Insight into the Unexpectedly Rapid Degradation of Dihydroxyacetone-Based Hydrogels

Abstract

Biodegradable hydrogels are an important class of biomaterials with a diverse range of applications. In some cases, a rapid hydrogel degradation rate is advantageous. Polycarbonate hydrogels based on dihydroxyacetone (DHA), a natural metabolite, have been reported to undergo surprisingly fast hydrolytic degradation. In the present work, insight into the key features of DHA that contribute to the observed degradation rates is gained. In vitro degradation (mass loss) of three different chemically cross‐linked polycarbonate hydrogels is investigated to shed light on the role of the ketone functional group, as well as the carbon‐chain length between the ketone and carbonate bonds. The ketone is found to be the major cause of rapid degradation. Also, mass loss is accelerated by increased temperature and pH, offering insight into potential tuning parameters and storage conditions. The results show that DHA is a promising monomeric unit for the design of rapidly degrading, biocompatible, and functional biomaterials.

Development of an Efficient Route to 2-Ethynylglycerol for the Synthesis of Islatravir

“…Dissolution of the dimer in protic solvents such as water and methanol shifts the solution equilibrium towards the monomer and allows for its isolation, although it reverts to the dimer upon storage. 9 However, these solvents prohibit the use of most organometallic 1,2-addition protocols. In order to deconvolute issues with the monomer/dimer equilibrium from potential issues with a 1,2-addition on a substrate with two unprotected hydroxy groups, our early studies used isolated 1,3-dihydroxyacetone monomer 15 as starting material.…”

Degradable high Tg sugar-derived polycarbonates from isosorbide and dihydroxyacetone

“…Based on the previous findings on DHA-containing poly (ester)s and poly(carbonate)s, it is apparent that these polymers show a rate higher than the expected rate of hydrolysis. 8,12 Neighboring group participation of β-carbonyls for Fig. 3 TGA-thermograms for poly(isosorbide) and poly(Iso-co-DHA).…”

“…29,30 In a recent study by Ricapito et al on poly(ethylene glycol) (PEG) and poly (DHA) carbonate hydrogels, it was shown that having an extra methylene group on each side, in the case of 1,5-dihydroxypentan-3-one, provided significantly slower degradation compared to hydrogels formed with PEG and DHA-carbonates. 12 As the dilution study suggested, decreasing the polarity of the surrounding medium and decreasing the electron-withdrawing effect on the α-carbons limit the ability to form hydrates, which subsequently affects the hydrolytic degradation of the compound. In the polymer case, being confined to a hydrophobic micro-environment together with limited conformational mobility, chemical degradation rates are expected to be less pronounced.…”

“…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.…”

The Reagent‐depending Nitration of 1,3‐Dihydroxyacetone Dimer

“…DHA is a natural product in human, bacteria, and plants metabolism and plays an important role in the research of new biomaterials, biological polymers and drug designs. The low toxicity of DHA (LD 50 = 160000 mg · kg –1 ) proposes hopefully comparable properties for nitrated derivatives. Based on the fact, that sugars can react with primary amines to form brown pigments, DHA, a three‐carbon sugar, can also react with amino acids .…”