extracellular matrix present in all connective tissues [20] and involved in a variety of biological functions [5,21], including direct receptor-mediated effects on cell adhesion, growth and migration [22], as well as acting as a signaling molecule in cell mortality [23], inflammation [24] or wound healing [25].…”

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“…Hydrogels, such as fibrin, hyaluronic acid and Pluronic F127, have shown promising result for effective growth factor delivery 56 . As reported by Dhillon et al, 57 blending PLGA with a plasticizer, such as polyethylene glycol (PEG), allows the production of temperature-sensitive material with a reduced Tg of 37 °C.…”

Hyaluronic Acid Bioconjugates for the Delivery of Bioactive Molecules

“…Furthermore, it has been shown that the opening of sugar rings by periodate oxidation results in a HA derivative that lacks its cellular recognition properties [80]. Varghese et al proposed a simple and versatile synthetic strategy to graft aldehyde moieties on HA without compromising the structural integrity of the polymer [81].…”