Objective To investigate the preparation and properties of the novel silica (SiO2)/hydroxyapatite (HAP) whiskers porous ceramics scaffold. Methods The HAP whiskers were modified by the SiO2 microspheres using the Stöber method. Three types of SiO2/HAP whiskers were fabricated under different factors (for the No.1 samples, the content of tetraethoxysilane, stirring time, calcination temperature, and soaking time were 10 mL, 12 hours, 560℃, and 0.5 hours, respectively; and in the No.2 samples, those were 15 mL, 24 hours, 650℃, and 2 hours, respectively; while those in the No.3 samples were 20 mL, 48 hours, 750℃, and 4 hours, respectively). The phase and morphology of the self-made HAP whisker and 3 types of SiO2/HAP whiskers were detected by the X-ray diffraction analysis and scanning electron microscopy. Taken the self-made HAP whisker and 3 types of SiO2/HAP whiskers as raw materials, various porous ceramic materials were prepared using the mechanical foaming method combined with extrusion molding method, and the low-temperature heat treatment. The pore structure of porous ceramics was observed by scanning electron microscopy. Its porosity and pore size distribution were measured. And further the axial compressive strength was measured, and the biodegradability was detected by simulated body fluid. Cell counting kit 8 method was used to conduct cytotoxicity experiments on the extract of porous ceramics. Results The SiO2 microspheres modified HAP whiskers and its porous ceramic materials were prepared successfully, respectively. In the SiO2/HAP whiskers, the amorphous SiO2 microspheres with a diameter of 200 nm, uniform distribution and good adhesion were attached to the surface of the whiskers, and the number of microspheres was controllable. The apparent porosity of the porous ceramic scaffold was about 78%, and its pore structure was composed of neatly arranged longitudinal through-holes and a large number of micro/nano through-holes. Compared with HAP whisker porous ceramic, the axial compressive strength of the SiO2/HAP whisker porous ceramics could reach 1.0 MPa, which increased the strength by nearly 4 times. Among them, the axial compressive strength of the No.2 SiO2/HAP whisker porous ceramic was the highest. The SiO2 microspheres attached to the surface of the whiskers could provide sites for the deposition of apatite. With the content of SiO2 microspheres increased, the deposition rate of apatite accelerated. The cytotoxicity level of the prepared porous ceramics ranged from 0 to 1, without cytotoxicity. Conclusion SiO2/HAP whisker porous ceramics have good biological activity, high porosity, three-dimensional complex pore structure, good axial compressive strength, and no cytotoxicity, which make it a promising scaffold material for bone tissue engineering.
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.
Calcium phosphate cement (CPC) has been widely used as bone fillers because of its excellent bioactivity and biocompatibility. Meanwhile, CPC is also an attractive candidate for the incorporation of drug or microspheres, because the preparing procedure avoids sintering and heating release. This paper summarizes the clinical applications of microspheres incorporated in CPC from the aspects of sustained drug release, accelerated degradation, porous structure and improved mechanical properties. The paper is aimed to analyze the methods and principles of microspheres loaded CPC, and so as to lay a foundation for the further research of improving and manufacturing the CPC with ideal properties.
Objective To investigate the performance of loading naringin composite scaffolds and its effects on repair of osteochondral defects. Methods The loading naringin and unloading naringin sustained release microspheres were prepared by W/O/W method; with the materials of the attpulgite and the collagen type I, the loading naringin, unloading naringin, and loading transforming growth factor β1 (TGF-β1) osteochondral composite scaffolds were constructed respectively by " 3 layers sandwich method”. The effect of sustained-release of loading naringin microspheres, the morphology of the composite scaffolds, and the biocompatibility were evaluated respectively by releasingin vitro, scanning electron microscope, and cell counting kit 8. Forty Japanese white rabbits were randomly divided into groups A, B, C, and D, 10 rabbits each group. After a osteochondral defect of 4.5 mm in diameter and 4 mm in depth was made in the intercondylar fossa of two femurs. Defect was not repaired in group A (blank control), and defect was repaired with unloading naringin composite scaffolds (negative control group), loading naringin composite scaffolds (experimental group), and loading TGF-β1 composite scaffolds (positive control group) in groups B, C, and D respectively. At 3 and 6 months after repair, the intercondylar fossa was harvested for the general, HE staining, and toluidine blue staining to observe the repair effect. Western blot was used to detect the expression of collagen type II in the new cartilage. Results Loading naringin microspheres had good effect of sustained-release; the osteochondral composite scaffolds had good porosity; the cell proliferation rate on loading naringin composite scaffold was increased significantly when compared with unloading naringin scaffold (P<0.05). General observation revealed that defect range of groups C and D was reduced significantly when compared with groups A and B at 3 months after repair; at 6 months after repair, defects of group C were covered by new cartilage, and new cartilage well integrated with the adjacent cartilage in group D. The results of histological staining revealed that defects were filled with a small amount of fibrous tissue in groups A and B, and a small amount of new cartilage in groups C and D at 3 months after repair; new cartilage of groups C and D was similar to normal cartilage, but defects were filled with a large amount of fibrous tissue in groups A and B at 6 months after repair. The expression of collagen type II in groups C and D was significantly higher than that in groups A and B (P<0.05), but no significant difference was found between groups C and D (P>0.05). Conclusion Loading naringin composite scaffolds have good biocompatibility and effect in repair of rabbit articular osteochondral defects.
