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PubMed1987

Graft copolymer emulsions of sodium alginate with hydroxyalkyl methacrylates for microencapsulation.

A hybrid material with interesting capsule forming properties has been prepared by gamma-initiated polymerization of hydroxyethyl methacrylate (HEMA) or other acrylic monomers in the presence of aqueous sodium alginate. For example, an aqueous solution of HEMA (1 wt%) and sodium alginate (1 wt%) was irradiated in a gamma-source at a dose of 0.15 MR, to produce a stable emulsion which coalesced in the form of a homogeneous precipitate when added to 0.1 M CaCl2. Polymerization of HEMA was presumed to be initiated by free radicals generated in the alginate by gamma-irradiation. The emulsion consisted largely of polyHEMA homopolymer stabilized by an alginate-polyacrylate graft (or block) copolymer of highly branched and ill-defined character, which acts as surfactant to prevent coagulation of the emulsion. Erythrocytes were encapsulated in such an emulsion by extrusion of cell/copolymer emulsion mixture into HEPES buffered CaCl2 (10 mM Ca). Cells appeared intact and functional after encapsulation. By SEM it appeared that the capsule wall consisted of microspheres of polyHEMA on the inner and outer surfaces held together by the alginate. Furthermore the capsule did not contain the internal meshwork, characteristic of calcium alginate homopolymer gels. Although much remains to be learned about these materials, the combination of the easy gelling characteristics of the alginate with the range of desirable properties (e.g. biocompatibility) afforded by the acrylic monomers may have a significant impact on the development of cell microencapsulation technology.

Alginates↗

PubMed2004

Pain control via opioid analgesic-local anesthetic loaded IPNs.

Relief of chronic pain is an important clinical problem requiring special care and approaches. The present study was designed for the construction of a controlled release system for local application of analgesics (hydromorphone (HM), morphine (M), and codeine (C)) and a local anesthetic, bupivacaine (BP). An interpenetrating network (IPN) drug release system was prepared by using a biocompatible, biodegradable copolyester, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and another biocompatible but synthetic, nondegradable polymer, poly (2- hydroxyethyl methacrylate), (PHEMA). In situ release kinetics of the IPN system was first order for BP but could not be fitted to any known equation for the other drugs. Complete release from the IPNs occurred within a considerably short time (24 h for 80 % of the drugs) most probably due to the significant hydrophilicity of PHEMA. In order to slow down the release rate these IPNs were coated with PHBV. Release from these coated IPNs (cIPN) resulted in rates that could be described by Higuchi's equations. In vivo measurement of antinociceptive efficacy was carried out in rats with tail flick and paw-withdrawal tests after inducing chronic pain created by sciatic nerve ligation at the right side. Control groups received placebo implants. In vivo studies showed potent, prolonged (2-3 days) antinociception at the site of injury (right paw) for strong opioids (HM and M) and about 2 days for the weak opioid (C) and local anesthetic (BP). In all cases the release rate was found to be as important as the antinociceptive potency. The weakest opioid analgesic of those evaluated (C) had a higher first day antinociception than its stronger counterpart M, probably due to its higher initial concentration that was expected from its faster release rate in the in situ experiments.

Analgesics, Opioid↗

PubMed2005

Molecularly engineered p(HEMA)-based hydrogels for implant biochip biocompatibility.

