Recombinant Basic Fibroblast Growth Factor Research Articles

Successful Management of Wound Dehiscence after Total Knee Arthroplasty by Topically Using Recombinant Basic Fibroblast Growth Factor

Wound complications are estimated to be affected in about 9% of TKA patients, which may increase the risk of deep periprosthetic infection and results in re-operation, joint fusion, or amputation. Here we have reported a female patient who suffered wound rupture due to early post-operation mobilization and weight-bearing. The wound dehiscence was successfully managed by applying recombinant basic fibroblast growth factor-2 and anti-infective treatment without removing prosthetic joint.

Epidermal Necrosis of Forearm and Wrist due to Extravasation of Sodium Bicarbonate and Application of Epidermal Growth Factor for Therapy in Extremely Low Birth Weight Infant

Extravasation occurs when an intravenous drug is inadvertently administered into the perivascular space or subcutaneous tissue. This can have various consequences, from local irritation to severe tissue loss. Extravasation occur more frequently in neonatal populations, especially in younger gestational ages and with lower birth weights. There is no established method of treatment for extravasation. Conservative treatments such as saline wash, wet dressing, hyaluronidase, and hydrogel dressing should be performed. Recently, two full-term newborns have been reported to successfully treat skin necrosis with recombinant human basic fibroblast growth factor. We report for the first time that extravasation in extremely very low birth weight infants can be successfully treated with recombinant human epidermal growth factor.

Observation of curative effect of recombinant human basic fibroblast growth factor combined with compound polymyxin B ointment and local application of insulin on wound healing of deep second-degree burn in diabetes mellitus: a randomized study.

We aimed at investigating the clinical efficacy of recombinant human basic fibroblast growth factor combined with compound polymyxin B ointment and the local application of insulin on wound healing of deep second-degree burn in diabetes mellitus. 80 diabetes mellitus patients complicated with deep second-degree burn treated from 2016 to December 2017 were selected and divided into observation group (n=40) and control group (n=40) using the random number method. Patients in control group were treated with compound polymyxin B ointment, while those in observation group were treated with basic fibroblast growth factor based on the treatment in control group. The time of wound pain relief, wound scarring, and wound healing was compared. The number of positive bacteria in the wound was recorded and the duration of infection was also recorded. Moreover, the changes in the expressions of Advanced Glycation End products (AGEs) and Vascular Endothelial Growth Factor (VEGF) were analyzed. In observation group, the time of wound pain relief, wound scarring, and wound healing was significantly shorter than that in control group (p<0.05). At 3, 14, and 28 days after the treatment, the levels of AGEs in observation group were lower than those in control group, while the levels of VEGF in the observation group were higher than those in control group (p<0.05). The proportions of wound infection, skin necrosis, systemic blood infection, hypoglycemia, and hyperglycemia and the ineffective rate in observation group were significantly lower than that in control group (p<0.05). The application of compound polymyxin B ointment and the local application of insulin combined with recombinant human basic fibroblast growth factor in diabetes mellitus patients complicated with a deep second-degree burn can effectively alleviate the pain, reduce the wound infection rate, promote the wound healing, and improve the overall therapeutic effect.

Optimizing a serum-free/xeno-free culture medium for culturing and promoting the proliferation of human dental pulp stem cells.

Dental pulp stem cells (DPSCs) hold great promise for utilization in tissue repair and regenerative medicine. Routinely, culture media used for culturing stem cells are supplemented with animal serum for promoting growth and successful maintenance of stem cells. However, there is a growing demand for optimizing a well-defined culture media that could safely increase the efficacy and reproducibility of the cultured cells. In this study, we aimed at optimizing a serum-free/xeno-free culture medium. A cocktail of various supplements intended to enrich DPSCs proliferation in defined concentrations was designed. It consisted of recombinant human basic fibroblast growth factor (hbFGF), insulin transferrin selenium (ITS), ascorbic acid (vitamin C), Beta mercaptoethanol and cholesterol. The effect of this optimized media on the proliferation of DPSCs was assessed by MTT assay and flow cytometric analysis (FACS) of early apoptotic marker annexin V. Expression of stemness-related genes (OCT4, SOX and NANOG) was assessed by qRT-PCR. Proliferation results by MTT illustrated a significant increase in the proliferation rate of DPSCs cultured in the proposed media. FACS analysis of annexin V expression was nil. Expression of OCT4, SOX and NANOG genes was also up-regulated. The proposed combination of supplements utilized in the proposed culture media successfully increased the proliferation potential of DPSCs in addition to enhancing the stemness properties. Thus, it can be considered a promising and safe substitute to traditional animal derived supplements like fetal bovine serum (FBS).

