Surface Modification of Aliphatic Polyester to Enhance Biocompatibility.

Aliphatic polyester is a kind of biodegradable implantable polymers, which shows promise as scaffolds in tissue engineering, drug carrier, medical device, and so on. To further improve its biocompatibility and cell affinity, many techniques have been used to modify the surface of the polyester. In the present paper, the key factors of influencing biocompatibility of aliphatic polyester were illuminated, and the different surface modification methods such as physical, chemical, and plasma processing methods were also demonstrated. The advantages and disadvantages of each method were also discussed with the hope that this review can serve as a resource for selection of surface modification of aliphatic products.

Cell affinity for bFGF immobilized heparin-containing poly(lactide-co-glycolide) scaffolds.

In order to effectively and uniformly immobilize basic fibroblast growth factor (bFGF) to thick PLGA scaffold, the heparin-conjugated PLGA (H-PLGA) was synthesized at the first by reaction between heparin and a low molecular weight PLGA. Then heparin-containing PLGA (H-PLGA/PLGA) scaffold was fabricated by blending the H-PLGA with a high molecular weight PLGA. Finally, bFGF was immobilized on the H-PLGA/PLGA scaffold mainly by static electricity action between them. The effect of H-PLGA content on bFGF binding efficiency of the H-PLGA/PLGA scaffolds was investigated. It was found that bFGF binding efficiency increased with increasing H-PLGA content. The bound bFGF can release in vitro slowly from the H-PLGA/PLGA scaffolds and last over two weeks. The released bFGF has still preserved its bioactivity. The attachment and growth of mouse 3T3 fibroblasts on the H-PLGA/PLGA scaffolds were better than that on the PLGA scaffold, however bFGF immobilized H-PLGA/PLGA scaffolds showed much better cell affinity. Therefore, the method to use the H-PLGA/PLGA scaffold for immobilizing bFGF is not only effective for slow delivering bFGF with bioactivity, but also can be used for fabricating thick scaffold where bFGF could be combined and uniformly distributed.

An injectable scaffold: rhBMP-2-loaded poly(lactide-co-glycolide)/hydroxyapatite composite microspheres.

Poly(lactide-co-glycolide)/hydroxyapatite(50/50) (PLGA/HA(50/50)) composite microspheres were fabricated and treated with a mixture of 0.25M NaOH aqueous solution and ethanol (v/v=1/1) at 37 degrees C. The properties of untreated and treated PLGA/HA(50/50) composite microspheres were determined and compared. The results showed that the surface roughness, HA content and hydrophilicity of the treated PLGA/HA(50/50) composite microspheres increased with treatment time. However, the treatment time should be kept within 2h in order to maintain the shape of the PLGA/HA(50/50) microspheres. At the same time, a degradation study showed that both the untreated and treated microspheres degraded gradually with time, with the treated microspheres degrading faster in the first 4 weeks. The rhBMP-2-loaded PLGA/HA(50/50) composite microspheres were prepared by solution dipping treated PLGA/HA(50/50) composite microspheres. Mouse OCT-1 osteoblast-like cells were cultured on the untreated, treated and rhBMP-2-loaded PLGA/HA(50/50) composite microspheres and the cell affinity of the various microspheres was assessed and compared. It was found that the surface-treated PLGA/HA(50/50) composite microspheres clearly promoted osteoblast attachment, proliferation and alkaline phosphatase activity. It was considered that the hydrophilicity, osteoconductivity and surface roughness were increased by the increase in the HA component, which facilitated cell growth. Moreover, the rhBMP-2 loaded on the treated PLGA/HA(50/50) composite microspheres could be slowly released and further enhanced osteoblast differentiation. The good cell affinity and enhanced osteogenic potential of the rhBMP-2-loaded PLGA/HA composite microspheres indicate that they could be used as an injectable scaffold.

The bioactivity of rhBMP-2 immobilized poly(lactide-co-glycolide) scaffolds.

