Objective
To review the research progress of growth factor sustained-release microspheres in fat transplantation.
Methods
The recently published 1iterature at home and abroad related the growth factor sustained-release microspheres in fat transplantation was reviewed and analyzed.
Results
The sustained-release microsphere carrier materials include natural polymer materials and synthetic polymer materials.The sustained-release complexes of different microsphere materials with different growth factors can promote the vascularization of transplanted fat in a timely manner, improve the survival rate of grafts, and reduce the incidence of complications such as liquefaction, calcification, and necrosis.
Conclusion
The growth factor sustained-release microspheres have the characteristics of persistence and controllability, which is a research hotspot in the field of fat transplantation and has broad application prospects.
Objective To investigate the growth of tumors and the natural life length of the rats after the adriamycinethylcellulose microspheres(ADM-EC mc) were injected in the rats bearing transplantable liver cancer through their hepatic arteries.Methods ADM-EC mc were infused into the proper hepatic arteries of the Wistar rats (W256). All of the rats were divided randomly into five groups, group 1: control, group 2: normal saline, group 3: conventional ADM, group 4: placebo ethylcellulose microspheres, and group 5: ADM-EC mc. Results As compared with other four groups, the ADM-EC mc (group 5) showed the best inhibition of the growth of tumors and the longest mean life length of the rats. Conclusion Hepatic arterial infusion of ADM-EC mc can inhibit the growth of the tumor, aggravate the necrosis, and improve the effects of the chemotherapy of liver cancer.
Four pigs underwent the hepatic arterial infusion with 32P glass microsphere (32PGM) and pigs were killed in 15th, 30th and 90th days separately. Pathological study showed that in early stage there were many small necrotic areas scattered along the hepatic arterioles. Three months later, these necrosis were gradually absorbed and replaced by regenerating hepatic cells. Tumor-inhibition experiment was performed in 40 Bal B/C mice bearing H22 hepatoma. Intratumoral injection of 0.2ml of 32PGM/glycerine suspension (group A, n=20) or 0.2ml of blank glass microsphere/glycerine suspension (group B, n=20) were performed. The average survival time in group A and group B was 24.8 and 11.8 days respectively. Five mice in group A were alive beyond 40 days after treatment, disappearance of tumor was found in two of them. This experiment demonstrates that 32PGM is effective for treatment of experiment hepatoma. The damage to hepatic tissue after infusion is associated with the irregular distribution of microsphere, and this lesion can completely recover within three months.
ObjectiveTo prepare polyurethane (PU) microspheres and evaluate its physicochemical properties and biocompatibility for biomedical applications in vitro.
MethodsThe PU microspheres were prepared by self-emulsification procedure at the emulsification rates of 1 000, 2 000, 3 000, and 4 000 r/min. The molecular structure was tested by Fourier transform infrared spectrometer and the surface and interior morphology of PU microspheres were observed by scanning electron microscopy (SEM). PU microspheres prepared at best emulsification rate were selected for the subsequent experiment. The human umbilical vein endothelial cells (HUVECs) were cultured and seeded on the materials, then cell morphology and adhesion status were observed by calcein-acetoxymethylester/pyridine iodide (Calcein-AM/PI) staining. The cells were cultured in the H-DMEM containing 10%FBS with additional 1% phenol (group A), in the extracts of PU prepared according to GB/T 16886.12 standard (group B), and in H-DMEM containing 10%FBS (group C), respectively. Cell counting kit 8 (CCK-8) assay was used to detect the cell viability. The blood compatibility experiments were used to evaluate the blood compatibility, the PU extracts as experimental group, stroke-physiological saline solution as negative control group, and distilled water as positive control group. The hemolytic rate was calculated.
ResultsThe SEM results of PU microspheres at the emulsification rate of 2 000 r/min showed better morphology and size. The microstructure of the PU was rough on the surface and porous inside. The Calcein-AM/PI staining showed that the HUVECs attached to the PU tightly and nearly all cells were stained by green. CCK-8 assays demonstrated that group B and group C presented a significantly higher cell proliferative activity than group A (P<0.05), indicating low cytotoxicity of the PU. The absorbance value was 0.864±0.002 in positive control group and was 0.015±0.001 in negative control group. The hemolysis rate of the PU extracts was 0.39%±0.07% (<5%), indicating no hemolysis.
ConclusionThe PU microspheres are successfully prepared by self-emulsification. The scaffold can obviously promote cell attachments and proliferation and shows low cytotoxicity and favorable blood compatibility, so it might be an ideal filler for soft tissue.
