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Platelet interactions with calcium-phosphate-coated surfaces
Kikuchi, L., J. Y. Park, et al. (2005), Biomaterials 26(26): 5285-95.
Abstract: Many studies have shown that calcium-phosphate (CaP)-coated endosseous implants exhibit more peri-implant bone formation and bone contact at early healing times than uncoated implants. Since the rate of healing is influenced by blood/implant interactions and possibly the degree of blood platelet activation, the aim of this study was to determine whether the topography, microtopography, or the presence of calcium (Ca) and phosphate (PO(4)) ions in the implant surface plays a predominant role in platelet activation. We define the threshold between topography and microtopography as the limit of the scale range of platelets themselves; thus, a microtopographic surface is defined by one which exhibits features 3mum. With the help of four international collaborating laboratories, we prepared 11 titanium and CaP-modified titanium surfaces each with different (micro)topographies and interrogated these surfaces with both platelet adhesion (lactate dehydrogenase activity) and platelet activation (microparticle formation and P-selectin expression) assays. Our results show that: calcium (Ca)- and phosphate (PO(4))-containing surfaces of increasing surface microtopographical complexity exhibit increasing platelet activation; surfaces with similar surface microtopographies show similar levels of platelet activation regardless of the presence of Ca and PO(4) in the surface; and that surface microtopography is responsible for platelet activation rather than the presence of Ca and PO(4) in the surface.

Platelet-platelet interactions and non-adhesive encounters on biomaterials
Butruille, Y. A., E. F. Leonard, et al. (1975), Trans Am Soc Artif Intern Organs 21: 609-16.

Platelet-rich plasma combined with a porous hydroxyapatite graft for the treatment of intrabony periodontal defects in humans: a comparative controlled clinical study
Okuda, K., H. Tai, et al. (2005), J Periodontol 76(6): 890-8.
Abstract: BACKGROUND: The aim of the present controlled clinical study was to compare platelet-rich plasma (PRP) combined with a biodegradable ceramic, porous hydroxyapatite (HA) with a mixture of HA and saline in the treatment of human intrabony defects. METHODS: Seventy interproximal intrabony osseous defects in 70 healthy, non-smoking subjects diagnosed with chronic periodontitis were included in this study. Thirty-five subjects each were randomly assigned to either the test group (PRP and HA) or control group (HA with saline). Clinical and radiographic measurements were determined at baseline and the 12-month evaluation. RESULTS: When compared to baseline, the 12-month results indicated that, while both treatment modalities resulted in significant changes in all clinical parameters (gingival index, bleeding on probing, probing depth, clinical attachment level, and intrabony defect fill; P <0.001), the test group exhibited statistically significant changes compared to the control sites in probing depth reduction: 4.7 +/- 1.6 mm versus 3.7 +/- 2.0 mm (P <0.05); clinical attachment gain: 3.4 +/- 1.7 mm versus 2.0 +/- 1.2 mm (P <0.001); and vertical relative attachment gain: 70.3% +/- 23.4% versus 45.5% +/- 29.4% (P <0.001). CONCLUSION: Treatment with a combination of PRP and HA compared to HA with saline led to a significantly more favorable clinical improvement in intrabony periodontal defects.