In this study, immobilization of rhBMP-2 on polylactone-type polymer scaffolds via plasma treatment was investigated. To introduce proper functional groups on the surface of poly(lactide-co-glycolide) (PLGA) matrix, PLGA films were treated under different atmospheres, such as oxygen, ammonia and carbon dioxide, respectively, and then incubated in rhBMP-2 solution of de-ionized water. The effect of various plasma-treated PLGA films on binding rhBMP-2 was investigated and compared. It was found that PLGA binding ability to rhBMP-2 was enhanced by carbon dioxide and oxygen plasma treatment, and the binding ability of the oxygen plasma-treated PLGA (OT-PLGA) to rhBMP-2 was the strongest after oxygen plasma treating for 10 min under a power of 50 W. The changes of surface chemistry and surface topography of PLGA matrix induced by oxygen plasma treatment played main roles in improving the PLGA binding ability to rhBMP-2. The stability of rhBMP-2 bound on OT-PLGA film was determined under a dynamic condition by a Parallel Plate Flow Chamber. The result showed that the rhBMP-2 had been immobilized on the OT-PLGA film. Mouse OCT-1 osteoblast-like cell as a model cell was cultured on the rhBMP-2 bound OT-PLGA (OT-PLGA/BMP) in vitro, which showed that the bound rhBMP-2 via oxygen plasma treatment was bioactive. Depending on hydrophilicity and rich polar O-containing groups of the OT-PLGA scaffold, different amount of rhBMP-2 could be evenly immobilized on the surface of the OT-PLGA scaffold. The immobilized rhBMP-2 had stimulated differentiation of OCT-1 cell and accelerated process of mineralization of OCT-1 cell in the scaffold. It revealed the rhBMP-2 immobilized PLGA scaffold had good cell affinity.

Multi-morphological biodegradable PLGE nanoparticles and their drug release behavior.

A series of amphiphilic tri-block copolymers based on poly(lactide-co-glycolide)-b-poly(ethylene oxide)-b-poly(lactide-co-glycolide) (PLGE) with various segment ratios of PEO/PLGA and segment lengths of PEO were synthesized. Multi-morphological biodegradable nanoparticles - PLGE-NPs were fabricated by an improved emulsion/solvent evaporation technique in the absence of surfactant. By adjusting segment ratio of PLGA/PEO (w/w) and molecular weight of PEO, various morphological and nanoscale sized spheres, elliptic spheres, short rods and threads could be formed. The auto-assembling mechanism of the PLGE-NPs and influencing effectors of composition of the PLGE on morphology of the PLGE-NPs were discussed. The PLGE-NPs were biodegradable, and the factors that affected the degradation rate of the PLGE-NPs were also discussed. By using the amphiphilic PLGE polymer, the biodegradable nanoscale immunosuppressive agent - multi-morphological Cyclosporine (CsA)-loaded PLGE-NPs was fabricated. CsA release behavior of the CsA-loaded PLGE-NPs in vitro was determined, and the effect factors on CsA release behavior of the CsA-loaded PLGE-NPs were discussed.

[Fabrication and characteristics of oriental poly (lactic-co-glycolic acid) scaffold: a preliminary study].

OBJECTIVE: To explore the method of fabricating oriental scaffolds and investigate the biocompatibility of the scaffolds as well as cells distribution within the scaffolds in vitro. METHODS: The oriental poly (lactic-co-glycolic acid) (PLGA) scaffolds were fabricated with modified emulsion-phase separation method. The scaffolds were treated with plasma and then anchored with collagen I. Articular chondrocytes were loaded into the scaffolds. The growth status and distributing characteristic of the cells were investigated by environmental scanning electron microscope. RESULTS: The scaffold was well compatible with the articular chondrocytes. The cells could reach to 2.5 mm depth with unilateral loading. The cells distributed evenly in the scaffold and lined along the inner pipes. CONCLUSIONS: The oriental scaffold fabricated could significantly promote the distributing characteristics of the chondrocytes. The vertical alignment of the chondrocytes within the scaffold is closely similar to that of articular cartilage.

Preparation and cell affinity of microtubular orientation-structured PLGA(70/30) blood vessel scaffold.

In this study, a kind of microtubular orientation-structured blood vessel mimicking natural structure was fabricated with poly(lactide-co-glycolide)(70/30) (PLGA(70/30)) solutions in 1,4-dioxane by an improved thermal-induced phase separation (TIPS) technique. The effect of main factors of the TIPS technique, such as environmental temperature, temperature gradient and concentration of the polymer solution on the structure and morphology of formed vessel scaffold was investigated. It was observed that the outer-wall of the scaffold became thick obviously and the microtubules neighboring the outer-wall became disordered with environmental temperature increasing. The diameter of microtubules of vessel scaffolds reduced with temperature gradient increasing or concentration of the polymer solution increasing. By controlling parameters of the TIPS, the scaffolds with various morphologies could be manufactured, which had different diameters of microtubules. On the other hand, inner-diameter and outer-diameter of the vessel scaffolds could be controlled by adjusting size of the polyethylene mould. Cell affinity of the scaffolds was tested in vitro by using A10 cell as model cells. Results showed that the cells grew well in the vessel scaffolds which were modified by ammonia plasma treatment and then anchored with collagen. The cells could array along the direction of the microtubules.

