title: Poly(ester amide) co-polymers promote blood and tissue compatibility.
abstract: A family of biodegradable poly(ester amide) (PEA) co-polymers based on naturally occurring alpha-amino acids has been developed for applications ranging from biomedical device coatings to delivery of therapeutic biologics. An important feature of PEA co-polymer coatings may be their ability to promote a natural healing response. To gain insight into this process, representative elastomeric PEAs designed for a cardiovascular stent coating were compared to non-degradable and biodegradable polymers in a series of in vitro assays to examine blood and cellular responses. Each PEA contained L-leucine and L-lysine with the latter derivatized by either benzyl alcohol or the nitroxide radical 4-amino TEMPO as a pendant group. Monocytes adherent to PEA secreted reduced levels of the pro-inflammatory interleukins (IL)-6 and IL-1 beta into the culture supernatant compared to those on comparison polymers but secreted significantly higher amounts of the anti-inflammatory mediator, IL-1 receptor antagonist. As a measure of pro-healing tissue compatibility for cardiovascular applications, endothelial cells adhered, spread, and proliferated on PEA. PEA was also determined to be non-hemolytic and did not deplete platelets or leukocytes from whole blood. ATP release from freshly isolated human platelets on PEA, a measure of their activation, was comparable to the well-known and compatible comparison polymers poly(lactic-co-glycolic acid) and n-poly(butyl methacrylate). Taken together, these in vitro studies of the blood and tissue compatibility of these biodegradable, alpha-amino-acid-based PEAs suggest that they may support a more natural healing response by attenuating the pro-inflammatory reaction to the implant and promoting growth of appropriate cells for repair of the tissue architecture.
authors.affiliation: MediVas, LLC, 6275 Nancy Ridge Drive, San Diego, CA 92121, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: DeFife
authors.forename: Kathy
authors.initials: K
authors.lastname: Grako
authors.forename: Gina
authors.initials: G
authors.lastname: Cruz-Aranda
authors.forename: Sharon
authors.initials: S
authors.lastname: Price
authors.forename: Ron
authors.initials: R
authors.lastname: Chantung
authors.forename: Kassie
authors.initials: K
authors.lastname: Macpherson
authors.forename: Ramina
authors.initials: R
authors.lastname: Khoshabeh
authors.forename: Sindhu
authors.initials: S
authors.lastname: Gopalan
authors.forename: William G
authors.initials: WG
authors.lastname: Turnell
mesh_terms: D020341:Absorbable Implants; D000577:Amides / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism; D006016:Glycolates / Q000737:chemistry; D006648:Histocompatibility; D006801:Humans; D019344:Lactic Acid; D009757:Nylons / Q000737:chemistry*; D010974:Platelet Aggregation; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000577:Amides; D001672:Biocompatible Materials; D006016:Glycolates; D009757:Nylons; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid