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Gelatin-based hydrogels emerged as promising biodegradable cell-compatible 3D-printable materials with tunable mechanical properties that serve tissue engineering and applications in regenerative medicine. Nevertheless, these materials are very challenging to monitor in vivo, which has hampered the further development of these materials and their translation into clinical practice. To overcome this limitation, we designed a cross-linked 3D-printable gelatin-based hydrogel endowed with poly[N-(2,2-difluoroethyl)acrylamide] (PDFEA). Such PDFEA-containing hydrogels can be monitored in vivothrough fluorine-19 magnetic resonance imaging (19F MRI), which enables to monitor such implants in vivoand to assess their in vivobiodegradation kinetics. Herein, we prepared three different PDFEA-containing hydrogels with varying cross-linking degrees and studied their physicochemical properties (storage modulus, Young’s modulus, swelling ratio, in vitrodegradation rate). Next, we administered these samples subcutaneously into mice and exploited 19F MRI to detect the biodegradation kinetics over 370 days. Hydrogels with a high cross-linking degree did not extensively degrade in vitronor in vivowithin the evaluated time frame. In contrast, hydrogels characterized by a low degree of cross-linking extensively degraded in vitroas well as in vivo(half-life of 228 ± 21 days). We demonstrated that endowing hydrogels with PDFEA enables monitoring of these hydrogels in vivo. Our results may become a benchmark in forthcoming studies of biodegradable hydrogels and the development of 19F MRI detectable gelatin-based hydrogels, paving the way toward their entry in clinical practice.

Expression of neuroendocrine (NE) markers in primary ovarian non-NE epithelial tumors has rarely been evaluated. The aim of our study was to evaluate the expression of the most widely used NE markers in these neoplasms and to determine any prognostic significance of NE marker expression. The cohort consisted of 551 primary ovarian tumors, including serous borderline tumors, low-grade serous carcinomas, high-grade serous carcinomas (HGSC), clear cell carcinomas, endometroid carcinomas, mucinous borderline tumors, and mucinous carcinomas. Immunohistochemical analysis was performed using antibodies against INSM1, synaptophysin, chromogranin, and CD56 on tissue microarray. Positivity for INSM1, synaptophysin, chromogranin, and CD56 was most frequently observed in mucinous tumors (48.7%, 26.0%, 41.5%, and 100%, respectively). The positivity for these NE markers was mostly restricted to nonmucinous elements distributed throughout the tumor. The mucinous borderline tumor and mucinous carcinomas groups had similar proportions of positivity (mucinous borderline tumor: 53%, mucinous carcinomas: 39%). In the other tumor types, except for HGSC, there was only focal expression (5%–10%) or negativity for NE markers. HGSC showed high CD56 expression (in 26% of cases). Survival analysis was only performed for CD56 in HGSC as this was the only group with sufficient positive cases, and it showed no prognostic significance. Except for mucinous tumors, expression of NE markers in non-NE ovarian epithelial tumors is low. CD56 expression in HGSC occurs frequently but is without diagnostic or prognostic value.