The strategy of phospholipid-based biomimicry has been used to molecularly engineer poly(2-hydroxyethyl methacrylate) [p(HEMA)]-based hydrogels for improved in vitro and potential in vivo biocompatibility. Two methacrylate-based monomers, poly(ethylene glycol) (200) monomethacrylate (PEGMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC), were incorporated at varying mole fractions of 0.0-0.5 mol% PEGMA and 0-10 mol% MPC respectively, into 3 mol% tetraethyleneglycol diacrylate (TEGDA) cross-linked p(HEMA) networks. Upon hydration of these engineered hydrogels, a reduction in receding contact angle from 22+/-1.2 degrees for p(HEMA) to 8+/-2.7 degrees for p(HEMA) containing 0.5:10 mol% PEGMA:MPC was observed, reflecting the significant increase in surface hydrophilicity with increasing PEGMA and MPC content upon prolonged hydration. Hydrogels containing MPC showed a temporal increase in hydrophilicity following continuous immersion in DI water over 5 days. Hydrogels containing 0.5 mol% PEGMA and MPC in the range of 5-10 mol% displayed reduced protein adsorption when incubated with the common extracellular matrix proteins; fibronectin, collagen or laminin, producing up to 64% less protein adsorption compared to p(HEMA). Compositional optima for cell viability and proliferation established from two-factor Central Composite design analysis of human muscle fibroblasts cultured on these hydrogels suggest that those containing PEGMA between 0.3 and 0.5 mol% and MPC levels around 5-10 mol% exhibit desirable characteristics for implant material coatings-high viability (>80%) with low proliferation (<40%), confirming a lack of cytotoxicity.

Adsorption↗

PubMed1989

Development and in vitro evaluation of an intra-oral controlled-release delivery system for chlorhexidine.

Copolymers of hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA) were prepared and used to fabricate a membrane-controlled reservoir-type controlled-release delivery system for chlorhexidine that should be suitable for intra-oral use. The reservoir of the system was prepared by softening an 80:20 mixture of chlorhexidine diacetate and 50:50 HEMA:MMA copolymer with methyl ethyl ketone (MEK), and pressing standard amounts of the resulting dough-like mixture into silicone rubber molds. A membrane was applied to the reservoirs by rotating them through a solution of 30:70 HEMA:MMA copolymer in MEK. The finished oval-shaped controlled-release pellets were approximately 4.7 mm wide, 3.3 mm high, and 7.4 mm long, and contained 45.0 +/- 3.7 mg of chlorhexidine diacetate. The mean in vitro release rate of chlorhexidine diacetate from the pellets into 37 degrees C water was 608 +/- 55 micrograms/24 h for days 2 through 11, and 389 +/- 50 micrograms/24 h for days 15 to 30 of the test period. The chlorhexidine released on day 30 was biologically active, as determined by a serial dilution assay against Streptococcus mutans. The extended release of biologically active chlorhexidine at a controlled rate from this system suggests that it is worthy of further evaluation for the intra-oral therapy of chlorhexidine-treatable oral infections in non-compliant and physically or mentally compromised individuals.

Analysis of Variance↗

PubMed2004

Characterization of the surface of conventional hydrogel and silicone hydrogel contact lenses by time-of-flight secondary ion mass spectrometry.

PURPOSE: To characterize the surfaces of unworn conventional hydrogel and silicone hydrogel contact lenses. METHODS: Near-identical formulations of poly(hydroxyethyl methacrylate) (pHEMA) were used to manufacture lathe-cut, spun-cast, and cast-molded contact lenses. The surfaces of two of each of these lens types and two of each of two commercially available silicone hydrogel lenses-balafilcon A (PureVision) and lotrafilcon A (Focus Night and Day)-were analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS). RESULTS: The ToF-SIMS spectra revealed the presence of the bulk polymer pHEMA at the surface of all three hydrogel lenses, along with other contaminants, such as poly(dimethyl siloxane), alkyl sulfates, alkyl-aryl sulfonates, dioctyl phthalate, Irgafos 168, sodium, chlorine, aluminum, potassium, calcium, copper, and fluorine, which are primarily derived from the various processing steps undertaken in lens manufacture, handling, and storage. The amount of bulk polymer detected at the surface of the PureVision lens was greater than that detected at the surface of the Night and Day lens. In addition, contaminants similar to those found on the surfaces of the conventional hydrogel lenses were detected. The Focus Night and Day lens appears to be coated with an organo-nitrogen material, which results from the plasma deposition of reactive precursors on the surface. CONCLUSIONS: We confirm that ToF-SIMS has the capacity to characterize the surface chemistry of contact lenses. The ongoing application of this technique can assist researchers and clinicians to understand the clinical performance of contact lenses.

Contact Lenses, Hydrophilic↗

PubMed2000

[In vitro study of the effect of bisphosphonates on mineralization induced by a composite material: poly 2(hydroxyethyl) methacrylate coupled with alkaline phosphatase].

We have immobilized the mineralizing agent alkaline phosphatase (AlkP) in a hydrophilic polymer (poly 2(hydroxyéthyl) methacrylate) (pHEMA) in a copolymerization technique. Histochemical study on polymer sections revealed that AlkP has retained its biological 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 bisphosphonates (etidronate, alendronate and tiludronate) on this system. 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 inhibit the calcospherite deposition onto the pHEMA-AlkP material in a similar way. Both bisphosphonates possess three sites for mineral complexion. On the other hand, tiludronate having only two sites was associated with a reduced inhibitory effect on mineralization. When used in microgravity conditions, mineralization was impaired with etidronate and larger crystals were obtained with tiludronate. However, these effects were obtained in non-physiological conditions (a 20 degrees C temperature was used during the STS80 flight of the space shuttle). The pHEMA-AlkP material provides an interesting method to study the effects of pharmacological compounds and environmental factors on the bone and cartilage mineralization process.

Alkaline Phosphatase↗

PubMed1990

Staining sections of water-miscible resins. 1. Effects of the molecular size of stain, and of resin cross-linking, on the staining of glycol methacrylate embedded tissues.

Penetration of hydrophilic acid and basic dyes into sections cut from glycol methacrylate (GMA)-embedded tissues was studied; as were the effects on such staining of superficial coatings of thin layers of GMA. Dye size was a major factor in controlling penetration of resin and staining of tissues. 'Large' dyes (greater than 1000 Da) entered GMA very slowly, and only stained those tissue components poorly infiltrated by resin. 'Small' dyes (less than 550 Da) penetrated GMA readily, and stained tissue components whether or not they were resin-infiltrated. Dyes of intermediate size penetrated the resin, but the staining of resin-infiltrated tissue elements was slow. Background staining of resin also varied with dye size. Large dyes gave no staining of GMA. Small dyes did, but were readily removed by water washing. Dye of intermediate size penetrated resin slowly, and once inside were lost slowly. This gave background staining which required use of the plasticizing solvent ethanol for its removal. Increases in resin cross-linking also reduced staining rates. As a consequence, it is possible to predict the probable suitability, or otherwise, of various staining reagents proposed for use with GMA sections; and also the probable influences of histoprocessing on stain penetration. In particular it is suggested that penetration of colloidal metals and macromolecular reagents (e.g. labelled antibodies and lectins) will be limited to resin-free structures, and to the surface of resin sections. The use of superficial GMA coatings as convenient semipermeable membranes for enzyme histochemistry is also noted.

Animals↗

PubMed1997

The differential effects of poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate)/poly(caprolactone) polymers on cell proliferation and collagen synthesis by human lung fibroblasts.

Because of its chemical versatility and demonstrated biocompatibility, poly(2-hydroxyethyl methacrylate) (pHEMA) has been widely used as a polymer for biomedical applications. Since this hydrophilic material shows a poor interface with cells, blendings with other polymers were done to improve cytocompatibility. In our polymer, the presence of hydrophobic dominions on the material surface, due to the interpenetrating polymerization of pHEMA with poly(caprolactone) (PCL), seems to ameliorate the cytocompatibility in terms of cell adhesion and metabolism. For our experiments, we used IMR-90 human fibroblasts, as these cells strongly regulate DNA, RNA, and protein synthesis as anchorage-dependent variables. Cell attachment on a pHEMA/PCL interpenetrating polymer network was optimal, suggesting a strong adhesion between the cells and the polymer surface. Cell adhesion was weaker on pHEMA, as a significant fraction of the fibroblasts revealed a lack of spreading, with most cells remaining spherical. Moreover, only fibroblasts seeded on pHEMA significantly decreased mRNA synthesis; collagen production and cell shapes ranged from fully flat and proliferating, to minimally spread and nonproliferating. Finally, DNA synthesis, as a measure of cell proliferation, was markedly inhibited in cells cultured on pHEMA but not on pHEMA/PCL. In conclusion, our results suggest that control of cell growth and metabolism by biomedical polymers is based on physicochemical mechanism(s) in which the hydrophilicity/hydrophobicity ratio of the material surfaces may play an important role.

Base Sequence↗

PubMed2006

Solid molecular dispersions of poorly water-soluble drugs in poly(2-hydroxyethyl methacrylate) hydrogels.

The applicability of cross-linked hydrogels in forming solid molecular dispersions to enhance the delivery of poorly soluble drugs has not been fully explored. The purpose of this study is to characterize physicochemical parameters affecting the formation of solid molecular dispersions of poorly water-soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels and to investigate the effect of storage humidity levels on their physical stability. Samples were prepared by an equilibrium solvent loading process, using diclofenac sodium, piroxicam and naproxen as model drugs. These were characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), as well as changes in the physical state during storage under different humidity conditions. The results show that a threshold drug loading level of about 30% exists in these solid molecular dispersions, above which amorphous to crystalline transition may occur. At any given drug loading, the onset of such change in physical state is accelerated at higher relative humidity levels during storage. The presence of hydrogen bonding between the polymer and the drug, as reflected in the observed FTIR band shifts, improves the compatibility between the drug and the polymer. This, together with a decreased mobility in the glassy polymer, helps to retard the crystallization event below the loading threshold. An increase in dissolution rate is also observed from the polymeric solid molecular dispersion as compared with that of the crystalline pure drug. These physicochemical results indicate that solid molecular dispersions based on PHEMA hydrogels can effectively enhance the dissolution and therefore should be potentially useful in improving the oral bioavailability of poorly water-soluble drugs.

Administration, Oral↗

PubMed1996

Dopamine secretion by PC12 cells microencapsulated in a hydroxyethyl methacrylate--methyl methacrylate copolymer.

A rat pheochromocytoma cell line (PC12) was encapsulated in a water-insoluble hydroxyethyl methacrylate-methyl methacrylate copolymer by interfacial precipitation from a polyethylene glycol 200 solution into phosphate-buffered saline. The resulting capsules (660 +/- 44 microns in diameter; 84 +/- 27 microns wall thickness) contained viable PC12 cells in a spheroidal arrangement, much like tumour spheroids, the latter grown on surfaces unsuitable for cell attachment. In these spheroids, the viable cells formed a band approximately 100 microns thick, surrounding an inner core of necrotic cells. A similar arrangement was seen 14, 28 and 42 days after encapsulation, with capsules maintained in an in vitro tissue culture environment; the annular ring was roughly constant in size, although the packing density appeared to increase over the 6 week observation period. During the first 4 weeks, when measurements were made the encapsulated cells converted a tetrazolium dye (MTT) into an insoluble formazan product, in a time-after-encapsulation-dependent manner. This indicated that PC12 cells retained viability despite encapsulation and an ability to increase (at least in part) their metabolic capacity, presumably by a combination of proliferation and altered cellular activity. The encapsulated PC12 cells also secreted dopamine when incubated in a high potassium release medium but not in a low potassium, conventional tissue culture medium (RPMI 1640). Consistent with the MTT results, the amount of dopamine released was also dependent on the time after encapsulation, as well as the cell density at the time of encapsulation.

Animals↗

PubMed2003

Subjective experience with high-oxygen and low-oxygen permeable soft contact lenses in France.

PURPOSE: This article reports the subjective results of a study comparing extended-wear high-oxygen permeable (HDk) silicone hydrogel soft contact lenses with low-oxygen permeable (LDk) hydroxyethyl methacrylate lenses. METHODS: Six practitioners in France enrolled 134 subjects in this 4-month, open-label, multicenter, prospective, randomized, cross-over study. Subjects were randomized to receive prescriptions of either an HDk lotrafilcon A or an LDk etafilcon A soft contact lens. Subjects then crossed over to the alternative lens after either 3 months' experience with the HDk lens or 1 month's experience with the LDk lens. Clinical and subjective data were collected at scheduled follow-up visits. RESULTS: The clinical data has been reported in a separate article. After 1 month of wear. HDk lenses were rated better than LDk lenses for all aspects of comfort and overall average symptoms. Subjects were satisfied with both lenses, and lens features were comparable through 1 month. The preference was higher for HDk lenses after crossing over, either from or to LDk lenses. Eighty-six percent of HDk and 85% of LDk subjects reported wearing their lenses while sleeping for 7 nights per week during the study. Seventy-seven percent of HDk and 21% of LDk subjects reported wearing their lenses while sleeping for 22 to 31 nights during the study. CONCLUSIONS: Based on subjective results, therefore, the HDk lens offers another option to patients and practitioners for extended-wear or continuous-wear soft contact lenses.