PLGA-(L-Asp-alt-diol)(x)-PLGAs with different contents of pendant amino groups: synthesis and characterization
Zhao, J., D. Quan, et al. (2005), Macromol Biosci 5(7): 636-43.
Abstract: A series of novel biodegradable multi-block copolymers PLGA-(L-Asp-alt-diol)(x)-PLGA with pendant amino groups was synthesized by ring-opening polymerization of D,L-lactide/glycolide(D,L-LA/GA) (75/25) using poly(N-Cbz-L-Asp-alt-diol)s as macroinitiator and stannous octoate as catalyst, in which the N-Cbz-L-Asp represents N-carbobenzyloxy-L-aspartic acid and diols are ethylene glycol, triethylene glycol, PEG200, and PEG600, respectively. Their structures and properties were characterized by FTIR, (1)H NMR, DSC, GPC, and elemental analysis (EA). The contents of the L-Asp unit in the copolymers were increased from 12.9 to 79.3 mmol.g(-1) with decreasing the chain length of the diol, while the glass transition temperatures of the copolymers were decreased from 27.1 to 11.7 degrees C with increasing the chain length of the diol. Thus, the results in this study provide a way to prepare biomaterials with different L-Asp unit densities or different number of bioactive sites as well as different properties through adjusting the chain length of the diol.Synthesis of PLGA-(N-Cbz-L-Asp-alt-diol)(x)-PLGA copolymers.

Polishing occlusal surfaces of direct Class II composite restorations in vivo
Jung, M., K. Hornung, et al. (2005), Oper Dent 30(2): 139-46.
Abstract: This study evaluated the effects of four polishing methods on the occlusal surfaces of direct Class II composite restorations under clinical conditions. Forty premolars and 40 molars were treated with direct Class II restorations using the hybrid composite Herculite XRV (Kerr). After placement of the restorations, all of which were on occlusal surfaces, they were finished with a sequence of 30 microm diamonds and tungsten carbide instruments. Twenty restorations each, consisting of 10 premolars and 10 molars, were polished with one of the four following methods: (1) Diafix-oral (Mueller-Dental), (2) MPS gel (Premier), (3) P 403-W (Dentsply) and (4) Occlubrush (KerrHawe). Selection of the polishing methods followed a randomized protocol. Replicas of the restored teeth were fabricated and the occlusal surfaces were evaluated quantitatively for roughness with the help of profilometry. Qualitative assessment of the surfaces by SEM was done with respect to roundness of contours and surface roughness. The results were analyzed statistically by two-way ANOVA, chi-squared test for crosstables and Kruskal-Wallis test. Analysis of the quantitative data showed that there was no significant effect of the polishing methods on occlusal surface roughness (p>0.05). Localization of the restoration in premolars or molars had no effect on surface roughness (p>0.05). With respect to occlusal relief, SEM examination revealed that the use of the Occlubrush resulted in significantly more edged contours compared to the other polishing methods (p=0.008). Qualitative roughness evaluation showed that there were no significant differences among the four polishing methods (p>0.05).

Pollutant removal from aquaculture wastewater using the biopolymer chitosan at different molecular weights
Chung, Y. C., Y. H. Li, et al. (2005), J Environ Sci Health A Tox Hazard Subst Environ Eng 40(9): 1775-90.
Abstract: Removal of organic compounds, inorganic nutrients, and bacteria from aquaculture wastewaters before discharge cannot only minimize deterioration of receiving water quality, but can also make possible the reuse of the original water in the culture of prawn, fish, and shellfish. In this study, the feasibility of using chitosan, a multifunctional environmentally friendly biopolymer, at different molecular weights to simultaneously remove various pollutants from the discharge of an eel culture pond is evaluated. Experimental results indicated chitosan with a high molecular weight was best at removing turbidity, suspended solids, and biological and chemical oxygen demand (BOD and COD). In contrast, chitosan of a low molecular weight excelled at removing NH3 and PO4(3-) from wastewater. Additionally, chitosan with a high molecular weight did well at eliminating suspended solids of various particle sizes relative to chitosan with a low molecular weight. The best performance of chitosan in removing turbidity, suspended solids, BOD, COD, NH3, PO4(3-), and bacteria was 87.7%, 62.6%, 52.3%, 62.8%, 91.8%, 99.1%, and 99.998% removal, respectively. When chitosan with a high molecular weight was added at 12 mg/L, the quality of treated wastewater successfully complied with government discharge standards. Furthermore, the relatively low bacteria amount in the wastewater after treatment with chitosan was confirmed by both the plate count method and molecular analysis technique. These results indicated that the application of chitosan is feasible in an effort to recycle the effluents of a culture pond.

