Complex pediatric and general cardiac surgeries demand the use of tissue or synthetic patch material in reconstruction and repair, Despite significant draw backs, the gold standard tissue based material for cardiovascular surgery is glutaraldehyde crosslinked pericardium. Due to the chemical crosslinking process, this material is bound by 10 year maximum use before the nonviable tissue undergoes detrimental calcification and stenosis. The goal of this proposed work is to examine if by replacing the glutaraldehyde crosslinking of pericardium with a physical coating of a biodegradable polymer, the resulting biohybrid material will not only exhibit diminished calcification and immune response compared to GA-fixed pericardium, but by incorporating viable extracellular matrix (ECM)-based material, will provide a platform suitable for controlled regrowth and maintenance of the injured tissue. We hypothesize that a combination of the biodegradable polymer, poly(propylene fumarate) (PPF), and pericardium with engineered bioactive factor delivery can support remodeling and formation of a lasting tissue. The proposed work will investigate if 1) PPF-reinforced pericardium can provide appropriate physical and biological cues that encourage infiltration and matrix remodeling from vascular cells and macrophages; 2) releasing bioactive factors (SDF and IL4) from the polymer layer can stimulate matrix remodeling and influence a pro-healing macrophage phenotype, and if 3) this material can be used to direct regeneration of a vascular wall injury. Matrix remodeling will be represented with matrix-protein gene expression measurements (PCR) and histological staining techniques. Inflammation and immune response will be assessed using a combination of ELISA to identify expressed cytokines, and flow cytometry and immunohistochemistry to characterize macrophage phenotype. A material successful in this goal to direct a moderate remodeling with low inflammation, and thus create lasting tissue in the injury site, has potential to reduce subsequent surgical intervention by creating a lasting and living vascular patch.
Tissue based prosthetics for cardiovascular surgery and reconstruction in the pediatric population currently rely on glutaraldehyde crosslinked pericardium, despite its dangerous and inevitable failure due to calcification of the nonviable tissue. This proposal suggests that by replacing the chemical cross linking of pericardium with a layer of a biodegradable polymer, we can reduce calcification and failure of the implant. More importantly, by avoiding chemically masking the natural proteins and biological material that make up pericardium, and replacing it with a manmade polymer, we can create a platform suitable for controlled re-growth and eventual self-maintenance of the injured tissue.
| Bracaglia, Laura G; Smith, Brandon T; Watson, Emma et al. (2017) 3D printing for the design and fabrication of polymer-based gradient scaffolds. Acta Biomater 56:3-13 |