Adult↗

PubMed1993

Histologic and histometric responses to polymeric composite grafts.

The present study was designed to determine whether a polymeric composite promotes new attachment in artificially-induced bony defects in the dog model. HTR, hard tissue replacement, is a non-resorbable calcium-layered polymer of polymethyl-methacrylate and hydroxyethyl-methacrylate. It has been reported to be clinically non-inflammatory, osteophilic, and osteoconductive. For the study, 4 beagle dogs, 4 to 6 years old with no periodontal disease were used. Mucoperiosteal flaps were raised including the 2nd, 3rd, and 4th maxillary premolars. Buccal Class II furcation defects were created on these premolars. Reference notches were placed in the roots at the level of the bony defects. Test quadrants were selected by the toss of a coin, and furcations were filled with the polymeric composite particles wetted with sterile saline. Following grafting, the flaps were approximated and sutured. The contralateral side, serving as control, was treated by flap debridement only. Sutures were removed 7 days after surgery. Dogs were sacrificed 4 months following surgery. Mesio-distal histological sections were evaluated by descriptive histology. In addition, surface area determinations (in mm2) of the furcal tissues were carried out using the microscope attached to a digitizer and a computer. In 8 mesio-distal serial sections cut 30 microns apart in both experimental and control teeth, surface area determinations relative to the furcations were made evaluating: 1) the total fill of the furcation; 2) the area filled with alveolar bone; 3) the area occupied by connective tissue; 4) the area occupied by new deposited cementum; and 5) the area filled by epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Bone Loss↗

PubMed2004

Impact of manufacturing technology and material composition on the clinical performance of hydrogel lenses.

PURPOSE: To establish the clinical impact of three different methods of manufacture used to produce soft contact lenses. METHODS: Clinical performance of five lens types was investigated by undertaking a prospective, double-masked, randomized, crossover study. Three of the lenses were made from poly(hydroxyethyl methacrylate) (pHEMA) by three different manufacturing processes (lathing, spin casting, and cast molding), and the remaining two lenses were cast molded from different materials-hydroxyethyl methacrylate/methacrylic acid and hydroxyethyl methacrylate/glycerol methacrylate (HEMA/GMA). All lenses were specially fabricated for this work at the same manufacturing plant. Thirty-four soft contact lens wearers wore each lens for 1 month on a daily-wear basis. Several clinical variables, such as ocular response, visual acuity, lens fitting, prelens tear film, lens surface dehydration, subjective response, and protein deposition, were measured. RESULTS: In general, the spun-cast pHEMA lens performed inferiorly compared with the other pHEMA lenses. This lens induced significantly more limbal and conjunctival hyperemia than the cast-molded lens and provided poorer low contrast visual acuity (LCVA) than the other two lenses. It dehydrated more and had the least on-eye movement. However, the spun-cast lens deposited the least protein of the pHEMA lenses. In general, the HEMA/GMA lens performed inferiorly compared with the other cast-molded lenses. LCVA was worse with this lens, and subjective responses showed that this lens was thought to give the worst visual performance of the cast-molded lenses. It was also thought to be the most difficult lens to handle. Significantly more breakages occurred with this lens than any other. CONCLUSIONS: Overall, this work has shown that manufacturing method and material composition have a fundamental effect on many clinical properties of a lens. Therefore, method of manufacture is also an important consideration in the overall production of a soft lens.

Adult↗

PubMed2003

Evaluation of hard tissue replacement composite graft material as a ridge preservation/augmentation material in conjunction with immediate hydroxyapatite-coated dental implants.

