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ABSTRACT: In this study we have investigated the influence of the mechanism of microsphere degradation or erosion on the in vivo degradation of microsphere/calcium phosphate cement composites (microsphere CPCs) used in tissue engineering. Microspheres composed of poly(lactic-co-glycolic acid) (PLGA), gelatin and poly(trimethylene carbonate) (PTMC) were used as the model and the resulting microsphere CPCs were implanted subcutaneously for 4, 8 or 12weeks in the back of New Zealand white rabbits. Besides degradation, the soft tissue response to these formulations was evaluated. After retrieval, specimens were analyzed by physicochemical characterization and histological analysis. The results showed that all microsphere CPCs exhibited microsphere degradation after 12weeks of subcutaneous implantation, which was accompanied by decreasing compression strength. The PLGA microspheres exhibited bulk erosion simultaneously throughout the whole composite, whereas the gelatin type B microspheres were degradated from the outside to the center of the composite. High molecular weight PTMC microspheres exhibited surface erosion resulting in decreasing microsphere size. Furthermore, all composites showed a similar tissue response, with decreasing capsule thickness over time and a persistent moderate inflammatory response at the implant interface. In conclusion, microsphere CPCs can be used to generate porous scaffolds in an in vivo environment after degradation of microspheres by various degradation/erosion mechanisms.
Acta biomaterialia 12/2009; 6(6):2200-11. · 3.98 Impact Factor
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ABSTRACT: In this work, different modifications of photo-cross-linked poly(propylene fumarate)/poly(N-vinyl pyrrolidone) (PPF/PNVP) matrices were studied for their effect on the release kinetics of two ophthalmic drugs. The hydrophilicity of solid PPF/PNVP matrices loaded with acetazolamide (AZ) or timolol maleate (TM) was increased by adding various amounts of poly(ethylene glycol) (PEG) or by increasing the amount of N-vinyl pyrrolidone (NVP) in the polymer mixture prior to cross-linking. The in vitro release studies that utilized high-performance liquid chromatography for quantification revealed highly accelerated drug release from the matrices with increasing contents of the hydrophilic modifier. AZ was released from matrices containing 5% PEG in 56 days, which equals approximately 25% of the release period found for the unmodified matrices. A comparable acceleration in drug release was found for TM-loaded samples modified with 5% PEG. These studies further revealed that 1% PEG is sufficient to shorten the TM release duration by one-third. A significant acceleration in drug release was also found for the samples that were fabricated from a PPF-NVP mixture with increased NVP content. Matrix water content and erosion were assessed gravimetrically. Micro-computed tomography was used to image structural changes of the release systems and shed light on the drug-release mechanism. This study showed that hydrophilic matrix modifications of PPF/PNVP matrices accelerate the drug release of two ophthalmic drugs and represent a suitable tool to adjust drug-release rates from PPF-based matrices for different therapeutic needs.
Journal of Biomaterials Science Polymer Edition 02/2009; 20(1):49-69. · 1.69 Impact Factor
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ABSTRACT: To improve the in vivo resorption of an injectable calcium phosphate cement (CPC) for bone tissue engineering purposes, in previous experiments macroporosity was introduced by the in situ degradation of incorporated gelatin microspheres. Gelatin microspheres are also suitable carriers for osteoinductive drugs/growth factors, where release occurs concomitantly with degradation of the hydrogel. Introduction of these microspheres into CPC can alter the release pattern of the cement, which usually shows a marginal release of incorporated drugs. The goal of this study was to determine the in vitro release characteristics of gelatin microsphere CPC. For this, recombinant human TGF-beta1, bFGF, and BMP-2 were labeled with (125)I and loaded onto gelatin type A (porcine, pI = 7.0-9.0)/type B (bovine, pI = 4.5-5.0) microspheres for a short (instant) and longer (prolonged) time before mixing them with the cement. Radioactivity of the resulting 5 or 10 wt % gelatin microsphere CPC composites was monitored for 6 weeks when subjected to proteolytic medium. Drug-loaded CPC was used as control. Results showed that release pattern/efficiency of gelatin microsphere CPCs and CPC controls was highly dependent on the type of growth factor but unaffected by the amount of growth factor. With gelatin microsphere CPC, release was also dependent on the type of gelatin, total volume of incorporated microspheres, and loading method.
