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Bioactive IGF-1 release from collagen-GAG scaffold to enhance cartilage repair in vitro.

Mullen LM, Best SM, Ghose S, Wardale J, Rushton N, Cameron RE - J Mater Sci Mater Med (2015)

Bottom Line: Osteoarthritic (OA) chondrocytes seeded within scaffolds containing adsorbed IGF-1 deposited decorin and type II collagen in a dose dependent manner and the highest type II collagen deposition was achieved via loading the scaffold with 50 μg/ml IGF-1.Cells seeded within the IGF-1 loaded scaffolds also deposited more extracellular matrix than the no growth factor control group thus the IGF-1 released from the scaffold remained bioactive and exerted an anabolic effect on OA chondrocytes.The effectiveness of adsorbing IGF-1 onto the scaffold may be due to protection of the molecule from proteolytic digestion allowing a more sustained release of IGF-1 over time compared to adding multiple doses of exogenous growth factor.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge, CB2 3QZ, UK, mcm.leanne@gmail.com.

ABSTRACT
Tissue engineering is a promising technique for cartilage repair. Toward this goal, a porous collagen-glycosaminoglycan (CG) scaffold was loaded with different concentrations of insulin-like growth factor-1 (IGF-1) and evaluated as a growth factor delivery device. The biological response was assessed by monitoring the amount of type II collagen and proteoglycan synthesised by the chondrocytes seeded within the scaffolds. IGF-1 release was dependent on the IGF-1 loading concentration used to adsorb IGF-1 onto the CG scaffolds and the amount of IGF-1 released into the media was highest at day 4. This initial IGF-1 release could be modelled using linear regression analysis. Osteoarthritic (OA) chondrocytes seeded within scaffolds containing adsorbed IGF-1 deposited decorin and type II collagen in a dose dependent manner and the highest type II collagen deposition was achieved via loading the scaffold with 50 μg/ml IGF-1. Cells seeded within the IGF-1 loaded scaffolds also deposited more extracellular matrix than the no growth factor control group thus the IGF-1 released from the scaffold remained bioactive and exerted an anabolic effect on OA chondrocytes. The effectiveness of adsorbing IGF-1 onto the scaffold may be due to protection of the molecule from proteolytic digestion allowing a more sustained release of IGF-1 over time compared to adding multiple doses of exogenous growth factor. Incorporating IGF-1 into the CG scaffold provided an initial therapeutic burst release of IGF-1 which is beneficial in initiating ECM deposition and repair in this in vitro model and shows potential for developing this delivery device in vivo.

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Type II Collagen Deposition on the Scaffold a Type II collagen Western Blot indicating the type II collagen deposited by OA chondrocytes within the scaffold 1 0 µg/ml IGF-1, 2 25 µg/ml IGF-1, 3 50 µg/ml IGF-1, 4 100 µg/ml IGF-1, 5 Standard (purified human type II collagen). b Quantification of western blot shown in (a) by densitometry. The significant differences (*P < 0.05) between groups. N = 3. The error bars represent the standard error of the mean
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Fig3: Type II Collagen Deposition on the Scaffold a Type II collagen Western Blot indicating the type II collagen deposited by OA chondrocytes within the scaffold 1 0 µg/ml IGF-1, 2 25 µg/ml IGF-1, 3 50 µg/ml IGF-1, 4 100 µg/ml IGF-1, 5 Standard (purified human type II collagen). b Quantification of western blot shown in (a) by densitometry. The significant differences (*P < 0.05) between groups. N = 3. The error bars represent the standard error of the mean

Mentions: Decorin deposition on the Scaffold. a Western blot indicating decorin deposited by OA chondrocytes within the scaffold 1 0 μg/ml IGF-1, 2 25 μg/ml IGF-1, 3 50 μg/ml IGF-1, 4 100 μg/ml IGF-1, 5 Standard (recombinant decorin). b Quantification of western blot shown in Fig. 3a by densitometry. The significant differences (*P < 0.05) between groups. N = 4. The error bars represent the standard error of the mean


Bioactive IGF-1 release from collagen-GAG scaffold to enhance cartilage repair in vitro.