BACKGROUND: Immediate placement of dental implants (DI) in fresh extraction sockets is associated with remaining voids around the DI and often a partial dehiscence or thin facial alveolar plate. Bone replacement grafts are often used to correct these problems. This study evaluated the use of a layered composite of PMMA (poly-methyl-methacrylate), PHEMA (poly-hydroxyl-ethyl-methacrylate), and calcium hydroxide grafts (HTR) as a ridge preservation/ augmentation material used in conjunction with an immediate DI placement technique. METHODS: Twenty-three patients requiring 1 or 2 extractions that were treatment planned for immediate DI placement received 4.0 or 3.25 mm diameter hydroxyapatite-coated cylindrical implants in the extraction sockets. HTR was used to fill the remaining socket void and enhance the facial ridge width. A collagen hemostatic was placed to cover the DI sites, flaps released, and primary closure attempted with sutures. DI uncovering was performed at about 6 months. Measurements were taken to the nearest 0.5 mm of the internal socket width and total ridge width at DI placement and uncovering. RESULTS: Thirty DIs were placed in the 23 patients. Mean initial internal socket width was 6.9 mm. The total ridge width showed a mean change from 9.1 mm to 8.4 mm; 60% of the areas showed a net increase or no change, while 40% showed a decrease in overall ridge width. DI success rate was 97% out to 6 months of loading. CONCLUSION: The results of this study suggest that HTR is a useful adjunct in the placement of immediate DIs for filling of socket voids and preservation of ridge width.

Adolescent↗

PubMed1996

5-FU loaded pHEMA drainage implants for glaucoma-filtering surgery: device design and in vitro release kinetics.

Implantable monolithic and reservoir-like water-swellable drainage devices were developed for the subconjunctival sustained release of 5-fluorouracil (5-FU) in glaucoma-filtering surgery. A water-swellable matrix was formed of a copolymer of 2-hydroxyethyl methacrylate (HEMA) with different amounts of ethylene glycol dimethacrylate (EGDMA). Drug incorporation was done before polymerization and cross-linking. Briefly, to prepare the monolithic device the monomer-drug mixture is compression moulded into a 10 mm cylinder of 1 mm length. Furthermore, reservoir-like devices were obtained by coating the monolithic devices with a highly cross-linked polymer of HEMA (pHEMA) composition. The pHEMA devices containing 5-FU or not were well characterized by means of dynamic swelling studies, structural and thermal analysis. The release of 5-FU from these implants was studied in vitro. The rate of drug release was controlled by changing the drug loading (i.e. 10 mg or 20 mg 5-FU per device), cross-linking density of polymer matrix and type of implantable device, i.e. monolithic or reservoir-like device. While monolithic devices are releasing total releasable 5-FU during the first 10 h, reservoir-like devices prolong 5-FU release for up to 120 h. The 5-FU diffusion coefficient in swollen devices (Ds,s) is in the order of 10(-8) cm2 s-1 (approximately 10 times smaller than Dw,g values) and it is dependent on the cross-linking density of polymeric matrix and device load. These preliminary results suggested that 20 mg 5-FU-loaded reservoir-like devices may be a potentially effective system to deliver 5-FU into the subconjunctiva.

Animals↗

PubMed2002

Manufacture of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) hydrogel tubes for use as nerve guidance channels.

Hydrogel tubes of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (p(HEMA-co-MMA)) made by liquid-liquid centrifugal casting are being investigated as potential nerve guidance channels in the central nervous system. An important criterion for the nerve guidance channel is that its mechanical properties are similar to those of the spinal cord, where it will be implanted. The formulated p(HEMA-co-MMA) tubes are soft and flexible, consisting of a gel-like outer layer, and an interconnected macroporous, inner layer. The relative thickness of the gel phase to macroporous phase is controlled by the formulation chemistry, and specifically by the ratio of co-monomers, HEMA and MMA. By varying the surface chemistry of the mold within which the tubes are synthesized, tubes were prepared with either a "cracked" or a smooth outer morphology. Tubes with the cracked outer morphology had periodic channels that traversed the wall of the tube, which resulted in a lower modulus than smooth outer morphology tubes, yet likely greater diffusive permeability. For tubes (and not rods) to be formed, phase separation must precede gelation as is detailed in a formulation phase diagram for HEMA, MMA and water. The tensile elastic modulus of p(HEMA-co-MMA) tubes reflected the formulation chemistry, with greater moduli (up to 400 kPa) recorded for tubes having 10 wt% MMA. The p(HEMA-co-MMA) tubes therefore had similar mechanical properties to those of the spinal cord, which has a reported elastic modulus range between 200 and 600 kPa.