Journal of Biomedical Materials Research Part A 12/2008; 91(2):614-22. · 2.63 Impact Factor
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ABSTRACT: The function of a photocrosslinked poly(propylene fumarate) (PPF)/poly(N-vinyl pyrrolidone) (PVP) matrix for the sustained release of three ophthalmic model drugs, acetazolamide (AZ), dichlorphenamide (DP), and timolol maleate (TM), was investigated. The drugs differ in molecular weight and degree of dissociation in aqueous environments; both are parameters that significantly influence drug diffusivity. AZ, DP, and TM-loaded cylindrical rods (10 mm length, 0.6 mm diameter) were fabricated by photoinduced cross-copolymerization of PPF and N-vinyl pyrrolidone (NVP) in molds. The released amounts of AZ, DP, TM, and NVP were determined by high-performance liquid chromatography (HPLC). The effects of drug properties and loading on the release kinetics were investigated. The in vitro release of AZ, DP, and TM was well sustained from the polymer matrices over a period of approximately 210, 270, and 250 days, respectively. The release kinetics correlated with the HPLC retention profiles of the different drugs. Following a small initial burst release (<10%), a dual modality release controlled by diffusion and bulk erosion was found for all drugs. Drug release rates of up to 4 microg/day were reached. Matrix drug loading generally affected the extent of the burst release, release kinetics, as well as the matrix water content and matrix degradation that were determined gravimetrically. Microcomputed tomography was used to image structural and dimensional changes of the devices. A preliminary rabbit implantation study revealed promising ocular biocompatibility of drug-free PPF/PVP matrices. All results indicate the potential of photocrosslinked PPF-based matrices as polymeric carriers for long-term ophthalmic drug delivery.
Journal of Biomedical Materials Research Part A 05/2008; 88(4):976-89. · 2.63 Impact Factor
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ABSTRACT: The objective of this study was to investigate the effect of poly(propylene fumarate) (PPF) molecular weight on the release kinetics of two ophthalmic model drugs, acetazolamide (AZ) and timolol maleate (TM), from matrices prepared by photo-induced copolymerization of PPF with N-vinyl pyrrolidone (NVP). PPF macromers of different number average molecular weight (M(n)) and polydispersity index (PI) were used in the experiments. Photo-crosslinked matrices were loaded with 5wt.% AZ or TM. The amounts of released drug and NVP were determined using high-performance liquid chromatography (HPLC). The release kinetics of both drugs was influenced by the molecular weight of the constituent PPF macromer. An increased M(n) led to an increased burst release and an accelerated drug release. Dependent on the PPF M(n), the initial AZ loading was released within periods ranging from 35 days (M(n) = 3670, PI = 1.9) to 220 days (M(n) = 2050, PI=1.5). TM-loaded matrices revealed similar release kinetics dependent on the PPF M(n). The amount of released NVP from photo-crosslinked matrices during the course of a release experiment was independent of the PPF M(n) for both drugs. Matrix swelling and erosion were determined gravimetrically. The network structures of non-loaded matrices were further characterized by determining their crosslinking densities and the relative double bond conversions of fumaric acid (FAA) and NVP. Independent of PPF M(n), PPF and NVP similarly participated in the formation of the PPF/polyNVP copolymer network. The observed differences in drug release might therefore be explained by differences in the microstructural organization of the copolymer networks. Overall, the results demonstrate that drug release kinetics from photo-crosslinked PPF/polyNVP matrices is strongly dependent on the M(n) of the PPF macromer.