Effects of Periploca forrestii Schltr on wound healing by Src meditated Mek/Erk and PI3K/Akt signals

Ethnopharmacological relevancePeriploca forrestii Schltr. (PF) is a traditional folk medicine in China that has been used widely for treating rheumatoid arthritis and traumatic injuries for a long history. Previously, we have roughly demonstrated that the ethanol extract of PF possessed in vitro wound healing potential, and more in depth research deserves to be conducted. Aim of the studyThe present study is aiming to fully evaluate the wound healing activity of PF in vitro and in vivo, clarify the mechanism of actions and the primary constituents responsible for wound healing. Materials and methodsThe total extract of Periploca forrestii Schltr. (EPF) and its fraction (65% ethanol fraction, EPFE65) were obtained and evaluated on in vitro wound healing properties using mouse dermal fibroblasts (L929). Cell proliferation was tested by MTT and EdU assay, confirmed by cell cycle analysis, cell migration was evaluated by scratch and transwell assay and collagen production was also determined. Then EPFE65 was tested on in vivo wound healing activity using the excision rat models. The wounded skin of rats was topically applied with 0.1% EPFE65 once daily for 6 days with hydrogel as the carrier and the recombinant bovine basic fibroblast growth factor hydrogel (rbFGF) as positive control. Histopathology of the wounded skin on day 6 and day 12 was studied via hematoxylin and eosin (HE) staining. The expression of phosphorylation of Src, Akt and Erk1/2 was determined after the treatment with EPFE65 by western blot. In order to figure out whether the activation of Src, Akt and Erk1/2 was directly in conjunction with wound healing process promoted by EPFE65, cell proliferation and migration were tested in the presence of three inhibitors of Src, Akt and Erk1/2. Finally, the chemical composition of the effective fraction EPFE65 was analyzed by HPLC-Q-TOF-MS/MS. ResultsIn vitro experiments suggested that EPFE65 was comparable to EPF that had potent effect on promoting L929 fibroblasts proliferation, migration and increasing collagen production. 0.1% EPFE65 hydrogel also exhibited significant effect on promoting wound healing in rats. The wound closure was significantly faster in EPFE65 and positive rbFGF group than that in negative control group since the third day post wounding (p < 0.05). Specifically, on day10–12, the wounds in EPFE65 and rbFGF group were almost healed as the wound areas diminished into 13.3–5.3% and 7.7–4.0%, while the wound in control group was still apparent with 36.8–22.1% wound area. HE staining demonstrated that EPFE65 and rbFGF group could advance re-epithelialization in the early days and promote the transition of granulation tissue into complete dermis tissue with more skin appendages resembling those of normal skin in the last days. Western blot results suggested that the active fraction EPFE65 could increase the phosphorylation of Src, Akt and Erk1/2 in both dose-dependent and time-dependent manner, whereas Akt and Erk1/2 phosphorylation caused by EPFE65 could be abolished by Src inhibition. Inhibition experiments confirmed that the activation of Src, Akt and Erk1/2 were involved in cell proliferation and migration. All of these demonstrated that EPFE65 promoted wound healing at least in part via Src mediated Mek/Erk and PI3K/Akt signaling pathways. Analysis of chemical composition of EPFE65 revealed that cardiac glycosides were major components in EPFE65, among which periplocin showed effectiveness on promoting fibroblasts proliferation indicating that cardiac glycosides in EPFE65 maybe the active compounds responsible for wound healing. ConclusionThe present study confirmed that EPFE65, ethanol extract of Periploca forrestii Schltr. could accelerate wound healing in vitro and in vivo through Src meditated Mek/Erk and PI3K/Akt signaling pathways.

Local supplementation with plant-derived recombinant human FGF2 protein enhances bone formation in critical-sized calvarial defects.