Objective To study the release properties of basic fibroblast growth factor (bFGF) chitosan microspheres prepared by cross-linking-emulsion method using chitosan as a carrier material so as to lay a foundation for further study. Methods Using 0.6% sodium tripolyphosphate solution as a crosslinking agent and 1.5% solution of chitosan as a carrier material, bFGF chitosan microspheres were prepared by cross-linking-emulsion method. Laser particle size analyzer and Zeta electric potential analyzer were used to measure the particle diameter distribution, scanning electronic microscope to observe the morphology, and ELISA to determine the drug loading, the encapsulation rate, and the drug release properties. Results The particle size of bFGF chitosan microspheres ranged 20.312-24.152 μm. The microspheres were round with a smooth surface and uniform distribution, and it had no apparent porosity. The drug loading and encapsulation rate of microspheres were (7.57 ± 0.34) mg/g and 95.14% ± 1.58%, respectively. The bFGF chitosan microspheres could continuously release bFGF for 24 days; the bFGF level increased gradually with time and reached (820.45 ± 21.34) ng/mL at 24 days; and the microspheres had a burst effect, and the burst rate was 18.08%, and the accumulative release rate of the microspheres reached 82.05% during 24 days. Conclusion It is easy-to-operate to prepare the bFGF chitosan microspheres with the cross-linking-emulsion method. The bFGF chitosan microspheres have smooth surface, uniform distribution, and no apparent porosity.
Objective To prepare a novel hyaluronic acid methacrylate (HAMA) hydrogel microspheres loaded polyhedral oligomeric silsesquioxane-diclofenac sodium (POSS-DS) patricles, then investigate its physicochemical characteristics and in vitro and in vivo biological properties. Methods Using sulfhydryl POSS (POSS-SH) as a nano-construction platform, polyethylene glycol and DS were chemically linked through the “click chemistry” method to construct functional nanoparticle POSS-DS. The composition was analyzed by nuclear magnetic resonance spectroscopy and the morphology was characterized by transmission electron microscopy. In order to achieve drug sustained release, POSS-DS was encapsulated in HAMA, and hybrid hydrogel microspheres were prepared by microfluidic technology, namely HAMA@POSS-DS. The morphology of the hybrid hydrogel microspheres was characterized by optical microscope and scanning electron microscope. The in vitro degradation and drug release efficiency were observed. Cell counting kit 8 (CCK-8) and live/dead staining were used to detect the effect on chondrocyte proliferation. Moreover, a chondrocyte inflammation model was constructed and cultured with HAMA@POSS-DS. The relevant inflammatory indicators, including collagen type Ⅱ, aggrecan (AGG), matrix metalloproteinase 13 (MMP-13), recombinant A disintegrin and metalloproteinase with thrombospondin 5 (Adamts5), and recombinant tachykinin precursor 1 (TAC1) were detected by immunofluorescence staining and real-time fluorescence quantitative PCR, with normal cultured chondrocytes and the chondrocyte inflammation model without treatment as control group and blank group respectively to further evaluate their anti-inflammatory activity. Finally, by constructing a rat model of knee osteoarthritis, the effectiveness of HAMA@POSS-DS on osteoarthritis was evaluated by X-ray film and Micro-CT examination. Results The overall particle size of POSS-DS nanoparticles was uniform with a diameter of about 100 nm. HAMA@POSS-DS hydrogel microspheres were opaque spheres with a diameter of about 100 μm and a spherical porous structure. The degradation period was 9 weeks, during which the loaded POSS-DS nanoparticles were slowly released. CCK-8 and live/dead staining showed no obvious cytotoxicity at HAMA@POSS-DS, and POSS-DS released by HAMA@POSS-DS significantly promoted cell proliferation (P<0.05). In the chondrocyte anti-inflammatory experiment, the relative expression of collagen type Ⅱ mRNA in HAMA@POSS-DS group was significantly higher than that in control group and blank group (P<0.05). The relative expression level of AGG mRNA was significantly higher than that of blank group (P<0.05). The relative expressions of MMP-13, Adamts5, and TAC1 mRNA in HAMA@POSS-DS group were significantly lower than those in blank group (P<0.05). In vivo experiments showed that the joint space width decreased after operation in rats with osteoarthritis, but HAMA@POSS-DS delayed the process of joint space narrowing and significantly improved the periarticular osteophytosis (P<0.05). Conclusion HAMA@POSS-DS can effectively regulate the local inflammatory microenvironment and significantly promote chondrocyte proliferation, which is conducive to promoting cartilage regeneration and repair in osteoarthritis.