The immobilization of basic fibroblast growth factor on plasma-treated poly(lactide-co-glycolide).

In this study, possibility of the method of immobilization of basic fibroblast growth factor (bFGF) on polylactone-type polymer scaffolds via plasma treatment was investigated. To introduce acid carboxylic functional groups on the surface of the polymer matrix, poly(lactide-co-glycolide) (PLGA) film was treated with carbon dioxide (CO2) plasma and then incubated in a phosphate buffer saline (PBS, pH 7.4) solution of bFGF. The bFGF binding efficiency to the CO2 plasma-treated PLGA (PT-PLGA) films under different treating parameters was investigated and compared. It was found bFGF binding efficiency to PLGA was enhanced by CO2 plasma treatment. The binding efficiency of bFGF to PLGA was variational with CO2 plasma treating time and it reached a maximum after a treating time of 20min under the power of 20W. The changes of surface chemistry and surface topography induced by CO2 plasma treatment played main roles in improving binding efficiency. Bound bFGF was released continuously from the films for up to 7 days in vitro. The stability of bFGF immobilized on PLGA film via CO2 plasma treatment was tested further under dynamic conditions by a Parallel Plate Flow Chamber. Mouse 3T3 fibroblasts were cultured on the bFGF bound PLGA with a prior plasma treatment (20W, 20min) (PT-PLGA/bFGF) film, which showed that bFGF released from PT-PLGA/bFGF film was bioactive. Adhesion and growth of cells on PLGA scaffolds were greatly improved by immobilization of bFGF on them. Therefore, the method of CO2 plasma treatment combining bFGF anchorage not only was usable in delivering bFGF, but also could be applied extensively for surface modification of scaffolds in tissue engineering.

Combining oxygen plasma treatment with anchorage of cationized gelatin for enhancing cell affinity of poly(lactide-co-glycolide).

Surface characteristics greatly influence attachment and growth of cells on biomaterials. Although polylactone-type biodegradable polymers have been widely used as scaffold materials for tissue engineering, lack of cell recognition sites, poor hydrophilicity and low surface energy lead to a bad cell affinity of the polymers, which limit the usage of polymers as scaffolds in tissue engineering. In the present study, surface of poly (L-lactide-co-glycolide) (PLGA) was modified by a method of combining oxygen plasma treatment with anchorage of cationized gelatin. Modification effect of the method was compared with other methods of oxygen plasma treatment, cationized gelatin or gelatin coating and combining oxygen plasma treatment with anchorage of gelatin. The change of surface property was compared by contact angles, surface energy, X-ray photoelectron spectra (XPS), attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and scanning electron microscopy (SEM) measurement. The optimum oxygen pretreatment time determined by surface energy was 10 min when the power was 50 W and the oxygen pressure was 20 Pa. Analysis of the stability of gelatin and cationized gelatin anchored on PLGA by XPS, ATR-FTIR, contact angles and surface energy measurement indicated the cationized gelatin was more stable than gelatin. The result using mouse NIH 3T3 fibroblasts as model cells to evaluate cell affinity in vitro showed the cationized gelatin-anchored PLGA (OCG-PLGA) was more favorable for cell attachment and growth than oxygen plasma treated PLGA (O-PLGA) and gelatin-anchored PLGA (OG-PLGA). Moreover cell affinity of OCG-PLGA could match that of collagen-anchored PLGA (AC-PLGA). So the surface modification method combining oxygen plasma treatment with anchorage of cationized gelatin provides a universally effective way to enhance cell affinity of polylactone-type biodegradable polymers.

[Research on cell affinity of poly-L-lactide/porcine-derived xenogeneic bone composite in vitro].

