SYNTHESIS OF A BIOCOMPATIBLE, BIODEGRADABLE, AND TUNABLE SHAPE MEMORY POLYMER TRIGGERED AT BODY TEMPERATURE

Abstract

The present invention is a method to produce a biodegradable thermally induced shape memory polymer (SMP) based on poly(ε-caprolactone) (PCL) and ethyl cellulose (EC). In this synthesis method, after grafting the PCL on the linear EC, the PCL chains are end-functionalized with furan and maleimide moieties. The cross-linked network is prepared via Diels-Alder (DA) reaction between furanyl and N- maleimidyl PCL chains. The synthesized SMP demonstrates excellent shape memory properties at near body temperature (41° C.). Moreover, the polymer network is recyclable and re-processable, since the DA reaction is thermally reversible. The SMP of the present invention is well suited for numerous applications, especially in medical devices, given their excellent shape memory performance, tunable materials properties, body temperature-based stimulus, biocompatibility, and potential for biodegradation and resorption.

Claims

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[5.2.1.0.sup.2,6]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[5.2.1.0.sup.2,6]-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.

2) The method of claim 1, wherein the first flask is 50-ml flame dried three-neck round-bottom flask with a magnetic stir bar.

3) The method of claim 1, wherein the second, third and sixth flasks are 500-mL flame dried three-neck round-bottom flask with a magnetic stir bar.

4) The method of claim 1, wherein the fourth flask is 250-mL flame dried three-neck round-bottom flask.

5) The method of claim 1 wherein the fifth flask is 100-mL flame dried three-neck round-bottom flask.

6) The method of claim 1, wherein the washing solution is 20 ml of diethyl ether. mp 113-115° C.; FT-IR u = 3091, 3040, 1849, 1780, 1057 cm.sup.-1.

7) The method of claim 1, wherein the vacuum filtration is mp136-137° C.; FT-IR u = 3462, 2929, 2874, 1664, 1095 cm.sup.-1.

8) The method of claim 1, wherein the mold is 35×35 cm.sup.2 mold with 1 mm thickness.

9) The method of claim 1, wherein the degree of swelling is 94.4% and 396.186%.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0023] Embodiments herein will hereinafter be described in conjunction with the appended drawings provided to illustrate and not to limit the scope of the claims, wherein like designations denote like elements, and in which:

[0024] FIG. 1 is a schematic view of the main synthesis process according to the present invention;

[0025] FIG. 2A is a spectrum showing the FT-IR of the EC corresponding to stretching vibration of C-O-C and O-H respectively;

[0026] FIG. 2B is a spectrum showing the FT-IR of the EC-PCL corresponding to stretching vibration of C=O in ester bond;

[0027] FIG. 3A illustrates the FT-IR of EC-PCL-COOH;

[0028] FIG. 3B illustrates the typical FT-IR of formed EC-PCL-Furan;

[0029] FIG. 3C illustrates the FT-IR of EC-PCL-Maleimide;

[0030] FIG. 4 illustrates DSC analysis of the synthesized EC-PCL-SMP;

[0031] FIG. 5 illustrates DMAT (Dynamic mechanical thermal analysis) demonstration of EC-PCL-SMP;

[0032] FIG. 6A illustrates the permanent shape of the Shape Memory behavior of EC-PCL-SMP;

[0033] FIG. 6B illustrates the temporary shape of the Shape Memory behavior of EC-PCL-SMP;

[0034] FIG. 6C illustrates the recovered shape of the Shape Memory behavior of EC-PCL-SMP;

[0035] FIG. 7A illustrates the processability for permanent shape of Shape Memory behavior of re-molded EC-PCL-SMP;

[0036] FIG. 7B illustrates the temporary shape of Shape Memory behavior of re-molded EC-PCL-SMP;

[0037] FIG. 7C illustrates the recovered shape of Shape Memory behavior of re-molded EC-PCL-SMP, and

[0038] FIG. 8 is a schematic diagram of SMP synthesis showing the reactions and the sequence of reactions to synthesize the shape memory polymer.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0039] The present invention is a new approach developed for synthesis of a EC/PCL SMP which activate around body temperature accompanying with excellent and reliable shape memory properties. To achieve that, in current invention, a SMP network was synthesized based on PCL and EC via reversible DA reaction. This strategy could provide a potential platform for enhancing the mechanical strength and reprocessability of environmentally friendly final product (FIG. 1). The network structure of the polymer was formed by linear EC backbones which were linked by grafted PCL chains.

