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Apatite formation on/in hydrogel matrices using an alternate soaking process (III): effect of physico-chemical factors on apatite formation on/in poly(vinyl alcohol) hydrogel matrices.

The aim of this study is to clarify the physico-chemical factors which influence apatite formation on/in a hydrogel during a novel alternate soaking process. A poly(vinyl alcohol) (PVA) gel was used as a model matrix. The amount of apatite formed on/in PVA gels decreased with an increase in the reaction temperature during the same reaction cycles. This suggested that the equilibrium swelling ratios decreased with increasing reaction temperatures; that is, the diffusion of calcium and phosphate ions reduced at high reaction temperature. However, the crystallinity of apatite formed on/in PVA gels was greater at higher reaction temperatures. The amount of apatite formed on/in PVA gels increased with an increase in the calcium and phosphate solution concentrations, and increased by shaking at the first three reaction cycles. A few influences could be observed when the solution volume was changed, however, the soaking order was not effective in this study. These results indicate that the amount of apatite formation on/in PVA gels can be controlled by changing the reaction temperature and the Ca- and P-solution concentrations, and that the crystallinity of apatite can be also changed by controlling the reaction temperatures.

Apatites↗

Short-term physiologic response in neophyte subjects fitted with hydrogel and silicone hydrogel contact lenses.

PURPOSE: To investigate the short-term physiologic response to three soft lens materials with different oxygen permeability characteristics. METHODS: Forty-three neophytes were randomly prescribed Acuvue 2, Acuvue Advance (Johnson & Johnson Vision Care), or Focus Night & Day (CIBA Vision) for 4 weeks on a daily-wear basis. A further 19 subjects did not wear lenses (control). Experimental and control subjects were examined 2 and 4 weeks after dispensing. Ocular physiologic response was measured with a slitlamp biomicroscope in a strictly masked fashion. RESULTS: Limbal redness increased in the Acuvue 2 group compared with the other two groups. Conjunctival redness increased more in the Acuvue 2 group than in the Acuvue Advance group. More conjunctival staining was seen with the Acuvue Advance and Focus Night & Day groups compared with the Acuvue 2 group. Increased scores for papillary conjunctivitis were seen in the Focus Night & Day group compared with the Acuvue Advance group. CONCLUSIONS: The reduced level of limbal redness seen with the Acuvue Advance and Focus Night & Day groups suggests that these lenses provide more oxygen to the ocular surface than the Acuvue 2 lens to a degree that can be observed clinically. The conjunctival staining response was similar for the Acuvue Advance and Focus Night & Day groups. The results for the Acuvue Advance and Focus Night & Day groups for papillary conjunctivitis may reflect differences in their material and surface properties.

Adult↗

Clinical comparison of the (polymacon) spin-cast hydrogel contact lens to the (polymacon) lathe-cut hydrogel lenses.

The purpose of this study was to compare the clinical acceptability of polymacon spin-cast to polymacon lathe-cut hydrophilic contact lenses. Ten patients successfully wearing polymacon spin-cast lenses were studied. Each patient had one eye refitted with polymacon lathe-cut lenses. Comparison of the two types of lenses was then made. Objective evaluation included centration, movement, visual acuity, and over-refraction. Subjective criteria were based on patient comfort and stability and quality of vision. Results indicate that lathe-cut lenses can be just as clinically satisfactory as the spincast ones.

Clinical Trials as Topic↗

Controlled release of fibroblast growth factors and heparin from photocrosslinked chitosan hydrogels and subsequent effect on in vivo vascularization.