OBJECTIVE: To evaluate the feasibility of poly-L-lactide(PLLA)/porcine-derived xenogeneic bone (PDXB) composite as a scaffold for the bone tissue engineering. METHODS: The film and the scaffold of the PLLA-PDXB composite were respectively prepared by a solution casting method and a solution casting-particle leaching method. The composite film and scaffold were further treated by the surface alkaline hydrolysis. The surface morphology of the composite was observed by the scanning electron microscopy, and hydrophilicity degree of the composite was measured. The OCT-1 osteoblast-like cells were cultured and amplified in vitro as the seeding cells, which were then implanted on the film and scaffold. The adherence rate, adherence shape,proliferating activity, and growing morphology of the OCT-1 osteoblast-like cells were observed on the film. RESULTS: The PDXB particle 50 microm in diameter on average had a similar phase structure to that of hydroxyapatite. But its Ca/P ratio was lower than that of hydroxyapatite. After the surface alkaline hydrolysis, the PDXB particle could be exposed on the surface of the PLLA-PDXB composite. The surface roughness and hydrophilicity of the PLLA-PDXB composite were obviously enhanced. The cell adherence rate and the cell proliferation activity of the PLLA-PDXB composite were higher than those of the pure PLLA material. The cells tended to grow on the exposed surface of the PDXB particles. The cells seeded on the composite scaffold could migrate to the inside of the composite scaffold and grew well. CONCLUSION: The PLLA-PDXB composite has a good cell affinity, and this kind of composite can hopefully become a new scaffold material to be used in the bone tissue engineering.

The effect of oxygen plasma pretreatment and incubation in modified simulated body fluids on the formation of bone-like apatite on poly(lactide-co-glycolide) (70/30).

In this study, biodegradable poly(lactide-co-glycolide) (PLGA) (70/30) films and scaffolds were first treated with oxygen plasma and then incubated in a modified simulated body fluid 1.5SBF0 to prepare a bone-like apatite layer. The formation of the apatite and its influence on osteoblast-like cells growth were investigated. It was found that the bone-like apatite formability of PLGA(70/30) was enhanced by plasma pretreatment. The changes of surface chemistry and surface topography induced by oxygen plasma treatment were both effective for apatite formation. The apatite formability increased with increasing plasma-treating time. Under a treating condition of 20 W for 30 min, oxygen plasma treatment could penetrate into the inner scaffold. After 6 days incubation, the apatite formed in plasma-treated scaffold was better distributed than in untreated scaffold, and the weight and mechanical strength of the plasma-treated scaffold were both enhanced. Compared with PLGA(70/30), the apatite layer formed on oxygen plasma-treated PLGA(70/30) surface enhanced adhesion and proliferation of OCT-1 osteoblast-like cell, but had no significant effect on cell's ALP activity at day 7. A prolonged investigation is being in process to further verify the bone-like apatite effects on osteogenic differentiation.

Manufacturing and morphology structure of polylactide-type microtubules orientation-structured scaffolds.

Tissue engineering using scaffold not only should have biodegradability and a certain 3D structure, but also its morphology structure should be mimetic to that of the repaired natural tissue. So to manufacture the scaffold with a biomimetic structure as the natural tissues is important. In this research, highly porous poly(L-lactic acid) (PLLA) and poly(L-lactic-co-glycolic acid) (PLGA) scaffolds with microtubules orientation structure were designed and fabricated by using dioxane as solvent and an improved thermal-induced phase separation (TIPS) technique. All the factors which will affect solvent crystallization and microtubules orientation structure of the scaffold, such as the type of the solvent and polymer, concentration of the polymer solution, and temperature-gradient of the system have been studied carefully. So the porosity, diameter, tubular morphology and orientation of the microtubules could be controlled by adjusting the concentration of the polymer solution and temperature-gradient of the system. The scaffold with diameter of microtubules from 40 to 240microm and high porosity up to 96% could be obtained by adjusting temperature-gradient during the TIPS process. By increasing concentration of the polymer solution the regularity of the microtubular scaffold has been improved and the thickness of wall of the microtubules has been increased as well. In vitro cell culture results show that after the scaffolds have been improved by the ammonia plasma treatment and then collagen anchorage method, the human transparent cartilage cells H144, could be seeded deeply into the microtubules orientation-structured scaffolds and grew well there.

Influences of ammonia plasma treatment on modifying depth and degradation of poly(L-lactide) scaffolds.

Hydrophobicity of poly(L-lactide) scaffolds is a main drawback in obtaining a sufficient mass of seeded cells for satisfying the requirements of tissue engineering. Plasma treatment is a useful technique to enhance the hydrophilicity of the scaffolds. However, the effect of this technique on the modifying depth and degradation of the scaffolds should be considered. In this paper, the influence of NH3 plasma treatment on the modifying depth and degradation of scaffolds were investigated. The results showed that the modifying depth of the scaffolds increased with treating time and the plasma power ranging from 20 to 80 W influenced the depth slightly. However, the degradation of the scaffolds increased with increasing treatment time and plasma power. The results also showed that the plasma intruded the scaffolds gradually from top to bottom. For a 4 mm thick scaffold, the optimized treatment condition was 20 W of power in a 30 Pa ammonia atmosphere for 30 min of treating time. Under this condition, the integrity of scaffold could be relatively well kept. NH3 plasma treatment enabled the penetration of cells into scaffolds and facilitated the proliferation of cells in them.

