title: Nanostructured gellan and xanthan hydrogel depot integrated within a baghdadite scaffold augments bone regeneration.
abstract: Controlled delivery of biological cues through synthetic scaffolds to enhance the healing capacity of bone defects is yet to be realized clinically. The purpose of this study was development of a bioactive tissue-engineered scaffold providing the sustained delivery of an osteoinductive drug, dexamethasone disodium phosphate (DXP), encapsulated within chitosan nanoparticles (CN). Porous baghdadite (BD; Ca3ZrSi2O9) scaffolds, a zirconia-modified calcium silicate ceramic, was coated with DXP-encapsulated CN nanoparticles (DXP-CN) using nanostructured gellan and xanthan hydrogel (GX). Crosslinker and GX polymer concentrations were optimized to achieve a homogeneous distribution of hydrogel coating within BD scaffolds. Dynamic laser scattering indicated an average size of 521 ± 21 nm for the DXP-CN nanoparticles. In vitro drug-release studies demonstrated that the developed DXP-CN-GX hydrogel-coated BD scaffolds (DXP-CN-GX-BD) resulted in a sustained delivery of DXP over the 5 days (78 ± 6% of drug release) compared with burst release over 1 h, seen from free DXP loaded in uncoated BD scaffolds (92 ± 8% release in 1 h). To estimate the influence of controlled delivery of DXP from the developed scaffolds, the effect on MG 63 cells was evaluated using various bone differentiation assays. Cell culture within DXP-CN-GX-BD scaffolds demonstrated a significant increase in the expression of early and late osteogenic markers of alkaline phosphatase activity, collagen type 1 and osteocalcin, compared to the uncoated BD scaffold. The results suggest that the DXP-releasing nanostructured hydrogel integrated within the BD scaffold caused sustained release of DXP, improving the potential for osteogenic differentiation. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
authors.forename: Rekha R
authors.initials: RR
authors.lastname: Sehgal
authors.affiliation: Biomaterials and Tissue Engineering Research Unit, School of Aerospace Mechanical and Mechatronic Engineering, University of Sydney, Australia.
authors.forename: S I
authors.initials: SI
authors.lastname: Roohani-Esfahani
authors.affiliation: Biomaterials and Tissue Engineering Research Unit, School of Aerospace Mechanical and Mechatronic Engineering, University of Sydney, Australia.
authors.forename: Hala
authors.initials: H
authors.lastname: Zreiqat
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, India.
authors.forename: Rinti
authors.initials: R
authors.lastname: Banerjee
mesh_terms: D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002516:Ceramics / Q000494:pharmacology*; D048271:Chitosan / Q000737:chemistry; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D019245:Compressive Strength; D065546:Drug Liberation; D055119:Elastic Modulus; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D007700:Kinetics; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D011135:Polysaccharides, Bacterial / Q000737:chemistry / Q000494:pharmacology*; D016062:Porosity; D012212:Rheology; D017640:Silicates / Q000494:pharmacology*; D013997:Time Factors; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: C000592768:Ca(3)ZrSi(2)O(9); D020099:Coated Materials, Biocompatible; D011135:Polysaccharides, Bacterial; D017640:Silicates; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C048288:gellan gum; D048271:Chitosan; C002563:xanthan gum
keywords: baghdadite; bone tissue engineering; chitosan nanoparticle; controlled drug delivery; dexamethasone; gellan; hydrogel; xanthan