A Novel Copolymer Poly(Lactide-co-β-Malic Acid) with Extended Carboxyl Arms Offering Better Cell Affinity and Hemacompatibility for Blood Vessel Engineering

Abstract

Despite their increasing uses for cardiovascular and cerebrovascular tissue engineering, synthetic polymeric conduits still have their limitations in clinical applications, particularly in small vessels, mainly due to the thrombus formation. Seeding the synthetic scaffolds with endothelial cells (ECs) will potentially solve this problem, but this endothelialization approach demands synthetic materials with better hemacompatibility and cell affinity. To improve the currently used materials and screen for better surface properties, we synthesized copolymer of poly(lactide-co-beta-malic acid) (PLMA), and its derivatives with pendant hydroxyl arms (PLMAHE) or extended carboxyl arms (PLMA-ECA). We analyzed their physical and chemical properties, their hydrophilicity, and their degradation in physiological conditions. More importantly, their blood compatibility was investigated by the measurements of prothrombin time, activated partial thromboplastin time, and interaction with platelets; their cell affinity and cell growth potentials were observed using the human umbilical vein EC cultures. Results from these experiments showed that the copolymer with the carboxyl arms attracted little platelets, and exhibited better cell affinity and supported the cell proliferation, thus demonstrating the potential usefulness of PLMA-ECA for tissue engineering. We speculate that this novel material will offer new opportunities for the design of better vascular-engineered scaffolds owing to its improved biological and chemical properties.

Peptide REDV‐modified polysaccharide hydrogel with endothelial cell selectivity for the promotion of angiogenesis

“…The results indicated that the peptide content of all the samples was similar and that the peptide densities on the surfaces were 1.3 pmol/ cm 2 approximately. 26,27 The wettability of the surfaces was not measured in this work, because the similarity of the peptide content and structure of the ALG-Pep modified surfaces would result in similar contact angles. The roughness of the surface was characterized by the value of root mean square roughness (RMS, Table I).…”

“…This indicated that the variation in surface morphology would not affect the results of latter studies. 26,27 The wettability of the surfaces was not measured in this work, because the similarity of the peptide content and structure of the ALG-Pep modified surfaces would result in similar contact angles. 28…”

Clinical Potential of Adult Vascular Progenitor Cells

“…40,41 Large vascular conduits appear to be a more feasible target, and preclinical and early clinical studies indicate successful single and combination cell seeding of synthetic vascular grafts. 40,41 An alternative strategy includes mobilization of endogenous progenitors onto grafts and stents in vivo. This has been achieved using CD34 antibodies (EPC stent) and has undergone successful human safety trials.…”

Periodic Incorporation of Pendant Hydroxyl Groups in Repeating Sequence PLGA Copolymers

“…Under the majority of common catalytic hydrogenolysis conditions including 1, 3, or 6 atm of hydrogen, a range of catalysts (Pd/C, Pd(OH) 2 /C, or PdCl 2 /Pd black) and a variety of solvents (ethyl acetate, methylene chloride, acetic acid, or THF), no deprotection was observed. [21,23,24,28,29] Only in DMF was the deprotection viable. [30] We hypothesize that DMF promotes the hydrogenolysis by optimal solvation of both the relatively non-polar benzyl-protected polymer and the considerably more polar poly(hydroxyl) product and/or by providing the minimum activation enthalpy between the benzyl-protected polymers and the more polar transition state.…”