BME Ph.D. Thesis Defense Seminar
Sara Nowacki, advised by Hani Awad
Tuesday, July 18, 2017
K-307, Room 3-6408 Medical Center
“SHORT-TERM PARATHYROID HORMONE TREATMENT AIDS IN EARLY CARTILAGE REPAIR BUT CANNOT RESCUE MATRIX-ASSISTED REPAIR”
Microfracture is the gold-standard for small lesion cartilage repair due to its simplicity as a surgical procedure, however this repair results in a compositionally and mechanically inferior cartilage tissue termed fibrocartilage that results in long-term failure. We proposed a dual-treatment method of a cartilage-derived matrix (CDM) in conjunction with parathyroid hormone (1-34) (PTH(1-34)) to improve the compositional quality of repair tissue in an osteochondral defect in rabbit medial femoral condyles, and explored how PTH(1-34) modulated chondroregeneration of mesenchymal stem cells (MSC) embedded in CDM in vitro over the course of 28 days. The CDM in conjunction with chondrogenic factors upregulated MSC aggrecan gene expression and proteoglycan deposition, however there was also upregulation of hypertrophic markers MMP13 and COL10A1 compared to MSCs embedded in a type I collagen matrix in vitro. There was suppression of chondrogenic as well as fibrotic and hypertrophic gene expression regardless of PTH(1-34) dosing in MSCs concurrently treated with chondrogenic factors, namely TGF-β3. Osteochondral defects treated with two weeks of PTH(1-34) showed improved repair immediately after treatment, however these effects subsided and by later time points there was no difference in repair tissue composition or Pineda score. The addition of CDM resulted in a delayed healing response regardless of PTH(1-34) treatment, however due to poor CDM cell infiltration there was suboptimal repair in these defects. A case analysis of samples with cell-infiltrated CDM indicated that, upon degradation, tissue composition was comparable to microfracture-only defects and there was improvement in Pineda score. Based on improvement in early repair and the case analysis, these results show that PTH must be administered long-term rather than short-term, and that CDM concurrent with PTH treatment has potential as a surgical adjuvant after future matrix optimization.