Introduction: Poly(beta-amino esters) (PBAEs) are a class of hydrogel polymers that are of interest as degradable cell scaffolding and drug delivery biomaterials. PBAEs have material properties and degradation periods that are tunable through their macromer composition. The degradation profiles of many PBAE combinations have been observed in previous studies[1],[2], and have shown some difficulties concerning the life cycle of longer lasting species. PBAEs with more hydrophobic characteristics may display lifespans upwards to three months, which can pose significant time and material constraints. Previous attempts at acid catalysis on the degradation of A6 and AH6 3:1 PBAEs have proven successful, but further acceleration may be possible; the thermal acceleration of chemical reactions is a process which may be applicable to the degradation of PBAEs, and may present synergistic effects with decreased pH. This study's purpose is to evaluate the effect of elevated temperature and decreased pH on PBAE degradation alone and in combination to enable accelerated testing protocols to be used with longer lasting PBAEs.
Methods: AH6 3:1 and AH6 5:1 single macromer hydrogels were prepared in accordance with previous studies2, punched into 1mm thick 9mm diameter rounds and immersed in 2ml of PBS solution at pH 7.4, pH 6, and pH 5 and incubated at 37ºC, 50ºC, and 60ºC on an orbital shaker in individually sealed polyethylene tubes. Samples were removed from incubation and dried of surface moisture before weighing. Weighed samples were placed in a 45ºC oven for four days to dry and reweighed to determine dry weight. In this study AH6 3:1 and AH6 5:1 samples were examined over the course of 10 days with daily time points, or 60 days with time points every three days respectively. At each time point all samples that were not removed received a solution change to avoid accumulation of degradation products.
Additional column shaped samples were incubated alongside the disc shaped samples and were mechanically tested in compression to monitor the change in compressive modulus for both wet and dry states. These samples share time the same time point structure as the disc shaped samples, but were first dried at 37ºC for 24 hours to prevent damage from rapid solvent evaporation.
Results and Discussion: This study show significant differences between degradation profiles of PBAE samples in elevated temperature environments; AH6 3:1 polymer samples degraded 32-71% faster in elevated temperature conditions than at physiological temperature. Samples did not display significant differences in peak swelling or swelling rate, but did show significant differences in degradation rate.
AH6 3:1 polymers degraded 27-40% faster in solutions between pH 7 and pH 5 at 37ºC, and displayed earlier and lower peak swelling compared to samples in physiological pH.
Figure 1. Wet weight of AH6 5:1 samples compared to initial vs time
Figure 2. Dry weight of AH6 5:1 samples compared to initial vstime
Figure 2. Dry weight of AH6 3:1 samples compared to initial vs time
Conclusions: Preliminary data indicates that incubation temperature has an influence on the rate of degradation of AH6 3:1 PBAEs. Elevated temperature appears to accelerate degradation without impacting the swelling characteristics of the sample. The relative ease and accessibility of this form of accelerated testing holds promise for use with other PBAE compounds with extended life cycles.
References:
[1] Anderson DG. Adv Mater. 2006;18:2614-2618
[2] Hawkins AM. Polymer 2013;54:4422-4426