Biomedical subjects

Yasuhiko Tabata

Publications and source records attributed to Yasuhiko Tabata.

At least 55 records · Page 3Linked to original sources

PubMed2006

Acceleration of aneurysm healing by hollow fiber enabling the controlled release of basic fibroblast growth factor.

OBJECTIVE: The objective of this study was to develop an embolization material of hollow fiber combined with gelatin hydrogel for the controlled release of basic fibroblast growth factor (bFGF). We examined feasibility of the material in embolization healing aneurysm by bFGF-induced tissue organization. METHODS: An aneurysm was prepared at the common carotid artery of 60 rabbits by the end-to-side anastomosis of jugular venous pouch. The hollow fibers combined with or without 100 microg free bFGF or gelatin hydrogel incorporating 0, 10, 50, or 100 microg bFGF were applied to the aneurysm. Tissue appearance or histological observation was performed 1, 2, 3, and 6 weeks after application to evaluate the area embolized by fibrous organization in the aneurysm and the neointima formation at the aneurysm orifice. RESULTS: When applied with the hollow fibers combined with gelatin hydrogel containing 100 microg bFGF, the aneurysm was histologically occupied by fibrous tissue newly formed 3 weeks later, whereas neointima was formed at the aneurysm orifice. The histological area occupied by fibrous tissue was significantly larger than that of hollow fibers combined with 100 microg bFGF. No influence of bFGF dose on the aneurysm healing by the fibers combined with hydrogels incorporating bFGF was observed. CONCLUSION: Local, controlled release of bFGF from the hollow fibers combined with gelatin hydrogel incorporating bFGF accelerated the aneurysm healing by tissue organization.

Aneurysm↗

PubMed2006

Combined treatment of sustained-release basic fibroblast growth factor and sarpogrelate enhances collateral blood flow effectively in rabbit hindlimb ischemia.

BACKGROUND: The effectiveness of sustained-release basic fibroblast growth factor (bFGF) in potentiating arteriogenesis and angiogenesis was evaluated, as well as determining whether chronic oral administration of sarpogrelate, a serotonin blocker, would further increase collateral blood flow in the rabbit hindlimb following surgical induction of ischemia by femoral artery extraction. METHODS AND RESULTS: Two weeks after femoral artery removal, the rabbits were assigned to 1 of 4 experimental groups and treated for 4 weeks: group A, no treatment; group B, supplemented with diet containing sarpogrelate; group C, single intramuscular injection of sustained-release form of bFGF microspheres; group D: combined treatment with sustained-release bFGF and sarpogrelate. Endpoint measurements performed at 6 weeks found that the ischemic hindlimb blood flow was significantly improved in the rabbits that received sustained-release bFGF, with a further significant improvement in those with the additional administration of sarpogrelate. Angiographic assessment revealed augmented density of collateral vessels in the medial thigh region in the rabbits given the combined treatment. CONCLUSIONS: The findings demonstrate that sustained-release bFGF stimulated the development of collateral vessels, and additional administration of sarpogrelate produced a further improvement in hindlimb blood flow in the rabbit hindlimb ischemia model.

Animals↗

PubMed2006

Drug delivery from ocular implants.

Developing an intraocular drug delivery system (DDS) is urgently needed because most vitreoretinal diseases are refractory to conventional pharmacological approaches; eye drops and systemically administered drugs cannot deliver therapeutic drug concentrations into vitreoretinal tissue. Intraocular DDSs address this problem. Intraocular sustained-drug release via implantable devices or injectable microparticles has been investigated to treat vitreoretinal diseases. A nonbiodegradable implant was first used in 1996 for cytomegalovirus retinitis secondary to the acquired immunodeficiency syndrome. Biodegradable implants, composed of hydrophilic or hydrophobic polymers, in the shape of rods, plugs, discs or sheets have been investigated. An injectable rod is presently being assessed in a Phase III trial to treat macular oedema secondary to diabetic retinopathy or branch-retinal vein occlusion. Intraocular DDSs using a biodegradable implant may soon be successfully used to treat serious intraocular disorders.

