Enhanced wound healing and hemostasis with exosome-loaded gelatin sponges from human umbilical cord mesenchymal stem cells

BACKGROUND Rapid wound healing remains a pressing clinical challenge,necessitating studies to hasten this process.A promising approach involves the utilization of human umbilical cord mesenchymal stem cells(hUC-MSCs)derived exosomes.The hypothesis of this study was that these exosomes,when loaded onto a gelatin sponge,a common hemostatic material,would enhance hemostasis and accelerate wound healing.AIM To investigate the hemostatic and wound healing efficacy of gelatin sponges loaded with hUC-MSCs-derived exosomes.METHODS Ultracentrifugation was used to extract exosomes from hUC-MSCs.Nanoparticle tracking analysis(NTA),transmission electron microscopy(TEM),and western blot techniques were used to validate the exosomes.In vitro experiments were performed using L929 cells to evaluate the cytotoxicity of the exosomes and their impact on cell growth and survival.New Zealand rabbits were used for skin irritation experiments to assess whether they caused adverse skin reactions.Hemolysis test was conducted using a 2%rabbit red blood cell suspension to detect whether they caused hemolysis.Moreover,in vivo experiments were carried out by implanting a gelatin sponge loaded with exosomes subcutaneously in Sprague-Dawley(SD)rats to perform biocompatibility tests.In addition,coagulation index test was conducted to evaluate their impact on blood coagulation.Meanwhile,SD rat liver defect hemostasis model and full-thickness skin defect model were used to study whether the gelatin sponge loaded with exosomes effectively stopped bleeding and promoted wound healing.RESULTS The NTA,TEM,and western blot experimental results confirmed that exosomes were successfully isolated from hUC-MSCs.The gelatin sponge loaded with exosomes did not exhibit significant cell toxicity,skin irritation,or hemolysis,and they demonstrated good compatibility in SD rats.Additionally,the effectiveness of the gelatin sponge loaded with exosomes in hemostasis and wound healing was validated.The results of the coagulation index experiment indicated that the gelatin sponge loaded with exosomes had significantly better coagulation effect compared to the regular gelatin sponge,and they showed excellent hemostatic performance in a liver defect hemostasis model.Finally,the full-thickness skin defect healing experiment results showed significant improvement in the healing process of wounds treated with the gelatin sponge loaded with exosomes compared to other groups.CONCLUSION Collectively,the gelatin sponge loaded with hUC-MSCs-derived exosomes is safe and efficacious for promoting hemostasis and accelerating wound healing,warranting further clinical application.

Comparison of ethanol-soaked gelatin sponge and microspheres for hepatic arterioportal fistulas embolization in hepatic cellular carcinoma

Hepatic arterioportal fistulas(APFs)are common in hepatocellular carcinoma(HCC).Moreover,correlated with poor prognosis,APFs often complicate antitumor treatments,including transarterial chemoembolization(TACE).AIM To compare the efficacy of ethanol-soaked gelatin sponges(ESG)and microspheres in the management of APFs and their impact on the prognosis of HCC.METHODS Data from patients diagnosed with HCC or hepatic APFs between June 2016 and December 2019 were retrospectively analyzed.Furthermore,APFs were embolized with ESG(group E)or microspheres(group M)during TACE.The primary outcomes were disease control rate(DCR)and objective response rate(ORR).The secondary outcomes included immediate and first follow-up APF improvement,overall survival(OS),and progression-free survival(PFS).RESULTS Altogether,91 participants were enrolled in the study,comprising 46 in group E and 45 in group M.The DCR was 93.5%and 91.1%in groups E and M,respectively(P=0.714).The ORRs were 91.3%and 66.7%in groups E and M,respectively(P=0.004).The APFs improved immediately after the procedure in 43(93.5%)patients in group E and 40(88.9%)patients in group M(P=0.485).After 2 mo,APF improvement was achieved in 37(80.4%)and 33(73.3%)participants in groups E and M,respectively(P=0.421).The OS was 26.2±1.4 and 20.6±1.1 mo in groups E and M,respectively(P=0.004),whereas the PFS was 16.6±1.0 and 13.8±0.7 mo in groups E and M,respectively(P=0.012).CONCLUSION Compared with microspheres,ESG embolization demonstrated a higher ORR and longer OS and PFS in patients of HCC with hepatic APFs.