Poloxamine hydrogels with a quaternary ammonium modification to improve cell attachment
Sosnik, A. and M. V. Sefton (2005), J Biomed Mater Res A 75(2): 295-307.
Abstract: Four-arm poly(ethylene oxide) and poly(propylene oxide) (PEO-PPO) block copolymer (poloxamine, Tetronic 1107) hydrogels were modified with positively charged groups with the aim of overcoming the low cell adhesion properties of these PEO-rich systems. Different matrices containing poloxamine-methacrylate (6-12%) and a quaternary ammonium methacrylate ([2-(methacryloyloxy)ethyl]-trimethylammonium chloride [MAETAC], 0-0.48 M) were produced by a photo-initiated free radical copolymerization. A sharp increase in water content for MAETAC-containing gels was seen during the first 2 days of incubation in distilled water; some of the gels showed water uptakes as high as 12 times the initial wet weight. In phosphate-buffered saline (PBS), this effect was less pronounced because of the decrease in the osmotic gradient. In addition, a gradual increase of both the storage and the loss modulus of the gels resulted from increasing the MAETAC content [e.g., G' values increased from 13,500 Pa for 12% poloxamine-methacrylate gels without MAETAC to 151,000 Pa for 0.48M MAETAC contents (at 1 Hz, 100 Pa of oscillatory stress)]. Although on pure poloxamine-methacrylate gels HepG2 and HUVEC cells attached poorly, on MAETAC-containing specimens a well-spread morphology and confluent monolayers were obtained, at least after preincubation in serum containing medium. Although not having all the cell compatibility of collagen, these fully synthetic quaternary ammonium-modified PEO-rich gels may have some utility in tissue-engineering applications where stiff gels and cell attachment after gelation are desired.

Poly(2-hydroxy ethyl methacrylate)-alkaline phosphatase: a composite biomaterial allowing in vitro studies of bisphosphonates on the mineralization process
Filmon, R., M. F. Basle, et al. (2000), J Biomater Sci Polym Ed 11(8): 849-68.
Abstract: We have immobilized the mineralizing agent alkaline phosphatase (AlkP) in a hydrophilic polymer: poly(2-hydroxy ethyl methacrylate) - (pHEMA) - in a copolymerization technique. Histochemical study on polymer sections revealed that AlkP has retained its enzymic activity. The image analysis of sections using a tessellation method showed a lognormal distribution of the area of the tiles surrounding AlkP particles, thus confirming a homogeneous distribution of the enzyme in the polymer. Pellets of pHEMA-AlkP were incubated with a synthetic body fluid containing organic phosphates (beta-glycerophosphate). Mineral deposits with a rounded shape (calcospherites) were obtained in about 17 days. We have investigated the effects of three bisphosphonic pharmacological compounds (etidronate, alendronate and tiludronate) on this system which mimics the mineralization process of cartilage and woven bone. Bisphosphonates at a concentration of 10(-2) M totally inhibited AlkP in solution at a concentration of 10(-4) mg/ml. Inhibition has been reported being due to the chelation of a metal cofactor (Zn2+). Etidronate and alendronate appeared to similarly inhibit the calcospherite deposition onto the pHEMA-AlkP material. Both bisphosphonates possess three sites for the mineral complexion by Ca chemisorbtion. On the other hand, tiludronate having only two sites, was associated with a reduced inhibitory effect on mineralization but larger crystals were obtained. The pHEMA-AlkP material contains an immobilized enzyme in a hydrogel and mimics the physiological conditions of matrix vesicles entrapped within the cartilage (or bone) matrix. It provides an interesting method to study the effects of pharmacological compounds on the mineralization process in bone and cartilage in a non cellular and protein-free model.