Numerous studies have demonstrated the advantages of plant cell suspension culture systems in producing bioactive recombinant human growth factors. This study investigated the biological activity of recombinant basic human fibroblast growth factor (rhFGF2) protein produced by a plant culture system to enhance new bone formation in a bone defect mouse model. The human FGF2 cDNA gene was cloned into a plant expression vector driven by the rice α-amylase 3D promoter. The vector was introduced into rice calli (Oryza sativa L. cv. Dongjin), and the clone with the highest expression of rhFGF2 was selected. Maximum accumulation of rhFGF2 protein (approximately 28mg/l) was reached at 13day post-incubation. Male C57BL/6 mice underwent calvarial defect surgery and the defects were loaded with absorbable collagen sponge (ACS) only (ACS group) or ACS impregnated with 5μg of plant-derived rhFGF2 (p-FGF2) protein or E. coli-derived rhFGF2 (e-FGF2) protein. Similar to the effects of e-FGF2, local delivery with p-FGF2 enhanced bone healing in the damaged region to higher levels than the ACS group. Exogenous addition of p-FGF2 or e-FGF2 exhibited similar effects on proliferation, mineralization, and osteogenic marker expression in MC3T3-E1 cells. Together, the current findings support the usefulness of this plant-based expression system for the production of biologically active rhFGF2.

Effect of recombinant bovine basic fibroblast growth factor gel on repair of rosacea skin lesions: A randomized, single-blind and vehicle-controlled study.

The aim of the present study was to assess the effect of topical use of recombinant bovine basic fibroblast growth factor (rbFGF) gel on the repair of facial skin lesions in patients with rosacea. In the present single-blind study, a total of 1,287 patients with Demodex mite-induced rosacea who received treatment with ornidazole tablets were randomized to rbFGF gel treatment group (n=651) or control group (n=636) without revealing the group identity. Patients in the treatment group were treated with topical application of rbFGF gel over the skin lesions (0.2 g/cm2) for up to 8 weeks, whereas patients in the control group received gel vehicle treatment unless ulceration occurred. Skin lesions of all patients were scored prior to and following treatment with rbFGF gel and subjected to histological analysis. All patients were followed up for 6 months. Significant improvement in the total effective rates for erythema, papules, desquamation and dryness were observed in the rbFGF treatment group. At the end of the 2, 4 and 6 months of follow-up, the total effective rates for patients in the treatment group were significantly higher than those in the control group (81.67 vs. 28.84%; 85.11 vs. 40.81%, and 96.56 vs. 55.82%, respectively). Following treatment for 6 months, none of the patients in the rbFGF group exhibited ulceration or scar formation. In the control group, 61% of patients experienced exacerbation of skin lesions, of which, 12% exhibited ulceration and were treated with rbFGF gel to prevent scar formation. Histological analysis revealed gradual reduction in epidermal hyperplasia and resolution of dermal edema in skin lesions treated with rbFGF gel. In conclusion, rbFGF gel may improve the repair of facial rosacea skin lesions in patients treated with anti-Demodex.

Adaptive change in temporomandibular joint tissue and mandibular morphology following surgically induced anterior disc displacement by bFGF injection in a rabbit model

PurposeThe purpose of this study was to examine the effect of injecting basic fibroblast growth factor following surgical induced anterior disc displacement in temporomandibular joints (TMJ). Materials and methodsAdult male Japanese white rabbits (n = 16; 2.0–2.5 kg; 10 weeks old) were assigned to experimental and control groups. In the experimental group, anterior disc displacement was induced in the bilateral TMJ. Recombinant human basic fibroblast growth factor (rh bFGF) 0.1 μg/1 μL aqueous solution was injected into the left retro-discal connective tissue close to the disc (ADL group), and saline alone was injected into the same site on the right (ADR group). In the control group, a sham operation without disc position change was performed in the bilateral TMJ (CR group and CL group). Four animals from the experimental (ADR and ADL) and control (CR and CL) groups were sacrificed at 1 and 12 weeks postoperatively to evaluate the mandibular morphology and computed tomographic (CT) value of the condylar head, using 3 dimensional computed tomography. Furthermore, cartilage layers and disc tissue were examined histologically. ResultsRegarding CT value at the 0° site of the condylar surface, ADR showed the lowest value after 1 week (P = 0.0325). However, there were no significant differences among the 4 groups regarding CT values at the other degree sites after 1 and 12 weeks. Regarding mandibular length, ADR showed the lowest value after 12 weeks (P = 0.0079). In condylar width, ADR showed the lowest value after 1 week (P = 0.0097). ConclusionThis study suggested that surgically induced anterior disc displacement could affect condylar morphology in the early stage, and could decrease mandibular length in the late stage. However, bFGF injection into the TMJ might prevent the degenerative change derived from anterior disc displacement and inhibition of sequential mandibular growth.

