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Record 3461 to 3480

Radiographic evaluation of a monoblock acetabular component: a multicenter study with 2- to 5-year results
Gruen, T. A., R. A. Poggie, et al. (2005), J Arthroplasty 20(3): 369-78.
Abstract: Serial radiographs of a porous tantalum monoblock acetabular cup design were evaluated for cup stability and signs of successful osteointegration. Of 574 primary consecutive total hip replacements in 542 patients performed by 9 surgeons at 7 hospitals, 414 cases were available for minimum 2-year follow-up. Follow-up averaged 33 months and ranged from 24 to 58 months. Postoperative radiographs revealed acetabular gaps in 100 zones in 80 (19%) hips: 29 in zone I, 67 in zone II, and 4 in zone III. At last follow-up, 84 (84%) of the zones with gaps completely filled in, and all 4- and 5-mm gaps filled in. There was no progression of any postoperative gap, no evidence of continuous periacetabular interface radiolucencies, no evidence of lysis, and no revisions for loosening. Although these short-term results are encouraging, further follow-up will be required to assess whether the monoblock design and the low modulus of elasticity of porous tantalum will reduce the incidence of periacetabular stress shielding and occurrence of osteolysis.

Radiographic methods for the assessment of polyethylene wear after total hip arthroplasty
McCalden, R. W., D. D. Naudie, et al. (2005), J Bone Joint Surg Am 87(10): 2323-34.
Abstract: All wear-measurement techniques assess femoral head penetration and therefore cannot distinguish between true polyethylene wear and bedding-in. Multiple wear measurements that are made at different time-intervals after bedding-in has occurred are required to determine the true wear rate. Computer-assisted edge-detection techniques offer improved accuracy and precision compared with manual techniques and appear to be ideally suited for the retrospective and prospective examination of large groups of patients with intermediate to long-term radiographic follow-up (more than five years). While radiostereometric analysis offers improved accuracy and precision compared with computer-assisted edge-detection techniques, widescale clinical application is limited because of its relative expense, the required expertise, and the fact that it can only be used in a prospective fashion.

Radiolabelling of poly(histidine) derivatized biodegradable microspheres with the 188Re tricarbonyl complex [188Re(CO)3(H2O)3]+
Yu, J., U. O. Hafeli, et al. (2005), Nucl Med Commun 26(5): 453-8.
Abstract: OBJECTIVES: Many radiopharmaceuticals have been studied as radiation synovectomy agents. In this study, we developed a new potential agent for radiation synovectomy: poly(lactic acid)-histidine (PLA-his) microspheres radiolabelled with [188Re(CO)3(H2O)3]+. METHODS: The reaction conditions for the chelation of [188Re(CO)3(H2O)3]+ and the radiolabelling of PLA microspheres were optimized and the stabilities for both steps tested in vitro. RESULTS: The chelation efficiency of [188Re(CO)3(H2O)3]+ reached 93.12 +/- 1.82% with >95% radiochemical purity once the colloidal and free 188Re were removed by a small Sep-Pak column (Plus QMA). More than 90% of radioactivity stayed in the [188Re(CO)3(H2O)3]+ form over 5 h. The radiolabelling efficiency of PLA-his microspheres with [188Re(CO)3(H2O)3]+ was above 92%. After 3 days incubation at 37 degrees C in calf serum, more than 80% of the radioactivity was still bound to the microspheres. CONCLUSION: Such microspheres are potentially useful as a radiation synovectomy agent for the treatment of chronically inflamed arthritic joints. Furthermore, they might be valuable in cancer brachytherapy.

