Acidic Gelatin Research Articles

Carboxymethyl chitosan-methacrylic acid gelatin hydrogel for wound healing and vascular regeneration

At present, wound dressings in clinical applications are primarily used for superficial skin wounds. However, these dressings have significant limitations, including poor biocompatibility and limited ability to promote wound healing. To address the issue, this study used aldehyde polyethylene glycol as the cross-linking agent to design a carboxymethyl chitosan-methacrylic acid gelatin hydrogel with enhanced biocompatibility, which can promote wound healing and angiogenesis. The CSDG hydrogel exhibits acid sensitivity, with a swelling ratio of up to 300%. Additionally, it exhibited excellent resistance to external stress, withstanding pressures of up to 160 kPa and self-deformation of 80%. Compared to commercially available chitosan wound gels, the CSDG hydrogel demonstrates excellent biocompatibility, antibacterial properties, and hemostatic ability. Both in vitro and in vivo results showed that the CSDG hydrogel accelerated blood vessel regeneration by upregulating the expression of CD31, IL-6, FGF, and VEGF, thereby promoting rapid healing of wounds. In conclusion, this study successfully prepared the CSDG hydrogel wound dressings, providing a new approach and method for the development of hydrogel dressings based on natural macromolecules.

Rheological Study on Blend Solutions of Non-mulberry Silk Fibroin and Gelatin Biopolymers

In current research work, we have studied the blending effect of non-mulberry silk fibroin (10% weight/volume basis) and gelatin (20% weight/volume basis) in formic acid. Several blends as SF10G0, SF2G8, SF3G7, SF5G5 and SF0G10 have been made and their rheological behaviour was investigated. The blend solutions were subjected to a steady shear rheological study in the variety of range of shear rates, namely 0.01–500 sec-1 and the viscosities of blend solutions were noticed to decrease in comparison to pure silk solution. The frequency sweep was employed in dynamic rheological tests to determine complex viscosity of these solutions from range of angular sweep 0.1–100 rad/sec. The consistent shear-thinning behaviour was noted for all the blends. The difference in numerical values of shear and complex viscosities indicated disobedience of Cox-Merz rule. Such analysis can be utilised for tailoring the properties of solution prior to processing them to create a versatile range of materials.

Immune-defensive microspheres promote regeneration of the nucleus pulposus by targeted entrapment of the inflammatory cascade during intervertebral disc degeneration

Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration (IVDD). Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc. This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1 (TGF-β1) (T-NNPs) onto the surface of methacrylic acid gelatin anhydride microspheres (GM) via amide bonds. The nanoparticle-microsphere complex (GM@T-NNPs) sustained the long-term release of T-NNPs with excellent cell-like functions, effectively bound to pro-inflammatory cytokines, and improved the release kinetics of TGF-β1, maintaining a 36 day-acting release. GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro, downregulated the expression of inflammatory factors and matrix metalloproteinase, and upregulated the expression of collagen-II and aggrecan. GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model. The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.

Antibacterial, ROS scavenging and angiogenesis promoting ϵ-Polylysine/gelatin based hydrogel containing CTLP to regulate macrophages for pressure ulcer healing

Pressure ulcers (PUs) have emerged as a substantial burden on individuals and society. The introduction of innovative dressings that facilitate the healing of pressure ulcer wounds represents a cost-effective alternative for treatment. In this study, the emphasis is on the preparation of Carthamus tinctorius L. polysaccharide (CTLP) as hydrogel microspheres (MPs), which are then encapsulated within a hydrogel matrix crosslinked with phenylboronic acid gelatin (Gelatin-PBA) and ϵ-polylysine-grafted catechol (ϵ-PL-Cat) to enable sustained release for promoting pressure ulcer healing. The presented Gelatin-PBA/ϵ-PL-Cat (GPL)/CTLP-MPs hydrogel demonstrated outstanding self-healing properties. In addition, in vitro experiments revealed that the hydrogel exhibited remarkable antibacterial activity, excellent biocompatibility. And it showed the capacity to promote vascular formation, effectively scavenge reactive oxygen species, and facilitate macrophage polarization from the M1 to M2 phenotype. In vivo wound healing of mice PUs indicated that the prepared GPL/CTLP-MPs hydrogel effectively accelerated the formation of granulation tissue and facilitated the healing of the wounds. In summary, in vivo and in vitro experiments consistently highlight the therapeutic potential of GPL/CTLP-MPs hydrogel in facilitating the healing process of PUs.