Porcine-derived xenogeneic bone/poly(glycolide-co-lactide-co-caprolactone) composite and its affinity with rat OCT-1 osteoblast-like cells.

Porcine-derived xenogeneic bone (PDXB) was derived from cancellous bone of adult porcine. Its morphology and structure were characterized by SEM, FTIR and XRD. A series of composite films consisting of PDXB and poly(glycolide-co-lactide-co-caprolactone) (PGLC) polymer were prepared. Because of the introduction of PGLC polymer, the PDXB/PGLC composites especially PDXB/PGLC(30/70) and PDXB/PGLC(50/50) showed good processability and mechanical properties. In addition, the hydrophilicity of the composites was enhanced as well since the PDXB component was hydrophilic. Osteoblast-like cells (OCT-1) were used as an in-vitro model to assess the affinity of the PDXB/PGLC composites. It was found that compared with the pure PGLC film, PDXB/PGLC(30/70) and PDXB/PGLC(50/50) composite films promoted cell attachment, proliferation and ALP (alkaline phosphatase) activity obviously. In addition, the cells preferred growing on the areas of exposed PDXB. It was considered that the hydrophilicity, osteoconductivity and appropriate surface roughness (Sa=3.30, 4.00 microm) induced by PDXB facilitate cell growth. However, the introduction of too much PDXB, such as PDXB/PGLC(70/30) film, would obtain an adverse effect on the cell growth since the value of Sa was up to 7.33 microm. It indicated that only the composites with appropriate surface topography could favor cell growth. Surface topography probably has a more important effect on cell growth process than surface chemistry.

Adhesion and proliferation of OCT-1 osteoblast-like cells on micro- and nano-scale topography structured poly(L-lactide).

The impact of the surface topography of polylactone-type polymer on cell adhesion was to be concerned because the micro-scale texture of a surface can provide a significant effect on the adhesion behavior of cells on the surface. Especially for the application of tissue engineering scaffold, the pore size could have an influence on cell in-growth and subsequent proliferation. Micro-fabrication technology was used to generate specific topography to investigate the relationship between the cells and surface. In this study the pits-patterned surfaces of polystyrene (PS) film with diameters 2.2 and 0.45 microm were prepared by phase-separation, and the corresponding scale islands-patterned PLLA surface was prepared by a molding technique using the pits-patterned PS as a template. The adhesion and proliferation behavior of OCT-1 osteoblast-like cells morphology on the pits- and islands-patterned surface were characterized by SEM observation, cell attachment efficiency measurement and MTT assay. The results showed that the cell adhesion could be enhanced on PLLA and PS surface with nano-scale and micro-scale roughness compared to the smooth surfaces of the PLLA and PS. The OCT-1 osteoblast-like cells could grow along the surface with two different size islands of PLLA and grow inside the micro-scale pits of the PS. However, the proliferation of cells on the micro- and nano-scale patterned surface has not been enhanced compared with the controlled smooth surface.

Preparation and evaluation of poly(L-lactide-co-glycolide) (PLGA) microbubbles as a contrast agent for myocardial contrast echocardiography.

A kind of absorbable PLGA microbubble-based contrast agent (PLGA microspheres with porous or hollow inner structure) was fabricated by an improved double emulsion-solvent evaporation method. The contrast efficiency was evaluated and proved both in vitro and in vivo. By adjusting the polymer concentration and volume of the inner aqueous phase during the fabrication of microbubbles, the inner structure of the microbubbles could be controlled. Both air-filled and perfluoropropane-filled microbubbles can opacify the left ventricle. However, when compared with air-filled microbubbles, perfluoropropane-filled microbubbles can produce significantly longer enhancement in left ventricle in the dog model due to the lower diffusivity and lower solubility of perfluoropropane in blood. A suspension of perfluoropropane-filled PLGA microbubbles (1.8 microm average microbubbles size, 2 x 10(8) microbubbles/mL concentration) has successfully and safely achieved myocardial opacification in closed-chest dogs. A perfusion defect was observed in both of the two dogs with acute myocardial infarction with Power Contrast Imaging (PCI) triggered technology. In the examination of contrast in both ventricular and myocardial opacification, the high mechanical index (MI) was found to have superior contrast sensitivity over the low MI for PLGA-based contrast agents.