Radiopaque polymeric materials for medical applications. Current aspects of biomaterial research
Mottu, F., D. A. Rufenacht, et al. (1999), Invest Radiol 34(5): 323-35.
Abstract: The aim of this review is to give an overview and some insight into different radiopaque polymeric materials that are currently used as medical implants or inserts. The advantages and limitations of each radiopaque polymeric material are summarized. The main method used to make medical implants radiologically visible is based on blending polymers with conventional radiopaque agents, blends which usually are a physical mixture of acrylic derivatives and inorganic salts. Other methods reported involve either the formation of single-phase radiopaque polymer salt complexes somehow preventing the release of the radiopacifying element by entrapment of the complex in a crosslinked network, or radiopaque polymerized monomers characterized by a radiopacifying element associated with the monomer unit prior to polymerization. In the near future, research will certainly concentrate on biocompatible radiopaque polymers with covalently bound opaque elements leading to stable polymers with properties equivalent to the nonopaque, parent polymer.

Raman investigation of calcium carbonate bone substitutes and related biomaterials
Penel, G., E. C. Pottier, et al. (2003), Bull Group Int Rech Sci Stomatol Odontol 45(2-3): 56-9.
Abstract: The interaction between biomaterials used in surgical procedures and the host bone is not yet perfectly understood. It appears that these problems may have been encountered because of insufficient characterisation of the basic component used in the synthesis of such biomaterials. Calcium carbonate (CaCO3) is interesting for bone filling or regeneration procedures because of its resorbability. The aim of this work is to compare different CaCO3 biomaterials and their basic source with the help of microRaman spectroscopy. Bionacre and Biocoral are analysed. The main bands of carbonate internal modes are observed around 1084-86 and 704-12 cm-1. In the lattice modes region, for both Biocoral and synthetic aragonite, two bands at 206 and 155 cm-1 are observed. The eggshell, oyster shell and synthetic calcite samples exhibit bands at 281 and 155 cm-1. Three bands are present at 280, 206 and 155 cm-1 on the Bionacre sample. The 206 and the 280 cm-1 bands are due to aragonite and calcite forms respectively. Therefore it appears to be a mixture of aragonite and calcite whereas Biocoral is pure aragonite. Additional Raman investigations should be of great interest in evaluating the structural modifications and their influence on the biological behaviour of these biomaterials. Lity index, the percentage of prematurity and of low birth weight are the indices of national health status.

Raman piezo-spectroscopic analysis of natural and synthetic biomaterials
Pezzotti, G. (2005), Anal Bioanal Chem 381(3): 577-90.
Abstract: Raman piezo-spectroscopy of bone, teeth, and artificial joints is reviewed with emphasis placed on confocal microprobe techniques. Characteristic spectra are presented and quantitative assessments of their phase structure and stress dependence are shown. Vibrational spectroscopy is used here to study the microscopic stress response of cortical bone to external stress (with or without internal damages), to define microscopic stresses across the dentine-enamel junction under increasing external compressive load, and to characterize interactions between prosthetic implants and biological environment. Confocal spectroscopy allows acquisition of spatially resolved spectra and stress imaging with high spatial resolution.

Raman spectroscopy: noninvasive determination of silicone oil in the eye: potential applications for intraocular determination of biomaterials
Erckens, R. J., K. Hosseini, et al. (2002), Retina 22(6): 796-9.

Raman study of TiO2 role in SiO2-Al2O3-MgO-TiO2-ZnO glass crystallization
Furic, K., L. Stoch, et al. (2005), Spectrochim Acta A Mol Biomol Spectrosc 61(7): 1653-9.
Abstract: Tough glass-ceramic material of special mechanical properties with nanosize crystal phases formed by appropriately controlled crystallization was studied by Raman spectroscopy. It was obtained by TiO2 activated crystallization of Mg-aluminosilicate glass of SiO2-Al2O3-MgO-TiO2-ZnO composition. Crystallization was preceded by a change in the TiO2 structural position and state, which is manifested by a changed color of glass from yellow into blue shortly before the glass transformation (Tg) temperature. Raman spectroscopy was applied to explain the mechanism of this process and to establish the role of TiO2 in the early stage of glass crystallization that precedes a complete crystal phase formation. The starting glasses were found in almost complete disorder, since all bands were weak, broad and dominated by a Bose band at about 90 cm-1. After the sample annealing all bands turned out better resolved and the Bose band practically disappeared, both confirming the amorphous structure reorganization process. A multiplet observed in the vicinity of 150 cm-1 we assigned to the anatase and other titania structures that can be considered prime centers of crystallization. Finally, in the closest neighborhood of the Rayleigh line the low frequency mode characterizing nanoparticles was observed. According to this band theory, the mean size of initial titania crystallites is about 10nm for all samples, but the size distribution varies within factor two among them.

