Hemocompatibility evaluation of poly(diol citrate) in vitro for vascular tissue engineering

Abstract

One of the ongoing challenges in tissue engineering is the synthesis of a hemocompatible vascular graft. Specifically, the material used in the construct should have antithrombogenic properties and support the growth of vascular cells. Our laboratory has designed a novel biodegradable, elastomeric copolymer, poly(1,8-octanediol citrate) (POC), with mechanical and degradation properties suitable for vascular tissue engineering. The hemocompatibility of POC in vitro and its ability to support the attachment and differentiation of human aortic endothelial cell (HAEC) was assessed. The thrombogenicity and inflammatory potential of POC were assessed relative to poly(l-lactide-co-glycolide) and expanded poly(tetrafluoroethylene), as they have been used in FDA-approved devices for blood contact. Specifically, platelet aggregation and activation, protein adsorption, plasma clotting, and hemolysis were investigated. To assess the inflammatory potential of POC, the release of IL-1beta and TNF-alpha from THP-1 cells was measured. The cell compatibility of POC was assessed by confirming HAEC differentiation and attachment under flow conditions. POC exhibited decreased platelet adhesion and clotting relative to control materials. Hemolysis was negligible and protein adsorption was comparable to reference materials. IL-1beta and TNF-alpha release from THP-1 cells was comparable among all materials tested, suggesting minimal inflammatory potential. POC supported HAEC differentiation and attachment without any premodification of the surface. The results described herein are encouraging and suggest that POC is hemocompatible and an adequate candidate biomaterial for in vivo vascular tissue engineering.

Engineering biodegradable polyester elastomers with antioxidant properties to attenuate oxidative stress in tissues

“…MALDI spectra further confirmed the low-molecular-mass of POC and POCA pre-polymers (Mw 915 and 917 Da, Mn 836 and 828, PD 1.09 and 1.11, respectively), in good agreement with previous results [28, 29, 41]. Characteristic spacing between clusters of peaks exist of 128 Da, 174 Da and 302 Da, corresponding to the addition of an octanediol (D), citric acid (C) or C 1 D 1 segment to oligomers, respectively, with evidence of pre-polymer oligomers of up to C 5 D 5 length present in the prepolymer mixture (Figure 3).…”

“…Our laboratory has previously described the synthesis and characterization of polydiolcitrates (PDC), biodegradable non-toxic polyesters that have been shown to be useful for several tissue engineering applications [28–31]. Herein we demonstrate that these polymers can be easily engineered to have enhanced, biologically relevant antioxidant activity by incorporating ascorbic acid (AA) into the polymer network (Figure 1).…”

“…The hydrolytic degradation rate also was not affected by incorporation of ascorbic acid, with polymer discs losing structural integrity after 2 months of incubation in PBS at 37°C, when approximately 25% mass loss had occurred (supplemental data S1). The substantial equivalence between POCA and POC is important to note, since POC has been shown to have favorable properties for both in vitro and in vivo compatibility of devices, as well as tissue engineering applications [28, 29, 31, 41]. …”

Development and characterization of elastic nanocomposites for craniofacial contraction osteogenesis

“…[20][21][22] Although many resorbable biopolymers are available, there are only a few that are elastomeric, including biodegradable polyurethane (PEU), poly(trimethylene carbonate) (TMC), poly (glycerol sebacate) (PGS), poly-4-hyroxybutyrate (P4HB), and poly (1,8 octanediol citrate)-(POC). 14,17,[22][23][24][25][26][27][28] Among these, poly (diol citrate) POC is one of the easiest to synthesis and cost of monomer materials is low. A schematic of the structure of POC is shown in Figure 1.…”

“…Resorbable biopolymers with modifiable mechanical properties have been developed for closure of bone defects [11][12][13][14] and creation of artificial cartilage, 15,16 vascular systems, [17][18][19] and nerve constructs. [20][21][22] Although many resorbable biopolymers are available, there are only a few that are elastomeric, including biodegradable polyurethane (PEU), poly(trimethylene carbonate) (TMC), poly (glycerol sebacate) (PGS), poly-4-hyroxybutyrate (P4HB), and poly (1,8 octanediol citrate)-(POC).…”