Analysis on the treatment of blepharospasm in children

Objective To observe the treatment efficacy of blepharospasm in children. Methods The data of 240 eyes of 120 cases with blepharospasm from May 2016 to Apr.2017 were collected. The optical history, symptom, visual acuity, refraction, Schirmer Ⅰtest(SIT), fluorescent staining(FL) and break-up time(BUT) were observed.All cases received application of recombinant bovine basic fibroblast growth factor(r-bFGF) eye-gel combined with warm compress to the lid.Compound tropicamide eye drops was applied to children with myopia.The followed up time was half a year. Results According to the degree of blepharospasm, 13 cases were grade Ⅰ, grade Ⅱ in 88 cases, and grade Ⅲ in 19 cases. There were 60 cases with myopia, 6 cases with astigmatism, and 3 cases with amblyopia. SIT were≤10 mm in 77 cases, BUT were<10 s in 73 cases, and FL were positive in 23 cases.After treatment, 91 cases had complete remission, 29 cases had partial remission, and the efficiency rate was 100%. Conclusion Dioptroscopy should be performed on children with blepharospasm, and half of the children with ametropia. Application of r-bFGF eye-gel combined with warm compress to the lid for the treatment of children with blepharospasm are effective. Key words: Blepharospasm, children; r-bFGF eye-gel; Ametropia; Treatment

Nerve growth factor and substance P may be involved in moist exposed burn ointment-mediated chronic refractory wound healing.

Moist exposed burn ointment (MEBO) is becoming increasingly popular in China as it shortens wound-healing time and reduces scar formation. However, its exact mechanism in mediating the wound-healing process is not yet clear. In the present study a total of 90 healthy adult male Wistar rats of specific-pathogen-free grade were divided equally into a control group, wound group, MEBO group, recombinant bovine basic fibroblast growth factor (rb-bFGF) group and sham operation group. Wound healing was observed from the extracted granulation tissues and recorded at three time points on 3, 7 and 14 days. Different levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in tissue homogenate were detected using ELISA. Western blot analysis and quantitative PCR were used to detect the expression of nerve growth factor (NGF), substance P (SP) as well as tyrosine kinase A (TrkA) receptor protein and the corresponding mRNA levels in granulation tissue. It was observed that the wound healing progressed faster in the MEBO and rb-bFGF groups compared with the wound group (P<0.01). TNF-α and IL-6 had an upward-downward trend at three time points, with the wound group demonstrating the most obvious increase (P<0.01). NGF and SP mRNA and protein levels in granulation tissue in MEBO, rb-bFGF and sham operation groups reached their highest levels on day 7 and then decreased on day 14. The expression level of TrkA was also measured simultaneously and its expression pattern was similar to that of NGF and SP. These results suggested that MEBO may promote nerve repair and accelerate wound healing through mediating the expression levels of NGF and SP, as well as TrkA.

Production of a biologically active human basic fibroblast growth factor using silkworm-baculovirus expression vector system

Abstract As a therapeutic treatment, recombinant human basic fibroblast growth factor (rhbFGF) is usually employed in tissue regeneration, and as an essential component in culture medium for maintaining the induced pluripotent stem (iPS) cell and embryonic stem (ES) cell in an undifferentiated state. Therefore, a large amount of biologically active rhbFGF is required. In this study, silkworm-baculovirus expression vector system (silkworm-BEVS) is employed to achieve a high productivity of recombinant rhbFGF with two small affinity tags (His-tag and STREP-tag) at the N or C-terminus. It is observed that rhbFGF with 30 K signal peptide of silkworm were successfully expressed but are not sufficiently secreted into the culture medium of cultured insect cells. Then we purified the N- or C-tagged intracellular rhbFGF protein and obtained a yield of about 0.7 mg/larva and 1.2 mg/larva, respectively. Although the final yield of the C-tagged rhbFGF is higher than that of the N-tagged, rhbFGF with N-tag demonstrated promising and comparable biological activity, which is evaluated through a mammalian cell proliferation assay. Taken together, these results indicate that silkworm-BEVS could contribute to the mass-production of the biologically active rhbFGF for medical uses.

