Gelatin-based hydrogel functionalized with taurinemoieties for in vivo skin tissue regeneration

Functionalized hydrogels stimulate the migration and morphogenesis of endothelial cells(ECs)and are useful substrates for wound healing.The present study investigates the feasibility of covalent conjugation of taurine(Tau)on a gelatin-based hydrogel.This hydrogel is expected to maintain positive charged growth factors such as basic fibroblast growth factor(bFGF)and vascular endothelial growth factors(VEGFs)near ECs within the hydrogel microenvironment.The gelatin was conjugated with hydroxyl phenol(Ph)and Tau moieties,and in following that Ph residues were crosslinked through a horseradish peroxidase-catalyzed reaction.The migration characteristics of ECs were analyzed by scratch migration assay and microparticle-based cell migration assay.Cellular morphology and amounts of angiopoietin 1(Ang 1),bFGF,and VEGF proteins were evaluated for encapsulated cells.The potential of synthesized hydrogels in wound healing was assessed by the percentage of reduction from the original wound size and histopathological analyses of rat skin.The incorporated Tau molecules within the hydrogel remained stable through covalent bonds during incubation.During extended incubation,the gelatin-based hydrogel conjugated with Tau improved the migration distance and number of existing migrated ECs.Immobilized Tau within the gelatin-based hydrogel induced high motility of ECs,accompanied by robust cytoskeleton extension and a cell subpopulation that expressed CD44 and CD31 receptors as well as enhancement of Ang 1,bFGF,and VEGF.We found that injectable Gel-Ph-Tau effectively improves wound-healing parameters.

Liver-directed treatment is associated with improved survival and increased response to immune checkpoint blockade in metastatic uveal melanoma:results from a retrospective multicenter trial

Metastases of uveal melanoma(UM)spread predominantly to the liver.Due to low response rates to systemic therapies,liver-directed therapies(LDT)are commonly used for tumor control.The impact of LDT on the response to systemic treatment is unknown.A total of 182 patients with metastatic UM treated with immune checkpoint blockade(ICB)were included in this analysis.Patients were recruited from prospective skin cancer centers and the German national skin cancer registry(ADOReg)of the German Dermatologic Cooperative Oncology Group(DeCOG).Two cohorts were compared:patients with LDT(cohort A,n=78)versus those without LDT(cohort B,n=104).Data were analyzed for response to treatment,progression-free survival(PFS),and overall survival(OS).The median OS was significantly longer in cohort A than in cohort B(20.1 vs.13.8 months;P=0.0016)and a trend towards improved PFS was observed for cohort A(3.0 vs.2.5 months;P=0.054).The objective response rate to any ICB(16.7%vs.3.8%,P=0.0073)and combined ICB(14.1%vs.4.5%,P=0.017)was more favorable in cohort A.Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.