Regulation of Articular Cartilage Volumetric and Compressive Properties by Sequential Application of IGF-1 and TGF-β1 During In Vitro Growth

Author(s):  
Kristin J. Dills ◽  
Jennifer R. Van Donk ◽  
Gregory M. Williams ◽  
Stephanie A. Smith ◽  
Albert C. Chen ◽  
...  

Articular cartilage (AC) is a load bearing material that provides a low friction wear resistant interface in synovial joints. Naturally-occurring and stimulated intrinsic repair of damaged AC is challenging [1]. Thus, there is a need to guide the formation of tissue of specific size and mechanical properties for AC repair. Previous studies [2,3] with immature cartilage have shown that culture with medium containing TGF-β1 results in enhanced mechanical integrity while culture with IGF-1 results in diminished mechanical integrity. Conversely, culture with medium containing IGF-1 results in substantial volumetric growth while culture with TGF-β 1 results in little or no volumetric growth.

Author(s):  
Michael E. Stender ◽  
Christian R. Flores ◽  
Kristin J. Dills ◽  
Gregory M. Williams ◽  
Kevin M. Stewart ◽  
...  

Articular cartilage (AC) is a load bearing material that provides a low friction wear resistant interface in synovial joints. Naturally-occurring and stimulated intrinsic repair of damaged AC is ineffective. Thus, there is a desire to engineer effective replacement tissue that could be used for AC repair. Previous studies [1] have shown that culture of immature cartilage with medium including TGF-β1 will result in a more mature tissue than culture with IGF-1. Detailed characterization of tissue mechanical properties would be helpful for development of cartilage growth models [2].


2012 ◽  
Vol 134 (3) ◽  
Author(s):  
Nathan T. Balcom ◽  
Britta Berg-Johansen ◽  
Kristin J. Dills ◽  
Jennifer R. Van Donk ◽  
Gregory M. Williams ◽  
...  

In vitro cultures with insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1) have previously been shown to differentially modulate the growth of immature bovine articular cartilage. IGF-1 stimulates expansive growth yet decreases compressive moduli and increases compressive Poisson’s ratios, whereas TGF-β1 maintains tissue size, increases compressive moduli, and decreases compressive Poisson’s ratios. The current study’s hypothesis was that sequential application of IGF-1 and TGF-β1 during in vitro culture produces geometric and compressive mechanical properties that lie between extreme values produced when using either growth factor alone. Immature bovine articular cartilage specimens were harvested and either untreated (D0, i.e., day zero) or cultured in vitro for either 6 days with IGF-1 (D6 IGF), 12 days with IGF-1 (D12 IGF), or 6 days with IGF-1 followed by 6 days with TGF-β1 (D12 SEQ, i.e., sequential). Following treatment, all specimens were tested for geometric, biochemical, and compressive mechanical properties. Relative to D0, D12 SEQ treatment enhanced volumetric growth, but to a lower value than that for D12 IGF. Furthermore, D12 SEQ treatment maintained compressive moduli and Poisson’s ratios at values higher and lower, respectively, than those for D12 IGF. Considering the previously described effects of 12 days of treatment with TGF-β1 alone, D12 SEQ induced both growth and mechanical property changes between those produced with either IGF-1 or TGF-β1 alone. The results suggest that it may be possible to vary the durations of select growth factors, including IGF-1 and TGF-β1, to more precisely modulate the geometric, biochemical, and mechanical properties of immature cartilage graft tissue in clinical repair strategies.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Yuan Li ◽  
Yanping Liu ◽  
Qiang Guo