[0040] The DA reaction is a well-known reaction and widely used to synthesis various types of polymer such as biodegradable polymer, copolymer, self-healing polymer, SMPs and etc. DA reaction leads normally to chemically cross-linked network which is thermally reversible and the final product will possess reprocessable and recyclable features.

[0041] PCL and linear EC were chosen as soft and hard segment respectively, due to their biocompatibility, biodegradability and non-toxic features and most importantly strain-induced crystallization characteristic and suitable and tunable melting point.

Method

Synthesis of Ethyl Cellulose Polymer (ε-Caprolactone) (EC-PCL-OH)

[0042] To a 50-ml flame dried three-neck round-bottom flask with a magnetic stir bar was added 2.25 g of EC and 15 of mL ε-caprolactone. After complete solubilization of EC in ε-caprolactone at 130° C. under argon atmosphere, 0.5 wt.% of Stannous octoate was added and the mixture was stirred at 130° C. for 6 h under argon atmosphere. The resulting polymer cooled to room temperature then dissolved in dichloromethane and precipitated from n-hexane.

Synthesis of Carboxylic Acid-Terminated Ethyl Cellulose Polymer (ε-Caprolactone) (EC-PCL-COOH)

[0043] 16 g of EC-PCL-OH (14.3 mmol OH containing) and 300 mL freshly dried DMF was added to a 500-mL flame dried three-neck round-bottom flask with a magnetic stir bar. After solubilization of EC-PCL-OH, 1.431 g (14.3 mmol) of succinic anhydride, 1.98 g (14.3 mmol) of triethylamine were added to the solution. Then, the solution stirred at 45° C. under argon atmosphere for 16 h. The final solution cooled to room temperature and EC-PCL-COOH precipitated from methanol.

Synthesis of Furan-Terminated Ethyl Cellulose Polymer (ε-Caprolactone) (EC-PCL-Furan)

[0044] 7.5 g (7.15 mmol COOH containing) of EC-PCL-COOH was transferred to a 500-mL flame dried three-neck round-bottom flask and 250 ml of freshly dried dichloromethane was added. After solubilization of EC-PCL-COOH, 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 was added to the solution. The solution stirred at room temperature under argon atmosphere for 16 h. After the filtration of formed dicyclohexylurea, the EC-PCL-furan precipitated from Methanol.

Synthesis of 4,10-Dioxatricyclo[5.2.1.0.SUP.2,6.]Dec-8-Ene-3,5-Dione (A)

[0045] 13.48 g (137 mmol) of maleic anhydride, 80 mL of Benzene was transferred to a 250-mL flame dried three-neck round-bottom flask. After solubilization of maleic anhydride, 10 mL (137 mmol) of Furan was added. The reaction was stirred at room temperature under argon atmosphere for 24 h. The product was precipitated and removed out of the solution and washed three times with 20 ml of diethyl ether. mp 113-115° C.; FT-IR u = 3091, 3040, 1849, 1780, 1057 cm.sup.-1.

Synthesis of 4-(2-Hydroxy-Ethyl)-10-Oxa-4-Aza-Tricyclo[5.2.1.0.SUP.2,6.]-Dec-8-Ene-3,5-Dione (B)

[0046] 10 g (60.2 mmol) of product A was suspended in 25 ml of freshly dried methanol in a 100-mL flame dried three-neck round-bottom flask with reflux condenser. Then 3.64 g (60.2 mmol) of ethanolamine was added. The solution was brought to reflux for 24 h. The solution cooled to room temperature and begun to crystalize. The crystals collected via vacuum filtration. mp 136-137° C.; FT-IR u = 3462, 2929, 2874, 1664, 1095 cm.sup.-1.