Application of ultraviolet (UV) irradiation to a photocrosslinkable chitosan (Az-CH-LA) aqueous solution resulted within 10 s in an insoluble, flexible hydrogel. A low molecular weight acidic molecule like trypan blue and various high molecular weight molecules such as bovine serum albumin (BSA), heparin and protamine were all retained within the hydrogel, while a low molecular weight basic molecule like toluidine blue was rapidly released from the hydrogel. In the present work, we examined the retaining capability of the chitosan hydrogel for growth factors and controlled release of growth factors from the chitosan hydrogel in vitro and in vivo. Fibroblast growth factor-1 (FGF-1), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor(165) (VEGF(165)), heparin-binding epidermal growth factor (HB-EGF) in phosphate buffered saline (PBS) were mixed with Az-CH-LA aqueous solution to form growth factor-incorporated chitosan hydrogels. About 10-25% of the growth factor was released from a growth factor-incorporated chitosan hydrogel into PBS within the first day, after which no further substantial release took place. The growth factors interacted with Az-CH-LA molecules poly-ion complexation, and probably were unable to be released after the first day under the in vitro nondegradation conditions of the hydrogel. Although the FGF-1, FGF-2, and VEGF(165)-incorporated chitosan hydrogels on a culture plate significantly stimulated HUVEC growth, the stimulating activity of the growth factor-incorporated chitosan hydrogel was completely cancelled out by washing the hydrogel with PBS solution for 3 days or more. The stimulating activity on the HUVEC growth were however highly recovered by treating the washed growth factor-incorporated chitosan hydrogel during 7 days with chitinase and chitosanase to partly degrade the hydrogel, strongly suggesting that the growth factors within the hydrogel retained their biologically active forms. The chitosan hydrogel (100 microl) when implanted into the back of a mouse was biodegraded in about 10-14 days. When FGF-1- and FGF-2-incorporated chitosan hydrogels were subcutaneously implanted into the back of a mouse, significant neovascularization was induced near the implanted site of the FGF-1- and FGF-2-incorporated chitosan hydrogels. Furthermore, addition of heparin with either FGF-1 or FGF-2 into the hydrogel resulted in a significantly enhanced and prolonged vascularization effect. These results indicate that the controlled release of biologically active FGF-1 and FGF-2 with heparin is caused by biodegradation of the chitosan hydrogel, and subsequent induction of vascularization.

Animals↗

Bone regeneration at rabbit skull defects treated with transforming growth factor-beta1 incorporated into hydrogels with different levels of biodegradability.

OBJECT: Skull bone regeneration induced by transforming growth factor-beta1 (TGFbeta1)-containing gelatin hydrogels (TGFbeta1-hydrogels) was investigated using a rabbit skull defect model. Different strengths of TGFbeta1 were examined and compared: different TGFbeta1 doses in gelatin hydrogels with a fixed water content, different water contents in gelatin hydrogels with a fixed TGFbeta1 dose, and TGFbeta1 in solution form. In addition, regenerated skull bone was observed over long time periods after treatment. METHODS: Soft x-ray, dual energy x-ray absorptometry, and histological studies were performed to assess the time course of bone regeneration at a 6-mm-diameter skull defect in rabbits after treatment with TGFbeta1-hydrogels or other agents. The influence of TGFbeta1 dose and hydrogel water content on skull bone regeneration by TGFbeta1-hydrogels was evaluated. Gelatin hydrogels with a water content of 95 wt% that incorporated at least 0.1 microg of TGFbeta1 induced significant bone regeneration at the rabbit skull defect site 6 weeks after treatment, whereas TGFbeta1 in solution form was ineffective, regardless of dose. The in vivo degradability of the hydrogels, which varied according to water content, played an important role in skull bone regeneration induced by TGFbeta1 -hydrogels. In our hydrogel system, TGFbeta1 is released from hydrogels as a result of hydrogel degradation. When the hydrogel degrades too quickly, it does not retain TGFbeta1 or prevent ingrowth of soft tissues at the skull defect site and does not induce bone regeneration at the skull defect. It is likely that hydrogel that degrades too slowly physically impedes formation of new bone at the skull defect. Following treatment with 0.1-microg TGFbeta1-hydrogel (95 wt%), newly formed bone remained at the defect site without being resorbed 6 and 12 months later. The histological structure of the newly formed bone was similar to that of normal skull bone. Overgrowth of regenerated bone and tissue reaction were not observed after treatment with TGFbeta1 -hydrogels. CONCLUSIONS: A TGFbeta1-hydrogel with appropriate biodegradability will function not only as a release matrix for the TGFbeta1, but also as a space provider for bone regeneration. The TGFbeta1-hydrogel is a promising surgical tool for skull defect repair and skull base reconstruction.