Ramus graft and 1-stage implant placement: a case report
Vassos, D. M. (2005), J Oral Implantol 31(4): 192-6.
Abstract: Althougth hard-tissue grafting protocols have typically recommended a 6-month healing period before placement of any dental implants at the graft site, it may be possible to secure an onlay graft to a wide but shallow alveolar ridge using implants that are then submerged and allowed to osseointegrate. This approach has the advantage of expediting treatment and making it less traumatic for the patient. A case is described in which a portion of an edentulous mandible was augmented with ramus bone secured with 2 dental implants.

Randomized clinical trial comparing OASIS Wound Matrix to Regranex Gel for diabetic ulcers
Niezgoda, J. A., C. C. Van Gils, et al. (2005), Adv Skin Wound Care 18(5 Pt 1): 258-66.
Abstract: OBJECTIVE: To compare healing rates at 12 weeks for full-thickness diabetic foot ulcers treated with OASIS Wound Matrix, an acellular wound care product, versus Regranex Gel. DESIGN: Randomized, prospective, controlled multicenter trial at 9 outpatient wound care clinics. SUBJECTS: A total of 73 patients with at least 1 diabetic foot ulcer were entered into the trial and completed the protocol. INTERVENTION: Patients were randomized to receive either OASIS Wound Matrix (n = 37) or Regranex Gel (n = 36) and a secondary dressing. Wounds were cleansed and debrided, if needed, at a weekly clinic visit. Dressings were changed as needed. The maximum treatment period for each patient was 12 weeks. PRIMARY OUTCOME MEASURE: Incidence of healing in each group at 12 weeks. RESULTS: After 12 weeks of treatment, 18 (49%) OASIS-treated patients had complete wound closure compared with 10 (28%) Regranex-treated patients. CONCLUSION: Although the sample size was not large enough to demonstrate that the incidence of healing in the OASIS group was statistically superior (P =.055), the study results showed that treatment with OASIS is as effective as Regranex in healing full-thickness diabetic foot ulcers by 12 weeks.

Randomized comparison of carbon ion-implanted stent versus bare metal stent in coronary artery disease: the Asian Pacific Multicenter Arthos Stent Study (PASS) trial
Kim, Y. H., C. W. Lee, et al. (2005), Am Heart J 149(2): 336-41.
Abstract: BACKGROUND: Heavy metal ions can cause allergic and inflammatory reactions that might be associated with in-stent restenosis. This randomized multicenter clinical study was designed to determine if carbon ion-implanted stents reduce luminal late loss by blocking heavy metal ion diffusion into the surrounding tissue. METHODS: A total of 225 patients with 230 native coronary lesions were randomly assigned to receive either a carbon ion-implanted Arthos Inert stent (group 1, n = 113) or a bare metal Arthos stent (group 2, n = 117). The primary endpoint was in-stent luminal late loss at 6-month angiographic follow-up, and the secondary endpoints were the 6-month angiographic restenosis rate and the occurrence of the major adverse cardiac events (MACE) including death, nonfatal myocardial infarction, and target lesion revascularization at 12 months. RESULTS: The baseline characteristics were similar in the 2 groups. In-hospital events did not occur in any patients. Angiographic follow-up at 6 months was obtained in 184 lesions (80%). At follow-up, the luminal late loss was similar in the 2 groups (0.91 +/- 0.77 mm in group 1 vs 0.88 +/- 0.80 mm in group 2, P =.79), and the angiographic restenosis rates were 11.0% in group 1 and 16.1% in group 2 (P =.31). The occurrence rates of MACE at 12 months were 9.1% in group 1 and 10.4% in group 2 (P =.73). CONCLUSIONS: The initial and long-term outcomes of the carbon ion-implanted stent were excellent. However, it did not improve long-term outcomes vs the bare metal stent.

