Back to 2026 Abstracts
Biochemical Modulation To Prevent Ex Vivo Fibrosis And Enable Extended Storage Of Living Valvular Allografts
Daniel Chaparro, PhD in Biomedical Engineering1, Elizabeth Cordoves2, Lucie Chicaud2, Baoqi Liu1, David Kalfa, MD., PhD.1.
1Florida International University, Miami, FL, USA, 2Columbia University, New York, NY, USA.
Objective(s): Widespread adoption of Living allogeneic valve transplantation (LAVT) would be helped by “off the shelf” readily available living valves for transplantation. However, clinical translation is hindered by maladaptive fibrotic remodeling during ex-vivo culture systems and mechanical conditioning. Within two weeks of dynamic culture, valve leaflets undergo significant thickening, fibroblast activation, collagen expansion, and loss of trilaminar microarchitecture, rendering allografts unsuitable for implantation and restricting donor-recipient matching. We hypothesized that targeted inhibition of TGF-β signaling using SB-431542 would attenuate mechanically induced leaflet fibrosis, preserving tissue viability and architecture during extended ex-vivo storage.
Methods: Pulmonary valve leaflet and pulmonary artery grafts from porcine donors underwent controlled mechanical stimulation (20-60 rpm orbital rocking) for up to two weeks, a high-throughput model recapitulating whole-allograft bioreactor remodeling. Specimens were treated with SB-431542 (TGF-β receptor I inhibitor) or left untreated. Outcomes included leaflet thickness, α-smooth muscle actin (α-SMA) immunofluorescence, histological microarchitecture (Movat’s pentachrome), and cellular viability (TUNEL/ AlamarBlue).
Results: Untreated controls exhibited significant leaflet thickening, fibroblast proliferation, neo-layer formation, and strong α-SMA expression, confirming valvular interstitial cell (VIC) activation. SB-431542 significantly preserved leaflet thickness, markedly reduced α-SMA expression, attenuated fibroblast proliferation, and maintained leaflet and arterial wall viability. Collagen-driven fibrosa expansion was mitigated, though GAG and elastin reduction persisted.
Conclusions: Pharmacologic TGF-β inhibition can abate maladaptive remodeling in ex-vivo living valve tissue preserved under mechanical conditioning. Integrated with our bioreactor-based platform, this approach is a transformative step toward scalable, off-the-shelf availability of living heart valves.
Back to 2026 Abstracts