Acta Biomaterialia 02/2008; 4(1):1-10. · 4.86 Impact Factor
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ABSTRACT: For tissue engineered bone constructs, calcium phosphate cement (CPC) has a high potential as scaffold material because of its biocompatibility and osteoconductivity. However, in vivo resorption and tissue ingrowth is slow. To address these issues, microspheres can be incorporated into the cement, which will create macroporosity after in situ degradation. The goal of this study was to investigate the handling properties and degradation characteristics of CPC containing gelatin microspheres. Setting time and injectability were determined and an in vitro degradation study was performed. Samples were assayed on mass, compression strength, E-modulus, and morphology. A supplementary degradation test with gelatin microspheres was performed to investigate the influence of physical conditions inside the cement on microsphere stability. The gelatin microsphere CPCs were easy to inject and showed initial setting times of less than 3 min. After 12-weeks in vitro degradation no increase in macroporosity was observed, which was supported by the small mass loss and stabilizing mechanical strength. Even a clear densification of the composite was observed. Explanations for the lack of macroporosity were recrystallization of the cement onto or inside the gelatin spheres and a delayed degradation of gelatin microspheres inside the scaffold. The supplementary degradation test showed that the pH is a factor in the delayed gelatin microsphere degradation. Also differences in degradation rate between types of gelatin were observed. Overall, the introduction of gelatin microspheres into CPC renders composites with good handling properties, though the degradation characteristics should be further investigated to generate a macroporous scaffold.
Journal of Biomedical Materials Research Part A 02/2008; 87(3):643-55. · 2.63 Impact Factor
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ABSTRACT: Bone cements with biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres have already been proven to provide a macroporous calcium phosphate cement (CPC) during in situ microsphere degradation. Furthermore, in vitro/in vivo release studies with these PLGA microsphere/CPC composites (PLGA/CPCs) showed a sustained release of osteo-inductive growth factor when drug was distributed inside/onto the microspheres. The goal of this study was to elucidate the mechanism behind drug release from PLGA/CPC. For this, in vitro release and degradation characteristics of a low-molecular-weight PLGA/CPC (M(w) = 5 kg/mol) were determined using bovine serum albumin (BSA) as a model protein. Two loading mechanisms were applied; BSA was either adsorbed onto the microspheres or incorporated inside the microspheres during double-emulsion. BSA release from PLGA microspheres and CPC was also measured and used as reference. Results show fast degrading polymer microspheres which produced a macroporous scaffold within 4 weeks, but also showed a concomitant release of acidic degradation products. BSA release from the PLGA/CPC was similar to the CPC samples and showed a pattern consisting of a small initial release, followed by a period of almost no sustained release. Separate PLGA microspheres exhibited a high burst release and release efficiency that was higher with the adsorbed samples. Combining degradation and release data we can conclude that for the PLGA/CPC samples BSA re-adsorbed to the cement surface after being released from the microspheres, which was mediated by the pH decrease during microsphere degradation.
Journal of Biomaterials Science Polymer Edition 02/2008; 19(9):1171-88. · 1.69 Impact Factor
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ABSTRACT: This study sought to develop an injectable formulation for long-term ocular delivery of fluocinolone acetonide (FA) by dissolving the anti-inflammatory drug and the biodegradable polymer poly(propylene fumarate) (PPF) in the biocompatible, water-miscible, organic solvent N-methyl-2-pyrrolidone (NMP). Upon injection of the solution into an aqueous environment, a FA-loaded PPF matrix is precipitated in situ through the diffusion/extraction of NMP into surrounding aqueous fluids. Fabrication of the matrices and in vitro release studies were performed in phosphate buffered saline at 37 degrees C. Drug loadings up to 5% were achieved. High performance liquid chromatography was employed to determine the released amount of FA. The effects of drug loading, PPF content of the injectable formulation, and additional photo-crosslinking of the matrix surface were investigated. Overall, FA release was sustained in vitro over up to 400 days. After an initial burst release of 22 to 68% of initial FA loading, controlled drug release driven by diffusion and bulk erosion was observed. Drug release rates in a therapeutic range were demonstrated. Release kinetics were found to be dependent on drug loading, formulation PPF content, and extent of surface crosslinking. The results suggest that injectable, in situ formed PPF matrices are promising candidates for the formulation of long-term, controlled delivery devices for intraocular drug delivery.