Rapamycin-coated expanded polytetrafluoroethylene bypass grafts exhibit decreased anastomotic neointimal hyperplasia in a porcine model
Cagiannos, C., O. R. Abul-Khoudoud, et al. (2005), J Vasc Surg 42(5): 980-8.
Abstract: OBJECTIVE: We tested the hypothesis that rapamycin coated onto, and eluted from, expanded polytetrafluoroethylene (ePTFE) grafts would diminish neointimal hyperplasia in a porcine model. METHODS: Rapamycin (also called sirolimus) was coated onto the luminal surface of 6-mm-internal-diameter thin-walled ePTFE grafts by using an adhesive polymer that allows timed release of the drug. An adhesive polymer that allows timed release of rapamycin from ePTFE was developed with commercially available chemicals and applied on 6-mm ePTFE grafts. Graft integrity was characterized by scanning electron microscopy, and rapamycin levels were quantified by using high-performance liquid chromatography. Twenty-two mongrel pigs were randomized into three groups: untreated ePTFE (n = 6), adhesive-only coated ePTFE (n = 6), or adhesive- and rapamycin-coated ePTFE (n = 10). End-to-side unilateral aortoiliac bypasses were performed by using 6-mm-internal-diameter ePTFE grafts and standardized anastomotic lengths. Unilateral end-to-side aortoiliac ePTFE grafts (6-mm internal diameter) were inserted by using polypropylene sutures, 6-0 proximally and 7-0 distally; all anastomoses were 12 mm long. All animals received aspirin (325 mg orally) daily. All animals were given oral aspirin (325 mg) daily beginning on the day before surgery. At 28 days, the animals were killed, and the grafts were explanted in continuity with the adjacent aortic cuff and the outflow iliac artery. Variables compared between groups included graft patency, distal anastomotic length and cross-sectional narrowing, and intimal thickness at the arterial-graft junction indexed to the adjacent graft thickness. Microscopic analysis was performed with hematoxylin and eosin and Masson trichrome stains on paraffin sections. A pathologist blinded to experimental groups graded sections for collagen deposition, neointima formation, inflammatory cellular infiltrates, medial necrosis, and aneurysmal degeneration. RESULTS: All animals survived until they were killed without clinical evidence of limb ischemia or graft infection. Preplanned t tests in the context of one-way analysis of variance showed no difference in outcome measures between the untreated ePTFE and adhesive-only coated ePTFE groups; therefore, they were combined in further comparisons with the adhesive- and rapamycin-coated ePTFE group. The Rapamycine eluting expanded polytetrafluoroethylene group had longer anastomoses (85.6% vs 60.6% of the initial anastomotic length maintained; P <.0001) and less cross-sectional narrowing in the outflow graft (16.2% vs 28.5%; P =.0007) when compared with the other two groups by using two-tailed Student t tests. There was no evidence of medial necrosis or aneurysmal degeneration. All patent grafts had complete endothelialization on hematoxylin and eosin sections. Rapamycin was detectable and quantifiable in the arterial wall at 28 days after implantation. CONCLUSIONS: Rapamycin can be coated onto and eluted from ePTFE by using a nonionic polymer and a simple coating technique. At 4 weeks after implantation, the rapamycin-eluting ePTFE grafts demonstrate gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with non-drug-eluting ePTFE. Four weeks after implantation in a porcine model, rapamycin-eluting ePTFE grafts demonstrated gross, pathologic, and morphometric features of diminished neointimal hyperplasia when compared with untreated and adhesive-only coated ePTFE grafts. CLINICAL RELEVANCE: Rapamycin-eluting ePTFE grafts decrease neointimal hyperplasia in a porcine model. Further studies are needed to evaluate whether patency will be improved. Rapamycin-eluting ePTFE grafts may allow the use of prosthetic grafts in situations in which autologous vein is unavailable and in which neointimal hyperplasia is pronounced, such as in small-diameter (<6-mm) vessels typical of infrapopliteal interventions.