Establishment of an orthotopic transplantation tumor model of hepatocellular carcinoma in mice

AIM:To improve the outcome of orthotopic transplantation in a mouse model,we used an absorbable gelatin sponge(AGS) in nude mice to establish an orthotopic implantation tumor model.METHODS:MHCC-97L hepatocellular carcinoma(HCC)cells stably expressing the luciferase gene were injected into the subcutaneous region of nude mice.One week later,the ectopic tumors were harvested and transplanted into the left liver lobe of nude mice.The AGS was used to establish the nude mouse orthotopic implantation tumor model.The tumor suppressor gene,paired box gene 5(PAX5),which is a tumor suppressor in HCC,was transfected into HCC cells to validate the model.Tumor growth was measured by bioluminescence imaging technology.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) and histopathology were used to confirm the tumorigenicity of the implanted tumor from the MHCC-97L cell line.RESULTS:We successfully developed an orthotopic transplantation tumor model in nude mice with the use of an AGS.The success rate of tumor transplantation was improved from 60% in the control group to 100% in the experimental group using AGS.The detection of fluorescent signals showed that tumors grew in all live nude mice.The mice were divided into 3 groups:AGS-,AGS+/PAX5-and AGS+/PAX5 +.Tumor size was significantly smaller in PAX5 transfected nude mice compared to control mice(P < 0.0001).These fluorescent signal results were consistent with observations made during surgery.Pathologic examination further confirmed that the tissues from the ectopic tumor were HCC.Results from RT-PCR proved that the HCC originated from MHCC-97L cells.CONCLUSION:Using an AGS is a convenient and efficient way of establishing an indirect orthotopic liver transplantation tumor model with a high success rate.

Arterial chemoembolization for hepatocellular carcinoma

IM To study the therapeutic effects of transcatheter arterial threesegment chemoembolization for hepatocellular carcinoma (HCC).METHODS According to the anatomy of vessels, the tumor capillary networks, muscular arterioles and feeding arteries were successively occluded using lipiodol ultrafluid (LUF), sinobufagin microsphere (SBMs) and particles of gelatin sponge (PGS). In this series of 80 cases, therapeutic effects were evaluated in 76 cases.RESULTS There were 22 cases (289%) with partial response and 41 (539%) with minor response in the 76 evaluated patients. The 6month, 1year, 2year and 3year survival rates were 974%, 868%, 461% and 276% respectively.CONCLUSION This regimen was a rational chemoembolization method for HCC patients.

Relation between eardrum flap area and healing outcome of traumatic eardrum perforation

Objective： To retrospectively study the clinical effects of eardrum flap area on the healing outcome following traumatic perforation.Methods： Totally 291 traumatic eardrum perforations with in-/everted edges were included in this study. They were randomly divided into three groups and received conservative treatment, epidermal growth factor （EGF） via Gelfoam patching, or edge-approximation plus Gelfoam patching respectively. Patients in each group were further divided into two subgroups according to the eardrum flap area ≤ 1/2 or 〉1/2 of the perforation size. The healing rate and mean closure time after tympanic membrane perforation were evaluated at three months.Results： Of the total 291 participants, 281 were included in the final statistical analysis. The area of curled edge did not affect the healing outcome significantly in any groups （P〉0.05）. The healing rate varied slightly： 90.7% vs 92.3% in spontaneous healing group, 98.2% vs 97.4% in EGF via Gelfoam patching group, and 96.5% vs 100% in edge-approximation plus Gelfoam patching group. In addition, in all groups the area of curled edge did not affect the mean closure time significantly （P〉0.05）. The closure time was （32.3±2.4） d vs （30.6±3.1） d in sponaneous healing group, （13.4±2.5） d vs （13.1± 1.9） d in EGF via Gelfoam patching group, and （11.9±3.1） d vs （12.2±2.1） d in edge-approximation plus Gelfoam patching group.Conclusion： The eardrum flap area of traumatic eardrum perforation does not significantly affect the clinical outcomes.