Synthesis of N-Maleimide-Terminated Ethyl Cellulose Polymer (ε-Caprolactone) (EC-PCL-Maleimide)

[0047] 7.5 g (7.15 mmol COOH containing) of EC-PCL-COOH was transferred to a 500-mL flame dried three-neck round-bottom flask. 250 mL of freshly dried dichloromethane was added. After solubilization of EC-PCL-COOH, 1.499 g (7.15 mmol) of B, 1.483 g (7.15 mmol) of DCC, 0.0875 g (0.715 mmol) of DMAP was added to the solution. The solution was stirred at room temperature under argon atmosphere for 16 h. After the filtration of formed dicyclohexylurea, the EC-PCL-maleimide precipitated from methanol then filtered and dried by vacuum. The polymer was then heated at 105° C. for 6 h to eliminate furan.

Preparation of Cross-Linked Network by Diels-Alder Reaction

[0048] 6.1 g (7.15 mmol) of EC-PCL-furan and 5.7 g (7.15 mmol) of EC-PCL-maleimide were heated and blended at 105° C. for 30 minutes. Then the mixture was placed in 35×35 cm.sup.2 mold (the thickness was adjusted 1 mm). The mold was kept constantly under load of 10 Kg at 65° C. in the oven for 72 h. The mold cooled to room temperature then recovered as a flat sheet and was kept at room temperature for 7 days.

Retro Diels-Alder Reaction:

[0049] The final SMP was heated at 120° C. for 20 minutes and was blended then re-molded again at same conditions.

Characterization Techniques

[0050] Products were characterized by IR spectrum. IR spectra were obtained on Perkin-Elmer model Spectrum Two FT-IR spectrophotometer. Melting points are determined on a Thermo Scientific 9200 apparatus. Differential scanning calorimetry was performed using Mettler Toledo instrument model DSC1 under nitrogen atmosphere. For this measurement, the sample was first cooled down to -80° C. then heated to 80° C., then the sample was cooled to -80° C. and finally heated to 80° C., the cooling and heating rate was 5.sup.°C/.sub.min. Glass transition temperature (T.sub.g), melting point (T.sub.m), Crystallization temperature (T.sub.c) and enthalpy change were obtained from the second heating. Shape memory properties were measured by DMTA Triton instrument model TTDMA with 5.sup.°C/.sub.min heating and cooling rate.

[0051] FIG. 1 demonstrate the preparation of end functionalized EC-PCL chains. At first, ε-caprolactone was grafted to EC by ring opening polymerization with the 12% wt EC content.

[0052] FIGS. s 2A and 2B show the FT-IR of the EC and EC-PCL-OH respectively. The absorption peaks at 1063 and 3481 cm.sup.-1 which is shown in FIG. 2A were corresponding to stretching vibration of C-O-C and O-H, respectively. Moreover, the absorption peaks were at 2879 and 2978 cm.sup.-1 were attributed to stretching vibration of aliphatic C-H. However, the appearance of sharp absorption peak at 1728 cm.sup.-1 in FIG. 2B was related to stretching vibration of C=O in ester bond. As it is obvious in FIGS. s 2A and 2B, the PCL chains were grafted to EC and ring opening polymerization has been successfully performed.

[0053] At the following to achieve a thermally reversible cross-linked EC-PCL, the PCL chains were end functionalized with DA moieties; Furan and Maleimide. For this purpose, first EC-PCL-OH chains were reacted with Succinic anhydride and Carboxylic acid terminated chains (EC-PCL-COOH) were achieved.

[0054] FIG. 3A illustrates the FT-IR of EC-PCL-COOH. It can be observed that the absorption peak at 1729 cm.sup.-1 was assumed to be related to stretching vibration of C=O in ester bond. Furthermore, the absorption peak of hydroxyl group of COOH was located at 3442 cm.sup.-1.