Rapid detection of enteroviruses in small volumes of natural waters by real-time quantitative reverse transcriptase PCR
Fuhrman, J. A., X. Liang, et al. (2005), Appl Environ Microbiol 71(8): 4523-30.
Abstract: Despite viral contamination of recreational waters, only bacterial, not viral, indicators are monitored routinely, due to a lack of rapid and cost-effective assays. We used negatively charged filters to capture enteroviruses from seawater and freshwater. Viral RNA was extracted using a commercial kit, and the viruses were quantified by real-time quantitative reverse transcriptase PCR (qRT-PCR). Poliovirus (6.6 to 330,000 virus particles/ml) was added to samples from watersheds in Los Angeles, California, and analysis showed that with 50-ml samples, a cellulose acetate/nitrate (HA) filter yielded final recovery of 51% (r2= 0.99) in fresh water and 23% (r2= 0.90) in seawater. However, for additions of low levels of virus (more likely to represent field samples; <10(4) enterovirus particles/ml), the recovery was lower and more variable, with HA being best in freshwater (17%, r2= 0.97) and the type GF/F glass filter having higher average recovery in seawater (GF/F, 17%; r2= 0.93; HA 12%, r2= 0.87). The optimized method was used with 1-liter field samples from two very different freshwater "creeks" that drain into Santa Monica Bay, California: Topanga Creek (TC), a relatively pristine mountain creek, and Ballona Creek (BC), a concrete-lined urban storm drain. One TC site out of 10 and 2 BC sites out of 7 tested significantly positive for enteroviruses, with higher enterovirus concentrations in BC than in TC (ca. 10 to 25 versus 1 equivalent enterovirus particle/ml). The presented filtration-qRT-PCR approach is fast (<8 h from sampling to results), sensitive, and cost efficient and is promising for monitoring viral contamination in environmental water samples.

Rapid endothelialization of PhotoFix natural biomaterial vascular grafts
Carnagey, J., D. Hern-Anderson, et al. (2003), J Biomed Mater Res B Appl Biomater 65(1): 171-9.
Abstract: To date, no off-the-shelf graft has performed better than the autologous vessel in applications requiring small-bore (< 6-mm diameter) vascular grafts. Much research has been devoted to seeding endothelial cells on synthetic grafts to improve their long-term clinical performance. One key challenge is the ability to retain the endothelium on the graft lumen for extended times. The goal of this research was to develop a process to seed endothelial cells inside a vascular graft and to quickly condition the cells so as to minimize their damage or removal under physiological flow. In addition, the use of PhotoFix(R) natural biomaterial grafts as an improved substrate for human umbilical vein endothelial cells has been evaluated. A motorized system that provides uniform cell seeding of a small-diameter graft (4-mm inner diameter, 10-cm length) by automated radial rotation has been developed. The same system is subsequently adapted for gradual increases in flow rates to strengthen the endothelium, which ultimately was exposed to a final flow rate of 300 ml/min. This process is accomplished without graft transfer, decreasing risks of contamination and physical damage. Cell coverage and cell morphology were evaluated with the use of fluorescence microscopy and scanning-electron microscopy to determine the effectiveness of the flow conditioning process. It was found that endothelial cells exhibit roughly 20-50% improved adhesion to PhotoFix vessels compared to fibrin-treated polytetrafluoroethylene (PTFE) synthetic grafts. Flow conditioning for 6 h enhanced in vitro cell retention by 24% and 40% on PhotoFix and PTFE grafts, respectively.