Efficient Chlorostannate Modification of Magnetite Nanoparticles for Their Biofunctionalization.

Magnetite nanoparticles (MNPs) are highly favored materials for a wide range of applications, from smart composite materials and biosensors to targeted drug delivery. These multifunctional applications typically require the biofunctional coating of MNPs that involves various conjugation techniques to form stable MNP-biomolecule complexes. In this study, a cost-effective method is developed for the chlorostannate modification of MNP surfaces that provides efficient one-step conjugation with biomolecules. The proposed method was validated using MNPs obtained via an optimized co-precipitation technique that included the use of degassed water, argon atmosphere, and the pre-filtering of FeCl2 and FeCl3 solutions followed by MNP surface modification using stannous chloride. The resulting chlorostannated nanoparticles were comprehensively characterized, and their efficiency was compared with both carboxylate-modified and unmodified MNPs. The biorecognition performance of MNPs was verified via magnetic immunochromatography. Mouse monoclonal antibodies to folic acid served as model biomolecules conjugated with the MNP to produce nanobioconjugates, while folic acid-gelatin conjugates were immobilized on the test lines of immunochromatography lateral flow test strips. The specific trapping of the obtained nanobioconjugates via antibody-antigen interactions was registered via the highly sensitive magnetic particle quantification technique. The developed chlorostannate modification of MNPs is a versatile, rapid, and convenient tool for creating multifunctional nanobioconjugates with applications that span in vitro diagnostics, magnetic separation, and potential in vivo uses.

Effect and mechanism of a concentration-dependent inorganic ion biomimetic periosteum in a repairing bone defect

An inorganic ion functionalized biomimetic periosteum constitutes a new strategy for the design and application of new bone repair materials. However, the effect of cumulative concentration of inorganic ions (e.g. inorganic ion (Si4+)) on bone immune microenvironment in promoting bone repair is still unclear. Here, we used different mesoporous bioactive glass nanoparticles (MBGNs) contents and a methacrylic acid gelatin (GelMA) organic–inorganic double crosslinking techniques to construct low, medium, and high content inorganic ion biomimetic periosteum. As the inorganic ion concentration increased, the compression modulus of LM@G, MM@G, and HM@G (1, 3, and 5 wt% MBGNs, respectively) was 1.6, 3.2, and 2.1 times higher than that of the GelMA hydrogel and the Si4+ release was 35.4 ± 0.4, 59.5 ± 0.2, and 71.5 ± 1.2 ppm in vitro, respectively. The ERK1/2 and p65 inhibition in the HM@G was 51.9% and 40.2% higher than that in the LM@G; however, the stem cell recruitment was about 85.2% lower than that in the LM@G, and the vascular germination degree was 35.4% lower than that in the MM@G. Contradiction between immune regulation and bone repair was found. However, the anti-inflammation in the MM@G was 30.8%, 30.1% higher than that in the LM@G, and stem cell recruitment and vascular sprouting were 3.4 and 1.6 times higher, respectively than those in the HM@G. In summary, the anti-inflammatory effect of MM@G group is stronger than that of LM@G group, and the effect of stem cell recruitment is more significant than that of HM@G group. We not only explore the biological mechanism of Si4+ coordinating macrophages and stem cells to promote bone repair, but also provide research basis for designing inorganic ion based immunofunctional biomaterials.

Antifriction and anti-wear performances of bionic lubricating fluid containing gelatin nanoparticles for artificial joint materials