[0055] In the next step, the EC-PCL-COOH chains were reacted with Furfuryl alcohol with the presence of DCC/DMAP. Consequently, Furan terminated chains (EC-PCL-Furan) were recovered. FIG. 3B shows the typical FT-IR of formed EC-PCL-Furan. The disappearance of OH peak at 3400 cm.sup.-1 is proven of formation of new ester bond.

[0056] On the other hand, to achieve Maleimide terminated EC-PCL chains, the EC-PCL-COOH was reacted with 4-(2-Hydroxy-ethyl)-10-oxa-4-azatricyclo[5.2.1.0.sup.2,6]-dec-8-ene-3,5-dione in the presence of DCC/DMAP and followed by heating at 105° C. to eliminate the Furan and as result, EC-PCL-Maleimide was recovered.

[0057] FIG. 3C demonstrates the FT-IR of EC-PCL-Maleimide. It can be of formation of new ester bond between Carboxylic acid group of the EC-PCL-COOH chains and hydroxyl group of the Maleimide observed that the elimination of wide peak at 3400 cm.sup.-1 was a delicate sign.

[0058] Finally, For DA reaction between Furan terminated PCL chains and Maleimide terminated PCL chains, EC-PCL-Furan and EC-PCL-Maleimide were reacted with each other in the stoichiometric ratio of DA moieties (Furan and Maleimide) as explained in section 2.3.7. and a chemically cross-linked SMP network was achieved. To study the cross-link density of the network the swelling experiments in chloroform was carried out at room temperature. The cross-linked EC-PCL pieces were first weighted and placed in chloroform which is a good solvent for PCL in dark place at room temperature for two days. Then the formed gel was collected and weighted. In the next step, the gel was dried via vacuum and weighted. The degree of swelling and gel content calculated on basis of following equations:

[00001]$\text{degree}\text{of}\text{swelling}=\frac{\text{swollen}\text{weight}-\text{dried}\text{material}\text{weight}}{\text{dried}\text{material}\text{weight}}\times 100$

[00002]$\text{gel}\text{content}=\frac{\text{dried}\text{material}\text{weight}}{\text{initial}\text{material}\text{weight}}\times 100$

[0059] The calculated gel content and degree of swelling was 94.4% and 396.186% respectively. The obtained results proved the significant degree of cross-linking.

Thermal Properties

[0060] The thermal properties of the SMP were studied by DSC. In FIG. 4 the second DSC scan for EC-PCL-SMP. T.sub.g, T.sub.m, T.sub.c, enthalpy of fusion (ΔH.sub.m) and the degree of crystallization (X.sub.c) are given in the table 1.

[0061] X.sub.c was calculated on basis of following equation:

[00003]${\text{X}}_{\text{c}}=\frac{\text{Δ}{\text{H}}_{\text{m}}}{\text{Δ}{\text{H}}_{100\%}}\times 100$

where the ΔH.sub.100% is heat fusion of 100% crystalline PCL.

[0062] Table 1. Shows the Main thermal characteristics for EC-PCL-SMP.

TABLE-US-00001 shows the Main thermal characteristics for EC-PCL-SMP T.sub.g T.sub.m T.sub.c ΔH.sub.m X.sub.c -60° C. 41° C. 10° C. -71.12 jg.sup.-1 52.68%

Shape Memory Properties

[0063] The shape memory (SM) properties are typically quantified by the shape fixity (R.sub.f) and shape recovery ratios (R.sub.r).For cyclic shape memory evaluation, the polymer was cut to 13.00×3.00×1.00 mm.sup.3 samples. The samples were first heated and maintained to maximum temperature of 45° C. for five minutes. Then, 0.5 MPa stress (σ.sub.m ) was applied. Consequently, the samples were stretched to 50% elongation ( ε.sub.m). Next, samples were cooled and maintained to 0° C. for five minutes at σ.sub.m. After that, the stress was released and temporary strain (ε.sub.u) was obtained. Then, samples reheated to 45° C. again in order to recover the permanent shape (ε.sub.p). This process was repeated five times and the results are shown in FIG. 5.