Poly(amidoamine) dendrimer-based multifunctional engineered nanodevice for cancer therapy
Majoros, I. J., T. P. Thomas, et al. (2005), J Med Chem 48(19): 5892-9.
Abstract: Multifunctional cancer therapeutic nanodevices have been designed and synthesized using the poly(amidoamine) (PAMAM) dendrimer as a carrier. Partial acetylation of the generation 5 (G5) PAMAM dendrimer was utilized to neutralize a fraction of the primary amino groups, provide enhanced solubility of the dendrimer during the conjugation reaction of fluorescein isothiocyanate (FITC) (in dimethyl sulfoxide (DMSO)), and prevent nonspecific targeting interactions (in vitro and in vivo) during delivery. The remaining nonacetylated primary amino groups were utilized for conjugation of the functional molecules fluorescein isothiocyanate (FITC, an imaging agent), folic acid (FA, targets overexpressed folate receptors on specific cancer cells), and methotrexate (MTX, chemotherapeutic drug). The appropriate control nanodevices have been synthesized as well. The G5 PAMAM dendrimer molecular weight and number of primary amino groups were determined by gel permeation chromatography (GPC) and potentiometric titration for stoichiometric design of ensuing conjugation reactions. Additionally, dendrimer conjugates were characterized by multiple analytical methods including GPC, nuclear magnetic resonance spectroscopy (NMR), high performance liquid chromatography (HPLC), and UV spectroscopy. The fully characterized nanodevices can be used for the targeted delivery of chemotherapeutic and imaging agents to specific cancer cells. Here, we present a more extensive investigation of our previously reported synthesis of this material with improvements directed toward scale-up synthesis and clinical trials (Pharm. Res. 2002, 19 (9), 1310-1316).

Poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate) supports in vitro osteogenesis
Kumarasuriyar, A., R. A. Jackson, et al. (2005), Tissue Eng 11(7-8): 1281-95.
Abstract: Studies have demonstrated that polymeric biomaterials have the potential to support osteoblast growth and development for bone tissue repair. Poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate) (PHBV), a bioabsorbable, biocompatible polyhydroxy acid polymer, is an excellent candidate that, as yet, has not been extensively investigated for this purpose. As such, we examined the attachment characteristics, self-renewal capacity, and osteogenic potential of osteoblast-like cells (MC3T3-E1 S14) when cultured on PHBV films compared with tissue culture polystyrene (TCP). Cells were assayed over 2 weeks and examined for changes in morphology, attachment, number and proliferation status, alkaline phosphatase (ALP) activity, calcium accumulation, nodule formation, and the expression of osteogenic genes. We found that these spindle-shaped MC3T3-E1 S14 cells made cell-cell and cell-substrate contact. Time-dependent cell attachment was shown to be accelerated on PHBV compared with collagen and laminin, but delayed compared with TCP and fibronectin. Cell number and the expression of ALP, osteopontin, and pro-collagen alpha1(I) mRNA were comparable for cells grown on PHBV and TCP, with all these markers increasing over time. This demonstrates the ability of PHBV to support osteoblast cell function. However, a lag was observed for cells on PHBV in comparison with those on TCP for proliferation, ALP activity, and cbfa-1 mRNA expression. In addition, we observed a reduction in total calcium accumulation, nodule formation, and osteocalcin mRNA expression. It is possible that this cellular response is a consequence of the contrasting surface properties of PHBV and TCP. The PHBV substrate used was rougher and more hydrophobic than TCP. Although further substrate analysis is required, we conclude that this polymer is a suitable candidate for the continued development as a biomaterial for bone tissue engineering.