The antifriction and antiwear effects of gelatin nanoparticles (GLN-NP) on artificial joint materials in bionic joint lubricant were investigated to provide a theoretical basis for the development of new bionic joint lubricant. GLN-NP was prepared by cross-linking collagen acid (type A) gelatin with glutaraldehyde by acetone method, and the particle size and stability of GLN-NP were characterized. The biomimetic joint lubricants with different concentrations were prepared by mixing 5, 15, and 30 mg/mL GLN-NP with 15 and 30 mg/mL hyaluronic acid (HA), respectively. The friction reduction and antiwear effects of the biomimetic joint lubricants on zirconia ceramics were investigated on a tribometer. The cytotoxicity of each component of bionic joint lubricant on RAW264.7 mouse macrophages was evaluated by MTT assay. The particle size of GLN-NP was about 139 nm, and the particle size distribution index was 0.17, showing a single peak, indicating that the particle size of GLN-NP was uniform. In complete culture medium, pH7.4 PBS, and deionized water at simulated body temperature, the particle size of GLN-NP did not change more than 10 nm with time, indicating that GLN-NP had good dispersion stability and did not aggregate. Compared with 15 mg/mL HA, 30 mg/mL HA, and normal saline, the friction coefficient, wear scar depth, width, and wear volume were significantly reduced by adding different concentrations of GLN-NP ( P<0.05); there was no significant difference between different concentrations of GLN-NP ( P>0.05). Biocompatibility test showed that the cell survival rate of GLN-NP, HA, and HA+GLN-NP solution decreased slightly with the increase of concentration, but the cell survival rate was more than 90%, and there was no significant difference between groups ( P>0.05). The bionic joint fluid containing GLN-NP has good antifriction and antiwear effect. Among them, GLN-NP saline solution without HA has the best antifriction and antiwear effect.

Preparation of Collagen/Hydroxyapatite Composites Using the Alternate Immersion Method and Evaluation of the Cranial Bone-Forming Capability of Composites Complexed with Acidic Gelatin and b-FGF.

Bone-substitute materials are essential in dental implantology. We prepared collagen (Col)/hydroxyapatite (Hap)/acidic gelatin (AG)/basic fibroblast growth factor (b-FGF) constructs with enhanced bone-forming capability. The Col/Hap apatite composites were prepared by immersing Col sponges alternately in calcium and phosphate ion solutions five times, for 20 and 60 min, respectively. Then, the sponges were heated to 56 °C for 48 h. Scanning electron microscopy/energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction analyses showed that the Col/Hap composites contained poorly crystalline Hap precipitates on the Col matrix. Col/Hap composite granules were infiltrated by AG, freeze-dried, and immersed in b-FGF solution. The wet quaternary constructs were implanted in rat cranial bone defects for 8 weeks, followed by soft X-ray measurements and histological analysis. Animal studies have shown that the constructs moderately increase bone formation in cranial bone defects. We found that an alternate immersion time of 20 min led to the greatest bone formation (p &lt; 0.05). Constructs placed inside defects slightly extend the preexisting bone from the defect edges and lead to the formation of small island-like bones inside the defect, followed by disappearance of the constructs. The combined use of Col, Hap, AG, and b-FGF might bring about novel bone-forming biomaterials.

Comparison of Wound Healing Effect of Skin Micrograft Impregnated into Two Kinds of Artificial Dermis in a Murine Wound Model.

Skin MG was prepared from the skin of C57BL/6JJcl mice using Rigeneracons and administered onto Pelnac Gplus and Integra sheets. The amount of MG suspension impregnated in Pelnac Gplus and Integra was evaluated. Pelnac Gplus and Integra sheets combined with MG were applied to murine defects, and wound area, neoepithelium length, granulation tissue formation, and newly formed capillaries were compared with the control groups on days 7 and 14. The weight percentage of the MG absorbed by Pelnac Gplus and Integra was 88.8% ± 3.5% and 28.2% ± 7.0%, respectively (P < 0.05). In the in vivo experiment, the area of newly formed granulation tissue and both the number and area of newly formed capillaries in the PelnacG + MG group were significantly larger than those in the control group at 14 days after implantation (P < 0.05). Skin MG was successfully impregnated into Pelnac Gplus by simple administration but not into Integra. Administration of skin MG into the Pelnac Gplus promoted granulation formation and angiogenesis. Pelnac Gplus was more suitable than Integra in the combination therapy.

