Synthesis of a biocompatible, biodegradable, and tunable shape memory polymer triggered at body temperature

1) A method of making a shape memory polymer (SMP), comprising steps of:

• a) Synthesizing ethyl cellulose polymer (ε-caprolactone) (EC-PCL-OH) comprising steps of:
• i) adding 2.25 g of ethyl cellulose (EC) and 15 mL ε-caprolactone (PCL) to a first flask;
• ii) solubilizing EC in ε-caprolactone at 130° C. under argon atmosphere to make a first mixture;
• iii) adding 0.5 wt.% of Stannous octoate to the first mixture and stirring at 130° C. for 6 hour under argon atmosphere to make a first polymer;
• iv) cooling the first polymer to room temperature, and dissolving it in dichloromethane and precipitating EC-PCL-OH from n-hexane;
• b) synthesizing carboxylic acid-terminated ethyl cellulose polymer (ε-caprolactone) (EC-PCL-COOH) comprising the steps of:
• i) adding 16 g of EC-PCL-OH, containing 14.3 mmol OH, and 300 mL of freshly dried Dimethylformamide (DMF) to a second flask;
• ii) solubilizing EC-PCL-OH in 1.431 g (14.3 mmol) of succinic anhydride;
• iii) adding 1.98 g (14.3 mmol) of triethylamine to form a second mixture and stirring the second mixture at 45° C. under argon atmosphere for 16 h;
• iv) cooling it to room temperature and precipitating EC-PCL-COOH from methanol;
• c) synthesizing furan-terminated ethyl cellulose polymer (ε-caprolactone) (EC-PCL-furan) comprising the steps of:
• i) transferring 7.5 g (containing 7.15 mmol COOH) of EC-PCL-COOH to a third flask;
• ii) adding 250 ml of freshly dried dichloromethane to make a third mixture;
• iii) solubilizing EC-PCL-COOH and adding 0.622 mL (7.15 mmol) of furfuryl alcohol, 1.483 g (7.15 mmol) of DCC, 0.0875 g (7.15 mmol) of DMAP to the third mixture;
• iv) stirring the third mixture at room temperature under argon atmosphere for 16 h;
• v) filtering dicyclohexylurea and precipitating EC-PCL-furan from Methanol;
• d) synthesizing 4,1 0-Dioxatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione (product A) comprising the steps of:
• i) transferring 13.48 g (137 mmol) of maleic anhydride, 80 mL of Benzene to a fourth flask;
• ii) solubilizing maleic anhydride;
• iii) adding 10 mL (137 mmol) of Furan and stirring at room temperature under argon atmosphere for 24 h to make a fourth mixture;
• iv) precipitating product A and removing it from the fourth mixture and washing three times with a washing solution;
• e) synthesizing 4-(2-Hydroxy-ethyl)-10-oxa-4-aza-tricyclo[5.2.1.02,6]-dec-8-ene-3,5-dione (product B) comprising the steps of:
• i) suspending 10 g (60.2 mmol) of product A in 25 ml of freshly dried methanol in a fifth flask with a reflux condenser;
• ii) adding 3.64 g (60.2 mmol) of ethanolamine to make a fifth mixture;
• iii) refluxing the fifth mixture for 24 h;
• iv) cooling the fifth mixture to room temperature and crystalizing to form crystals;
• v) collecting crystals by a vacuum filtration;
• f) synthesizing N-maleimide-terminated ethyl cellulose polymer (ε-caprolactone) (EC-PCL-maleimide) comprising the steps of:
• i) transferring 7.5 g (containing 7.15 mmol COOH) of EC-PCL-COOH to a sixth flask;
• ii) adding 250 mL of freshly dried dichloromethane;
• iii) solubilizing EC-PCL-COOH;
• iv) adding 1.499 g (7.15 mmol) of product B, 1.483 g (7.15 mmol) of DCC and 0.0875 g (0.715 mmol) of DMAP to make a sixth mixture;
• v) stirring the sixth mixture at room temperature under argon atmosphere for 16 h;
• vi) filtering formed dicyclohexylurea and precipitating EC-PCL-maleimide from methanol and filtering and drying by vacuum;
• vii) heating EC-PCL-maleimide at 105° C. for 6 h to eliminate furan;
• g) preparing a cross-linked network by Diels-Alder reaction comprising steps of:
• i) heating and blending 6.1 g (7.15 mmol) of EC-PCL-furan (from step c) and 5.7 g (7.15 mmol) of EC-PCL-maleimide (from step f) at 105° C. for 30 minutes to form a seventh mixture;
• ii) placing the seventh mixture in a mold;
• iii) keeping the mold constantly under load of 10 kg at 65° C. in the oven for 72 h;
• iv) cooling the mold to room temperature and recovering a first SMP as a flat sheet and keeping it at room temperature for 7 days to form a second SMP;
• h) heating and blending the second SMP at 120° C. for 20 minutes to make a final SMP, and
• wherein the network structure of the final SMP is formed by linear EC backbones which are linked by grafted PCL chains, and
• whereby the switching temperature of shape memory polymer is tunable.