Mullen LM, Best SM, Ghose S, Wardale J, Rushton N, Cameron RE - J Mater Sci Mater Med (2015)

Type II Collagen Deposition on the Scaffold a Type II collagen Western Blot indicating the type II collagen deposited by OA chondrocytes within the scaffold 1 0 µg/ml IGF-1, 2 25 µg/ml IGF-1, 3 50 µg/ml IGF-1, 4 100 µg/ml IGF-1, 5 Standard (purified human type II collagen). b Quantification of western blot shown in (a) by densitometry. The significant differences (*P < 0.05) between groups. N = 3. The error bars represent the standard error of the mean
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4289525&req=5

Fig3: Type II Collagen Deposition on the Scaffold a Type II collagen Western Blot indicating the type II collagen deposited by OA chondrocytes within the scaffold 1 0 µg/ml IGF-1, 2 25 µg/ml IGF-1, 3 50 µg/ml IGF-1, 4 100 µg/ml IGF-1, 5 Standard (purified human type II collagen). b Quantification of western blot shown in (a) by densitometry. The significant differences (*P < 0.05) between groups. N = 3. The error bars represent the standard error of the mean
Mentions: Decorin deposition on the Scaffold. a Western blot indicating decorin deposited by OA chondrocytes within the scaffold 1 0 μg/ml IGF-1, 2 25 μg/ml IGF-1, 3 50 μg/ml IGF-1, 4 100 μg/ml IGF-1, 5 Standard (recombinant decorin). b Quantification of western blot shown in Fig. 3a by densitometry. The significant differences (*P < 0.05) between groups. N = 4. The error bars represent the standard error of the mean

Bottom Line: Osteoarthritic (OA) chondrocytes seeded within scaffolds containing adsorbed IGF-1 deposited decorin and type II collagen in a dose dependent manner and the highest type II collagen deposition was achieved via loading the scaffold with 50 μg/ml IGF-1.Cells seeded within the IGF-1 loaded scaffolds also deposited more extracellular matrix than the no growth factor control group thus the IGF-1 released from the scaffold remained bioactive and exerted an anabolic effect on OA chondrocytes.The effectiveness of adsorbing IGF-1 onto the scaffold may be due to protection of the molecule from proteolytic digestion allowing a more sustained release of IGF-1 over time compared to adding multiple doses of exogenous growth factor.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials Science and Metallurgy, University of Cambridge, Pembroke Street, Cambridge, CB2 3QZ, UK, mcm.leanne@gmail.com.

ABSTRACT
Tissue engineering is a promising technique for cartilage repair. Toward this goal, a porous collagen-glycosaminoglycan (CG) scaffold was loaded with different concentrations of insulin-like growth factor-1 (IGF-1) and evaluated as a growth factor delivery device. The biological response was assessed by monitoring the amount of type II collagen and proteoglycan synthesised by the chondrocytes seeded within the scaffolds. IGF-1 release was dependent on the IGF-1 loading concentration used to adsorb IGF-1 onto the CG scaffolds and the amount of IGF-1 released into the media was highest at day 4. This initial IGF-1 release could be modelled using linear regression analysis. Osteoarthritic (OA) chondrocytes seeded within scaffolds containing adsorbed IGF-1 deposited decorin and type II collagen in a dose dependent manner and the highest type II collagen deposition was achieved via loading the scaffold with 50 μg/ml IGF-1. Cells seeded within the IGF-1 loaded scaffolds also deposited more extracellular matrix than the no growth factor control group thus the IGF-1 released from the scaffold remained bioactive and exerted an anabolic effect on OA chondrocytes. The effectiveness of adsorbing IGF-1 onto the scaffold may be due to protection of the molecule from proteolytic digestion allowing a more sustained release of IGF-1 over time compared to adding multiple doses of exogenous growth factor. Incorporating IGF-1 into the CG scaffold provided an initial therapeutic burst release of IGF-1 which is beneficial in initiating ECM deposition and repair in this in vitro model and shows potential for developing this delivery device in vivo.

Show MeSH
Related in: MedlinePlus