Abstract P403: Three-dimensional Bioprinting Of Adhesive Cardiac Patch Systems

Rapid advancements in 3D bioprinting have enabled the design of functionalized bioinks to create scaffolds with robust adhesive properties. These constructs are of great interest in cardiac tissue engineering, where the integration of grafted patch with the host myocardium, through sutures, staples, or adhesives, faces risks such as bleeding, cytotoxicity, and infection. We introduce the first generation of functional adhesive bioinks that can be bioprinted through various modalities to fabricate patch structures with intrinsic adhesive properties. A dopamine-modified hyaluronic acid methacrylate (HAMA-Dopa) and gelatin methacrylate (gelMA) composite bioink is used to create the patch via air and embedded bioprinting. Constructs are crosslinked onto a collagen sheet substrate simulating the host cardiac tissue ( Figure 1A-C ). We developed novel in vitro methods to assess adhesion properties of printed patch under shear, tension, or dynamic loading ( Figure 1C ). Our approach allowed for steady and precise application of stress to the adhesion interface. Embedded-printed HAMA-Dopa/gelMA scaffold showed significantly enhanced adhesion strength (1025 Pa) compared to gelMA (495 Pa) and HAMA (477 Pa) control groups under tension, and under shear (548 Pa vs. 234 and 239 Pa). The adhesion strength of air-printed HAMA-Dopa/gelMA constructs was markedly higher (10,128 Pa) than the embedded ones, possibly due to the more effective, in-situ crosslinking. We also investigated the dynamic adhesive properties in aqueous environment using an ex vivo beating heart model. Air-printed HAMA-Dopa/gelMA showed the greatest adhesion under wet conditions, tolerating 345,600 cycles. We further characterized printing fidelity, mechanical properties, swelling, and biocompatibility of HAMA-Dopa/gelMA constructs, demonstrating adequate functionality of this bioprinted adhesive scaffold for cardiac tissue engineering applications. Figure 1 . Summary of workflow to develop bioprinted adhesive scaffolds. A: Embedded (top) or air (bottom) bioprinting was used to create 3D patch geometries. B: Printing fidelity assessment and optimization. C: Different adhesion mechanisms were assessed using novel customized tools and approaches to apply tensile ( C-i ), shear ( C-ii ), and dynamic ( C-iii ) loading.

One-step electrospun scaffold of dual-sized gelatin/poly-3-hydroxybutyrate nano/microfibers for skin regeneration in diabetic wound

This work aimed to implement an electrospinning protocol that allows simultaneous production of micro- and nanofibers in a single scaffold to mimic the extracellular matrix (ECM) combining biodegradable polymers and proteins, and to evaluate its capability to manage diabetic wounds. Poly-3-hydroxybutyrate (PHB) and gelatin (Ge) were chosen to prepare micro- and nanofibers, respectively. Electrospinning conditions were optimized testing various polymer concentrations, voltages, and flow rates. One-step dual-size fibers were obtained from 8%w/v PHB in chloroform (microfibers, 1.25 ± 0.17 μm) and 30%w/v gelatin in acetic acid (75%w/v) (nanofibers, 0.20 ± 0.04 μm), at 0.5 mL/h and 25 kV. A chemical characterization, swelling, hydrophilicity of scaffolds made of PHB-microfibers, Ge-nanofibers and their combination (Ge-PHB) were evaluated before and after crosslinking with genipin. All scaffolds showed excellent fibroblasts viability and attachment after incubation for 1, 3, and 7 days, and low levels of hemolysis. In vivo wound healing was evaluated in diabetic rats for 21 days. Ge-containing scaffolds promoted faster healing. The wounds treated with the Ge-PHB scaffolds proved to be in a late proliferative stage showing higher content of hair follicles and sweat glands and lower content in fibroblast compared with the control wounds.

----Evaluation of Design and Fabrication of Food-Grade Nanofibers from Chitosan-Gelatin for Nanoencapsulation of Stigmasterol Using the Electrospinning Method.

Purpose: In this research, electrospinning method was employed to fabricate food-grade nanofibers (NFs) from chitosan-gelatin combination for stigmasterol encapsulation. The spinnability of mixed chitosan and gelatin solutions was investigated at different polymer ratios, and the physicochemical properties of the NFs were evaluated.Methods: The mixture solution of chitosan (1.5 % w/v) and gelatin (20 % w/v) in acetic acid indicated spinnability under the following conditions: the ratio of 25:75, voltage of 17 kV, and 15 cm capillary collector distance with a flow rate of 0.2 mL/min. Stigmasterol (0.04 % w/v) was incorporated into NFs of chitosan-gelatin at a respective ratio of 25:75.Results: Encapsulation efficiency (EE) of loaded stigmasterol was found to be 87 ± 5 %. The antioxidant ability of loaded stigmasterol was considerably higher than that observed for free stigmasterol. Scanning electron microscopy (SEM) results demonstrated the formation of the ultrathin fibers with no bead (with diameters of 217 ± 43 nm). The concentration of polymeric solution and viscosity had a notable effect on the electrospinning efficiency of the chitosan-gelatin-based NFs. The thermal stability of chitosan and gelatin fibers was more than that of native gelatin and chitosan. The in vitro stigmasterol release from these NFs followed a controlled-release pattern. The released phytosterol from chitosan formula was less than from those without chitosan formula (46 ± 3 % and 96 ± 4 % respectively).Conclusion: The obtained results suggested that gelatin had a high potential for enhancing the spinnability of chitosan under acidic conditions at optimized concentrations.