Poly(D,L-lactide) coating is capable of enhancing osseous integration of Schanz screws in the absence of infection
Partale, K., P. Klein, et al. (2005), J Biomed Mater Res B Appl Biomater 74(1): 608-16.
Abstract: Pin loosening is a major complication in external fixation. Biological and mechanical conditions play an important role in the maintenance and enhancement of the implant-bone interface in fracture fixation. It is thought that biodegradable coatings may be capable of preventing pin track infection and pin loosening. The goal of this study was therefore to analyze the influence of a biodegradeable coating on the osseous integration of Schanz' screws during fracture treatment. Standardized osteotomies (3-mm fracture gap) of the right tibiae were performed on 16 sheep and stabilized by an AO mono-lateral external fixator. Additional, mechanically less loaded Schanz' screws were also mounted. All screws were randomly coated with biodegradable poly(D,L-lactide). The sheep were sacrificed after 9 weeks. All screws were removed and rolled on blood agar plates for microbiological analysis. Histological sections of the pin tracks were histochemically and morphometrically analyzed. Clinically, no signs of severe infection were visible. Microbiological analysis revealed 14.8% colonization by Staphylococcus aureus in the coated and 29% in the uncoated screws. Histomorphometry of the bone surrounding the Schanz' screws revealed that significantly more osseous integration had occurred on poly(D,L-lactide)-coated screws in the absence of bacterial colonization. Significantly more bone remodeling and a higher osteoclastic activity was seen near the screw-bone interface in the uncoated screw group. Up to a threefold increase in new bone formation and more severe remodeling was observed around the screw entry compared to the pin exit in all groups. Loaded screws showed significantly more callus formation around the exit sites than their less loaded counterparts. In the present study, poly(D,L-lactide) coating of Schanz' screws was found to enhance osseous integration in the absence of bacterial colonization in sheep by causing less cortical remodeling and less osteoclastic activity in the cortices compared to uncoated screws. Additionally, the coating appeared to reduce the instances of pin track infections. Mechanical loading showed an adverse effect on bone formation and remodeling. It has been shown that both biological and mechanical factors play an important role in the maintenance of osseous integrity of the pin-bone interface. Poly(D,L-lactide) coating of Schanz' screws does not prevent osseous destruction and severe bacterial colonization along the pin tracts, but can improve osseous integration of Schanz' screws in the absence of infection.

Poly(D,L-lactide-co-glycolide) protein-loaded nanoparticles prepared by the double emulsion method--processing and formulation issues for enhanced entrapment efficiency
Bilati, U., E. Allemann, et al. (2005), J Microencapsul 22(2): 205-14.
Abstract: Although extensive research in the field of biodegradable microparticles containing peptide or protein drugs has greatly advanced production know-how, the effects of critical parameters influencing successful drug entrapment have not yet been sufficiently investigated with nano-scaled carriers. This paper deals with the formulation and processing parameters of the w(1)/o/w(2) double emulsion method that can affect nanoparticle size and loading. Fluorescein isothiocyanate-labelled bovine serum albumin (FITC-BSA) was used as a model protein. Results showed that high FITC-BSA entrapment efficiencies were reached (>80%) when sonication was used for the two emulsification steps of the nanoparticle formation, independently of the mixing durations and intensities. By comparison, the use of a vortex mixer for obtaining the primary w(1)/o emulsion led to a rather poor entrapment efficiency (approximately 25%). Some inherent properties of the poly(D,L-lactic-co-glycolic acid) polymer, such as, for example, high molecular weight, high hydrophilicity or the presence of free carboxylic end groups, enhanced the drug entrapment efficiency. It was also demonstrated that a low nominal drug loading, a large volume of the inner w1 phase or the choice of methylene chloride instead of ethyl acetate as organic solvent favoured the drug entrapment, with entrapment efficiency values often reaching 100%. However, when using methylene chloride, the mean particle size was substantially increased, due to the presence of larger particles. Mean particle size increased also when the polymer concentration in the organic phase was increased.

