Advanced

Biocomposite macroporous cryogels as potential carrier scaffolds for bone active agents augmenting bone regeneration

Raina, Deepak Bushan LU ; Isaksson, Hanna LU ; Teotia, Arun Kumar; Lidgren, Lars LU ; Tägil, Magnus LU and Kumar, Ashok LU (2016) In Journal of Controlled Release 235. p.365-378
Abstract

Osteoinduction can be enhanced by combining scaffolds with bone morphogenic protein-2 (BMP-2). However, BMP's are known to also cause bone resorption. This can be controlled using bisphosphonates like zoledronic acid (ZA). In this study, we produced two different scaffolds containing silk-fibroin, chitosan, agarose and hydroxyapatite (HA) with and without bioactive glass. The aims of the study were to fabricate, physico-chemically characterize and evaluate the carrier properties of the scaffolds for recombinant human BMP-2 (rhBMP-2) and ZA. Scaffolds were characterized using various methods to confirm their composition. During cell-material interactions, both scaffolds exhibited gradual but sustained proliferation of both C2C12 and MSCs... (More)

Osteoinduction can be enhanced by combining scaffolds with bone morphogenic protein-2 (BMP-2). However, BMP's are known to also cause bone resorption. This can be controlled using bisphosphonates like zoledronic acid (ZA). In this study, we produced two different scaffolds containing silk-fibroin, chitosan, agarose and hydroxyapatite (HA) with and without bioactive glass. The aims of the study were to fabricate, physico-chemically characterize and evaluate the carrier properties of the scaffolds for recombinant human BMP-2 (rhBMP-2) and ZA. Scaffolds were characterized using various methods to confirm their composition. During cell-material interactions, both scaffolds exhibited gradual but sustained proliferation of both C2C12 and MSCs for a period of 6 weeks with augmentative effects on their phenotype indicated by elevated levels of alkaline phosphatase (ALP) cuing towards osteogenic differentiation. In-vitro effects of rhBMP-2 and ZA contained within both the scaffolds was assessed on MC3T3 preosteoblast cells and the results show a significant increase in the ALP activity of the cells seeded on scaffolds with rhBMP-2. Further, the scaffold with both HA and bioactive glass was considered for the animal study. In-vitro, this scaffold released nearly 25% rhBMP-2 in 21-days and the addition of ZA did not affect the release. In the animal study, the scaffolds were combined with rhBMP-2 and ZA, rhBMP-2 or implanted alone in an ectopic muscle pouch model. Significantly higher bone formation was observed in the scaffold loaded with both rhBMP-2 and ZA as seen from micro-computed tomography, histomorphometry and energy dispersive X-ray spectroscopy.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biocomposite, Biomaterial, Bone tissue engineering, Cryogel, Zoledronic acid
in
Journal of Controlled Release
volume
235
pages
14 pages
publisher
Elsevier
external identifiers
  • scopus:84975147694
  • wos:000379702700033
ISSN
0168-3659
DOI
10.1016/j.jconrel.2016.05.061
language
English
LU publication?
yes
id
cdf5bf94-51ac-4178-b250-674efd17bf54
date added to LUP
2016-12-06 15:33:55
date last changed
2017-11-19 04:35:39
@article{cdf5bf94-51ac-4178-b250-674efd17bf54,
  abstract     = {<p>Osteoinduction can be enhanced by combining scaffolds with bone morphogenic protein-2 (BMP-2). However, BMP's are known to also cause bone resorption. This can be controlled using bisphosphonates like zoledronic acid (ZA). In this study, we produced two different scaffolds containing silk-fibroin, chitosan, agarose and hydroxyapatite (HA) with and without bioactive glass. The aims of the study were to fabricate, physico-chemically characterize and evaluate the carrier properties of the scaffolds for recombinant human BMP-2 (rhBMP-2) and ZA. Scaffolds were characterized using various methods to confirm their composition. During cell-material interactions, both scaffolds exhibited gradual but sustained proliferation of both C2C12 and MSCs for a period of 6 weeks with augmentative effects on their phenotype indicated by elevated levels of alkaline phosphatase (ALP) cuing towards osteogenic differentiation. In-vitro effects of rhBMP-2 and ZA contained within both the scaffolds was assessed on MC3T3 preosteoblast cells and the results show a significant increase in the ALP activity of the cells seeded on scaffolds with rhBMP-2. Further, the scaffold with both HA and bioactive glass was considered for the animal study. In-vitro, this scaffold released nearly 25% rhBMP-2 in 21-days and the addition of ZA did not affect the release. In the animal study, the scaffolds were combined with rhBMP-2 and ZA, rhBMP-2 or implanted alone in an ectopic muscle pouch model. Significantly higher bone formation was observed in the scaffold loaded with both rhBMP-2 and ZA as seen from micro-computed tomography, histomorphometry and energy dispersive X-ray spectroscopy.</p>},
  author       = {Raina, Deepak Bushan and Isaksson, Hanna and Teotia, Arun Kumar and Lidgren, Lars and Tägil, Magnus and Kumar, Ashok},
  issn         = {0168-3659},
  keyword      = {Biocomposite,Biomaterial,Bone tissue engineering,Cryogel,Zoledronic acid},
  language     = {eng},
  month        = {08},
  pages        = {365--378},
  publisher    = {Elsevier},
  series       = {Journal of Controlled Release},
  title        = {Biocomposite macroporous cryogels as potential carrier scaffolds for bone active agents augmenting bone regeneration},
  url          = {http://dx.doi.org/10.1016/j.jconrel.2016.05.061},
  volume       = {235},
  year         = {2016},
}