ObjectiveTo evaluate the effect of bone morphogenetic protein 7 (BMP-7)/poly (lactide-co-glycolide) (PLGA) microspheres on in vitro proliferation and chondrogenic differentiation of rabbit bone marrow mesenchymal stem cells (BMSCs).MethodsBMP-7/PLGA microspheres were fabricated by double emulsion-drying in liquid method. After mixing BMP-7/PLGA microspheres with the chondrogenic differentiation medium, the supernatant was collected on the 1st, 3rd, 7th, 14th, and 21st day as the releasing solution. The BMSCs were isolated from the bilateral femurs and tibias of 3-5 days old New Zealand rabbits, and the 3rd generation BMSCs were divided into 2 groups: microspheres group and control group. The BMSCs in microspheres group were cultured by 200 μL BMP-7/PLGA microspheres releasing solution in the process of changing liquid every 2-3 days, while in control group were cultured by chondrogenic medium. The cell proliferation (by MTT assay) and the glycosaminoglycan (GAG) contents (by Alician blue staining) were detected after chondrogenic cultured for 1, 3, 7, 14, and 21 days. The chondrogenic differentiation of BMSCs was observed by safranine O staining, toluidine blue staining, and collagen type Ⅱ immunohistochemistry staining at 21 days.ResultsMTT test showed that BMSCs proliferated rapidly in 2 groups at 1, 3, and 7 days; after 7 days, the proliferation of BMSCs in the control group was slow and the BMSCs in microspheres group continued to proliferate rapidly. There was no significant difference of the absorbance (A) value at 1, 3, and 7 days between 2 groups (P>0.05), but theA value at 14 and 21 days in microspheres group was significantly higher than that in control group (P<0.05). Compared with control group at 21 days, in microsphere group, almost all nuclei were dyed bright red by safranine O staining, almost all the nuclei appeared metachromatic purple red by toluidine blue staining, and the most nuclei were yellow or brown by immunohistochemical staining of collagen type Ⅱ. Alcian blue staining showed that the content of GAG in 2 groups increased continuously at different time points; after 7 days, the increasing trend of the control group was slow and the microspheres group continued hypersecretion. There was no significant difference of the GAG content at 1, 3, and 7 days between 2 groups (P>0.05), but the GAG content at 14 and 21 days in microspheres group was significantly higher than that in control group (P<0.05).ConclusionBMP-7/PLGA microspheres prepared by double emulsion-drying in liquid method in vitro can promote proliferation and chondrogenic differentiation of rabbit BMSCs.
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.
Objective To evaluate the effect of the local del ivery of basic fibroblast growth factor 2 (bFGF-2) on the osseointegration around titanium implant of diabetic rats. Methods The bFGF-2-loaded poly (lactic-co-glycol ic acid) microspheres were prepared by water/oil/water (W/O/W) double-emulsion solvent evaporation method. Thirty-five male SPF level Sprague Dawley rats, weighing 220-250 g and aged 9 weeks, were selected as experimental animals. Ten rats were fedwith the routine diet as normal control group. The other 25 rats were made the diabetic animal model by giving high fat-sugar diet and a low dose streptozotocin (30 mg/ kg) intravenously; 20 rats were made the diabetic animal model successfully. Then 20 rats were randomly divided into diabetic control group (n=10) and bFGF-2 intervention group (n=10). A hole was drilled in the right tibia bone of all rats, and the titanium implant treated by micro-arc oxidation surface was planted into the hole. Simultaneously, the previously prepared microspheres and blood were mixed and were loaded on the surface of the implant before it was implanted into the rats of the bFGF-2 intervention group. At 4 and 8 weeks, the tibia containing implants was harvested, embedded with resin and made undecalcified tissue sl ices to compare the osseointegration. Results At 4 weeks, the implants of the normal control group were surrounded by new lamellar bone with continuity; whereas the tissue around the implants of the diabetic control group contained l ittle woven bone and some fibrous tissue; and obvious new formed bone with continuity was observed in bFGF-2 intervention group. At 8 weeks, the results of 3 groups were similar to those at 4 weeks. At 4 weeks, the percentage of bone-implant contact (BIC) in diabetic control group was significantly less than those in normal control group (P lt; 0.05) and in bFGF-2 intervention group (P lt; 0.05); the BIC in bFGF-2 intervention group was less than in normal control group, but showing no significant difference (P gt; 0.05). After 8 weeks, the BIC in normal control group and in bFGF-2 intervention group were significantly greater than that in diabetic control group (P lt; 0.05), but there was no significant difference between bFGF-2 intervention group and normal control group (P gt; 0.05). Conclusion Local del ivery of bFGF-2 around titanium implants may improve the osseointegration in diabetic rats.
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.
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.
Curcumin-loaded poly (α-isobutyl cyanoacrylate) microspheres (Cur-HP-β-CD-PiBCA) were prepared by one-step emulsification with α-isobutyl cyanoacrylate as materials, poloxamer 188 as emulsifier, and curcumin complex with hydroxypropyl-β-cyclodextrin (Cur-HP-β-CD) as drug prepared by kneading method. Effects of emulsifier and drug concentration on microspheres size and distribution, drug loading and encapsulation efficiency were investigated in detail. And the curcumin release of drug-loaded microspheres was also studied. Results showed that as the emulsifier concentration increased from 0.01% to 0.07%, particle size of the drug-loaded microspheres decreased while particle size distribution, drug loading and entrapment efficiency increased. The optimized concentration of surfactant was 0.05%. With increasing the concentration of drug from 0.03% to 0.07%, drug loading of Cur-HP-β-CD-PiBCA increased, but encapsulation efficiency decreased. Additionally, the results of drug release experiments revealed that the higher drug loading of Cur-HP-β-CD-PiBCA was, the lower cumulative release percentage was. Drug-loading of cumulative inclusions in HP-β-CD by PiBCA can improve its wettability, and increase the degree of dissolution and bioavailability.