Poly(d,l-lactide-co-glycolide)/montmorillonite nanoparticles for oral delivery of anticancer drugs
Dong, Y. and S. S. Feng (2005), Biomaterials 26(30): 6068-76.
Abstract: This research developed a novel bioadhesive drug delivery system, poly(d,l-lactide-co-glycolide)/montmorillonite (PLGA/MMT) nanoparticles, for oral delivery of paclitaxel. Paclitaxel-loaded PLGA/MMT nanoparticles were prepared by the emulsion/solvent evaporation method. MMT was incorporated in the formulation as a matrix material component, which also plays the role of a co-emulsifier in the nanoparticle preparation process. Paclitaxel-loaded PLGA/MMT nanoparticles were found to be of spherical shape with a mean size of around 310 nm and polydispersity of less than 0.150. Adding MMT component to the matrix material appears to have little influence on the particles size and the drug encapsulation efficiency. The drug release pattern was found biphasic with an initial burst followed by a slow, sustained release, which was not remarkably affected by the MMT component. Cellular uptake of the fluorescent coumarin 6-loaded PLGA/MMT nanoparticles showed that MMT enhanced the cellular uptake efficiency of the pure PLGA nanoparticles by 57-177% for Caco-2 cells and 11-55% for HT-29 cells, which was dependent on the amount of MMT and the particle concentration in incubation. Such a novel formulation is expected to possess extended residence time in the gastrointestinal (GI) tract, which promotes oral delivery of paclitaxel.

Poly(epsilon-caprolactone) and poly(epsilon-caprolactone)-polyvinylpyrrolidone-iodine blends as ureteral biomaterials: characterisation of mechanical and surface properties, degradation and resistance to encrustation in vitro
Jones, D. S., J. Djokic, et al. (2002), Biomaterials 23(23): 4449-58.
Abstract: This study describes the physicochemical properties and in vitro resistance to encrustation of solvent cast films composed of either poly(epsilon-caprolactone) (PCL), prepared using different ratios of high (50,000) to low (4000) (molecular weight) m.wt., or blends of PCL and the polymeric antimicrobial complex, poly(vinylpyrrolidone)-iodine (PVP-I). The incorporation of PVP-I offered antimicrobial activity to the biomaterials. Films were characterised in terms of mechanical (tensile analysis, dynamic mechanical thermal analysis) and surface properties (dynamic contact angle analysis, scanning electron microscopy), whereas degradation (at 37 degrees C in PBS at pH 7.4) was determined gravimetrically. The resistance of the films to encrustation was evaluated using an in vitro encrustation model. Reductions in the ratio of high:low-m.wt. PCL significantly reduced the ultimate tensile strength, % elongation at break and the advancing contact angle of the films. These effects were attributed to alterations in the amorphous content and the more hydrophilic nature of the films. Conversely, there were no alterations in Young's modulus, the viscoelastic properties and glass-transition temperature. Incorporation of PVP-I did not affect the mechanical or rheological properties of the films, indicative of a limited interaction between the two polymers in the solid state. Manipulation of the high:low m.wt. ratio of PCL significantly altered the degradation of the films, most notably following longer immersion periods, and resistance to encrustation. Accordingly, maximum degradation and resistance to encrustation was observed with the biomaterial composed of 40:60 high:low m.wt. ratios of PCL; however, the mechanical properties of this system were considered inappropriate for clinical application. Films composed of either 50:50 or 60:40 ratio of high:low m.wt. PCL offered an appropriate compromise between physicochemical properties and resistance to encrustation. This study has highlighted the important usefulness of degradable polymer systems as ureteral biomaterials.

