Positive impact of IGF-1-coupled nanoparticles on the differentiation potential of human chondrocytes cultured on collagen scaffolds

Abstract

Purpose In the present study, silica nanoparticles (sNP) coupled with insulin-like growth factor 1 (IGF-1) were loaded on a collagen-based scaffold intended for cartilage repair, and the influence on the viability, proliferation, and differentiation potential of human primary articular chondrocytes was examined. Methods Human chondrocytes were isolated from the hyaline cartilage of patients (n=4, female, mean age: 73±5.1 years) undergoing primary total knee joint replacement. Cells were dedifferentiated and then cultivated on a bioresorbable collagen matrix supplemented with fluorescent sNP coupled with IGF-1 (sNP–IGF-1). After 3, 7, and 14 days of cultivation, cell viability and integrity into the collagen scaffold as well as metabolic cell activity and synthesis rate of matrix proteins (collagen type I and II) were analyzed. Results The number of vital cells increased over 14 days of cultivation, and the cells were able to infiltrate the collagen matrix (up to 120 μm by day 7). Chondrocytes cultured on the collagen scaffold supplemented with sNP–IGF-1 showed an increase in metabolic activity (5.98-fold), and reduced collagen type I (1.58-fold), but significantly increased collagen type II expression levels (1.53-fold; P =0.02) after 7 days of cultivation compared to 3 days. In contrast, chondrocytes grown in a monolayer on plastic supplemented with sNP-IGF-1 had significantly lower metabolic activity (1.32-fold; P =0.007), a consistent amount of collagen type I, and significantly reduced collagen type II protein expression (1.86-fold; P =0.001) after 7 days compared to 3 days. Conclusion Collagen-based scaffolds enriched with growth factors, such as IGF-1 coupled to nanoparticles, represent an improved therapeutic intervention for the targeted and controlled treatment of articular cartilage lesions.

MicroRNA-125b-1-3p mediates intervertebral disc degeneration in rats by targeting teashirt zinc finger homeobox 3

“…In addition, certain cytokines promote the proliferation and inhibit the degeneration of NP cells, including insulin-like growth factor and thymosin β-4 (35)(36)(37).…”

Chondrogenic Differentiation of Human Chondrocytes and Stem Cells in Different Cell Culture Systems Using IGF-1-Coupled Particles

“…Cells were cultured in three-dimensional cell culture systems in terms of spheroid pellet culture. Additionally, BMMSCs were cultured onto a collagen-based scaffold, as has been done with human primary chondrocytes in our previous study [21]. The growth factor was added either in the form of soluble IGF-1 or IGF-1-coupled particles.…”

“…The detailed procedure was previously described [21]. In brief, the silica particles were prepared by a modified Stöber process including the covalent binding of fluorescent dye.…”

“…Both sPa-IGF-1 (group I) and sPa-Co (group II) were added only at the time of pellet formation. [21]. Both human chondrocytes and bone marrow-derived mesenchymal stem cells (BM-MSCs) were cultured as pellets in a 96-well plate up to 35 days in basic chondrogenic serum-free cell culture medium.…”

“…In our previous studies, we used collagen-based scaffolds enriched with IGF-1 coupled to silica particles (sPa) for the in vitro redifferentiation of human chondrocytes [21]. The application of IGF-1-coupled sPa increased the initial type II collagen synthesis in chondrocytes, indicating an accelerated chondrogenesis.…”