Bulk and surface modifications of polylactide.

This article reviews various methods of modifying the bulk and surface properties of poly(lactic acid) (PLA) so that the polymer may be used as a drug carrier in a drug delivery system (DDS) and as a cell scaffold in tissue engineering. Copolymerization of lactide with other lactone-type monomers or monomers with functional groups such as malic acid, copolymerization of lactide with macromolecular monomer such as poly(ethylene glycol) (PEG) or dextran, as well as blending polylactide and natural derivatives and other methods of bulk modification are discussed. Surface modifications of PLA-type copolymers, such as surface coating, chemical modification, and plasma treatment are described. Cell culture technology proves the efficiency of bulk and surface modification and the potential application of PLA in tissue engineering.

Characterization of surface property of poly(lactide-co-glycolide) after oxygen plasma treatment.

In this study, poly (lactide-co-glycolide) (PLGA) films were treated by oxygen plasma. The surface structure, topography and surface chemistry of treated PLGA films were characterized by contact angle measurement, scanning electron microscope observation, atomic force microscopy, and X-ray photoelectron spectrum analysis. The cell affinity of the oxygen plasma treated films was evaluated under dynamic conditions by Parallel Plate Flow Chamber (PPFC). The results showed that the hydrophilicity increased greatly after oxygen plasma treatment. High quantities of -C-O groups, such as hydroxyl and peroxyl groups could be incorporated into the surface of PLGA (70/30) by controlling appropriate plasma treatment conditions. Moreover, the oxygen plasma treatment resulted in formation of peaks and valleys on the sample surfaces, and the roughness increased with treatment time. Cells stretched very well and the ability to endure the shear stress was improved greatly after the PLGA (70/30) was modified by appropriate plasma treatment, i.e. under 50W for 2 or 10 min. However, when the treatment time was increased to 20 min, the percentage of adherent cells on the roughest surface decreased because the content of polar groups incorporated onto the surface decreased. The results showed that improved cell adhesion was attributed to the combination of surface chemistry and surface morphology of PLGA during plasma etching.

Synthesis and cell affinity of functionalized poly(L-lactide-co-beta-malic acid) with high molecular weight.

A novel functionalized biodegradable poly(L-lactide-co-beta-benzyl malolactonate) (p-PLMA) with high molecular weight was synthesized through ring-opening copolymerization. Three p-PLMA copolymers with different beta-benzyl malolactonate content were synthesized. The molecular weight (M(w)) and tensile strength of the copolymer with 4 mol% beta-benzyl malolactonate content were 179,800 and 19.0MPa respectively, the molecular weight (M(w)) and tensile strength of p-PLMA decreased with beta-benzyl malolactonate content increasing. The hydrophilicity of the de-protected product: poly(L-lactide-co-beta-malic acid) (d-PLMA) increased with malic acid content increasing. The results of 3T3 mice fibroblasts cultivated on d-PLMA films showed that the cell adhesion on d-PLMA was better than that of PLLA and the cell attached efficiency of d-PLMA with 8 mol% malic acid content was the highest. The cells grew well both on the surface and inside of d-PLMA scaffolds. The cell affinity of d-PLMA was better than that of PLLA.

[Drug release and biocompatibility of cyclosporine A drug delivery system implanting into the anterior chamber].

OBJECTIVE: To study the drug concentration in the aqueous humor and the biocompatibility of cyclosporine A drug delivery system (CsA DDS) implanting in the anterior chamber. METHODS: There were four different types of CsA DDS which had different biodegradable polymers as the vector or had different ratio between CsA and the vector. Thirty-six New Zealand rabbits were randomly divided into 4 groups to receive the 4 different types of CsA DDS. Three of nine New Zealand rabbits received CsA DDS in one eye and empty DDS in the contralateral eye. Three rabbits received empty DDS in one eye and keratotomy in the contralateral eye. Another three rabbits received CsA DDS in one eye and keratotomy in the contralateral eye. All DDS were implanted into the anterior chamber. The follow-up period was 12 weeks. RESULTS: No significantly acute or chronic intraocular toxic effects were found in all groups. The CsA release rate was different in these 4 groups. In type A and B CsA DDS, the drug released fast and maintained for a short period; in type C and D, the drug released slowly and could be maintained for a long period. CONCLUSION: CsA DDS implanted in the anterior chamber can be well tolerated in rabbit eyes. CsA DDS is a promising approach for the prevention (type C and D CsA DDS) and treatment (type A and B CsA DDS) of corneal graft rejection.