Journal of Biomedical Materials Research Part A 01/2008; 83(3):656-66. · 2.63 Impact Factor
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ABSTRACT: In this work, we evaluated the in vitro cytotoxicity and in vivo biocompatibility of a novel poly(propylene fumarate) (PPF)-based/alumoxane nanocomposite for bone tissue engineering applications. The incorporation of functionalized alumoxane nanoparticles into the PPF-based polymer was previously shown to significantly increase the material's flexural mechanical properties. In the current study, samples underwent accelerated in vitro degradation to allow the study of biological responses to these materials over the course of their degradation on a shortened timescale. The polymer, a macrocomposite composed of the polymer and micron-sized particles, and the nanocomposite were evaluated at three stages of degradation for in vitro cytotoxicity with a fibroblast cell line and in vivo soft-tissue response after 3 and 12 weeks of implantation in adult goats. All three material groups experienced mass loss during degradation, but the nanocomposite group eroded significantly faster than the other groups. Nondegraded materials demonstrated minimal cytotoxicity and a minor inflammatory response in soft tissue. On the contrary, predegraded samples elicited more pronounced responses, though these were due to the increase in surface area, surface roughness, and fragmentation associated with the degradation process. The presence of alumoxane nanoparticles in the PPF-based nanocomposite did not significantly affect its cytotoxicity or biocompatibility.
Journal of Biomedical Materials Research Part A 01/2008; 83(4):940-53. · 2.63 Impact Factor
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ABSTRACT: In this work, we evaluated the in vitro cytotoxicity and in vivo biocompatibility of a novel poly(propylene fumarate) (PPF)-based/alumoxane nanocomposite for bone tissue engineering applications. The incorporation of functionalized alumoxane nanoparticles into the PPF-based polymer was previously shown to significantly increase the material's flexural mechanical properties. In the current study, samples underwent accelerated in vitro degradation to allow the study of biological responses to these materials over the course of their degradation on a shortened timescale. The polymer, a macrocomposite composed of the polymer and micron-sized particles, and the nanocomposite were evaluated at three stages of degradation for in vitro cytotoxicity with a fibroblast cell line and in vivo soft-tissue response after 3 and 12 weeks of implantation in adult goats. All three material groups experienced mass loss during degradation, but the nanocomposite group eroded significantly faster than the other groups. Nondegraded materials demonstrated minimal cytotoxicity and a minor inflammatory response in soft tissue. On the contrary, predegraded samples elicited more pronounced responses, though these were due to the increase in surface area, surface roughness, and fragmentation associated with the degradation process. The presence of alumoxane nanoparticles in the PPF-based nanocomposite did not significantly affect its cytotoxicity or biocompatibility. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Journal of Biomedical Materials Research Part A 12/2007; 83A(4):940 - 953. · 2.63 Impact Factor
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ABSTRACT: As our population ages, treatment for joint pain associated with articular cartilage damage is becoming a prevalent challenge. Accordingly, this work investigates local delivery of two regulatory proteins - transforming growth factor-beta1 (TGF-beta1) and insulin-like growth factor-1 (IGF-1) - to cartilage defects from degradable scaffolds as a potential strategy for improving cartilage repair.
The effects of TGF-beta1 and/or IGF-1 delivery on osteochondral repair in adult rabbits were examined through histomorphometric analysis of 11 markers of osteochondral repair.
Complete scaffold degradation occurred allowing for assessment of the healing response at 12 weeks post-surgery. When compared to untreated defects, higher scores were observed with IGF-1-treated defects for the six markers of neo-surface repair: neo-surface morphology, cartilage thickness, surface regularity, chondrocyte clustering, and the chondrocyte/glycosaminoglycan content of the neo-surface and the cartilage surrounding the defect. Surprisingly, the benefits of IGF-1 delivery were not maintained when this growth factor (GF) was co-delivered with TGF-beta1, despite numerous in vitro reports of the combinatory actions of these GFs.
While localized delivery of IGF-1 may be a promising repair strategy, further in vivo assessment is necessary, since fibrous tissue was commonly observed in the neo-surface of all treatment groups. More importantly, this study highlights the need to rigorously examine GF interactions in the wound healing environment and demonstrates that in vitro observations do not directly translate to the in vivo setting.
