The stiffness of both types of cryogels was also not significantly different, indicating that tough cryogels preserve the deformability favorable for needle injection (Figure 4C)

The stiffness of both types of cryogels was also not significantly different, indicating that tough cryogels preserve the deformability favorable for needle injection (Figure 4C). clinical trial.[13] A covalently crosslinked methacrylated (MA)-alginate cryogel was developed to be a preformed injectable platform for cancer vaccination.[14] When the methacrylate groups on MA-alginate are crosslinked by free radical polymerization at ?20C, the crosslinking occurs around ice crystals. Thawing leads to cryogels with a macroporous structure that allows for DC trafficking. The cryogel also has excellent deformability and shape-memory that allows Isorhynchophylline minimally invasive delivery through a needle and syringe. Compared to typical injectable scaffolds that are formed after injection, the preformed cryogels hold several advantages, including the ability to create well-defined macrostructure and microstructure following injection, maintenance of a defined volume of gel at the injection site, bypassing the need for appropriate gelling conditions = 4. (C) Percentage of cryogels that were intact (% Intact) after needle injection through a 16G needle, as a function of soaking duration in a 200 mM calcium bath. = 6-10. (D) Scanning electron microscopy images of tough cryogels (10 min soaking in a 200 mM calcium bath) (left) and covalently crosslinked-only cryogels (right) after injection via an 18G needle. (E) Percentage of intact tough cryogels (10 min soaking in a 200 mM calcium bath) and covalently crosslinked-only cryogels after injection via an 18G needle. Some error bars are too small to be seen. = 9. Values presented were expressed as mean s.d. Data were analyzed by a binomial test.* p 0.05, ** p 0.01, **** p 0.0001. The ability of tough cryogels to be injected through a smaller, 18G needle (inner cross-sectional area 50% smaller than that of a 16G needle) without sustaining damage was then tested. SEM Mouse monoclonal to EGFP Tag images confirmed that the tough cryogels remained intact after 18G needle injection, whereas the covalently crosslinked-only cryogels were damaged after injection (Figure 2D). All tough gels could pass through an 18G needle intact, while all covalently crosslinked-only cryogels sustained damage after injection (Figure 2E, Movie S1). It was next determined whether tough cryogels reform and maintain their structure after subcutaneous needle injection. High frequency ultrasound (HFUS) imaging revealed that cryogel formulation was a significant factor Isorhynchophylline on Isorhynchophylline gel circularity and thickness post-injection (Figure 3A-C). Tough cryogels remained more circular than covalently crosslinked-only cryogels after injection, independent of the needle gauge used for injection, with circularity similar to the theoretical circularity for a cryogel (0.74). Furthermore, tough Isorhynchophylline cryogels maintained their thickness better than covalently X-linked only cryogels (actual thickness ~2.0 mm). Explantation of the cryogels confirmed that tough cryogels maintained their structure after both 16G and 18G needle injection while covalently X-linked only cryogels fractured post-injection (Figure 3D). Open in a separate window Figure 3. Tough cryogels remain intact after subcutaneous injection into the backs of mice.(A) Representative sagittal B-mode high frequency ultrasound images of cryogels injected via al6G or 18G needle. Circularity (B) and gel thickness (C) as a function of cryogel formulation (tough v. covalently crosslinked-only) and needle injection type (16 v. 18G). (D) Images of cryogels after explantation. = 3. Values presented were expressed as mean s.d. Data were analyzed by two-way ANOVAs with post hoc Students t-tests with Bonferroni corrections * Isorhynchophylline p 0.05. 2.2. Structural, mechanical and swelling properties Scanning electron microscopy (SEM) images showed that tough cryogels have a highly porous structure, which was maintained after needle injection (Figure 4A). Macroscopically, the tough cryogels structure was also maintained after needle injection, with no significant changes in diameter or thickness observed (Figure S1). The interconnected porosity, pore space dimension, stiffness, and swelling ratio of tough cryogels were next characterized, in comparison to covalently crosslinked-only cryogels. The presence of calcium did not dramatically affect interconnected porosity, as tough cryogels remained highly porous even though the difference was significant compared to.