Effect of different dosage of recombinant human basic fibroblast growth factor on skin and muscle

Objective To observe the effect of external recombinant human basic fibroblast growth factor (rh-bFGF) on the skin and muscles. Methods 40 BALB/c mice of 6 weeks were randomly divided into skin and muscle groups. The skin group was randomly divided into group A and group B. The skin group was injected with 100U rh-bFGF and the same dose of saline in the chin. The muscle groups were randomly divided into C, D, E, and F, and the muscle group was injected into the left calf muscle in order of 200, 400, 800U rh-bFGF and the same dose of normal saline. The materal was taken at week 8. HE staining was used to observe the submental tissue and muscle fiber morphology. Two groups of muscle fibers, collagen and fibrous tissue were detected by trichrome stain. Immunohistochemistry was used to determine the blood vessel density of the chin and gastrocnemius. Results In week 8, 10 mice in group A had a mass in the lower jaw, and the gastrocnemius of the groups C and D showed hypertrophy. Group A showed the thickness of epidermis, dermal papillary layer and mucosa, hair follicle and blood vessel quantity, glandular cavity, collagen and fiber content were sigificantly greater than that of group B (P<0.05). In the groups C, D and E, the gastrocnemius muscle was significantly thicker than that of group F, and the thickening of group D was the most obvious (P<0.05), and the contents of collagen and fiber in the groups C, D and E were significantly higher than that in group F. Conclusions Subcutaneous injection of rh-bFGF leads to submental skin thickening, vascular hyperplasia, increased diameter of hair follicle and higher collagen and fiber contents; intramuscular injection of it may induce the muscular hypertrophy and vascular proliferation. Key words: Rh-bFGF; Skin; Gastrocnemius

Ectopic osteogenesis effect of antigen-extracted xenogeneic cancellous bone graft with chitosan/rhBMP-2/bFGF sequential sustained-release nanocapsules.

To explore the ectopic osteogenesis effect of sequential sustained release application of recombinant human bone morphogenic protein-2 (rhBMP-2) and basic fibroblast growth factor (bFGF). Antigen-extracted xenogeneic cancellous bone coupled with growth factor-loaded chitosan nanocapsules were implanted in rats in intramuscular site in accordance with the following experimental pattern: group A: simultaneous burst release of rhBMP-2 and bFGF; group B: simultaneous sustained release of rhBMP-2 and bFGF; group C: preferential burst release of rhBMP-2, then sustained release of bFGF; group D: preferential burst release of bFGF, then sustained release of rhBMP-2; group E: sustained release of rhBMP-2 alone; group F: sustained release of bFGF alone, blank control group G: antigen-extracted xenogeneic cancellous bone graft only; negative control group H: not filled with anything. Specimens were obtained after executing the animals at 2 and 4 weeks for general observation and weighing, calcium content detection, micro-CT scanning and bone parameter measurement analysis, H&E staining, ALP staining and CD34 staining. The materials weight of A-2, B-2, C-2, A-4, B-4, C-4, D-4 and E-4 were significantly higher than that of preoperative materials ( P < 0.05). The concentration of calcium of group B-4 was the highest (414.7 ± 12.03 mg/dl). Micro-CT scanning and bone parameter measurement analysis showed that the values of bone mineral density and trabecular thickness of group A, B, D, E at 4 weeks were both higher than the ones at 2 weeks ( P < 0.05), and both the bone mineral density (367.52 ± 11.64 mg/cc) and the trabecular thickness (126.17 ± 11.36 μm) of group B-4 were the highest. H&E staining showed that a large region of calcified cartilage and haemopoietic tissues were newly formed, especially in group B-4. ALP staining and CD34 staining showed the most positive expression region in group B-4. Therefore, we conclude that simultaneous sustained release of rhBMP-2 and bFGF is the ideal way to release drug, and has better inducement of antigen-extracted xenogeneic cancellous bone graft.

Binding efficiency of recombinant collagen-binding basic fibroblast growth factors (CBD-bFGFs) and their promotion for NIH-3T3 cell proliferation.

