Browsing by Author "McGann, Megan E."

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    Ectopic models for endochondral ossification: comparing pellet and alginate bead culture methods
    (Wiley, 2017) Weiss-Bilka, Holly E.; McGann, Megan E.; Meagher, Matthew J.; Roeder, Ryan K.; Wagner, Diane R.; Engineering Technology, School of Engineering and Technology
    Key aspects of native endochondral bone development and fracture healing can be mimicked in mesenchymal stem cells (MSCs) through standard in vitro chondrogenic induction. Exploiting this phenomenon has recently emerged as an attractive technique to engineer bone tissue, however, relatively little is known about the best conditions for doing so. The objective of the present study was to compare the bone-forming capacity and angiogenic induction of hypertrophic cell constructs containing human adipose-derived stem cells (hASCs) primed for chondrogenesis in two different culture systems: high-density pellets and alginate bead hydrogels. The hASC constructs were subjected to 4 weeks of identical chondrogenic induction in vitro, encapsulated in an agarose carrier, and then implanted subcutaneously in immune-compromised mice for 8 weeks to evaluate their endochondral potential. At the time of implantation, both pellets and beads expressed aggrecan and type II collagen, as well as alkaline phosphatase (ALP) and type X collagen. Interestingly, ASCs in pellets formed a matrix containing higher glycosaminoglycan and collagen contents than that in beads, and ALP activity per cell was higher in pellets. However, after 8 weeks in vivo, pellets and beads induced an equivalent volume of mineralized tissue and a comparable level of vascularization. Although osteocalcin and osteopontin-positive osteogenic tissue and new vascular growth was found within both types of constructs, all appeared to be better distributed throughout the hydrogel beads. The results of this ectopic model indicate that hydrogel culture may be an attractive alternative to cell pellets for bone tissue engineering via the endochondral pathway.
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    Genipin crosslinking decreases the mechanical wear and biochemical degradation of impacted cartilage in vitro
    (Wiley, 2017-03) Bonitsky, Craig M.; McGann, Megan E.; Selep, Michael J.; Ovaert, Timothy C.; Trippel, Stephen B.; Wagner, Diane R.; Department of Engineering Technology, School of Engineering and Technology
    High energy trauma to cartilage causes surface fissures and microstructural damage, but the degree to which this damage renders the tissue more susceptible to wear and contributes to the progression of post-traumatic osteoarthritis (PTOA) is unknown. Additionally, no treatments are currently available to strengthen cartilage after joint trauma and to protect the tissue from subsequent degradation and wear. The purposes of this study were to investigate the role of mechanical damage in the degradation and wear of cartilage, to evaluate the effects of impact and subsequent genipin crosslinking on the changes in the viscoelastic parameters of articular cartilage, and to test the hypothesis that genipin crosslinking is an effective treatment to enhance the resistance to biochemical degradation and mechanical wear. Results demonstrate that cartilage stiffness decreases after impact loading, likely due to the formation of fissures and microarchitectural damage, and is partially or fully restored by crosslinking. The wear resistance of impacted articular cartilage was diminished compared to undamaged cartilage, suggesting that mechanical damage that is directly induced by the impact may contribute to the progression of PTOA. However, the decrease in wear resistance was completely reversed by the crosslinking treatments. Additionally, the crosslinking treatments improved the resistance to collagenase digestion at the impact-damaged articular surface. These results highlight the potential therapeutic value of collagen crosslinking via genipin in the prevention of cartilage degeneration after traumatic injury.