Poly(ester urethane)s consisting of poly[(R)-3-hydroxybutyrate] and poly(ethylene glycol) as candidate biomaterials: characterization and mechanical property study
Li, X., X. J. Loh, et al. (2005), Biomacromolecules 6(5): 2740-7.
Abstract: Poly(ester urethane)s with poly[(R)-3-hydroxybutyrate] (PHB) as the hard and hydrophobic segment and poly(ethylene glycol) (PEG) as the soft and hydrophilic segment were synthesized from telechelic hydroxylated PHB (PHB-diol) and PEG using 1,6-hexamethylene diisocyanate as a nontoxic coupling reagent. Their chemical structures and molecular characteristics were studied by gel permeation chromatography, 1H NMR, and Fourier transform infrared spectroscopy. Results of differential scanning calorimetry and X-ray diffraction indicated that the PHB segment and PEG segment in the poly(ester urethane)s formed separate crystalline phases with lower crystallinity and a lower melting point than those of their corresponding precursors, except no PHB crystalline phase was observed in those with a relatively low PHB fraction. Thermogravimetric analysis showed that the poly(ester urethane)s had better thermal stability than their precursors. The segment compositions were calculated from the two-step thermal decomposition profiles, which were in good agreement with those obtained from 1H NMR. Water contact angle measurement and water swelling analysis revealed that both surface hydrophilicity and bulk hydrophilicity of the poly(ester urethane)s were enhanced by incorporating the PEG segment into PHB polymer chains. The mechanical properties of the poly(ester urethane)s were also assessed by tensile strength measurement. It was found that the poly(ester urethane)s were ductile, while natural source PHB is brittle. Young's modulus and the stress at break increased with increasing PHB segment length or PEG segment length, whereas the strain at break increased with increasing PEG segment length or decreasing PHB segment length.

Poly(ethylene glycol) hydrogel system supports preadipocyte viability, adhesion, and proliferation
Patel, P. N., A. S. Gobin, et al. (2005), Tissue Eng 11(9-10): 1498-505.
Abstract: The ultimate goal of this research is to develop an injectable cell-scaffold system capable of permitting adipogenesis to abrogate soft tissue deficiencies resulting from trauma, tumor resection, and congenital abnormalities. The present work compares the efficacy of photopolymerizable poly(ethylene glycol) and specific derivatives as a scaffold for preadipocyte (adipocyte precursor cell) viability, adhesion, and proliferation. Four variations of a poly(ethylene glycol) scaffold are prepared and examined. The first scaffold consists of poly(ethylene glycol) diacrylate, which is not susceptible to hydrolysis or enzymatic degradation. Preadipocyte death is observed over 1 week in this hydrogel configuration. Adhesion sites, specifically the laminin-binding peptide sequence YIGSR, were incorporated into the second scaffold to promote cellular adhesion as a prerequisite for preadipocyte proliferation. Preadipocytes remain viable in this scaffold system, but do not proliferate in this nondegradable hydrogel. The third scaffold system studied consists of poly(ethylene glycol) modified with the peptide sequence LGPA to permit polymer degradation by cell-secreted collagenase. No adhesion peptide is incorporated into this scaffold system. Cellular proliferation is initially observed, followed by cell death. The previous three scaffold configurations do not permit preadipocyte adhesion and proliferation. In contrast, the fourth system studied, poly(ethylene glycol) modified to incorporate both LGPA and YIGSR, permits preadipocyte adherence and proliferation subsequent to polymer degradation. Our results indicate that a scaffold system containing specific degradation sites and cell adhesion ligands permits cells to adhere and proliferate, thus providing a potential cell-scaffold system for adipogenesis.

Poly(ethylene oxide)-b-poly(N-isopropylacrylamide) nanoparticles with cross-linked cores as drug carriers
Zeng, Y. and W. G. Pitt (2005), J Biomater Sci Polym Ed 16(3): 371-80.
Abstract: Micelle-like nanoparticles that could be used as drug-delivery carriers were developed. The unique feature of these nanoparticles was that the core of poly(ethylene oxide)-b-poly(N-isopropylacrylamide) (PEO-b-PNIPAAm) micelle was lightly cross-linked with a biodegradable cross-linker, N,N-bis(acryloyl)cystamine (BAC). The nanoparticles were characterized by dynamic light scattering and fluorescence measurements. When the BAC content ranged from 0.75 wt% to 0.2 wt% of the mass of NIPAAm, the diameters of the nanoparticles were less than 150 nm. The anti-cancer drug doxorubicin (Dox) and 1,6-diphenyl-1,3,5-hexatriene (DPH) were used as fluorescent probes to study the hydrophobicity of the cores of the nanoparticles; the results showed that the cores of the nanoparticles were hydrophobic enough to sequester Dox and DPH. The nanoparticles with 0.5 wt% BAC stored at room temperature were stable up to 2 weeks, even at dilute concentrations. The degradation of BAC by reducing agent beta-mercaptoethanol was investigated, and the nanoparticles were not detectable 14 days after adding beta-mercaptoethanol.