The recombinant basic fibroblast growth factor (bFGF) containing collagen-binding domain (CBD) has been found to be a potential therapeutic factor in tissue regeneration. However, its binding efficiency and quantification remain uncertain. In this research, massive recombinant bFGFs with good bioactivity for enhancing the proliferation of NIH-3T3 cells were achieved. An ELISA-based quantitative method was set up to investigate the binding efficiency of CBD-bFGFs on collagen films. It indicated that the CBDs significantly increased the collagen-binding ability of bFGF (P<.05), with the optimum binding condition first determined to be in the pH range of 7.5-9.5 (P<.05). Then, the relevant equations to calculate the binding density of bFGF, C-bFGF, and V-bFGF were acquired. Analysis confirmed that the bioactivity of immobilized bFGFs was well correlated with the density of growth factor on collagen films. Based on this research, the density of growth factor is a logical and applicable dosage unit for quantification of binding efficiency of growth factors, rather than traditional concentration of soluble growth factors in tissue engineering applications.

Establishment of protocol for preparation of gene-edited bovine ear-derived fibroblasts for somatic cell nuclear transplantation.

Recently, gene-editing using the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated protein 9 (Cas9) technique has attempted to utilize fibroblasts of livestock animals for somatic cell nuclear transfer. In this study, we establish the procedure for preparing skin fibroblast clones whose genes were edited by the CRISPR/Cas9 technique. After isolating fibroblasts from earlobes of Japanese Black cattle, subsequent collagenase-digestion and extensive wash procedures enabled us to avoid contamination of fungi. Electroporation using NEPA21, rather than lipofection using commercially available liposome reagents, allowed us to perform more efficient transfection of plasmid constructs. Although bovine ear-derived fibroblasts were not able to proliferate in single cell cultures in Dulbecco's modified Eagle medium containing 10% fetal calf serum, supplementation with insulin-transferrin-selenium mixture, human recombinant epidermal growth factor, or human recombinant basic fibroblast growth factor promoted proliferation of the cells, even in a single cell culture. Taking advantage of our established protocol, we eventually obtained eight ear-derived fibroblast clones with a recessive mutation in the isoleucyl-tRNA synthetase gene corrected by the CRISPR/Cas9 technique.

Evaluation of the use of recombinant human basic fibroblast growth factor in combination with negative pressure wound therapy with instillation and dwell time in porcine full-thickness wound model.

NPWT with instillation and dwell time (NPWTi-d), which combines NPWT with wound irrigation, has been clinically applied as a more effective treatment than conventional NPWT. Commercially available recombinant human basic fibroblast growth factor (rh-bFGF) has been demonstrated to be beneficial for use over the wound beds. The objective of this study was to evaluate the effectiveness of combined treatment with NPWTi-d and rh-bFGF. Six pigs received 12 full-thickness excisional skin wounds and were treated with six different treatment groups for each pair. The treatment regimens were composed NPWTi-d, NPWT, or advanced wound care with or without rh-bFGF. On day 6, the minimum granulation tissue thickness and blood vessel number of the group of combined treatment with NPWTi-d and rh-bFGF spray were significantly greater than that of the control group. Combined treatment with NPWTi-d and rh-bFGF spray reads to good granulation tissue formation and vascularization for accelerating wound healing.

The efficacy of basic fibroblast growth factor-loaded poly(lactic-co-glycolic acid) nanosheet for mouse wound healing.

Although human recombinant basic fibroblast growth factor (bFGF) is widely used for wound healing, daily treatment with bFGF is required because of its short half-life. An effective controlled-release system of bFGF is, therefore, desired in clinical settings. To investigate the efficacy of a bFGF-loaded nanosheet for wound healing, focusing on the controlled-release of bFGF, bFGF-loaded poly(lactic-co-glycolic acid) (PGLA) nanosheets were developed, and their in vitro release profile of bFGF and their in vivo efficacy for wound healing were examined. A polyion complex of positively charged human recombinant bFGF and negatively charged alginate was sandwiched between PLGA nanosheets (70 nm thick for each layer). The resulting bFGF-loaded nanosheet robustly adhered to silicon skin by observation using a microscratch test. bFGF was gradually and continuously released over three days in an in vitro incubation study. Treatment with the bFGF-loaded nanosheets (every 3 day for 15 days) as well as with a conventional bFGF spray effectively promoted wound healing of mouse dorsal skin defects with accelerated tissue granulation and angiogenesis, although the dose of bFGF used in the treatment with the bFGF nanosheets was approximately 1/20 of the sprayed bFGF. In conclusion, we developed a bFGF-loaded nanosheet that sustained a continuous release of bFGF over three days and effectively promoted wound healing in mice.