[0064] Shape recovery ratio (R.sub.r) and shape fixity ratio (R.sub.f) for each cycle was calculated on basis of following equations:

[00004]${\text{R}}_{\text{r}}=\frac{{\epsilon }_m-{\epsilon }_p\left(N\right)}{{\epsilon }_m-{\epsilon }_p\left(N-1\right)}$

[00005]${\text{R}}_{\text{f}}=\frac{{\epsilon }_u\left(N\right)}{{\epsilon }_m}$

Where the N is the number of each cycle.

[0065] As it is obvious in FIG. 5, the first cycle is different than the others. This phenomenon is predictable in SMPs and it can be related to the history of polymer. However, the synthesized SMP was demonstrated that the R.sub.r and R.sub.f for the first cycle are 87.85% and 79.88 %, respectively. While, in the other cycles, both R.sub.f and R.sub.r were increased to higher percentages. The results are given in the table 2. The synthesized SMP showed R.sub.f=90.03 after five cycles. This relatively high shape fixity was attributed to the crystallinity of the soft segment (X.sub.c = 52.59%). When the sample reached the T.sub.m of the soft segment, the PCL’s crystals were melt, then the sample was stretched and the sample was cooled down afterward, therefore began to crystallize. The crystallization process stabilizes the strained state via dissipation of the strain energy which leads to significant strain hardening, resulting in fixation of the temporary shape at the deformed state.

TABLE-US-00002 Shape memory properties of EC-PCL-SMP cycle 1 2 3 4 5 R.sub.r (%) 87.85 98.4 98.98 98.87 99.08 R.sub.f (%) 79.88 89.11 89.79 89.90 90.03

[0066] Furthermore, it can be seen in the FIG. 5 that the samples were started to recover the permanent shape at 38° C. DSC analysis should be considered to understand this behavior. As it can be seen in FIG. 4, the endothermic melting process was not accrued only at specific temperature of 41° C., in fact it happened in a specific temperature range that starts before 41° C. In other words, the 41° C. is the peak melting temperature, therefore when the significant amount of crystals melts in this temperature range, the sample logs in to recovery stage.

[0067] As shown in table 2, at the first cycle, the strain recovery was uncompleted, but EC-PCL-SMP demonstrated R.sub.r = 98.4% after one cycle and increased to 99.08% in the fifth cycle. This behavior was attributed to sufficient cross-link density and stable net points. Moreover, equilibrium nature of DA reaction should be considered. Therefore, even at 45° C., some retro-DA reactions can take place but in general, the shape memory properties were unaffected, otherwise the permanent shape would not completely recover.

[0068] FIGS. 6A, 6B and 6C show the Shape memory behavior of EC-PCL-SMP in (A) Permanent shape, (B) temporary shape and (C) recovered shape.

[0069] For cyclic shape memory evaluation, the polymer was cut to 13 × 3 × 1 mm3 samples. The samples were first heated and maintained at a maximum temperature of 45° C. for five minutes. Then, 0.5 MPa stress was applied. Consequently, the samples were stretched to 50% elongation. Next, samples were cooled and maintained to 0° C. for five minutes at 0.5 MPa. After that, the stress was released, and a temporary strain was obtained. Then, samples reheated to 45° C. again to recover the permanent shape.

[0070] To investigate the retro-DA reaction the molded EC-PCL-SMP was heated to 120° C. for 20 minutes while melt blended. Then, the mixture was re-molded exactly like the first time molding conditions. Because of thermally reversible characteristic of DA reaction between Furan and Maleimide, the re-molded SMP showed shape memory effect. Therefore, the original shape can be changed and a new permanent shape could be developed in the polymer, in other words the memory of the polymer could be removed and a new memory replaced. FIGS. s 7A, 7B and 7C represents shape memory effect of the re-molded SMP, in which 7A represents the permanent shape, 7B temporary shape and 7C recovered shape.