Absorptiometry, Photon↗

In vivo anti-tumor effect through the controlled release of cisplatin from biodegradable gelatin hydrogel.

This paper is an investigation to achieve the in vivo controlled release of cisplatin (CDDP) from a biodegradable hydrogel. Hydrogels with different water contents were prepared through the chemical crosslinking of gelatin by various concentrations of glutaraldehyde. The gelatin hydrogel incorporating CDDP (CDDP-hydrogel) was prepared by allowing CDDP aqueous solution to sorb into the freeze-dried hydrogel. Irrespective of the hydrogel water content, approximately 10-30% of incorporated CDDP was released from the hydrogel in phosphate-buffered saline solution (PBS) at 37 degrees C within the initial 6 h, while little release was observed thereafter. The amount of CDDP released initially decreased with an increase in the time period of CDDP sorption. When intratumorally applied into Meth-AR-1 tumor-bearing mice, CDDP-hydrogel suppressed in vivo tumor growth to a significantly higher extent than free CDDP at the same dose. The survival rate was significantly higher by the application of CDDP-hydrogel of 40 microg CDDP. The CDDP concentration in the tumor tissue was maintained at a higher level for a longer time period than that of free CDDP. However, no problematic change in the mouse body and blood biochemical parameters was observed on the application of the CDDP-hydrogel. The time course of in vivo CDDP retention was in a good accordance with that of hydrogel remaining. Larger CDDP release was observed from the front surface of hydrogel onto which free CDDP was sorbed, than the back surface of hydrogel. These findings demonstrate that the controlled release of CDDP was based on biodegradation of the hydrogel carrier, but not simple diffusion of CDDP. It is possible that the CDDP molecules immobilized in the gelatin hydrogel were released from the hydrogel only when the hydrogel was degraded to generate some water-soluble gelatin fragments.

Animals↗

Synthesis and degradation test of hyaluronic acid hydrogels.

Hyaluronic acid (HA) hydrogels prepared with three different crosslinking reagents were assessed by in vitro and in vivo degradation tests for various tissue engineering applications. Adipic acid dihydrazide grafted HA (HA-ADH) was synthesized and used for the preparation of methacrylated HA (HA-MA) with methacrylic anhydride and thiolated HA (HA-SH) with Traut's reagent (imminothiolane). (1)H NMR analysis showed that the degrees of HA-ADH, HA-MA, and HA-SH modification were 69, 29, and 56 mol%, respectively. HA-ADH hydrogel was prepared by the crosslinking with bis(sulfosuccinimidyl) suberate (BS(3)), HA-MA hydrogel with dithiothreitol (DTT) by Michael addition, and HA-SH hydrogel with sodium tetrathionate by disulfide bond formation. According to in vitro degradation tests, HA-SH hydrogel was degraded very fast, compared to HA-ADH and HA-MA hydrogels. HA-ADH hydrogel was degraded slightly faster than HA-MA hydrogel. Based on these results, HA-MA hydrogels and HA-SH hydrogels were implanted in the back of SD rats and their degradation was assessed according to the pre-determined time schedule. As expected from the in vitro degradation test results, HA-SH hydrogel was in vivo degraded completely only in 2 weeks, whereas HA-MA hydrogels were degraded only partially even in 29 days. The degradation rate of HA hydrogels were thought to be controlled by changing the crosslinking reagents and the functional group of HA derivatives. In addition, the state of HA hydrogel was another factor in controlling the degradation rate. Dried HA hydrogel at 37 degrees C for a day resulted in relatively slow degradation compared to the bulk HA hydrogel. There was no adverse effect during the in vivo tests.

Adipates↗

Biodegradation of hydrogel carrier incorporating fibroblast growth factor.