Poly(HEMA)-collagen composite as a biomaterial for hard tissue replacement
Stol, M., K. Smetana, Jr., et al. (1993), Clin Mater 13(1-4): 19-20.
Abstract: This article briefly reviews the possibilities for hard tissue replacement with a new biomaterial. The basic differences found experimentally for polymer (HEMA) and collagen composite at the biological environment are stressed. The influence of the collagen distribution and matrix porosity of composite material on biodegradation is also discussed.

Poly(iminocarbonates) as potential biomaterials
Kohn, J. and R. Langer (1986), Biomaterials 7(3): 176-82.
Abstract: Poly(iminocarbonates), based on diphenols such as hydroquinone or Bisphenol A were synthesized. Poly(iminocarbonates) degraded under physiological conditions. Compression moulded discs of poly-(hydroquinone-iminocarbonate) showed near zero-order release for low loadings (1%, w/w) of Eosin Y. Poly(Bisphenol A-iminocarbonate) formed transparent films and strong fibres. It is a tough polymer with high tensile strength. Under physiological conditions complete erosion of a thin film of poly(Bisphenol A-iminocarbonate) required about 200 d. The release profile for p-nitroaniline from solvent cast films of poly(Bisphenol A-iminocarbonate) was characterized by a lag period (20 d), followed by near zero-order release for 90 d. Initial toxicological studies revealed no inflammatory cell response after implantation in the corneas of rabbits or subcutaneously in mice.

Poly(lactic-co-glycolic acid) microspheres as an injectable scaffold for cartilage tissue engineering
Kang, S. W., O. Jeon, et al. (2005), Tissue Eng 11(3-4): 438-47.
Abstract: Injectable scaffold has raised great interest for tissue regeneration in vivo, because it allows easy filling of irregularly shaped defects and the implantation of cells through minimally invasive surgical procedures. In this study, we evaluated poly(lactic-co-glycolic acid) (PLGA) microsphere as an injectable scaffold for in vivo cartilage tissue engineering. PLGA microspheres (30-80 microm in diameter) were injectable through various gauges of needles, as the microspheres did not obstruct the needles and microsphere size exclusion was not observed at injection. The culture of chondrocytes on PLGA microspheres in vitro showed that the microspheres were permissive for chondrocyte adhesion to the microsphere surface. Rabbit chondrocytes were mixed with PLGA microspheres and injected immediately into athymic mouse subcutaneous sites. Chondrocyte transplantation without PLGA microspheres and PLGA microsphere implantation without chondrocytes served as controls. Four and 9 weeks after implantation, chondrocytes implanted with PLGA microspheres formed solid, white cartilaginous tissues, whereas no gross evidence of cartilage tissue formation was noted in the control groups. Histological analysis of the implants by hematoxylin and eosin staining showed mature and well-formed cartilage. Alcian blue/safranin O staining and Masson's trichrome staining indicated the presence of highly sulfated glycosaminoglycans and collagen, respectively, both of which are the major extracellular matrices of cartilage. Immunohistochemical analysis showed that the collagen was mainly type II, the major collagen type in cartilage. This study demonstrates the feasibility of using PLGA microspheres as an injectable scaffold for in vivo cartilage tissue engineering. This scaffold may be useful to regenerate cartilaginous tissues through minimally invasive surgical procedures in orthopedic, maxillofacial, and urologic applications.

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Last Modified: 8 February 2006