Fabrication of polyhydroxy butyric acid–Gelatin blended nanofibrous matrix integrated with silver sulfadiazine as an alternate wound dressing for treating burns

The design of an alternate wound dressing material is necessary to overcome difficulties such as less contact time formulations, more extended hospitalization, and prevent secondary infection. Herein, we report the electrospinning of Polyhydroxy butyric acid (PHB) -Gelatin (70:30) nanofibrous matrix loaded with Silver sulfadiazine (SSD) (0.2% w/v) to act as a carrier to prevent infection at second degree burn wound site. The nanofibrous matrix proves to facilitate good stability against exudates absorption and oxygen permeability. The controlled delivery of the SSD tends to reduce the dressing frequency. The biocompatibility and cell adhesion were assessed with NIH 3T3 fibroblast. The in vivo burn wounds supported enhanced re-epithelialization and MMP-9 production exhibited with fast healing of wound from day 18. Thus, the nanofibrous scaffold serves as an alternate wound dressing material in treating burns by reducing dressing frequency and lessening the adverse effects of antibiotics by its limited usage.

Assay optimization for measuring the alternate complement pathway activity in Asian seabass (Lates calcarifer)

Abstract. Hastuti SD, Barton MD, Pyecroft SB, Costabile M. 2020. Assay optimization for measuring the alternate complement pathway activity in Asian seabass (Lates calcarifer). Biodiversitas 21: 3034-3040. Complement proteins are one component of innate immunity present in fish. The measurement of complement activity in fish can be used to monitor the health status of fish. This is particularly important in Asian seabass (Lates calcarifer) aquaculture, where disease can impact on productivity. We have found an optimal condition assay for measuring the alternate complement pathway (ACP) activity of Asian seabass which includes Magnesium chloride (MgCl2) concentration, buffer pH, incubation temperature and incubation time. The assay was optimized using pooled serum of Asian seabass, diluted in Magnesium ethylenediamine tetraacetic acid gelatine veronal buffer (Mg-EDTA-GVB) and added with Rabbit red blood cells (RRBC) suspension. Subsequently, the suspension was incubated and centrifuged. The supernatant was removed and transferred to a well plate and the optical density (OD) was measured at 540 nm. The optimal condition obtained included a 7.5 mM MgCl2, pH optimum of 7.5, 25°C incubation temperature, and a 30 minutes incubation period. The presently developed assay was robust, rapid, and reliable to be used in monitoring the health status of Asian seabass in aquaculture farms. It can be used as guidance in further immunological studies on this fish.

A 2,5-Dihydroxybenzoic Acid-Gelatin Conjugate Inhibits the Basal and Hsp90-Stimulated Migration and Invasion of Tumor Cells.

The extracellular cell surface-associated and soluble heat shock protein 90 (Hsp90) is known to participate in the migration and invasion of tumor cells. Earlier, we demonstrated that plasma membrane-associated heparan sulfate proteoglycans (HSPGs) bind the extracellular Hsp90 and thereby promote the Hsp90-mediated motility of tumor cells. Here, we showed that a conjugate of 2,5-dihydroxybenzoic acid with gelatin (2,5-DHBA–gelatin), a synthetic polymer with heparin-like properties, suppressed the basal (unstimulated) migration and invasion of human glioblastoma A-172 and fibrosarcoma HT1080 cells, which was accompanied by the detachment of a fraction of Hsp90 from cell surface HSPGs. The polymeric conjugate also inhibited the migration/invasion of cells stimulated by exogenous soluble native Hsp90, which correlated with the inhibition of the attachment of soluble Hsp90 to cell surface HSPGs. The action of the 2,5-DHBA–gelatin conjugate on the motility of A-172 and HT1080 cells was similar to that of heparin. The results demonstrate a potential of the 2,5-DHBA–gelatin polymer for the development of antimetastatic drugs targeting cell motility and a possible role of extracellular Hsp90 in the suppression of the migration and invasion of tumor cells mediated by the 2,5-DHBA–gelatin conjugate and heparin.