In vivo release of basic fibroblast growth factor (bFGF) from a biodegradable gelatin hydrogel carrier was compared with the in vivo degradation of hydrogel. When gelatin hydrogels incorporating 125I-labeled bFGF were implanted into the back subcutis of mice, the bFGF radioactivity remaining decreased with time and the retention period was prolonged with a decrease in the water content of the hydrogels. The lower the water content of 125I-labeled gelatin hydrogels, the faster both the weight of the hydrogels and the gelatin radioactivity remaining decreased with time. The decrement profile of bFGF remaining in hydrogels was correlated with that of hydrogel weight and gelatin radioactivity, irrespective of the water content. Subcutaneous implantation of bFGF-incorporating gelatin hydrogels into the mice induced significant neovascularization. The retention period of neovascularization became longer as the water content of the hydrogels decreased. To study the decrease of activity of bFGF when implanted, bFGF-incorporating hydrogels were placed in diffusion chamber and implanted in the mouse subcutis for certain periods of time. When hydrogels explanted from the mice were again implanted, significant neovascularization was still observed, indicating that most of the biological activity of bFGF was retained in the hydrogels. It was concluded that, in our hydrogel system, biologically active bFGF was released as a result of in vivo degradation of the hydrogel. The release profile was controllable by changing the water content of hydrogels.

Animals↗

Vascularization effect of basic fibroblast growth factor released from gelatin hydrogels with different biodegradabilities.

Biodegradable gelatin hydrogels were prepared through the glutaraldehyde crosslinking of acidic gelatin with an isoelectric point (IEP) of 5.0 and the basic gelatin with an IEP of 9.0. The hydrogel water content was changed by the concentration of both gelatin and glutaraldehyde, used for hydrogel preparation. An aqueous solution of basic fibroblast growth factor (bFGF) was sorbed into the gelatin hydrogel freeze-dried to obtain a bFGF-incorporating gelatin hydrogel. Irrespective of the hydrogel water content, approximately 30% of the incorporated bFGF was released from the bFGF-incorporating acidic gelatin hydrogel, within the first day into phosphate-buffered saline solution at 37 degrees C, followed by no substantial release. Probably, the basic bFGF complexed with the acidic gelatin through poly-ion complexation would not be released under the in vitro non-degradation condition of gelatin. On the contrary, almost 100% of the incorporated bFGF was initially released from all types of basic gelatin hydrogels. This is due to the simple diffusion of bFGF because of no complexation between bFGF and the basic gelatin. When implanted subcutaneously into the mouse back, bFGF-incorporating acidic and basic gelatin hydrogels with higher water contents were degraded with time faster than those with lower water contents. Significant neovascularization was induced around the implanted site of the bFGF-incorporating acidic gelatin hydrogel. The induction period prolonged with the decrease in hydrogel water content. On the other hand, such a prolonged vascularization effect was not achieved by the bFGF-incorporating basic gelatin hydrogel and the hydrogel initially exhibited less enhanced effect, irrespective of the water content. These findings indicate that the controlled release of biologically active bFGF is caused by biodegradation of the acidic gelatin hydrogel, resulting in induction of vascularization effect dependent on the water content. It is possible that only the transient vascularization by the basic gelatin hydrogel is due to the initial large burst in bFGF release, probably because of the down regulation of bFGF receptor.

Animals↗

Refractive index and equilibrium water content of conventional and silicone hydrogel contact lenses.

