DMOG Negatively Impacts Tissue Engineered Cartilage Development

Abstract

Objective Articular cartilage exists in a hypoxic environment, which motivates the use of hypoxia-simulating chemical agents to improve matrix production in cartilage tissue engineering. The aim of this study was to investigate whether dimethyloxalylglycine (DMOG), a HIF-1α stabilizer, would improve matrix production in 3-dimensional (3D) porcine synovial-derived mesenchymal stem cell (SYN-MSC) co-culture with chondrocytes. Design Pellet cultures and scaffold-based engineered cartilage were grown in vitro to determine the impact of chemically simulated hypoxia on 2 types of 3D cell culture. DMOG-treated groups were exposed to DMOG from day 14 to day 21 and grown up to 6 weeks with n = 3 per condition and time point. Results The addition of DMOG resulted in HIF-1α stabilization in the exterior of the engineered constructs, which resulted in increased regional type II collagen deposition, but the stabilization did not translate to overall increased extracellular matrix deposition. There was no increase in HIF-1α stabilization in the pellet cultures. DMOG treatment also negatively affected the mechanical competency of the engineered cartilage. Conclusions Despite previous studies that demonstrated the efficacy of DMOG, here, short-term treatment with DMOG did not have a uniformly positive impact on the chondrogenic capacity of SYN-MSCs in either pellet culture or in scaffold-based engineered cartilage, as evidenced by reduced matrix production. Such 3D constructs generally have a naturally occurring hypoxic center, which allows for the stabilization of HIF-1α in the interior tissue. Thus, short-term addition of DMOG may not further improve this in cartilage tissue engineered constructs.

Effect of Dimethyloxalylglycine on Stem Cells Osteogenic Differentiation and Bone Tissue Regeneration—A Systematic Review

“…ADSCs from rats were utilized in three studies [42,66,67], human-derived ADSCs in two studies [48,69], and ADSCs from dogs [46] and rabbits [53] in one study each. Other studies explored the use of human PDLSCs [68] and porcine synovial-derived mesenchymal stem cells (SYN-MSCs) [78]. The most common method for cells extraction is tissue block enzyme digestion [31,[42][43][44][46][47][48]53,66,68,69,75].…”

“…The concentration of DMOG used to treat bone defects varied among studies due to different culture conditions. DMOG was incorporated into various scaffolds to investigate its impact on bone defects regeneration including gelatin sponge (GS) [43], β-tricalcium phosphate (β-TCP) [45], calcined bone calcium (CBC) scaffolds [58], nanoscale zeolitic imidazolate frameworks-8 (ZIF-8) and sodium alginate hydrogel (SA) [59], mesoporous silica nanospheres (MSN) [60][61][62], PCL grafts [61], nanofibrous gelatin-silica hybrid scaffold (GP) [62], natural wood elastic scaffolds [63], mesoporous bioactive glass (MBG) [64,65], sodium alginate-gelatin-β-tricalcium phosphate [66], nanocomposite hydrogel [67], poly (lactic-co-glycolic acid) fiber (PLGA) [68], nanoporous silica nanoparticles (NPSNPs) [69], MBG-dopedpoly(3-hydroxybutyrate-co-3-hydroxyhexanate) (PHMG) [72],calcium phosphate microparticle-s (CMPs) [73], metal-organic frameworks (MOFs) [74], polylactic acid scaffold (PLLA) [76], beaver nano hydrogel, chitosan (CS) and hydroxy propyl chitin hydrogel (HPCH) [77], and particulate-engineered scaffold [78]. The treatment duration ranged from 7 days to 18 weeks.…”

“…5 cartilage-related studies were conducted [55,[75][76][77][78] (Table 5). Focusing on the use of DMOG on human BMSCs in chondrogenic induction cultures, genes expression analysis at days 5, 7, 14, and 21 showed consistent up-regulation of VEGFA, cGMP-dependent protein kinase 1 (PKG1), EGLN, and Sox-9, while chondrogenic hypertrophy genes were suppressed [55].…”

Near infrared spectroscopic assessment of engineered cartilage for implantation in a pre-clinical model

“…BMSCs and chondrocytes (ratio of 4 MSCs to 1 chondrocyte) were photoencapsulated in 1% methacrylated HA (meHA) hydrogel as previously described 18 . Cell density was of 40 million cells/mL of meHA.…”

Applications of Vibrational Spectroscopy for Analysis of Connective Tissues

“…Additionally, polarized infrared light can be used with FTIR imaging to reveal the zonal distribution of differently oriented collagen fibers based on the ratio of the amide I to amide II absorbances [69]. The information in these foundational studies of native cartilage has subsequently been applied in many areas of cartilage research, including towards understanding of degraded osteoarthritic tissues [102,[114][115][116], and characterization of developing engineered constructs [60,[117][118][119].…”