Effect of osteoconductive hyaluronate hydrogels on calvarial bone regeneration.

Junseok Yeom,Byung Woo Hwang,Hong-In Shin,Sei Kwang Hahn,Dong Jun Yang

doi:10.1186/2055-7124-18-8

Junseok Yeom, Byung Woo Hwang + Show 3 more

Open Access

https://doi.org/10.1186/2055-7124-18-8

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Abstract

BackgroundWithout exploitation of possibly immunogenic and carcinogenic bone morphogenetic protein, we developed simple but clinically feasible artificial bone graft using osteoconductive hyaluronate (HA) hydrogels and bioactive MegaGen synthetic bone (MGSB).MethodsHA hydrogels were synthesized by the crosslinking reaction between carboxyl groups of HA and amine groups of gelatin (GEL). Then, artificial bone grafts were prepared by mixing MGSB with HA-GEL hydrogels. The bone regeneration by the MGSB/HA-GEL hydrogel complex was assessed in the skull of New Zealand white male rabbits in 4 and 8 weeks.ResultsHA hydrogels were synthesized by the crosslinking reaction between carboxyl groups of HA and amine groups of gelatin (GEL). Then, artificial bone grafts were prepared by mixing MGSB with HA-GEL hydrogels. In vitro proliferation of preosteogenic cells was enhanced with increasing molecular weight of HA. In addition, histological analysis of dissected tissues with hematoxylin and eosin staining confirmed the effective in vivo bone regeneration by the MGSB/HA-GEL hydrogel complex. The MGSB/HA-GEL hydrogels were well resorbed and partially substituted to the lamellar bone after implantation for 8 weeks.ConclusionsThe novel artificial bone graft of MGSB/HA-GEL hydrogel complex for effective bone regeneration might be clinically feasible for further development.

Highlights

Without exploitation of possibly immunogenic and carcinogenic bone morphogenetic protein, we developed simple but clinically feasible artificial bone graft using osteoconductive hyaluronate (HA) hydrogels and bioactive MegaGen synthetic bone (MGSB)
Two types of HA hydrogels were prepared by the crosslinking with divinyl sulfone (DVS) and GEL for comparison
HA-GEL hydrogels were synthesized by simple Ethyl-3-[3-(dimethylamino) propyl] carbodiimide (EDC) chemistry between carboxyl groups of HA and amine groups of GEL (Figure 1C)

Summary

Introduction

Without exploitation of possibly immunogenic and carcinogenic bone morphogenetic protein, we developed simple but clinically feasible artificial bone graft using osteoconductive hyaluronate (HA) hydrogels and bioactive MegaGen synthetic bone (MGSB). Ceramic based bone grafts have been regarded as one of the most successfully commercialized and widely prevalent biomaterials including Bio-Oss® made On account of these clinical issues, there have been plenty of attempts to utilize growth factors like recombinant human bone morphogenetic protein (rhBMP), or mesenchymal stem cells (MSC) with bone grafts [10,11]. These methods are complicated, possibly causing safety issues of immune reaction, and expensive for further clinical applications. Small fragments of HA with several repeating units can promote angiogenesis significantly [15,16], which is necessary for replacing the fragile woven bone to the sustainable lamellar bone [4]

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