PURPOSE: The purpose of the present study was to measure equilibrium water content (EWC) and refractive index of conventional and silicone hydrogel soft contact lenses (SCL) using a hand refractometer and an automated refractometer. METHODS: Sixteen SCL were used in this study including 12 conventional SCL not containing siloxane moieties (equilibrium water content (EWC) range: 38.6-74%) and the four silicone hydrogel based contact lenses currently available (WC range: 24-47%). Two experienced observers performed the measurements in a randomised order being masked by a third party during the three sessions at which the measurements were collected. The Atago N-2E hand refractometer and the CLR 12-70 digital refractometer were used. Data were analysed separately for conventional and silicone hydrogel materials. RESULTS: Measured EWC and refractive index correlate better when measured with the instruments used in this study (r(2) = 0.979, p < 0.001) than the nominal parameters (r(2) = 0.666, p < 0.001). The linear relationship that correlates nominal and measured EWC shows higher spread of data when all lenses are analysed together (r(2) = 0.840) than when conventional hydrogel (r(2) = 0.953) and silicone hydrogel contact lenses (r(2) = 0.967) are analysed separately. Regarding refractive index, the relationship between nominal and measured values when all the lenses are considered together (r(2) = 0.794) becomes weaker when conventional hydrogel are considered separately (r(2) = 0.688), while a stronger relationship is observed for silicone hydrogel lenses (r(2) = 0.939). Hence, hand refractometry overestimates the EWC of silicone hydrogels, while automated refractive index measurements are more accurate in silicone hydrogels than in conventional hydrogels. CONCLUSIONS: New relationships are presented that correlate nominal and measured values of EWC and refractive index for the silicone containing hydrogels. The linear relationships derived fit well to the data. Hand refractometry overestimates the EWC of silicone hydrogel materials and this bias is related to the proportion of siloxane moieties in the material. Conversely, refractive index can be obtained more accurately with automated refractometry for silicone hydrogels than for conventional hydrogels. Present results are of interest in planning future clinical studies involving the measurement of EWC of current hydrogels.

Contact Lenses, Hydrophilic↗

In vivo biocompatibility of dextran-based hydrogels.

Dextran-based hydrogels were obtained by polymerization of aqueous solutions of methacrylated dextran (dex-MA) or lactate-hydroxyethyl methacrylate-derivatized dextran (dex-lactate-HEMA). Both nondegradable dex-MA and degradable dex-lactate-HEMA disk-shaped hydrogels, varying in initial water content and degree of substitution (DS, the number of methacrylate groups per 100 glucose units), were implanted subcutaneously in rats. The tissue reaction was evaluated over a period of 6 weeks. The initial foreign-body reaction to the dex-MA hydrogels was characterized by infiltration of granulocytes and macrophages and the formation of fibrin, and exudate, as well as new blood vessels. This reaction depended on the initial water content as well as on the DS of the hydrogel and decreased within 10 days. The mildest tissue response was observed for the gel with the highest water content and intermediate DS. At day 21 all dex-MA hydrogels were surrounded by a fibrous capsule and no toxic effects on the surrounding tissue were found. No signs of degradation were observed. The initial foreign-body reaction to the degradable dex-lactate-HEMA hydrogels was less severe compared with the dex-MA gels. In general, the size of the dex-lactate-HEMA hydrogels increased progressively with time and finally the gels completely dissolved. Degradation of the dex-lactate-HEMA hydrogels was associated with infiltration of macrophages and the formation of giant cells, both of which phagocytosed pieces of the hydrogel. A good correlation between the in vitro and the in vivo degradation time was found. This suggests that extra-cellular degradation is not caused by enzymes but depends only on hydrolysis of the ester and/or carbonate bonds present in the crosslinks of the hydrogels. After 21 days, the degradable hydrogels, as such, could not be retrieved, but accumulation of macrophages and giant cells was observed, both of which contained particles of the gels intracellularly. As for the dex-MA hydrogels, no toxic effects on the surrounding tissue were found. The results presented in this study demonstrate that dextran-based hydrogels can be considered as biocompatible materials, making these hydrogels attractive systems for drug delivery purposes.

Animals↗

Bone regeneration by transforming growth factor beta1 released from a biodegradable hydrogel.