Animals↗

PubMed2006

Effects of basic fibroblast growth factor on experimental diabetic neuropathy in rats.

Basic fibroblast growth factor (bFGF) stimulates angiogenesis and induces neural cell regeneration. We investigated the effects of bFGF on diabetic neuropathy in streptozotocin-induced diabetic rats. Diabetic rats were treated with human recombinant bFGF as follows: 1) intravenous administration, 2) intramuscular injection into thigh and soleus muscles with cross-linked gelatin hydrogel (CGH), and 3) intramuscular injection with saline. Ten or 30 days later, the motor nerve conduction velocity (MNCV) of the sciatic-tibial and caudal nerves, sensitivity to mechanical stimuli, sciatic nerve blood flow (SNBF), and retinal blood flow (RBF) were measured. Delayed MNCV in the sciatic-tibial and caudal nerves, hypoalgesia, and reduced SNBF in diabetic rats were all ameliorated by intravenous administration of bFGF after 10, but not 30, days. Intramuscular injection of bFGF with CGH also improved sciatic-tibial MNCV, hypoalgesia, and SNBF after 10 and 30 days, but caudal MNCV was not improved. However, intramuscular injection of bFGF with saline had no significant effects. bFGF did not significantly alter RBF in either normal or diabetic rats. These observations suggest that bFGF could have therapeutic value for diabetic neuropathy and that CGH could play important roles as a carrier of bFGF.

Angiogenesis Inducing Agents↗

PubMed2005

Enhanced anti-fibrotic activity of plasmid DNA expressing small interference RNA for TGF-beta type II receptor for a mouse model of obstructive nephropathy by cationized gelatin prepared from different amine compounds.

The objective of this study is to increase the transfection efficiency of a plasmid DNA expressing small interference RNA (siRNA) for transforming growth factor-beta receptor (TGF-betaR) by various cationized gelatins of non-viral carrier and evaluate the anti-fibrotic effect with a mouse model of unilateral ureteral obstruction (UUO). Ethylenediamine, putrescine, spermidine or spermine was chemically introduced to the carboxyl groups of gelatin for the cationization. The plasmid DNA of TGF-betaR siRNA expression vector with or without complexation of each cationized gelatin was injected to the left kidney of mice via the ureter to prevent the progression of renal fibrosis of UUO mice. Irrespective of the type of cationized gelatin, the injection of plasmid DNA-cationized gelatin complex significantly decreased the renal level of TGF-betaR over-expression and the collagen content of mice kidney, in marked contrast to free plasmid DNA injection. It is concluded that retrograde injection of TGF-betaR siRNA expression vector plasmid DNA complexed with the cationized gelatin is available to suppress the progression of renal interstitial fibrosis.

Amines↗

PubMed2005

Intraocular sustained drug delivery using implantable polymeric devices.

Vitreoretinal diseases involving age-related macular degeneration (AMD) are refractory to most topical or systemic drugs. The retina and the vitreous cavity have a unique position regarding pharmacokinetics in that the inner and outer blood retinal barriers separate the retina and vitreous from the systemic circulation. Eye drops achieve minimal therapeutic concentrations in the vitreoretinal tissue. Drug delivery systems are a strategy to address this. Intraocular sustained drug release using implantable devices has been investigated to treat vitreoretinal diseases. Possible targeted diseases include those in which repeated intraocular injections are effective (cytomegalovirus retinitis, uveitis), diseases requiring surgery (proliferative vitreoretinopathy), and chronic diseases (AMD, macular edema, retinitis pigmentosa). Hydrophobic or hydrophilic polymers shaped into a sheet, disc, rod, plug, or a larger device can be implanted into the subretinal space, intrascleral space, vitreous space, peribulbar space, or at the pars plana. Many researchers suggest the feasibility of these implants to treat AMD.

Animals↗

PubMed2005

Gelatin as a delivery vehicle for the controlled release of bioactive molecules.

