Dynamic compression combined with SOX‐9 overexpression in rabbit adipose‐derived mesenchymal stem cells cultured in a three‐dimensional gradual porous PLGA composite scaffold upregulates HIF‐1α expression

Abstract

There is considerable interest in how the fate of adipose-derived stem cells is determined. Physical stimuli play a crucial role in skeletogenesis and in cartilage repair and regeneration. In the present study, we investigated the comparative and interactive effects of dynamic compression and SRY-related high-mobility group box gene-9 (SOX-9) on chondrogenesis of rabbit adipose-derived stem cells in three-dimensional gradual porous PLGA (polylactic-co-glycolic acid) composite scaffolds. Articular cartilage is stratified into zones delineated by characteristic changes in cellular, matrix, and nutritive components. As a consequence, biochemical and biomechanical properties vary greatly between the different zones, giving the tissue its unique structure and, thus, the ability to cope with extreme loading. The effects on development of the cartilage were examined using a combination of computational modeling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations. In addition, early chondrogenic differentiation was assessed via real-time PCR of mRNA expression levels for bone- and cartilage-specific gene markers. Our findings define the important role of dynamic compression combined with SOX-9 overexpression during in vitro generation of tissue-engineering cartilage and suggest that a 3D gradual porous PLGA composite scaffold may benefit articular cartilage tissue engineering in cartilage regeneration for better force distribution.

Stem cell origin differently affects bone tissue engineering strategies

“…Therefore, as reported by Liu et al ( 2008 ) in an experimental animal model PDL-SCs could be an ideal cellular source for periodontal ligament regeneration and this PDL-SC mediated treatment could in turn recover the heights of alveolar bone. As far as chondrogenic differentiation is concerned, scaffold geometry seemed essential to favor cells chondroblast differentiation, confirming recent observation of other researchers (Chen et al, 2015 ; Dinescu et al, 2015 ; Roberts et al, 2015 ).…”

Chondrogenic Differentiation Processes in Human Bone-Marrow Aspirates Seeded in Three-Dimensional-Woven Poly(ɛ-Caprolactone) Scaffolds Enhanced by Recombinant Adeno-Associated Virus–MediatedSOX9Gene Transfer

“…Most notably, administration of the rAAV SOX9 vector led to a significant, beneficial decrease in the levels of undesirable hypertrophic and osteogenic differentiation versus control treatments in the constructs over time (matrix mineralization, deposition of type-I and -X collagen), also consistent with the properties of SOX9 [32][33][34]40 and with the previous findings using scaffold-free cultures. 41 For comparison, and in marked contrast with the present findings using rAAV, chondrogenic effects of SOX9 gene transfer have been reported using other types of biocompatible materials such as alginates, 35 polyglycolic acid, 37 polylacticco-glycolic acid, 49 and a fibrin-polyurethane composite scaffold 36 in isolated MSCs either over short-term periods of time using less effective (nonviral vectors) or more toxic/immunogenic gene vehicles (adenoviral vectors; 7-14 days), 35,37,49 or solely upon additional mechanical loading. 36 The present evaluation provides evidence of effective and prolonged SOX9 gene transfer and overexpression in concentrated MSCs seeded in functional scaffolds as a convenient strategy to Figure 5.…”

Donor Cell Fate in Particulated Juvenile Allograft Cartilage for the Repair of Articular Cartilage Defects

“…Recent studies have shown that as an upstream gene, the transcription factor SOX9 can initiate cartilage formation and even coordinate signal transduction pathways such as TGF-β/Smad, Wnt/β-catenin, and HIF-1. 8 SOX9 protein is a powerful transcription activator both in vivo and in vitro, which can activate the transcription of target genes. SOX9 binds to specific sites on Col2al introns, directly regulating the expression of chondrocyte-specific marker Col2al 24 ; the regulation of SOX9 expression plays a central role in the cartilage repair process.…”

“…SOX9 binds to specific sites on Col2al introns, directly regulating the expression of chondrocyte-specific marker Col2al 24 ; the regulation of SOX9 expression plays a central role in the cartilage repair process. 6,8,23,39,40 The increasing expression of SOX9 protein may continue to cause an increase in Col2al and produce the same repair effect as the ACC transplant. 2 Adult chondrocytes have very weak proliferative capacity due to fewer blood vessels and lymphoid tissues.…”