Osteoarthritis and Cartilage 03/2007; 15(2):187-97. · 3.90 Impact Factor
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ABSTRACT: In this study, the release of rhBMP-2 loaded porous Ca-P cement was studied in vitro and in vivo. We hypothesized that adsorption sites of Ca-P ceramic with high affinity for rhBMP-2 can be blocked by pretreatment of the ceramic with albumin prior to rhBMP-2 loading, which would result in weaker rhBMP-2 binding and enhanced release of rhBMP-2. Preset porous Ca-P cement discs with a diameter of 6.35 mm (volume: 75 mm3) were pretreated by incubation in a solution of 10% rat serum albumin for 24 h or in ddH2O (control group) prior to administration of 5 mug radiolabeled 131I-rhBMP-2. Release was assessed in vitro in phosphate buffered saline (PBS) and fetal calf serum and in vivo by longitudinal scintigraphic imaging of radiolabeled 131I-rhBMP-2 and gamma counting of dissected implants. In vitro release from pretreated discs was higher during the first day. For both formulations, release in PBS was limited compared to release in serum. In vivo release considerably exceeded in vitro release. In vivo release kinetics showed no significant difference of half-lives between pretreated and control discs. Both formulations showed sustained release during at least 4 weeks. Ex vivo gamma counting of retrieved samples confirmed scintigraphic results and showed that the capsule and surrounding tissues only contained a minor fraction rhBMP-2. We conclude that 1. scintigraphy of 131I-labeled rhBMP-2 provides a reliable method for longitudinal measurement of rhBMP-2 release kinetics in vivo. 2. albumin pretreatment of porous Ca-P cement does not results in relevant increase of initial release of rhBMP-2 in vivo, and 3. preset rhBMP-2 loaded porous Ca-P cement discs exhibit one phase exponential release kinetics in the rat ectopic model, characterized by a retention of 20-30% after 4 weeks.
Journal of Materials Science Materials in Medicine 11/2006; 17(10):919-27. · 2.32 Impact Factor
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ABSTRACT: Intraocular drug delivery systems made from biodegradable polymers hold great potential to effectively treat chronic diseases of the posterior segment of the eye. This study is based on the hypothesis that crosslinked poly(propylene fumarate) (PPF)-based matrices are suitable long-term delivery devices for the sustained release of the anti-inflammatory drug fluocinolone acetonide (FA) due to their hydrophobicity and network density. FA-loaded rods of 10 mm length and 0.6 mm diameter were fabricated by photo-crosslinking PPF with N-vinyl pyrrolidone (NVP). The released amounts of FA and NVP were determined by HPLC analysis. The effects of drug loading and the ratio of PPF to NVP on the release kinetics were investigated using a 2(3-1) factorial design. Overall, FA release was sustained in vitro over almost 400 days by all tested formulations. Low burst release was followed by a dual modality release controlled by diffusion and bulk erosion with release rates up to 1.7 microg/day. The extent of the burst effect and the release kinetics were controlled by the drug loading and the matrix composition. Matrix water content and degradation were determined gravimetrically. Micro-computed tomography was used to image structural and dimensional changes of the devices. The results show that photo-crosslinked PPF-based matrices are promising long-term delivery devices for intraocular drug delivery.
Journal of Controlled Release 09/2006; 114(2):251-60. · 5.73 Impact Factor
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ABSTRACT: Calcium phosphate (CaP) cements show an excellent biocompatibility and often have a high mechanical strength, but in general degrade relatively slow. To increase degradation rates, macropores can be introduced into the cement, e.g., by the inclusion of biodegradable microspheres into the cement. The aim of this research is to develop an injectable PLGA microsphere/CaP cement with sufficient setting/cohesive properties and good mechanical and physical properties. PLGA microspheres were prepared using a water-in-oil-in-water double-emulsion technique. The CaP-cement used was Calcibon, a commercially available hydroxyapatite-based cement. 10:90 and 20:80 dry wt% PLGA microsphere/CaP cylindrical scaffolds were prepared as well as microporous cement (reference material). Injectability, setting time, cohesive properties and porosity were determined. Also, a 12-week degradation study in PBS (37 degree C) was performed. Results showed that injectability decreased with an increase in PLGA microsphere content. Initial and final setting time of the PLGA/CaP samples was higher than the microporous sample. Porosity of the different formulations was 40.8% (microporous), 60.2% (10:90) and 69.3% (20:80). The degradation study showed distinct mass loss and a pH decrease of the surrounding medium starting from week 6 with the 10:90 and 20:80 formulations, indicating PLGA erosion. Compression strength of the PLGA microsphere/CaP samples decreased siginificantly in time, the microporous sample remained constant. After 12 weeks both PLGA/CaP samples showed a structure of spherical micropores and had a compressive strength of 12.2 MPa (10:90) and 4.3 MPa (20:80). Signs of cement degradation were also found with the 20:80 formulation. In conclusion, all physical parameters were well within workable ranges with both 10:90 and 20:80 PLGA microsphere/CaP cements. After 12 weeks the PLGA was totally degraded and a highly porous, but strong scaffold remained.