Biocompatible Materials↗

PubMed2000

Making microencapsulation work: conformal coating, immobilization gels and in vivo performance.

Microencapsulation of cells as a means of insulin or other protein delivery (for example, for gene therapy) has not yet realized its potential. Three aspects of this problem are illustrated with reference to the use of poly(hydroxyethyl methacrylate-co-methyl methacrylate) (HEMA-MMA). Conformal coating was used to coat cell aggregates with a very thin layer of a water-insoluble HEMA-MMA membrane that conforms to the shape of the aggregate, and minimizes the polymer's contribution to the total transplant volume. Cell aggregates were coated at a liquid-liquid interface of a discontinuous density gradient composed of both aqueous and organic liquids. Aggregates of HepG2 cells were coated and remained viable. Immobilization matrices were co-encapsulated in order to control cell phenotype. Ultralow gelling temperature agarose promoted the proliferation of HEK293 cells, while the viability of transfected C2C12 cells was improved in microcapsules that contained Matrigel. Rat or human hepatoma cells in HEMA-MMA microcapsules lost viability within a week after implantation into an omental pouch in Wistar rats. The loss of viability was attributed to the tissue reaction, although it is not clear if the cells lost their viability in vivo leading to the aggressive tissue reaction or if the latter caused the cells to starve or otherwise die. On the other hand, intraperitoneal implantation of microcapsules containing L929 cells in 'syngeneic' C3H mice in a high-strength agarose gel resulted in maintenance of viability of approximately 50% of the encapsulated cells. While progress is being made on several fronts, this type of tissue engineering construct is still several years away from routine use in humans.

Animals↗

PubMed2002

Adherence of osteoblast-like cells on calcospherites developed on a biomaterial combining poly(2-hydroxyethyl) methacrylate and alkaline phosphatase.

The polymer poly(2-hydroxyethyl) methacrylate (pHEMA) can copolymerize with alkaline phosphatase (AlkP) to form a hybrid material. The enzyme retains its biological activity and forms hydroxyapatite nodules (calcospherites) when polymer pellets are incubated with a synthetic body fluid. Osteoblast-like cells (ROS 17/2.8) were seeded on pellets of pHEMA and pHEMA-AlkP on which calcospherites were grown. They were examined by scanning electron microscopy (SEM) with backscattered electron imaging. Cell surface and shape were measured by image analysis combining the SEM images. Cells grown on pHEMA-AlkP had an increased surface area (449 +/- 216 microm(2) vs. 204 +/- 80 microm(2)). The number of filopodia anchoring the cells on the free polymer surface was reduced on pHEMA-AlkP, but numerous thick pseudopodia permitted a direct anchorage on the calcospherites. Pseudopodia were wider and longer than the filopodia. The backscattered images revealed that each cell was seated on 7.1 +/- 1.5 calcospherites and partially covered 10.3 +/- 1.9 others. Antifibronectin and anti-bone sialoprotein antibodies were used to investigate cell attachment. With confocal microscopy, both molecules were located at the interface between the cells and the mineral, inside the cells, and as free molecules on the calcospherites. Immunogold labeling was done with the same antibodies and examined with transmission electron microscopy (TEM). Adsorption of fibronectin and bone sialoprotein was noticeable at the cell/calcospherite interface and on the surface of the hydroxyapatite crystals. Immunogold studies revealed adhesion proteins (bone sialoprotein, fibronectin) to be present at the surface of crystals and at focal points of cell contact.

Alkaline Phosphatase↗