The ability to modulate the degradation properties of biomaterials such as

The ability to modulate the degradation properties of biomaterials such as thermally responsive hydrogels is desirable when exploring new therapeutic strategies that rely on the temporary presence of a placed scaffold or gel. MAA residue introduction decreased the GRI 977143 pH inside the hydrogels and in surrounding buffered solutions. Accelerated degradation positively correlated with MAA content in pNHMMj polymers putatively by the accelerated cleavage of MAPLA residues to raise the transition temperature of the polymer above body temperature. Physical properties including thermal transition behavior and initial mechanical strength did not vary significantly with MAA content. A rat hindlimb injection model generally reflected the in vitro observation that higher MAA content resulted in more rapid degradation and cellular infiltration. The strategy of tuning the degradation of thermally responsive hydrogels where degradation or solubilization is determined by their polyester components might be applied to other tissue engineering and regenerative medicine applications where designed biomaterial degradation behavior is needed. < 0.05. Figure 2 (a) pH of supernatants of pNHMMj hydrogels after gelation. (b) Fluorescent emission intensity ratio between 540 nm and 440 nm of pNHMMj hydrogels mixed with LysoSensor pH-sensitive dye excited at 360 nm. A higher ratio reflects a lower pH. Data of pNHMM5 ... Results MAA content in the pNHMMj hydrogels The incorporation of MAA into the hydrogels was confirmed by NMR as the -COOH peak appeared at ~12 ppm on the 1H spectrum as shown in Figure 1a. The content of MAA in the copolymer calculated with peak areas shows a linear increase with the MAA feed ratio (Figure 1b) although this content is ~40% lower than the MAA feed ratio in the reaction system. This result was also confirmed with minor discrepancies from the NMR results by titrating the -COOH groups in the copolymer with HCl/NaOH for protonation/deprotonation (Figure 1b). GPC results showed that the molecular weights Mw of the pNHMMj copolymers were all between 22000 and 26000 g/mol. GRI 977143 Figure 1 (a) 1H NMR spectra of pNHMM2. (b) MAA weight percentages in copolymers as determined by NMR and acid titration. Degradation and dissolution of pNHMMj hydrogels The pH of the supernatant solution after gelation of the pNHMMj polymers in PBS buffer (15 wt% of copolymers) showed that with increased MAA content in the copolymer the more acidic the initial degradation environment was for PLA side chains in this limited volume system Figure 2. Measured immediately GRI 977143 after changing PBS the supernatant pH for all pNHMMj increased and showed no significant difference compared to the pH of PBS. After stabilization for 24 h to allow diffusion the supernatant pH of pNHMM0 pNHMM0.5 and pNHMM1 remained above 7.3 whereas the pH for pNHMM2 dropped below 7.1 (Supplemental Figure 1 pNHMM5 and pNHM10 degraded too quickly for this measurement). After another GRI 977143 cycle of PBS change and measurement after another 4 d the pNHMM2 continued to be able to reduce the pH versus the other hydrogels. On the other hand after gelation and placement in fresh PBS followed by 24 h stabilization the pH was GRI 977143 lower in and on the surface of pNHMM2 hydrogel compared to pNHMM0 pNHMM0.5 and pNHMM1 as indicated by a pH-sensitive dye (LysoSensor whose emission intensity ratio between 540 nm and 440 nm increases as pH decreases). In addition the pH of the interior of the pNHMM2 hydrogel was lower than Rabbit Polyclonal to EWSR1. the pH on the surface. No significant differences were found among the other 3 polymer types (data not available for pNHMM5 and pNHMM10 due to rapid degradation). The degradation rate increased significantly as MAA was added in increasing proportion into the polymer backbone as shown by the weight loss profile of the hydrogels in PBS Figure 3a. Without MAA pNHMM0 needed over 5 mo to lose 50% weight in PBS and the same loss required about 2 mo 1 mo 1 wk and 1 d GRI 977143 for MAA containing copolymers with the MAA feed ratio at 0.5% (pNHMM0.5) 1 (pNHMM1) 2 (pNHMM2) 5 (pNHMM5) and 10% (pNHMM10) as shown in Figure 3b. The temporal weight loss profiles of the pNHMMj hydrogels share a similar shape which begins with a slow weight loss stage followed by an abrupt decrease in remaining weight. Furthermore when incubated in PBS solution at pH 9.5 the abrupt weight loss for MAA10 was postponed for 1 d (Supplement Figure 2). Since pNHMM5 and pNHMM10 hydrogels were considered to degrade too quickly for potential in vivo applications hydrogels with less MAA were selected as candidates for further evaluation. Figure 3 (a) Weight loss profiles of pNHMMj hydrogels. (b) Time for 50% weight loss derived from (a). Thermal and.