Journal of Biomaterials Science Polymer Edition 02/2006; 17(9):1057-74. · 1.69 Impact Factor
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ABSTRACT: The release kinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded poly(dl-lactic-co-glycolic acid)/calcium phosphate cement (PLGA/Ca-P cement) composites were studied in vivo. RhBMP-2 was radiolabeled with (131)I and entrapped within PLGA microparticles or adsorbed onto the microparticle surface. PLGA microparticles were prepared of high molecular weight (HMW) PLGA (weight average molecular weight [M(w)] 49,100+/-1700) or low molecular weight (LMW) PLGA (M(w) 5,900+/-300) and used for preparation of 30:70 wt.% PLGA/Ca-P cement composite discs. Release of 131I-rhBMP-2 loaded composites was assessed by scintigraphic imaging according to a 2(2) two-level full factorial design in the rat ectopic model during four weeks. In vivo release kinetics varied among formulations. All formulations showed slow release without initial burst, and displayed a linear release from 3 to 28 days. Release of LMW entrapped rhBMP-2 composites (1.7+/-0.3%/day) was significantly faster than release from other formulations (p<0.01). After 28 days, retention within the composites was 65+/-5%, 75+/-4%, 50+/-4% and 70+/-6% of the initial rhBMP-2 for HMW entrapped, HMW adsorbed, LMW entrapped and LMW adsorbed rhBMP-2 composites, respectively. Release from the composite was probably slowed down by an interaction of rhBMP-2 and Ca-P cement after rhBMP-2 release from PLGA microparticles. We conclude that PLGA/Ca-P cement composites can be considered as sustained slow release vehicles and that the release and retention of rhBMP-2 can be modified according to the desired profile to a limited extent.
Journal of Controlled Release 09/2005; 106(1-2):162-71. · 5.73 Impact Factor
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ABSTRACT: The objective of the study presented here was to investigate the bone inductive properties as well as release kinetics of rhTGF-beta1- and rhBMP-2-loaded Ti-fiber mesh and CaP cement scaffolds. Therefore, Ti-fiber mesh and porous CaP cement scaffolds were provided with these growth factors and inserted in subcutaneous and cranial implant locations in rats and rabbits. In vitro, a rapid release of rhTGF-beta1 was observed during the first 2 h of the Ti-fiber mesh scaffolds. During this time, more than 50% of the total dose of rhTGF-beta1 was released. Following this initial peak, a decline in the level of rhTGF-beta1 occurred. After 1 week, the entire theoretical initial dose was observed to have been released. This in contrast to the rhTGF-beta1 and rhBMP-2 release of the porous CaP cement scaffolds. Here, no substantial initial burst release was observed. The scaffolds showed an initial release of about 1% after 1 day, followed by an additional marginal release after 1 week. Histological analysis revealed excellent osteoconductive properties of non-loaded Ca-P material. Inside non-loaded Ti-mesh fiber scaffolds, also bone ingrowth occurred. Quantification of the bone ingrowth showed that bone formation was increased significantly in all scaffold materials by administration of rhTGF-beta1 and rhBMP-2. Consequently, we conclude that the release kinetics of growth factors from porous CaP cement differs from other scaffold materials, like metals and polymers. Nevertheless, orthotopic bone formation in a rabbit cranial defect model was stimulated in rhTGF-beta1- and rhBMP-2-loaded CaP cement and Ti-fiber mesh scaffolds compared with non-loaded implants.
