Nettie Brown

BME PhD Proposal Presentation

Date:2022-03-24
Time: 2:00 P.M. - 4:00 P.M. EST
Location / Meeting Link: https://bluejeans.com/570970422/7475

Committee Members:
Scott J. Hollister, PhD (Co-Advisor) 

Johnna S. Temenoff, PhD (Co-Advisor) 

Rudolph Gleason, PhD 

Steven Goudy, MD 

Vahid Serpooshan, PhD 

David Zopf, MD

Title: Hybrid Hydrogel/3D-Printed Scaffold Composites for Cartilage Regeneration

Abstract: Microtia is a congenital deformity occurring in about 1 in 5,000 childbirths in the U.S. that affects the development of cartilage tissue and hinders the formation and aesthetic appearance of the outer ear. The current gold standard for surgical auricular reconstruction is autologous rib cartilage transplantation which presents limitations such as donor site morbidity, dehiscence, and fracture. Current auricular reconstruction strategies utilize in vitro expansions of autologous chondrocytes to obtain the large number of cells needed for cartilage formation, but this approach often leads to de-differentiation of chondrocytes, resulting in mechanically and biologically inferior fibrocartilage while also facing regulation challenges and high costs. In addition, there are still challenges to address cell sourcing in large quantities, promotion of chondrogenesis, and reduction of scaffold contraction, within a complex geometry. Tissue engineering strategies combining 3D printed scaffolds with hydrogels have become popular due to their ability to meet structural and biological needs. Treatment modalities that are designed to combine autologous tissues and biomaterial scaffolds at the time of tissue harvest, while minimizing operating room time, are ideal for reducing regulatory hurdles to clinical translation. 3D printing using selective laser sintering (SLS) provides a precise technique for developing patient-specific ear scaffolds that meet the need for anatomic shape and structural support. Heparin is a highly sulfated glycosaminoglycan that has been shown to maintain cartilage phenotype and promote cartilage extracellular matrix (ECM) formation in vitro and in vivo, but the role of heparin sulfation in cartilage deposition has not been studied. Minced cartilage and adipose-derived stem cells (ADSCs) will be incorporated into our system to increase available cell quantity at the time-of-surgery for large volumes. Thus, the overall objectives of this work are to (1) develop biologically active and structurally defined novel heparin hydrogel/3D printed scaffold composites (2) utilize these composites to evaluate the effects of heparin sulfation of minced cartilage/chondrocytes on cartilage ECM formation in vitro (3) and optimize cell density through a co-culture of minced cartilage/chondrocytes and ADSCs in vitro and in an in vivo ear model. The efficacy of our system will be determined by assessing cartilage matrix deposition and distribution, chondrogenic gene expression, and matrix stiffness for up to 8 weeks. Overall, this work aims to develop composite scaffolds supporting the growth of clinically relevant volumes of cartilage as an alternative to current auricular surgical and reconstructive strategies.