This paper describes the sustained release of transforming growth factor beta1 (TGF-beta1) from a biodegradable hydrogel based on polyion complexation for the enhancement of bone regeneration activity. Basic TGF-beta1 was adsorbed onto the biodegradable hydrogel of acidic gelatin with an isoelectric point of 5.0 by an electrostatic interaction. The TGF-beta1 could not be adsorbed onto basic gelatin. When acidic gelatin hydrogels incorporating 125I-labeled TGF-beta1 were implanted into the back subcutis of mice, the radioactivity decreased with time and the in vivo retention of TGF-beta1 was prolonged with a decrease in the water content of hydrogels. The higher the water content of hydrogels, the faster their biodegradation. The in vivo retention of TGF-beta1 correlated well with that of gelatin hydrogels, indicating that TGF-beta1 was released from the gelatin hydrogel as a result of hydrogel biodegradation. The ability of TGF-beta1-incorporated into acidic gelatin hydrogels to induce bone regeneration was evaluated in a rabbit calvarial defect model. Eight weeks after treatment, the gelatin hydrogels with water contents of 90 and 95 wt% induced significantly high bone regeneration compared with those with lower and higher water contents and free TGF-beta1. This indicates that the sustained release of TGF-beta1 from the hydrogel with suitable in vivo degradability is necessary to effectively enhance its osteoinductive function. Rapid hydrogel degradation will result in a retention time of TGF-beta1 which is too short to induce bone regeneration. It is possible that the slow degradation of the hydrogel physically blocked TGF-beta1-induced bone regeneration at the skull defect. It can be concluded that the gelatin hydrogel is a promising matrix of TGF-beta1 release to induce skull bone regeneration.

Absorbable Implants↗

Adhesion of Pseudomonas aeruginosa and Staphylococcus epidermidis to silicone-hydrogel contact lenses.

PURPOSE: The purpose of this study is to compare the adhesion capabilities of the most important etiologic agents of microbial ocular infection to the recently available silicone-hydrogel lenses with those to a conventional hydrogel lens. METHODS: In vitro static adhesion assays of Pseudomonas aeruginosa 10,145, Staphylococcus epidermidis 9142 (biofilm-positive), and 12,228 (biofilm-negative) to two extended-wear silicone-hydrogel lenses (balafilcon A and lotrafilcon A), a daily wear silicone-hydrogel lens (galyfilcon A) and a conventional hydrogel (etafilcon A) were performed. To interpret the adhesion results, lens surface relative hydrophobicity was assessed by water contact angle measurements. RESULTS: P. aeruginosa and S. epidermidis 9142 exhibited greater adhesion capabilities to the extended wear silicone-hydrogel lenses than to the daily wear silicone- and conventional hydrogel lenses (p < 0.05). No statistical differences were found between the adhesion extent of these strains to galyfilcon A and etafilcon A. The biofilm negative strain of S. epidermidis adhered in larger extents to the silicone-hydrogel lenses than to the conventional hydrogel (p < 0.05), but in much lower amounts than the biofilm-positive strain. The water contact angle measurements revealed that the extended wear silicone-hydrogel lenses are hydrophobic, whereas the daily wear silicone- and conventional hydrogel lenses are hydrophilic. CONCLUSIONS: As a result of their hydrophobicity, the extended wear silicone-hydrogel lenses (lotrafilcon A and balafilcon A) may carry higher risk of microbial contamination than both the hydrophilic daily wear silicone-hydrogel lens, galyfilcon A and the conventional hydrogel lens, etafilcon A.

Bacterial Adhesion↗

Controlled release of vascular endothelial growth factor by use of collagen hydrogels.