Gelatin is a commonly used natural polymer which is derived from collagen. The isoelectric point of gelatin can be modified during the fabrication process to yield either a negatively charged acidic gelatin, or a positively charged basic gelatin at physiological pH. This theoretically allows electrostatic interactions to take place between a charged biomolecule and gelatin of the opposite charge, forming polyion complexes. Various forms of gelatin carrier matrices can be fabricated for controlled-release studies, and characterization studies have been performed which show that gelatin carriers are able to sorb charged biomolecules such as proteins and plasmid DNA through polyion complexation. The crosslinking density of gelatin hydrogels has been shown to affect their degradation rate in vivo, and the rate of biomolecule release from gelatin carriers has been shown to have a similar profile, suggesting that complexed gelatin/biomolecule fragments are released by enzymatic degradation of the carrier in vivo. This review will emphasize how biomolecules released from gelatin controlled-release systems are able to retain their biological activity, allowing for their use in tissue engineering, therapeutic angiogenesis, gene therapy, and drug delivery applications.

Animals↗

PubMed2005

In vivo release of plasmid DNA from composites of oligo(poly(ethylene glycol)fumarate) and cationized gelatin microspheres.

Composites of cationized gelatin microspheres (CGMS), crosslinked with either 3 mM or 6 mM glutaraldehyde solution, and a novel hydrogel material, oligo(poly(ethylene glycol)fumarate) (OPF) were fabricated and investigated toward prolonging the release of plasmid DNA in vivo relative to the constituent materials. The composites and constituent materials were investigated in a subcutaneous murine model to assess the release of 125I-labeled plasmid DNA and 125I-labeled cationized gelatin in vivo. The time profiles of the radioactivity remaining were employed to compare the profiles of DNA release and cationized gelatin degradation. Both composite formulations (incorporating either 3 mM or 6 mM CGMS) prolonged the bioavailability of plasmid DNA relative to both injected plasmid DNA solution and the respective non-embedded cationized gelatin microspheres. Injected plasmid DNA solution persisted in the subject for only 7-10 days, whereas the persistence of DNA from composites of OPF and either 3 mM or 6 mM CGMS extended to at least day 42. The 3 mM and 6 mM CGMS each increased the persistence of DNA slightly, relative to injection of DNA solution, to between 28 and 35 days. Interestingly, the release profile of plasmid DNA from composites was not significantly different from the release of DNA from OPF alone. The release of plasmid DNA from the composites was in accord with the degradation of the microspheres within the OPF. These results show that composites of OPF and cationized gelatin microspheres are able to prolong the availability of plasmid DNA in vivo relative to cationized gelatin microspheres alone and provide a promising candidate material for the sustained, controlled release of plasmid DNA.

Cations↗

PubMed2005

Ultrasound enhances in vivo tumor expression of plasmid DNA by PEG-introduced cationized dextran.

This study is an investigation to experimentally confirm whether or not ultrasound (US) irradiation is effective in enhancing the in vivo gene expression of plasmid DNA in tumor. Dextran was cationized by introducing spermine to the hydroxyl groups to allow to polyionically complex with a plasmid DNA. The cationized dextran prepared was additionally modified with poly(ethylene glycol) (PEG) molecules which have an active ester and methoxy groups at each terminal, to obtain cationized dextran with different percentages of PEG introduced. Various cationized dextrans with or without PEG introduction were mixed with a plasmid DNA of LacZ to form cationized dextran-plasmid DNA complexes. Electrophoretical examination revealed that the plasmid DNA was complexed both with the cationized dextran and PEG-introduced cationized dextran, irrespective of the PEG introduction percentage, although the higher N/P ratio was needed for plasmid DNA complexation with the latter. By complexation with the cationized dextran, the zeta potential of plasmid DNA was changed to be positive. The charge of PEG-introduced cationized dextran-plasmid DNA complexes became close to 0 mV as their percentage of PEG introduced increased, although the molecular size was about 250 nm, irrespective of the PEG introduction. When cationized dextran-plasmid DNA complexes with or without PEG introduction were intravenously injected to mice carrying a subcutaneous Meth-AR-1 fibrosarcoma mass and the subsequent US irradiation to the tumor mass percutaneously, the PEG-introduced cationized dextran-plasmid DNA complex plus US irradiation enhanced the tumor level of gene expression to a significantly high extent compared with the cationized dextran-plasmid DNA complex and free plasmid DNA with or without US irradiation. The enhanced level depended on the time period and timing of US irradiation. Fluorescent microscopic studies revealed that the localization of plasmid DNA and the gene expression were observed in the tumor tissue injected with the PEG-introduced cationized dextran-plasmid DNA complex plus the subsequent US irradiation. We conclude that complexation with the PEG-introduced cationized dextran combined with US irradiation is a promising way to target the plasmid DNA to the tumor for gene expression.