Experimental study on accelerated healing of jaw fracture using gelatin sponge compound growth factor

To explore the role and mechanism of drug delivery systems using growth factor combined with gelatin sponge on accelerating the healing of jaw fracture and to seek better treatment of accelerating the maxillofacial fracture. About 100 μg recombinant human bone morphogenetic protein (BMP)-2 was completely dissolved in 1 mL recombinant bovine basic fibroblast growth factor (bFGF), and the solution (40 μL) was dropped in gelatin sponge (0.5 cm×0.5 cm×1.0 cm). Then, it was freeze dried and prepared into bFGF/BMP/gelatin sponge delivery systems. The mandibular fracture model on two sides were prepared in 12 New Zealand rabbits and randomly divided into two groups. The left side was the control group, which was only fixed with titanium plates. The right side was the experimental group, in which bFGF/BMP/gelatin sponge delivery systems were put under the titanium plates. General observation, X-ray, and histological examination were taken at 2, 4, and 12 weeks after surgery. After 2 weeks, more fibrous tissues were seen between the fracture ends in the experimental group than in the control group. After 4 weeks, fibrous fracture callus were seen in the fracture gap in the experimental group. The ingrowths of fibrous tissue and blood vessels were seen in the control group. The fracture healing of the experimental group was significantly faster than the control group at 2 and 4 weeks. After 12 weeks, the experimental and control groups all healed completely. bFGF/BMP/gelatin sponge can accelerate and improve fracture healing; thus, it has better clinical application prospect.

A pro-angiogenic degradable Mg-poly(lactic-co-glycolic acid) implant combined with rhbFGF in a rat limb ischemia model.

Magnesium (Mg)-based implant has been already used in patients with critical limb ischemia. Site-specific controlled release of recombinant human basic fibroblast growth factor (rhbFGF), has become a promising approach to improve peripheral vascular disease. We report here on a novel combination implant composed of spiral magnesium and a coating made using poly(lactic-co-glycolic acid) (PLGA) with encapsulated rhbFGF (Mg-PLGA-rhbFGF). The preparation method does not involve any complex processes and results in a high encapsulation efficiency (approximately 100%). The degradation of metal Mg raise the microclimate pH in the PLGA polymer, which could well preserve the bioactivity of rhbFGF incorporated in the implant. Mg-PLGA-based, sustained local delivery of rhbFGF promotes post-ischemic angiogenesis and blood flow recovery in rat limb ischemic model. This work marks the first report for controlled release of rhbFGF in combination with metal Mg, and suggests potential therapeutic usefulness of Mg-PLGA-rhbFGF for tissue ischemia.

Efficacy of two kinds of eye drops in stabilizing tear film and relieving dry eye after cataract surgery

Objective To compare the efficacy of recombinant bovine basic fibroblast growth factor (rb-bFGF) eye drops and hypromellose 2910 dextran 70 and glycerol eye drops in maintaining the tear film stability and relieving dry eye symptoms after age-related cataract surgery. Methods The data of 131 eyes of 100 patients with age-related cataract were selected, and they were divided randomly into the rb-bFGF group, 64 eyes of 50 cases; and the hydroxyl indican group, 67 eyes of 50 cases. All patients underwent phacoemulsification combined with intraocular lens implantation. After surgery, rb-bFGF group were treated with rb-bFGF eye drops and the hydroxyl indican group were treated with hydroxyl indican eye drops. All patients were followed up for 3 months, and efficacy were compared between the two groups. Results The schirmer I test (SIT) in rb-bFGF group 3 months after surgery was (14.47±4.69)mm and the break-up time (BUT) was(13.96±2.84)s, in hydroxyl indican group was (12.03±4.76) mm and (12.35±3.27) s. The difference were significant between the two groups (P=0.004, 0.003). The scores of cornea fluorescein staining (CFS) and dry eye symptoms in rb-bFGF group were significantly lower than those in hydroxyl indican group(P=0.011, 0.000). Conclusion Both rb-bFGF eye drops and hydroxyl indican eye drops can prolong BUT, improve tear film stability, relieve dry eye symptoms, and promote the repair and regeneration of corneal epithelial cells after age-related cataract surgery. Rb-bFGF eye drops have better effects. Key words: Cataract, age-related; Phacoemulsification; Lens, intraocular; Eye drops, recombinant bovine basic fibroblast growth factor (rb-bFGF), hypromellose 2910, dextran 70 and glycerol