Biocomposite macroporous cryogels as potential carrier scaffolds for bone active agents augmenting bone regeneration
(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.
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- author
- Raina, Deepak Bushan
LU
; Isaksson, Hanna
LU
; Teotia, Arun Kumar ; Lidgren, Lars LU ; Tägil, Magnus LU and Kumar, Ashok LU
- organization
- publishing date
- 2016-08-10
- 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
- pmid:27252151
- 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
- 2025-02-09 21:42:20
@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}}, keywords = {{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}}, doi = {{10.1016/j.jconrel.2016.05.061}}, volume = {{235}}, year = {{2016}}, }