Novel formulation of poly(glycerol sebacate) and gelatin hydrogel without the use of crosslinkers

摘要

Introduction: Poly(glycerol sebacate) (PGS) is an elastomeric, surface-eroding biomaterial with exceptional biocompatibility. Hydrogels are heavily used for tissue engineering applications due to their biomimetic physical and biocompatible properties; however as a hydrophobic polymer PGS does not swell in water. The present study demonstrates a novel method to mix PGS and gelatin without harsh solvents to create a stable hydrogel without the use of toxic crosslinkers. Materials and Methods: PGS Gelatin Formulation Briefly, gelatin dissolved in diH2O (15% w/w) was dispersed in molten PGS (38% w/w) with a dual asymmetric centrifugal mixer and allowed to gel. Hydrogel Crosslinking and Swelling Pre-crosslinked samples were soaked in a solvent bath for 24 hours to remove water and residual solvent was then removed by drying samples in a vacuum oven for 24 hours at 30°C. Finally, samples were crosslinked in a vacuum oven at 120°C for 13-24 hours. Hydrogel swelling was determined by incubating samples overnight in 7.4 pH PBS at 37°C and measuring both dry and hydrated mass. Analysis FTIR, DSC, SEM and rheology were performed on both uncrosslinked and crosslinked samples for characterization. The storage (G') and loss (G") modulus values were measured at a shear stress of 0.5% and angular frequency of 0.1 rad/s. Results: FTIR characterization demonstrated characteristic PGS and gelatin peaks as seen in Figure 1 which were present before and after crosslinking. SEM images of cross sections are seen in Figure 2 showing a porous network with pore sizes ≤ 50 μm. DSC, rheology, and swelling results are displayed in Figure 3. Uncrosslinked samples and crosslinked hydrogels exhibit typical crystallization temperatures of PGS resins and thermosets, respectively. The uncrosslinked samples disintegrated in PBS at 37°C, while the crosslinked hydrogels remained stable and swelled. Crosslinked hydrogel G' values were up to three times greater than uncrosslinked samples, and tan d (separation of G' and G") increased, indicative of a solid-like material. Discussion: A homogenous, manageable PGS-gelatin gel was obtained through shear mixing without the use of any additives. After dehydration the gel underwent a typical thermoset PGS method which aligned with dehydrothermal gelatin crosslinking. This resulted in a one-step processing method that was confirmed by a decreased crystallization temperature. The gel-like viscoelastic matrix was able to be water swollen at physiological temperatures and resulted in a stiffen stable material. Conclusion: The study demonstrates the feasibility of a PGS-gelatin hydrogel without the use of an additional crosslinker. Future work is currently looking into lyophilizing the hydrated sample as a means of dehydration. In addition, the customization of hydrogel properties based on crosslink time and the degradation mechanism as well as mechanical properties in association to degradation time is also being investigated.