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.

Regulation of the mechanical properties and heat resistance of the poly(l‐lactide‐co‐trimethylene carbonate) copolymer by the incorporation of a stereocomplex crystal and graphene oxide

“…With increasing awareness about environmental protection and sustainable development, biodegradable polyesters have received much attention in recent years . Among the varieties of biodegradable polyesters, polylactide (PLA) is deemed as the most promising because of its renewable raw materials, biocompatibility, and good mechanical properties.…”

Insight into the Unexpectedly Rapid Degradation of Dihydroxyacetone-Based Hydrogels

“…GE (I, Figure ) is the key contributor to gel hydrophilicity and TEGBC (II, Figure ) offers a facile synthetic method to create DHA cross‐links in the polymer matrix. Chloroformate‐containing compounds, such as TEGBC, react readily with primary alcohols like those in DHA, in the presence of a base, without interfering with the ketone functional group …”

“…Chloroformate-containing compounds, such as TEGBC, react readily with primary alcohols like those in DHA, in the presence of a base, without interfering with the ketone functional group. [ 23,35 ] Since the chloroformate groups of TEGBC are reactive with the primary alcohol groups on GE as well as DHA, the exact polymerization and crosslinking pattern is not predictable, which is characteristic of networks formed in this way. To maximize the likelihood of creating the desired polymers ( Figure 3 a) and to preserve consistency between batches, a molar ratio of GE (1): TEGBC (3): DHA (1.5) was employed.…”

Degradable high Tg sugar-derived polycarbonates from isosorbide and dihydroxyacetone

“…8,10 In terms of biodegradability, the presence of DHA in several materialsincluding random co-polymers of LA-DHA, alternating aliphatic poly(ester)s, block co-polymers with DHA and poly (ethylene)glycol (PEG) -can be related to their degradation profile. 8,[11][12][13] Surprisingly, to date little is known in regard to the mechanism behind the improved hydrolytic degradation exhibited by DHA. 3 Our group recently reported on a procedure to generate and tailor the final configuration of APCs from bis-carbonylimid-azolide monomers of 1,3-and higher diols.…”