Animals↗

PubMed2005

Osteochondral repair in the rabbit model utilizing bilayered, degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds.

In this study, hydrogel scaffolds, based on the polymer oligo(poly(ethylene glycol) fumarate) (OPF), were implanted into osteochondral defects in the rabbit model. Scaffolds consisted of two layers-a bottom, bone forming layer and a top, cartilage forming layer. Three scaffold formulations were implanted to assess how material composition and transforming growth factor-beta1 (TGF-beta1) loading affected osteochondral repair. Critical histological evaluation and scoring of the quantity and quality of tissue in the chondral and subchondral regions of defects was performed at 4 and 14 weeks. At both time points, no evidence of prolonged inflammation was observed, and healthy tissue was seen to infiltrate the defect area. The quality of this tissue improved over time with hyaline cartilage filling the chondral region and a mixture of trabecular and compact bone filling the subchondral region at 14 weeks. A promising degree of Safranin O staining and chondrocyte organization was observed in the newly formed surface tissue, while the underlying subchondral bone was completely integrated with the surrounding bone at 14 weeks. Material composition within the bottom, bone-forming layer did not appear to affect the rate of scaffold degradation or tissue filling. However, no bone upgrowth into the chondral region was observed with any scaffold formulation. TGF-beta1 loading in the top layer of scaffolds appeared to exert some therapeutic affect on tissue quality, but further studies are necessary for scaffold optimization. Yet, the excellent tissue filling and integration resulting from osteochondral implantation of these OPF-based scaffolds demonstrates their potential in cartilage repair strategies.

Absorbable Implants↗

PubMed2005

Combined chondrocyte-copolymer implantation with slow release of basic fibroblast growth factor for tissue engineering an auricular cartilage construct.

Basic fibroblast growth factor (b-FGF) may have a role in tissue-engineered chondrogenesis. However, when applied in solution, b-FGF rapidly diffuses from the implant site. In another approach for tissue engineering, poly-lactide-based copolymers have shown promise as scaffolds for chondrocytes used to tissue engineer auricular cartilage in the shape of an ear. This study evaluated the effectiveness of b-FGF impregnated in gelatin microspheres to achieve slow growth factor release for augmenting the in vivo chondrogenic response. Whereas 125I-labeled b-FGF injected in solution showed rapid in vivo clearance from the injection site (only 3% residual after 24 h), when incorporated into gelatin microspheres, 44% and 18% of the b-FGF remained at 3 and 14 days, respectively. Canine chondrocytes were isolated and grown in vitro onto ear-shaped poly-lactide/caprolactone copolymers for 1 week, then implanted into the dorsal subcutaneous tissue of nude mice; implants contained b-FGF either in free solution or in gelatin microspheres. A third group underwent preinjection of b-FGF in gelatin microspheres 4 days before chondrocyte-copolymer implantation. The implants with b-FGF-incorporated microspheres showed the greatest chondrogenic characteristics at 5 and 10 weeks postoperatively: good shape and biomechanical trait retention, strong (histologic) metachromasia, rich vascularization of surrounding tissues, and increased gene expression for type II collagen (cartilage marker) and factor VIII-related antigen (vascular marker). In the case of implant site preadministration with b-FGF-impregnated microspheres, the implant architecture was not maintained as well, and reduced vascularization and metachromasia was also apparent. In conclusion, these findings indicate that a sustained release of b-FGF augments neovascularization and chondrogenesis in a tissue-engineered cartilage construct.