Enhanced Allicin Cytotoxicity on HEPG-2 Cells Using Glycyrrhetinic Acid Surface-Decorated Gelatin Nanoparticles.

The cytotoxic potential of allicin was evaluated on different cancer cell lines, particularly, hepatic (HepG-2), breast (MCF-7), lung (A-549), and prostatic (PC-3), where allicin scored an IC50 score of 19.26 μM on HepG-2. In order to increase the cell uptake, optimized allicin-loaded gelatin nanoparticles (GNPs) were prepared where the optimum formulation was surface-conjugated to glycyrrhetinic acid. GNPs were optimized using a D-optimal design. The optimum formulation had a particle size of 370.7 ± 6.78 nm and polydispersity index of 0.0363 ± 0.009 and 39.13 ± 2.38% of drug entrapment. The conjugation of the ligand, glycyrrhetinic acid with allicin-loaded GNPs, was confirmed utilizing 1H NMR. Drug release profiles in the presence/absence of collagenase were obtained. Finally, a cytotoxicity study on HepG-2 was performed for the unconjugated and conjugated allicin-loaded GNPs scoring IC50 of 10.95 and 5.046 μM, revealing two- and fourfold enhancements in allicin cytotoxicity, respectively. To our knowledge, the ligand–carrier pair, glycyrrhetinic acid–gelatin, was not explored before, and the developed system poses a successful liver cancer therapy.

Study of the formulation optimization and reusability of a MAGAT gel dosimeter

PurposeThis study aims to optimize the formulation of a methacrylic acid gelatine and tetrakis (hydroxymethyl) phosphonium chloride (MAGAT) gel dosimeter to achieve acceptable dosimetric characteristics and the lowest final costs. This study also evaluates the reusability of the dosimeter. MethodsThe MAGAT gel dosimeter formulation was optimized. Tetrakis (hydroxymethyl) phosphonium chloride (THPC) concentrations (2, 5, 8, 10, 20, and 65 mM), methacrylic acid (MA) concentrations (2.0, 2.5, 3.0, 3.5, and 4.0% w/w) and gelatin concentrations (4.36, 6.45, 8.36, and 10.45% w/w) were evaluated to provide an adequate dosimetric response. The final dosimeter formulation linearity and dose rate dependence were evaluated. The reutilization methodology of the optimized gel formulation, but containing 2 mM of THPC, which was previously irradiated with a dose of 2 Gy, is also presented. ResultsThe optimized mass concentration of the dosimeter consists of 88.60% deionized water, 8.36% gelatin, 3.00% of MA and 0.04% THPC (5 mM). It presents a linear response for doses up to 10 Gy with a 1.16 Gy−1 s−1 sensitivity. A maximum sensitivity variation of less than 4.0% was found when varying the dose rate of the radiation beams from 300 to 500 cGy/min. It was possible to reuse the dosimeter, however the sensitivity decreased by 15% from the first to the second irradiation. ConclusionsA low-cost MAGAT gel dosimeter with optimized formulation that responds to radiation in a dose range of 0 to 10 Gy with small dose-rate dependence is presented. The MAGAT gel can be reused after a 2 Gy irradiation.

Effect of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogels on frozen‐thawed human ovarian tissue in a xenograft model

Ovarian tissue cryopreservation before cancer treatment is the only option to preserve fertility under some circumstances. However, tissue ischemia after transplantation while awaiting angiogenesis induces dysfunctional folliculogenesis and reduces ovarian reserve and is one of the disadvantages of frozen-thawed ovarian tissue transplantation. Basic fibroblast growth factor (bFGF) is a major regulator of angiogenesis. However, bFGF rapidly loses biological activity when its free form is injected in vivo. This study investigated whether administration of active bFGF helps establish a nurturing environment for follicular survival. A sheet form of a sustained release drug delivery system for bFGF was developed using biodegradable acidic gelatin hydrogel (bFGF sheet). The bFGF sheets or phosphate-buffered saline sheets, as a negative control, were transplanted with frozen-thawed human ovarian tissues subcutaneously into the backs of severe combined immunodeficient mice. Neovascularization, cell proliferation, fibrosis and follicular survival of ovarian grafts were analyzed at 6 weeks after xenografting. The bFGF sheets were optimized to release bFGF for at least 10 days. The transplantation of bFGF sheets with frozen-thawed ovarian tissues significantly increased human and mouse CD31-positive areas and stromal and endothelial cell proliferations. The administration of bFGF also significantly decreased the percentage of the fibrotic area in the graft, resulting in a significant increase in primordial and primary follicular density. Local administration of a sustained release of biologically active bFGF induced neovascularization in frozen-thawed ovarian tissue grafts, which could establish the nurturing environment required for follicular survival in heterotopic xenografts.