[0071] The biodegradable thermally induced SMP was designed based on EC/PCL via DA reaction. The synthesized SMP illustrated excellent shape memory effect around body temperature (41° C.). The resulting cross-linked polymer network exhibits excellent reversibility as proven by DMTA and the retention of properties upon reprocessing the material. Thermal analysis demonstrated very good shape fixity and moderate shape recovery in which R.sub.r = 99.08% and R.sub.f═ 90.03% after five cycles which was due to the significant crystallinity of the soft segment (X.sub.c = 52.59%) and stability of the hard segment. These reliable shape memory effect can introduce the final product as a good candidate for designing smart biomedicine devices.

[0072] FIG. 8 shows the reactions and the sequences of the reactions to synthesize the shape memory polymer. It also notes the reaction conditions such as time and temperature.

[0073] The first step is the preparation of Ethyl cellulose polymer (ε-caprolactam) (EC-PCL). ε-caprolactone was grafted to EC by ring-opening polymerization with 10-15 weight % EC content.

[0074] Step 2 shows the end functionalization of EC-PCL. To achieve a thermally reversible cross-linked EC-PCL, the PCL chains were end-functionalized with Diels-Alder (DA) moieties; Furan and Maleimide. For this purpose, first EC-PCL-OH chains were reacted with Succinic anhydride, which resulted in Carboxylic acid terminated chains (EC-PCL-COOH).In the next step, the EC-PCL-COOH chains were reacted with Furfuryl alcohol in the presence of DCC/DMAP. Consequently, Furan terminated chains (EC-PCL-Furan) were formed. To achieve Maleimide terminated EC-PCL chains, the EC-PCL-COOH was reacted with 4-(2-Hydroxy-ethyl)-10-oxa-4-azatricyclo[5.2.1.0]-dec-8-ene-3,5-dione in the presence of DCC/DMAP and followed by heating at 105° C. to eliminate the Furan, and as a result, EC-PCL-Maleimide was synthesized.

[0075] Step 3 shows the SMP network. For DA reaction between Furan terminated PCL chains and Maleimide terminated PCL chains, EC-PCL-Furan and EC-PCL-Maleimide were reacted with each other in the stoichiometric ratio of DA moieties (Furan and Maleimide), which resulted in a chemically cross-linked SMP network. Generally, a shape memory network consists of at least two segments, a hard segment and a soft segment. In the synthesized EC-PCL-SMP, the hard segment was achieved by chemically cross-linking the polymer network, where the PCL plays the role of the soft segment of the polymer network. Therefore, the synthesized SMP’s transition temperature is the melting temperature of the PCL (41° C.).

[0076] The convenient Diels Alder reaction between EC and PCL is the most important part of this invention. However, the functionalization of the initial EC-PCL chain with Furan and Maleimide moieties are equally important. The ratio of the soft segment to the hard segment also affects the properties of the SMP.

[0077] The necessary chemicals in this application are EC and PCL. However, other chemicals can be replaced. The processing temperature, time and chemical concentrations can be optimized to increase the throughput of the reaction and tune the mechanical properties such as triggering temperature and recovery.

[0078] The synthesis of the SMP can be scaled up by using appropriate equipment such as large reactors and mixers. The reaction can also be optimized by varying the process temperature, processing time, and material concentration. Many medical devices can be manufactured using this SMP. Different medical devices made from the SMP, such as surgical splints, mouthguards, orthodontic wire, wound closing sutures and staples, embolization devices, and stents.

[0079] Shape recovery properties necessary for real-life applications are challenging to achieve. The research optimized the recovery property by modifying the reaction. Various experiments and trial-and-error provided the suitable reaction conditions to synthesize the present SMP.

[0080] The foregoing is considered as illustrative only of the principles of the invention. Further, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the invention.

[0081] With respect to the above description, it is to be realized that the optimum relationships for the parts of the invention in regard to size, shape, form, materials, function and manner of operation, assembly and use are deemed readily apparent and obvious to those skilled in the art, and all equivalent relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by the present invention.