AbstractCartilage defects frequently occur around the knee joint yet cartilage has limited self-repair abilities. Hydrogel scaffolds have excellent potential for use in tissue engineering. Therefore, the aim of the present study was to assess the ability of silk fibroin (SF) hydrogel scaffolds incorporated with chitosan (CS) nanoparticles (NPs) to repair knee joint cartilage defects. In the present study, composite systems of CS NPs incorporated with transforming growth factor-β1 (TGF-β1; TGF-β1@CS) and SF incorporated with bone morphogenetic protein-2 (BMP-2; TGF-β1@CS/BMP-2@SF) were developed and characterized with respect to their size distribution, zeta potential, morphology, and release of TGF-β1 and BMP-2. Bone marrow stromal cells (BMSCs) were co-cultured with TGF-β1@CS/BMP-2@SF extracts to assess chondrogenesis in vitro using a cell counting kit-8 assay, which was followed by in vivo evaluations in a rabbit model of knee joint cartilage defects. The constructed TGF-β1@CS/BMP-2@SF composite system was successfully characterized and showed favorable biocompatibility. In the presence of TGF-β1@CS/BMP-2@SF extracts, BMSCs exhibited normal cell morphology and enhanced chondrogenic ability both in vitro and in vivo, as evidenced by the promotion of cell viability and the alleviation of cartilage defects. Thus, the TGF-β1@CS/BMP-2@SF hydrogel developed in the present study promoted chondrogenic ability of BMSCs both in vivo and in vitro by releasing TGF-β1 and BMP-2, thereby offering a novel therapeutic strategy for repairing articular cartilage defects in knee joints.


2007 ◽  
Vol 40 (16) ◽  
pp. 3607-3614 ◽  
Author(s):  
Timothy Ficklin ◽  
Gregory Thomas ◽  
James C. Barthel ◽  
Anna Asanbaeva ◽  
Eugene J. Thonar ◽  
...  

Biomaterials ◽  
2013 ◽  
Vol 34 (5) ◽  
pp. 1478-1487 ◽  
Author(s):  
Ilyas M. Khan ◽  
Lewis Francis ◽  
Peter S. Theobald ◽  
Stefano Perni ◽  
Robert D. Young ◽  
...  

Author(s):  
Nathan T. Balcom ◽  
Dominic J. Grisafe ◽  
Juan D. Gutierrez-Franco ◽  
Daniel J. Crawford ◽  
Chris B. Raub ◽  
...  

Articular cartilage (AC) supports and distributes loads in synovial joints while maintaining a nearly frictionless surface. Successful replacement of large AC defects with an osteochondral graft requires an appropriate geometrical match with the defect region. 1 In AC, collagen (COL) provides tensile support to the tissue, and glycosaminoglycans (GAG) provide a fixed negative charge that produce swelling and contribute to the compressive properties of the tissue. 2 Previous studies ( Fig. 1) have shown that 4 days of bending can reshape immature AC, but without a change in the total COL and GAG concentrations. 3 We hypothesized that more localized COL and/or GAG remodeling occurs during AC reshaping and may support the shape change. The objective of this study was to determine the presence, magnitude and depth-dependence of COL and GAG remodeling that accompany the shape change of AC.


Author(s):  
Michael E. Stender ◽  
Christopher B. Raub ◽  
Kevin A. Yamauchi ◽  
Reza Shirazi ◽  
Pasquale Vena ◽  
...  

Articular cartilage (AC) metabolism and mechanical properties are regulated by in vitro culture with transforming growth factor–beta 1 (TGF-β1) and insulin-like growth factor–1 (IGF-1) [1]. In general, TGF-β1 maintains tissue size accompanied by a maintenance or increase in tensile and compressive moduli and a maintenance or decrease of compressive Poisson’s ratios while IGF-1 produces significant tissue expansion at the expense of reduced tensile and compressive moduli and increased compressive Poisson’s ratios [1,2]. The goal of this study was to integrate experimental data including AC mechanical properties, biochemical contents including overall collagen (COL) volume fraction, and micro structural measures of COL fiber distribution with a continuum mixture model to predict how COL fiber modulus changes in vitro with TGF-β1 and IGF-1 treatment.


2010 ◽  
Vol 43 (13) ◽  
pp. 2501-2507 ◽  
Author(s):  
Gregory M. Williams ◽  
Kristin J. Dills ◽  
Christian R. Flores ◽  
Michael E. Stender ◽  
Kevin M. Stewart ◽  
...  

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