Animals↗

PubMed2005

Enhanced ectopic bone formation using a combination of plasmid DNA impregnation into 3-D scaffold and bioreactor perfusion culture.

The objective of this study is to enhance in vivo ectopic bone formation by combination of plasmid DNA impregnation into three-dimensional (3-D) cell scaffolds and a developed in vitro culture method. Gelatin was cationized by introducing spermine (Sm) to the carboxyl groups for complexation with the plasmid DNA. As the MSC scaffold, collagen sponge reinforced by incorporation of poly(glycolic acid) (PGA) fibers was used. A complex of the cationized gelatin and plasmid DNA of BMP-2 was impregnated into the scaffold. MCS were seeded into each scaffold and cultured by a static and perfusion methods. When MSC were cultured in the PGA-reinforced collagen sponge, the level of BMP-2 expression was significantly enhanced by the perfusion culture compared with static method. When the osteoinduction activity of the PGA-reinforced collagen sponges seeded with PBS, MSC, naked plasmid DNA-BMP-2, cationized gelatin-plasmid DNA-BMP-2 complex, and transfected MSC by static and perfusion method, were studied following the implantation into the back subcutis of rats in terms of histological and biochemical examinations, homogeneous bone formation was histologically observed throughout the sponges seeded with cationized gelatin-plasmid DNA of BMP-2 complex and transfected MSC by perfusion method, although the extent of bone formation was higher for the later one. The level of alkaline phosphatase activity and osteocalcin content at the implanted sites of sponges seeded with transfected MSC by perfusion method were significantly high compared with those seeded with other agents. We conclude that combination of plasmid DNA-impregnated PGA-reinforced collagen sponge and the perfusion method was promising to promote the in vitro gene expression for MSC and in vivo ectopic bone formation.

Animals↗

PubMed2005

Administration of control-released hepatocyte growth factor enhances the efficacy of skeletal myoblast transplantation in rat infarcted hearts by greatly increasing both quantity and quality of the graft.

BACKGROUND: We investigated whether simultaneous administration of control-released hepatocyte growth factor (HGF) enhances the efficacy of skeletal myoblast (SM) transplantation (Tx) through its antiapoptotic, angiogenic, and antifibrotic effects in myocardial infarction (MI). METHODS AND RESULTS: Forty-eight Lewis rats with chronic MI were divided into 4 groups. In Group I (n=14), neonatal SMs (5 x 10(6)) were transplanted in the MI area with a gelatin sheet incorporating 40 microg (1 g/L) of HGF applied. Group II (n=14) had SM Tx and placement of a saline sheet. Groups III (n=10) and IV (n=10) had culture medium injection plus HGF and saline sheet application, respectively. Four rats each from Groups I and II were sacrificed at day 1 for TUNEL assay on donor SMs. The percentage of TUNEL-positive donor cells was much lower in Group I than in Group II (P<0.05). At 4 weeks, in Group I, left ventricular diastolic dimension was smallest in echocardiography, end-systolic elastance was highest, and tau was the lowest (both P<0.0005 in ANOVA) in cardiac catheterization. Vascular density inside the graft was higher in Group I than in Group II (P<0.0001). The percentage of fibrotic area inside the graft was smaller in Group I than in Group II (P<0.001). The graft volume as estimated by fast skeletal myosin heavy chain-positive areas was approximately 7-fold larger in Group I than in Group II (P<0.0001). CONCLUSIONS: In SM Tx, HGF can greatly increase the graft volume and vascularity and reduce fibrosis inside the graft, which enhances the efficacy of SM Tx to infarcted hearts.