Journal of Controlled Release 02/2005; 101(1-3):127-36. · 5.73 Impact Factor
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ABSTRACT: Biodegradable polymers, such as poly(lactic acid) (PLA) and poly(lactic-coglycolic acid) (PLGA), are attractive materials for tissue engineering because of their degradative and mechanical properties, which permit scaffolds to be tailored to the individual requirements of different tissues. Although these materials support tissue development, their chemical properties offer no control of cell adhesion or function because their surfaces become immediately masked by adsorbing serum proteins when the materials come into contact with body fluids. Furthermore, adhesion proteins undergo conformational changes and a decrease in bioactivity when adsorbed to hydrophobic materials, such as PLA. To overcome these limitations, we modified the properties of PLA by synthesizing a diblock copolymer with poly(ethylene glycol) (PEG), which is known to reduce the amount of adsorbed proteins and to modify their conformation. By altering the PEG content of these diblock copolymers we were able to control the adsorption of adhesion proteins and, because cell adhesion takes place only in the presence of serum proteins, to control cell adhesion and cell shape. Marrow stromal cell differentiation to the osteoblastic phenotype was strongly improved on PEG-PLA compared with PLA, PLGA and tissue culture polystyrene and led to a 2-fold increase in alkaline phosphatase activity and mineralization.
Tissue Engineering 03/2003; 9(1):71-84. · 4.02 Impact Factor
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ABSTRACT: Retinal pigment epithelium (RPE) plays a key role in the maintenance of the normal functions of the retina, especially photoreceptors. Alteration in RPE structure and function is implicated in a variety of ocular disorders. Tissue engineering strategies using synthetic biodegradable polymers as temporary substrates for RPE cell culture and subsequent transplantation may provide a promising new therapy. In this review article, the manufacture of thin biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) films and their degradation behavior in vitro are discussed. RPE cell proliferation and differentiation on these PLGA films are reviewed. The fabrication of model substrates with desired chemical micropatterns in the micrometer scale is discussed and the effects of surface patterning on RPE morphology and function are assessed. Finally. the preparation of biodegradable micropatterns with adhesive PLGA and non-adhesive poly(ethylene glycol)/PLA domains to modulate RPE cell adhesion is presented.
Biomaterials 01/2002; 22(24):3345-55. · 7.40 Impact Factor
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ABSTRACT: Bone is an extremely complex tissue that provides many essential functions in the body. Bone tissue engineering holds great promise in providing strategies that will result in complete regeneration of bone and restoration of its function. Currently, such strategies include the transplantation of highly porous scaffolds seeded with cells. Prior to transplantation the seeded cells are cultured in vitro in order for the cells to proliferate, differentiate and generate extracellular matrix. Factors that can affect cellular function include the cell-biomaterial interaction, as well as the biochemical and the mechanical environment. To optimize culture conditions, good understanding of these parameters is necessary. The new developments in bone biology, bone cell mechanotransduction, and cell-surface interactions are reviewed here to demonstrate that bone mechanotransduction is strongly influenced by the biomaterial properties.
Biomaterials 11/2001; 22(19):2581-93. · 7.40 Impact Factor
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ABSTRACT: Culture of seeded osteoblastic cells in three-dimensional osteoconductive scaffolds in vitro is a promising approach to produce an osteoinductive material for repair of bone defects. However, culture of cells in scaffolds sufficiently large to bridge critical-sized defects is a challenge for tissue engineers. Diffusion may not be sufficient to supply nutrients into large scaffolds and consequently cells may grow preferentially at the periphery under static culture conditions. Three alternative culturing schemes that convect media were considered: a spinner flask, a rotary vessel, and a perfusion flow system. Poly(DL-lactic-co-glycolic acid) (PLGA) foam discs (12.7 mm diameter, 6.0 mm thick, 78.8% porous) were seeded with osteoblastic marrow stromal cells and cultured in the presence of dexamethasone and L-ascorbic acid for 7 and 14 days. Cell numbers per foam were found to be similar with all culturing schemes indicating that cell growth could not be enhanced by convection, but histological analysis indicated that the rotary vessel and flow system produced a more uniform distribution of cells throughout the foams. Alkaline phosphatase (ALP) activity per cell was higher with culture in the flow system and spinner flask after 7 days, while no differences in osteocalcin (OC) activity per cell were observed among culturing methods after 14 days in culture. Based on the higher ALP activity and better cell uniformity throughout the cultured foams, the flow system appears to be the superior culturing method, although equally important is the fact that in none of the tests did any of the alternative culturing techniques underperform the static controls. Thus, this study demonstrates that culturing techniques that utilize fluid flow, and in particular the flow perfusion system, improve the properties of the seeded cells over those maintained in static culture.
Biomaterials 07/2001; 22(11):1279-88. · 7.40 Impact Factor
