Morphology and mechanisms of a novel absorbable polymeric conduit in the pulmonary circulation of sheep

• Published in: Cardiovascular pathology Vol. 38; pp. 31 - 38
• Main Authors: Brugmans, Marieke, Serrero, Aurélie, Cox, Martijn, Svanidze, Oleg, Schoen, Frederick J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2019
• Subjects: Absorbable polymer; Arterial remodeling; Endogenous tissue restoration; Pulmonary artery graft; Tissue engineering; ETR; Endogenous tissue restoration; Tissue engineering; H&E; Absorbable polymer; Pulmonary artery graft; RVOT; UPy; Arterial remodeling
• ISSN: 1054-8807; 1879-1336
• DOI: 10.1016/j.carpath.2018.10.008

Right ventricular outflow tract (RVOT) conduits used in children with congenital heart disease often degenerate rapidly or develop other complications, and they do not grow with the patient. This leads to multiple surgeries until adult-sized conduits can be implanted. We report experimental in vivo experience with an entirely synthetic absorbable graft, designed to be replaced by tissue in-vivo by host cells, in a process termed Endogenous Tissue Restoration (ETR), and to grow commensurate with somatic growth.
We characterized the structure, mechanical properties, biocompatibility, and in vivo remodelling of a bioabsorbable polyester based on the self-complementary ureido-pyrimidinone (UPy) quadruple hydrogen-bonding motif. Electrospinning was used to process the polymer into a tubular graft with a highly porous wall structure, which was implanted as a pulmonary artery interposition graft in 9 adult sheep with a maximum follow-up of 1 year, followed by pathologic and mechanical analysis.
All grafts were patent by transthoracic echocardiography. Eight were intact at post-mortem examination. One graft had aneurysmal dilation. Graft polymer resorption in vivo was consistent among specimens. Histologic examination revealed progressive tissue replacement of graft polymer, ongoing at one year, with remodeling to a structure that had some key features of native vascular wall. Burst pressures for all explants at 8 weeks and beyond were higher than those of native pulmonary artery (PA) and largely determined by newly formed tissue.
Preclinical studies of a new, absorbable polymeric graft for PA replacement showed remodelling by endogenous cells up to one-year follow-up. Our results show that ETR leads to progressive and substantial replacement of an off-the-shelf synthetic bioabsorbable conduit by functional host tissue to one year in sheep. Thus, further development of this novel concept is warranted.
•A tubular graft with a highly porous wall structure, fabricated from bioabsorbable polyester based on the self-complementary ureido-pyrimidinone (UPy) quadruple hydrogen-bonding motif was implanted as a pulmonary artery interposition graft in 9 adult sheep with a maximum follow-up of one year.•The graft was designed to be replaced by tissue in-vivo.•Explanted grafts we analyzed by mechanical testing and histological examination, focusing on biocompatibility and in vivo remodeling.•Eight of 9 grafts were intact at post-mortem examination; one graft had aneurysmal dilation.•Histologic examination revealed progressive tissue replacement of graft polymer, ongoing at one year, with remodeling to a structure that had some key features of native vascular wall. Burst pressures for all explants at 8 weeks and beyond were higher than those of native pulmonary artery (PA) and largely determined by newly formed tissue.