Rapid fabrication and chemical patterning of polymer microstructures and their applications as a platform for cell cultures
Faid, K., R. Voicu, et al. (2005), Biomed Microdevices 7(3): 179-84.
Abstract: Much of the current knowledge regarding biological processes has been obtained through in-vitro studies in bulk aqueous solutions or in conventional Petri-dishes, with neither methodology accurately duplicating the actual in-vivo biological processes. Recently, a number of innovative approaches have attempted to address these shortcomings by providing substrates with controlled features. In particular, tunable surface chemistries and topographical micro and nanostructures have been used as model systems to study the complex biological processes. We herein report a versatile and rapid fabrication method to produce a variety of microstructured polymer substrates with precise control and tailoring of their surface chemistries. A poly(dimethylsiloxane) (PDMS) substrate, produced by replication over a master mold with specific microstructures, is modified by a fluoro siloxane derivative to enhance its anti-adhesion characteristics and used as a secondary replication mold. A curable material, deposited by spin coating on various substrates, is stamped with the secondary mold and crosslinked. The removal of the secondary mold produces a microstructured surface with the same topographical features as the initial master mold. The facile chemical patterning of the microstructured substrates is demonstrated through the use of microcontact printing methods and these materials are tested as a platform to guide cell attachment, growth and proliferation. The master mold and flexible fluorinated PDMS stamps can be used in a repeated manner without any degradation of the anti-adhesion characteristics opening the way to the development of high-throughput fabrication methods that can yield reliable and inexpensive microstructured and chemically patterned substrates.

Rapid separation of protein isoforms by capillary zone electrophoresis with new dynamic coatings
Chang, W. W., C. Hobson, et al. (2005), Electrophoresis 26(11): 2179-86.
Abstract: Many cellular functions are regulated through protein isoforms. Changes in the expression level or regulatory dysfunctions of isoforms often lead to developmental or pathological disorders. Isoforms are traditionally analyzed using techniques such as gel- or capillary-based isoelectric focusing. However, with proper electro-osmotic flow (EOF) control, isoforms with small pI differences can also be analyzed using capillary zone electrophoresis (CZE). Here we demonstrate the ability to quickly resolve isoforms of three model proteins (bovine serum albumin, transferrin, alpha1-antitrypsin) in capillaries coated with novel dynamic coatings. The coatings allow reproducible EOF modulation in the cathodal direction to a level of 10(-9) m2V(-1)s(-1). They also appear to inhibit protein adsorption to the capillary wall, making the isoform separations highly reproducible both in peak areas and apparent mobility. Isoforms of transferrin and alpha1-antitrypsin have been implicated in several human diseases. By coupling the CZE isoform separation with standard affinity capture assays, it may be possible to develop a cost-effective analytical platform for clinical diagnostics.

Rapid three-dimensional biointerfaces for real-time immunoassay using hIL-18BPa as a model antigen
Carrigan, S. D., G. Scott, et al. (2005), Biomaterials 26(35): 7514-23.
Abstract: With the goal of designing a rapid and affordable system of real-time immune monitoring for future diagnostic applications in sepsis, we have developed a biointerface composed of polyethyleneimine (PEI) and carboxymethylcellulose (CMC) to provide a means of prompt and facile immunoassay. Biointerface assembly is complete within 30 min, with all preparation performed and monitored within the measurement chamber of a quartz crystal microgravimetry with dissipation (QCM-D) sensor. Optimised biointerface composition, as determined by the mass of antibody immobilised, the level of antigen detection, and the amount of non-specific binding of human serum albumin, was determined to consist of a 4.0 mg/mL CMC hydrogel layer cross-linked to a 0.5 mg/mL PEI sub-layer. Tapping mode atomic force microscopy (AFM) in liquid demonstrates highly uniform and smooth surfaces using these hydrogels. Sensitivity of the biointerface for rhIL-18BPa is 400 ng/mL, with detection of 1 microg/mL achievable following 25 surface regenerations. Performance of the biointerface is verified using surface plasmon resonance (SPR), demonstrating the ability of the biointerface to be applied across platforms.