Dose rate and energy dependence study of methacrylic acid gelatin tetrakis (hydroxymethyl) phosphonium chloride gel with flattened and unflattened photon beams.

The aim of this study is to evaluate the dose rate and energy dependency of methacrylic acid gelatin tetrakis (hydroxymethyl) phosphonium chloride (MAGAT) gel in unflattened photon beam using X-ray computed tomography (CT) and ultraviolet (UV)-visible spectroscopy. MAGAT gel was prepared and it was exposed to 6 MV flattened and unflattened beams. The dose selected for irradiation was ranging from 3 to 15 Gy with an increment of 3 Gy. The dose rate dependency of the gel was investigated by exposing the gel to three different dose rates of 250, 500, and 1500 cGy/min for flattening filter free (FFF). To verify the energy dependency of the gel, it was exposed by both FFF and flattening filter (FF) for constant dose rate (250 cGy/min) and different energy (6 and 10 MV X-ray photons). The exposed gels were scanned by X-ray CT and UV-visible spectrophotometer. The change in dose sensitivity observed over the dose rate from 250 cGy/min to 1500 cGy/min was 58.00% and 57.89% using a UV-visible spectrophotometer and X-ray CT analysis method. Energy dependency was evaluated with respect to dose sensitivity and the variation between 6 MV FF and FFF photon beams was found to be 2.20% and 2.21% using UV-visible spectrophotometer analysis and X-ray CT, respectively. Similarly, the variation noticed with 10 MV FF and FFF was 2.30% using UV-visible spectrophotometer analysis and 2.22% using X-ray CT analysis. The results clearly show that the MAGAT gel was highly dose rate-dependent and less dependent on energy. The beam quality variation between FF and FFF was less. The similar results obtained using X-ray CT scanner and UV-visible spectrophotometer indicate that this study can be recommended for polymer gel scanning procedure.

Emergency transcatheter arterial embolization for massive gastrointestinal arterial hemorrhage.

To evaluate the different arteriographic manifestations of acute arterial massive hemorrhage of the gastrointestinal (GI) tract and the efficacy of emergency transcatheter arterial embolization (ETAE).A total of 88 patients with acute massive GI bleeding who experienced failure of initial endoscopy and/or conservative treatment were referred to our interventional department for acute GI arteriography from January 2007 to June 2015. After locating the source of bleeding, appropriate embolic agents, such as spring coil, hydroxyl methyl acrylic acid gelatin microspheres, polyvinyl alcohol (PVA) particles, etc., were used to embolize the targeted vessels. The angiographic manifestations and the effects of embolization of acute arterial massive hemorrhage of the GI tract were retrospectively analyzed.Of the 88 patients, 54 were diagnosed with arterial hemorrhage of the upper GI tract and 34 with arterial hemorrhage of the lower GI tract. Eighty cases were associated with positive angiography, which showed the following: contrast extravasation (only); gastroduodenal artery stenosis; pseudoaneurysm (only); pseudoaneurysm rupture with contrast extravasation; pseudoaneurysms merged with intestinal artery stenosis; GI angiodysplasia; and tumor vascular bleeding. Eight cases were diagnosed with negative angiography. Seven-two patients underwent successful hemostasis, and a total of 81 arteries were embolized. The technical and clinical success rates (no rebleeding within 30 days) in performing transcatheter embolization on patients with active bleeding were 100% and 84.71%, respectively (72 of 85). Within 30 days, the postoperative rebleeding rate was 15.29% (13/85). Of these rebleeding cases, 2 patients were formerly treated with “blind embolization,” 7 underwent interventional embolic retreatment, and 3 had surgical operations. All cases were followed-up for 1 month, and 3 patients died from multiple organ failure. No serious complications such as bowel ischemia necrosis were observed.ETAE is a safe, effective, and minimally invasive treatment; because of the diversified arteriographic manifestations of acute GI hemorrhage, the proper selection of embolic agents and the choice of reasonable embolization method are essential for successful hemostasis.