Slow degrading poly(glycerol sebacate) derivatives improve vascular graft remodeling in a rat carotid artery interposition model

Abstract

Porous synthetic grafts made of poly(glycerol sebacate) (PGS) can transform into autologous vascular conduits in vivo upon degradation of PGS. A long-held doctrine in tissue engineering is the necessity to match degradation of the scaffolds to tissue regeneration. Here, we tested the impact of degradation of PGS and its derivative in an interposition model of rat common carotid artery (CCA). Previous work indicates a complete degradation of PGS within approximately 2 weeks, likely at the fast end of the spectrum. Thus, the derivation of PGS focuses on delay degradation by conjugating the free hydroxy groups in PGS with a long chain carboxylic acid: palmitic acid, one of the most common lipid components. We evaluated two of the resultant palmitate-PGS (PPGS) in this study: one containing 9% palmitate (9-PPGS) and the other16% palmitate (16-PPGS). 16-PPGS grafts had the highest patency. Ultrasound imaging showed that the lumens of 16-PPGS grafts were similar to CCA and smaller than 9-PPGS and PGS grafts 12 weeks post-operation. Immunohistological and histological examination showed an endothelialized lumens in all three types of grafts within 4 weeks. Inflammatory responses to 16-PPGS grafts were limited to the adventitial space in contrast to a more diffusive infiltration in 9-PPGS and PGS grafts in week 4. Examination of calponin + and αSMA + cells revealed that 16-PPGS grafts remodeled into a distinctive bi-layered wall, while the walls of 9-PPGS grafts and PGS grafts only had one thick layer of smooth muscle-like cells. Correspondingly, the expression of collagen III and elastin displayed an identical layered structure in the remodeled 16-PPGS grafts, in contrast to a more spread distribution in 9-PPGS and PGS grafts. All the three types of grafts exhibited the same collagen content and burst pressure after 12 weeks of host remodeling. However, the compliance and elastin content of 16-PPGS grafts in week 12 were closest to those

Citrate Crosslinked Poly(Glycerol Sebacate) with Tunable Elastomeric Properties

“…The latter is typically used to make PGS scaffolds in our lab. [ 6,7,13,26 ] We therefore further explore the effects of curing time on the PGSC elastomer properties. To this end, citrate content is fixed at 6 mol% and curing time is varied from 1.5 to 6 h to make the elastomers, namely PGSC‐1.5h, PGSC‐3h, PGSC‐4.5h, and PGSC‐6h, for comparison.…”

“…In contrast, the acidity of the PGS is dependent on the unreacted carboxylic acids from sebacic acid and the effects on biocompatibility of PGS have been well established both in vitro and in vivo. [ 1,6,7,13,26 ] Given the difference of the p K a values between them, measurements of the pH levels could reflect the unreacted carboxylic acids relating to the added citric acid contents and the curing time. To this end, 100 mg of each ground sample are extracted in 5.0 mL of deionized water for 48 h to reach an equilibrium ionization for pH measurement.…”

“…[ 36 ] Our PGS scaffolds such as synthetic grafts cured for 24 h are degraded in vivo in about 2 weeks postimplantation. [ 6,13,26 ] For a longer degradation window, other studies have demonstrated longer curing times (44–114 h) could result in degradation over a month. [ 18 ] In a recent study, we also reported a fatty acid‐functionalized PGS to inhibit the degradation that could last for 4–12 weeks in vivo for a more efficient graft remodeling by host cells.…”

“…In our lab, we typically cure PGS at 150 °C for 24 h to make scaffolds for utilities including synthetic vascular grafts for arteries. [ 6,7,13,26 ] We would like the curing time to be as short as possible. Therefore, we investigate the PGSC elastomers made in different parameters such as curing temperature at 150 °C, curing time between 1.5 and 6 h and citrate contents ranged from 4 to 8 mol%.…”

Thick PCL Fibers Improving Host Remodeling of PGS‐PCL Composite Grafts Implanted in Rat Common Carotid Arteries

“…Porous poly(glycerol sebacate) (PGS) conduits sheathed with electrospun polycaprolactone (PCL) have good performances in arterial circulation in abdominal aortas [ 10 ] and carotid arteries in rats. [ 10c,11 ] In addition, the composite grafts show a near complete host remodeling with minimal graft materials left after 3 months in vivo. [ 12 ] However, a major issue associated with graft remodeling in vivo is limited neo‐tissue formation inside PCL layers.…”