Rat bone marrow stromal cell osteogenic differentiation and fibronectin adsorption on chitosan membranes: the effect of the degree of acetylation
Amaral, I. F., M. Lamghari, et al. (2005), J Biomed Mater Res A 75(2): 387-97.
Abstract: Cell adhesion, migration, and proliferation of a few anchorage-dependent cells cultured on chitosan (Ch) matrices are influenced by the degree of N-acetylation (DA) of Ch. In the present work, we examined the influence of the DA on the attachment, spreading, proliferation, and osteogenic differentiation of rat bone marrow stromal cells (rBMSCs). Ch membranes were characterized in terms of surface morphology, roughness, and wettability, and in terms of adsorption of an adhesive protein, fibronectin (Fn). Chs with DAs in the range of 4 to 49% were used. Among the Ch samples, the DA of 4% led to the highest Fn surface concentration, both from single protein solution and from diluted serum. Furthermore, the levels of Fn adsorbed from serum found for this DA were threefold higher than for the tissue culture polystyrene control, indicating that in the presence of competitive proteins Ch is more specific toward Fn adsorption than tissue culture polystyrene. rBMSCs cultured on Ch carrying a DA of 4% were able to spread, proliferate, and differentiate, reaching a higher level of osteogenic differentiation than on the control, despite the lower cell attachment observed for all Ch samples. Because the Ch sample with a DA of 4% showed the highest Fn adsorption from serum, we suggest that cell adhesion, spreading, and osteogenic differentiation of rBMSCs on Ch may be mediated by the adsorbed layer of Fn.

Rational development of GAG-augmented chitosan membranes by fractional factorial design methodology
Chen, Y. L., H. C. Chen, et al. (2006), Biomaterials 27(10): 2222-32.
Abstract: To develop a novel biomaterial for chondrocyte culture, 8 glycosaminoglycan (GAG)/chitosan membranes (groups N1-N8) were prepared, with the aid of a 2-level 2(4-1) fractional factorial design, by co-immobilizing chondroitin-4-sulfate (CSA), chondroitin-6-sulfate (CSC), dermatan sulfate (DS), and heparin to chitosan membranes. The fractional factorial design allowed us to partly interpret the effects of individual GAGs and two-way interactions between GAGs. Within the level range of -1 and +1, low CSA level (2.6mg) is favorable for collagen synthesis but not for cell proliferation. High CSC level (1.3mg) is favorable for GAG production but not for cell proliferation. Conversely, high heparin (0.33mg) and DS (0.13mg) levels are desired for cell proliferation but not for the production of collagen and GAG. Moreover, the two-way interactions between GAGs influence the cell behavior. Among the 8 GAG/chitosan membranes, N1 and N4 (containing low CSA and heparin levels) lead to the maintenance of proper chondrocyte phenotype, as judged by the chondrocyte-like morphology, modest cell expansion, higher GAG and collagen production and proper cartilage marker gene expression. In conclusion, this approach provides a means of rationally predicting and evaluating the proper formulation of GAG/chitosan membranes and may facilitate the rational design of other tissue engineering scaffolds.

Rationale for the design of biomaterials and the evaluation of their biocompatibility
Baquey, C., B. Dupuy, et al. (1991), Biorheology 28(5): 463-72.
Abstract: The biocompatibility of a material can be considered as the ideally expectable result of its interactions with living tissues with which it is interfaced. This property determines the ability of devices involving this material in their constitution, to correctly assume their ascribed function; reciprocally a bad fitting, between devices and their intended use, coming from a non-optimized design or from an inappropriate prescription, may alter the original biocompatibility of constitutive materials. Accordingly, the actual biocompatibility of a biomaterial depends upon both its intrinsic properties and the application in which it is involved. Such considerations must be taken into account by specialists who try to design more performant biomaterials, or new assist devices, should they be implantable or not; but they draw also methodological guidelines for the evaluation of the biocompatibility of these biomedical products.

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