Animals↗

PubMed2005

Delivery of plasmid DNA expressing small interference RNA for TGF-beta type II receptor by cationized gelatin to prevent interstitial renal fibrosis.

Renal interstitial fibrosis is the common pathway of chronic renal disease, while it causes end-stage renal failure. Transforming growth factor-beta (TGF-beta) is well recognized to be one of the primary mediators to induce accumulation of extracellular matrix (ECM) in the fibrotic area. Therefore, it is expected that local suppression of TGF-beta receptor (TGF-betaR) is one of the crucial strategies for anti-fibrotic therapy. The objective of this study is to investigate feasibility of small interference RNA (siRNA) for TGF-betaR in the selective degradation of TGF-betaR mRNAs, resulting in fibrotic inhibition. A plasmid DNA of TGF-betaR siRNA expression vector with or without complexation of a cationized gelatin was injected to the left kidney of mice via the ureter. Unilateral ureteral obstruction (UUO) was performed for the injected mice to evaluate the anti-fibrotic effect. The injection of plasmid DNA-cationized gelatin complex significantly decreased the level of TGF-betaR and alpha-smooth muscle actin (alpha-SMA) over-expression, the collagen content of mice kidney, and the fibrotic area of renal cortex, in contrast to free plasmid DNA injection. It is concluded that retrograde injection of TGF-betaR siRNA expression vector plasmid DNA complexed with the cationized gelatin is available to suppress progression of renal interstitial fibrosis.

Animals↗

PubMed2005

Accelerated wound healing through the incorporation of basic fibroblast growth factor-impregnated gelatin microspheres into artificial dermis using a pressure-induced decubitus ulcer model in genetically diabetic mice.

The objective of this study was to evaluate the effect of incorporating basic fibroblast growth factor (bFGF)-impregnated gelatin microspheres into an artificial dermis on impaired wound healing using a pressure-induced decubitus ulcer model in genetically diabetic mice. Daily 10 h prolonged pressure at 500 g/cm2 was loaded for 2 consecutive days over the femoral trochanter tertius of mice to produce ischemic necrosis. Five days after completion of the pressure load, the necrotic tissues were resected. Then, an artificial dermis incorporating bFGF-impregnated gelatin microspheres or bFGF in solution was implanted into the wound (n = 5). Mice were sacrificed at 5, 7, and 10 days after implantation, and a full-thickness biopsy was taken and stained with hematoxylin and eosin for histological analysis. All experimental animals were infected because diabetic mice have little tolerance for infection. Seven days after implantation, the incorporation of bFGF into the artificial dermis reduced infection and accelerated fibroblast proliferation and capillary formation. However, the accelerated effects were more significant with the incorporation of bFGF-impregnated gelatin microspheres than with free bFGF. We conclude that the incorporation of bFGF-impregnated gelatin microspheres into an artificial dermis induced tissue regeneration in an artificial dermis in an impaired wound healing model.

Animals↗

PubMed2005

Drug delivery system using microspheres that contain tacrolimus in porcine small bowel transplantation.

Rejection remains a major barrier to successful bowel transplantation, in spite of improved immunosuppressive techniques. Therefore, new, more effective, immunosuppressants, with fewer side effects, are needed. Biodegradable microspheres containing tacrolimus (FK506) were used in an experimental porcine small bowel transplantation. Twenty pigs underwent transplantation and were divided into four groups according to the immunosuppressive regimen. Group A (n = 5): no immunosuppression; group B (n = 6): 0.2 mg/kg per day of FK506; group C (n = 3): 1.0 mg/kg per day of FK506; group D (n = 6): 0.04 mg/kg per day of FK506 contained in biodegradable microspheres. Rejection was diagnosed macroscopically by endoscopic examination and histologically by biopsy specimen analysis. The mean survival time and standard deviation (SD) were 8.8+/-3.5, 11.0+/-1.4, 9.7+/-2.5 and 28.6+/-22.5 days for groups A, B, C, and D, respectively, with a statistically significant difference found between group D, on the one hand, and groups A, B and C, on the other. The mean trough blood concentration of FK506 was 10.5+/-2.2, 27.9+/-6.0 and 10.5+/-3.5 ng/ml in groups B, C and D, respectively. In groups A and B, all pigs died of rejection, without infection. In group C, all died of infection, without rejection. In contrast, none of the pigs in group D developed rejection or infection. Our results clearly show that the drug delivery system using biodegradable microspheres that contain FK506 is effective for controlling rejection with fewer side effects in the porcine small bowel transplantation.

