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

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.

[1]  A. Mikos,et al.  Strategies for controlled delivery of biologics for cartilage repair. , 2015, Advanced drug delivery reviews.

[2]  Fergal J O'Brien,et al.  A biomimetic multi-layered collagen-based scaffold for osteochondral repair. , 2014, Acta biomaterialia.

[3]  M. Szychlinska,et al.  New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review. , 2014, World journal of orthopedics.

[4]  Li Duan,et al.  Extracellular matrix production in vitro in cartilage tissue engineering , 2014, Journal of Translational Medicine.

[5]  S. Svenson,et al.  What nanomedicine in the clinic right now really forms nanoparticles? , 2014, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[6]  C. Grüttner,et al.  Synthesis and functionalisation of magnetic nanoparticles for hyperthermia applications , 2013, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[7]  E. Rummeny,et al.  Matrix-assisted autologous chondrocyte transplantation for remodeling and repair of chondral defects in a rabbit model. , 2013, Journal of visualized experiments : JoVE.

[8]  Farshid Guilak,et al.  Tissue engineering for articular cartilage repair--the state of the art. , 2013, European cells & materials.

[9]  J. Vacanti,et al.  Growth Factor Directed Chondrogenic Differentiation of Porcine Bone Marrow–Derived Progenitor Cells , 2013, The Journal of craniofacial surgery.

[10]  A. Rastogi,et al.  Role of autologous chondrocyte transplantation in articular cartilage defects: An experimental study , 2013, Indian journal of orthopaedics.

[11]  R. Reis,et al.  Controlled release strategies for bone, cartilage, and osteochondral engineering--Part I: recapitulation of native tissue healing and variables for the design of delivery systems. , 2013, Tissue engineering. Part B, Reviews.

[12]  Eric C. Carnes,et al.  Mesoporous silica nanoparticle nanocarriers: biofunctionality and biocompatibility. , 2013, Accounts of chemical research.

[13]  J. Elisseeff,et al.  An adhesive bone marrow scaffold and bone morphogenetic-2 protein carrier for cartilage tissue engineering. , 2013, Biomacromolecules.

[14]  Polina Prokopovich,et al.  In vitro growth factor-induced bio engineering of mature articular cartilage , 2013, Biomaterials.

[15]  M. Marcacci,et al.  Matrix assisted autologous chondrocyte transplantation for cartilage treatment , 2013, Bone & joint research.

[16]  M. Ahamed Silica nanoparticles-induced cytotoxicity, oxidative stress and apoptosis in cultured A431 and A549 cells , 2013, Human & experimental toxicology.

[17]  Yuhui Li,et al.  Techniques for fabrication and construction of three-dimensional scaffolds for tissue engineering , 2013, International journal of nanomedicine.

[18]  R. Bader,et al.  TGF-β1 and IGF-1 influence the re-differentiation capacity of human chondrocytes in 3D pellet cultures in relation to different oxygen concentrations. , 2012, International journal of molecular medicine.

[19]  G. Schmidmaier,et al.  Local Delivery of Growth Factors Using Coated Suture Material , 2012, TheScientificWorldJournal.

[20]  T. Takato,et al.  Inhibition of Insulin-like Growth Factor-1 (IGF-1) Expression by Prolonged Transforming Growth Factor-β1 (TGF-β1) Administration Suppresses Osteoblast Differentiation* , 2012, The Journal of Biological Chemistry.

[21]  Y. Chen,et al.  Insulin-like growth factor-1 boosts the developing process of condylar hyperplasia by stimulating chondrocytes proliferation. , 2012, Osteoarthritis and cartilage.

[22]  Guangdong Zhou,et al.  A novel method for the direct fabrication of growth factor-loaded microspheres within porous nondegradable hydrogels: controlled release for cartilage tissue engineering. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[23]  P. Schöttle,et al.  The dependence of autologous chondrocyte transplantation on varying cellular passage, yield and culture duration. , 2011, Biomaterials.

[24]  Liming Bian,et al.  Enhanced MSC chondrogenesis following delivery of TGF-β3 from alginate microspheres within hyaluronic acid hydrogels in vitro and in vivo. , 2011, Biomaterials.

