title: One-step synthesis, biodegradation and biocompatibility of polyesters based on the metabolic synthon, dihydroxyacetone.
abstract: The one-step synthesis of a polyester family containing dihydroxyacetone is described along with a quantitative analysis of in vitro/in vivo degradation kinetics and initial biocompatibility. Polyesters were synthesized by combining dihydroxyacetone, which is a diol found in the eukaryotic glucose metabolic pathway, with even-carbon aliphatic diacids (adipic, suberic, sebacic) represented in the long-chain alpha carboxylic acid metabolic pathway, by Schӧtten-Baumann acylation. We show that by using a crystalline monomeric form of dihydroxyacetone, well-defined polyesters can be formed in one step without protection and deprotection strategies. Both diacid length and polyester molecular weight were varied to influence polymer physical and thermal properties. Polyesters were generated with number-averaged (Mn) molecular weights ranging from 2200-11,500. Polydispersities were consistent with step-growth polymerization and ranged from 2 to 2.6. The melting (Tm) and recrystallization (Tc) temperatures were impacted in an unpredictable manner. Thermal transitions for the polyesters were highest for the adipic acid followed by suberic acid and sebacic acid, respectively. It was shown that the thermal response of the DHA-based polyesters was influenced by both the diacid length and molecular weight. In vitro degradation studies revealed first-order weight loss kinetics, the molecular weight loss followed first order kinetics with 25%-40% of the original mass remaining after 8 weeks. In vivo testing over 16 weeks highlighted that mass loss ranged from ∼70% to ∼6% depending upon initial molecular weight and diacid length. Histological analysis revealed rapid resolution of both acute and chronic inflammatory responses, normal foreign body responses were observed and no inflammation was present after week 4. This one-step synthesis proved robust with unique copolymers warranting further study as potential biomaterials.
authors.affiliation: Meinig School of Biomedical Engineering, Cornell University, Ithaca NY 14853, USA.
authors.forename: Julius N
authors.initials: JN
authors.lastname: Korley
authors.affiliation: Meinig School of Biomedical Engineering, Cornell University, Ithaca NY 14853, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Yazdi
authors.affiliation: Department of Biomedical Engineering Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: McHugh
authors.affiliation: Department of Biomedical Engineering Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: James
authors.initials: J
authors.lastname: Kirk
authors.affiliation: Department of Pathology, Cleveland, OH 44106, USA.
authors.forename: James
authors.initials: J
authors.lastname: Anderson
authors.affiliation: Meinig School of Biomedical Engineering, Cornell University, Ithaca NY 14853, USA; Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca NY 14853, USA. Electronic address: dap43@cornell.edu.
authors.forename: David
authors.initials: D
authors.lastname: Putnam
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002264:Carboxylic Acids / Q000737:chemistry; D004098:Dihydroxyacetone / Q000737:chemistry*; D005260:Female; D006207:Half-Life; D007700:Kinetics; D008422:Materials Testing / Q000379:methods*; D011091:Polyesters / Q000138:chemical synthesis* / Q000737:chemistry; D058105:Polymerization; D066244:Proton Magnetic Resonance Spectroscopy; D017207:Rats, Sprague-Dawley; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
chemical_list: D001672:Biocompatible Materials; D002264:Carboxylic Acids; D011091:Polyesters; D004098:Dihydroxyacetone
keywords: Biocompatibility; Biodegradation; Biomaterial; Dihydroxyacetone; Kinetics; Metabolic synthons; Polyester