In vivo profile of vascular endothelial growth factor (VEGF) release from collagen hydrogels was investigated comparing that of hydrogel degradation while angiogenesis induced by the released VEGF was assessed. Collagen sponges were chemically cross-linked with different amounts of glutaraldehyde for various time periods. When 125I-labeled collagen hydrogels incorporating VEGF were subcutaneously implanted into the back subcutis of mice, the hydrogel radioactivity decreased with time, the decrement profile depending on the cross-linking conditions. The radioactivity was retained for longer time periods as the glutaraldehyde concentration and cross-linking time increased. Implantation study of collagen hydrogels incorporating 125I-labeled VEGF revealed that the remaining VEGF radioactivity decreased with time and the retention period was prolonged with the decreased hydrogel biodegradation. The slower the hydrogel degradation, the longer the period of VEGF retention. The collagen hydrogel incorporating VEGF induced significant angiogenesis around the implanted hydrogel, in marked contrast to VEGF in the solution form and VEGF-free empty hydrogel. The retention period of angiogenesis became longer with a decrease of the in vivo degradation rate of hydrogels. It is possible that the slower degraded hydrogel achieves a longer period of VEGF release, resulting in prolonged angiogenetic effect. We concluded that in our hydrogel system, biologically-active VEGF was released as a result of in vivo degradation of the hydrogel.

Absorbable Implants↗

Controlled releases of FGF-2 and paclitaxel from chitosan hydrogels and their subsequent effects on wound repair, angiogenesis, and tumor growth.

A photocrosslinkable chitosan (Az-CH-LA) aqueous solution resulted in an insoluble hydrogel like a soft rubber within 30 sec of ultraviolet light (UV)-irradiation. The photocrosslinked chitosan hydrogel showed strong sealing strength and potential use as a new tissue adhesive in surgical application. Paclitaxel, which is an anti-tumor reagent and a vascularization-inhibitor, retained in the photocrosslinked chitosan hydrogel, and were gradually released from the photocrosslinked chitosan hydrogel in vivo upon the degradation of the hydrogel. The paclitaxel-incorporated photocrosslinked chitosan hydrogels effectively inhibited tumor growth and angiogenesis in mice. On the other hand, the fibroblast growth factor (FGF)-2 molecules also retained in both the photocrosslinked chitosan and an injectable chitosan/IO(4)-heparin hydrogels, and were gradually released from the hydrogels upon their in vivo biodegradations. The activity of FGF-2 in the hydrogels was stable for long time (more than 14 days). The controlled release of biologically active FGF-2 molecules from the hydrogels caused an induction of the angiogenesis and, possibly, collateral circulation occurred in the healing-impaired diabetic (db/db) mice and the ischemic limbs of rats. The purpose of this review is to describe the effectiveness of the chitosan hydrogels (photocrosslinkable chitosan hydrogel and chitosan/IO(4)-heparin hydrogel) as a local drug delivery carrier for FGF-2 and paclitaxel to control wound repair, tumor growth, and angiogenesis. It is thus proposed that the chitosan hydrogels may be a promising new local carrier for drugs such as FGF-2 and paclitaxel.

Animals↗

In vitro characterization of vascular endothelial growth factor and dexamethasone releasing hydrogels for implantable probe coatings.

Anti-fouling hydrogel coatings, copolymers of 2-hydroxyethyl methacrylate, 1-vinyl-2-pyrrolidinone, and polyethylene glycol, were investigated for the purpose of improving biosensor biocompatibility. These coatings were modified to incorporate poly(lactide-co-glycolide) (PLGA) microspheres in order to release dexamethasone (DX) and/or vascular endothelial growth factor (VEGF). DX and VEGF release kinetics from microspheres, hydrogels, and microspheres embedded in hydrogels were determined in 2-week and 1-month studies. Overall, monolithic, non-degradable hydrogel drug release had an initial burst followed by release at a significantly lower amount. Microsphere drug release kinetics exhibited an initial burst followed by sustained release for 1 month. Embedding microspheres in hydrogels resulted in attenuated drug delivery. VEGF release from embedded microspheres, 1.1+/-0.3 ng, was negligible compared to release from hydrogels, 197+/-33 ng. After the initial burst from DX-loaded hydrogels, DX release from embedded microspheres was similar to that of hydrogels. The total DX release from hydrogels, 155+/-35 microg, was greater than that of embedded microspheres, 60+/-6 microg. From this study, hydrogel sensor coatings should be prepared incorporating VEGF in the hydrogel and DX either in the hydrogel or in DX microspheres embedded in the hydrogel.

Biocompatible Materials↗