[25]  A. Grodzinsky,et al.  Effect of self-assembling peptide, chondrogenic factors, and bone marrow-derived stromal cells on osteochondral repair. , 2010, Osteoarthritis and cartilage.

[26]  Y. Yoshioka,et al.  Size-dependent cytotoxic effects of amorphous silica nanoparticles on Langerhans cells. , 2010, Die Pharmazie.

[27]  Feng Gao,et al.  Oxidative stress contributes to silica nanoparticle-induced cytotoxicity in human embryonic kidney cells. , 2009, Toxicology in vitro : an international journal published in association with BIBRA.

[28]  Laetitia Gonzalez,et al.  Size-dependent cytotoxicity of monodisperse silica nanoparticles in human endothelial cells. , 2009, Small.

[29]  Laura A. Smith,et al.  Tissue Engineering with Nano-Fibrous Scaffolds. , 2008, Soft matter.

[30]  Bruce Caterson,et al.  The potential of IGF-1 and TGFbeta1 for promoting "adult" articular cartilage repair: an in vitro study. , 2008, Tissue engineering. Part A.

[31]  Junzo Tanaka,et al.  Growth factor combination for chondrogenic induction from human mesenchymal stem cell. , 2004, Biochemical and biophysical research communications.

[32]  T. Schiestel,et al.  Development of an MHC-class I peptide selection assay combining nanoparticle technology and matrix-assisted laser desorption/ionisation mass spectrometry. , 2003, Journal of immunological methods.

[33]  M. Brittberg,et al.  Articular Cartilage Engineering with Autologous Chondrocyte Transplantation , 2003 .

[34]  E B Hunziker,et al.  Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. , 2002, Osteoarthritis and cartilage.

[35]  W. Richter,et al.  Molecular analysis of expansion, differentiation, and growth factor treatment of human chondrocytes identifies differentiation markers and growth-related genes. , 2002, Biochemical and biophysical research communications.

[36]  R. Loeser,et al.  Autocrine stimulation by insulin-like growth factor 1 and insulin-like growth factor 2 mediates chondrocyte survival in vitro. , 2000, Arthritis and rheumatism.

[37]  E. Livne,et al.  The role of transforming growth factor (TGF)-β, insulin-like growth factor (IGF)-1, and interleukin (IL)-1 in osteoarthritis and aging of joints , 1999, Experimental Gerontology.

[38]  R. Loeser Growth factor regulation of chondrocyte integrins: Differential effects of insulin-like growth factor 1 and transforming growth factor β on α1β1 integrin expression and chondrocyte adhesion to type VI collagen , 1997 .

[39]  C. Ohlsson,et al.  Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. , 1994, The New England journal of medicine.

[40]  J. Tyler Insulin-like growth factor 1 can decrease degradation and promote synthesis of proteoglycan in cartilage exposed to cytokines. , 1989, The Biochemical journal.

[41]  P. Conget,et al.  [Treatment of acute full-thickness chondral defects with high molecular weight hyaluronic acid; an experimental model]. , 2014, Revista espanola de cirugia ortopedica y traumatologia.

[42]  Bruce Caterson,et al.  The potential of IGF-1 and TGFbeta1 for promoting "adult" articular cartilage repair: an in vitro study. , 2008, Tissue engineering. Part A.

[43]  P. D. Di Cesare,et al.  Scaffolds for Articular Cartilage Repair , 2004, Annals of Biomedical Engineering.

[44]  D Mainard,et al.  Cartilage repair using new polysaccharidic biomaterials: macroscopic, histological and biochemical approaches in a rat model of cartilage defect. , 2003, Osteoarthritis and cartilage.

[45]  M. Brittberg,et al.  Articular cartilage engineering with autologous chondrocyte transplantation. A review of recent developments. , 2003, The Journal of bone and joint surgery. American volume.

[46]  V Vécsei,et al.  Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. , 2002, Osteoarthritis and cartilage.

[47]  M. Sefton,et al.  Tissue engineering. , 1998, Journal of cutaneous medicine and surgery.

[48]  R. Loeser Growth factor regulation of chondrocyte integrins. Differential effects of insulin-like growth factor 1 and transforming growth factor beta on alpha 1 beta 1 integrin expression and chondrocyte adhesion to type VI collagen. , 1997, Arthritis and rheumatism.