Objective To investigate the promotion effects of the collagen membrane incorporating bFGF impregnated microspheres on the wound healing of the pigskin losing its full-thickness layers. Methods The bFGF containing microspheres was added into the dry microspleres.The collagen membranes were prepared by incorporating bFGF-impregnated microspheres, and 6 York pig models of skin wounds with loss of their full-thickness layers were established for the ob servation of the effects on the wound healing. Results The healing time and the 28day healing rate were 27.30±1.14 days and 98.12%±1.97%, respectively.The healing rate was significantly higher and the healing time was significantl y shorter in the experimental group than in the control group (Plt;0.05). The histological examination showed that the proliferation condition of the epidermiswasalso much better in the experimental group. Conclusion Incorporation of bFGF-impregnated microspheres into the collagen membrane is a promising method of pro moting the healing of the wound with a loss of the fullthickness skin.
There are six important developmental milestones for yttrium 90 microspheres in treatment of hepatocellular carcinoma (HCC). These milestones are: ① development of concepts in treatment of HCC; ② development of concepts in internal radiation therapy; ③ from basic, translational and clinical researches to clinical application; ④ internationally recognized indications for palliative treat ment of HCC; ⑤ from palliative to curative treatment of HCC after tumor downstaging with yttrium 90 microspheres using liver resection or liver transplantation; ⑥ non-surgical treatments using yttrium 90 microsphere as curative treatments. The developmental stages of yttrium 90 microsphere in treatment of HCC have undergone a very prolonged period and these stages will continue to evolve. As HCC is prevalent in China, permission of the State Food and Drug Administration to allow yttrium 90 microsphere to be clinically used on HCC patients in China will benefit a lot of patients who were not treatable by other means.
The purpose of this study is to investigate the effect of superparamagnetic chitosan FGF-2 gelatin microspheres (SPCFGM) on the proliferation and differentiation of mouse mesenchymal stem cells. The superparamagnetic iron oxide chitosan nanoparticles (SPIOCNs) were synthesized by means of chemical co-precipitation, combined with FGF-2. Then The SPCFGM and superparamagnetic chitosan gelatin microspheres (SPCGM) were prepared by means of crosslinking-emulsion. The properties of SPCFGM and SPIONs were measured by laser diffraction particle size analyser and transmisson electron microscopy. The SPCFGM were measured for drug loading capacity, encapsulation efficiency and release pharmaceutical properties in vitro. The C3H10 cells were grouped according to the different ingredients being added to the culture medium: SPCFGM group, SPCGM group and DMEM as control group. Cell apoptosis was analyzed by DAPI staining. The protein expression level of FGF-2 was determined by Western blot. The proliferation activity and cell cycle phase of C3H10 were examined by CCK8 and flow cytometry. The results demonstrated that both of the SPIOCNs and SPCFGM were exhibited structure of spherical crystallization with a diameter of (25±9) nm and (140±12) μm, respectively. There were no apoptosis cells in the three group cells. Both the protein expression level of FGF-2 and cell proliferation activity increased significantly in the SPCFGM group cells(P<0.05). The SPCFGM is successfully constructed and it can controlled-release FGF-2, remained the biological activity of FGF-2, which can promote proliferation activity of C3H10 cells, and are non-toxic to the cell.
Objective To estimate the relationship between arterial blood ketone body ratio (AKBR) and liver function and to appraise the feasibility of adding AKBR into liver function estimate. MethodsFrom 1994 to 1998, 44 patients with unresectable liver cancer recieved the combined radiochemoembolization with mixed emulsion of phosphorus32 glass microspheres (32PGMS), chemoagent and glycerine or lipiodol, via intraoperative hepatic artery instillation, hepatic artery ligation and operational arterial embolization (HAL+OAE) or transcatheter hepatic artery embolization (TAE). Preoperative and postoperative function and energy change level of the liver were tested by liver function test and AKBR. CT, SPECT, AFP were used to judge the therapy effect; multivariate statistical analysis methods were used to evaluate the correlation between AKBR and liver function. Spearmen rank correlation analysis was used to evaluate whether there was any relationship between AKBR and liver function test, and to evaluate that there was any relationship between AKBR and survival time. ResultsA negative correlation showed between the level of AKBR and liver function. The correlation coefficient of the three level of AKBR before operation and survival time was 0.4409. Conclusion AKBR can well reflect the degree of liver function.