Animals↗

PubMed2005

Neovascularization and bone regeneration by implantation of autologous bone marrow mononuclear cells.

We examined whether transplantation of autologous bone marrow mononuclear cells (BM-MNCs) can augment neovascularization and bone regeneration of bone marrow in femoral bone defects of rabbits. Gelatin microspheres containing basic fibroblast growth factor (bFGF) were prepared for the controlled release of bFGF. To evaluate the in vivo effect of implanted BM-MNCs, we created bone defects in the rabbit medial femoral condyle, and implanted into them 5 x 10(6) fluorescent-labeled autologous BM-MNCs together with gelatin microspheres containing 10 microg bFGF on an atelocollagen gel scaffold. The four experimental groups, which were Atelocollagen gel (Col), Col + 5 x 10(6) BM-MNCs, Col + 10 microg bFGF, and Col + 5 x 10(6) BM-MNCs + 10 microg bFGF, were implanted into the sites of the prepared defects using Atelocollagen gel as a scaffold. The autologous BM-MNCs expressed CD31, an endothelial lineage cell marker, and induced efficient neovascularization at the implanted site 2 weeks after implantation. Capillary density in Col + BM-MNCs + bFGF was significantly large compared with other groups. This combination also enhanced regeneration of the bone defect after 8 weeks to a significantly greater extent than either BM-MNCs or bFGF on their own. In summary, these findings demonstrate that a combination of BM-MNCs and bFGF gelatin hydrogel enhance the neovascularization and the osteoinductive ability, resulting in bone regeneration.

Animals↗

PubMed2005

Dual growth factor delivery from degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds for cartilage tissue engineering.

This work describes the development of a non-invasive means of simultaneously delivering insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta1 (TGF-beta1) to injured cartilage tissue in a controlled manner. This novel delivery technology employs the water-soluble polymer, oligo(poly(ethylene glycol) fumarate) (OPF), in the fabrication of biodegradable hydrogels which encapsulate gelatin microparticles. Release studies first examined the effect of gelatin isoelectric point (IEP) and crosslinking extent on IGF-1 release from these microparticles. In the presence of collagenase, highly crosslinked, acidic gelatin (IEP=5.0) provided sustained release of IGF-1, 95.2+/-2.9% cumulative release at day 28, while less crosslinked microparticles and microparticles of alternate IEP exhibited similar release values after only 6 days. Encapsulation of these highly crosslinked microparticles in a network of OPF provided a means to further control release, reducing final cumulative release to 70.2+/-4.7% in collagenase-containing PBS. Final release values from OPF-gelatin microparticle composites could be altered by incorporating less crosslinked, non-loaded microparticles within these constructs. Finally, this technology was extended to the dual delivery of IGF-1 and TGF-beta1 by loading these growth factors into either the OPF hydrogel phase or gelatin microparticle phase of composites. Release profiles were successfully manipulated by altering the phase of growth factor loading and microparticle crosslinking extent. For instance, by loading TGF-beta1 into the gelatin microparticle phase, a burst release of 10.8+/-0.7% was achieved, while loading this growth factor into the OPF hydrogel phase resulted in a burst release of 25.2+/-1.5%. With either system, simultaneous, slow release of IGF-1 over a 4-week period was accomplished by selectively loading this protein into highly crosslinked, encapsulated microparticles. These results demonstrate the utility of these systems in future studies to assess the interplay and time course of multiple growth factors in cartilage repair.

Cartilage↗