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1.
ACS Appl Mater Interfaces ; 11(39): 35879-35887, 2019 Oct 02.
Article in English | MEDLINE | ID: mdl-31486629

ABSTRACT

Electric double-layer (EDL) gating using a custom-synthesized polyester single-ion conductor (PE400-Li) is demonstrated on two-dimensional (2D) crystals for the first time. The electronic properties of graphene and MoTe2 field-effect transistors (FETs) gated with the single-ion conductor are directly compared to a poly(ethylene oxide) dual-ion conductor (PEO:CsClO4). The anions in the single-ion conductor are covalently bound to the backbone of the polymer, leaving only the cations free to form an EDL at the negative electrode and a corresponding cationic depletion layer at the positive electrode. Because the cations are mobile in both the single- and dual-ion conductors, a similar enhancement of the n-branch is observed in both graphene and MoTe2. Specifically, the single-ion conductor decreases the subthreshold swing in the n-branch of the bare MoTe2 FET from 5000 to 250 mV/dec and increases the current density and on/off ratio by two orders of magnitude. However, the single-ion conductor suppressed the p-branch in both the graphene and the MoTe2 FETs, and finite element modeling of ion transport shows that this result is unique to single-ion conductor gating in combination with an asymmetric gate/channel geometry. Both the experiments and modeling suggest that single-ion conductor-gated FETs can achieve sheet densities up to 1014 cm-2, which corresponds to a charge density that would theoretically be sufficient to induce several percent strain in monolayer 2D crystals and potentially induce a semiconductor-to-metal phase transition in MoTe2.

3.
J Plast Reconstr Aesthet Surg ; 66(3): 414-22, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23122707

ABSTRACT

BACKGROUND: Seroma formation is a common postoperative complication following many surgical procedures including abdominoplasty. Recently, a lysine-derived urethane (LDU) surgical adhesive was shown to prevent seroma formation in short term studies in a canine model of abdominoplasty. This current study evaluates efficacy of the adhesive (TissuGlu®, Cohera Medical, Inc.) in the same model at longer time points, and examines the histological tissue response to extended exposure to the adhesive. MATERIALS AND METHODS: Bilateral subcutaneous pockets were created in the ventrolateral abdominal wall and additional tissue damage was inflicted using electrocautery. On one side, the tissue layers were treated with the adhesive prior to closure, whereas the control side received no treatment prior to standard closure of the incision. Seroma fluid accumulation was measured and histologic analysis was performed at 3 and 12 weeks. RESULTS: Seroma formation (mean±SD, 690±870 ml; median volume of 348.5 ml) was observed on the control side, whereas the treated side had adherence between the tissue layers, and minimal if any fluid accumulation (mean±SD, 44±53 ml; median volume of 15 ml) (p<0.01) (n=8) at 3 week necropsy. In animals survived to 12 weeks, two of the four control sides required aspiration of serous fluid, and dead space persisted for the entirety of the study in one animal. For the adhesive treated sites, none of the four animals showed signs of seroma at euthanasia, although serial aspiration was performed in one treatment site within the first month and resulted in resolution of the process. The adhesive was detected in the surgical site at 3 and 12 weeks, and independent histological analysis found it to be a non-irritant compared to control (no treatment). CONCLUSIONS: Long term evaluation of TissuGlu® Surgical Adhesive showed that it is capable of preventing the formation of seroma in this canine abdominoplasty model, indicating that it may be of clinical benefit in the prevention of seroma formation in patients undergoing abdominoplasty.


Subject(s)
Abdominoplasty/adverse effects , Seroma/prevention & control , Tissue Adhesives/therapeutic use , Abdominoplasty/methods , Animals , Biopsy, Needle , Disease Models, Animal , Dogs , Immunohistochemistry , Male , Postoperative Complications/prevention & control , Random Allocation , Reference Values , Seroma/etiology , Tensile Strength , Treatment Outcome
4.
Biomed Mater Eng ; 20(5): 269-81, 2010.
Article in English | MEDLINE | ID: mdl-21084739

ABSTRACT

Naphthalene analogs with differing hydroxyl and amine functionality were incorporated into degradable polyurethane foams synthesized from lysine diisocyanate and glycerol to determine if chemical structure can be used in controlled release systems. Excitation and emission spectra of the various naphthalene analogs in aqueous solution were collected to ensure they were capable of being quantitatively detected in aqueous solution at low concentrations. The fluorescence stability of the compounds was assessed over a 2-week period at 70°C; the analogs were all found to exhibit signal decay to varying degrees. Polyurethane foam materials containing the naphthalene analogs were synthesized and examined via scanning electron microscopy; incorporating naphthalene ligands did not grossly alter the polyurethane morphology. The analog distribution was then assessed via fluorescence microscopy, and the naphthalene analogs were found evenly dispersed throughout the polyurethane materials. Foam samples containing various analogs were then incubated in PBS buffer solution (pH 7.4) at 4, 22, 37 and 70°C for 11-weeks. Temperature dependent release of naphthalene analogs from the polyurethane foams was found to depend upon the functional groups present on the naphthalene analog. These results suggest that the chemical structure of a drug plays a unique role in controlling release from hydrolytically degradable drug delivery systems.


Subject(s)
Delayed-Action Preparations/pharmacology , Lysine/analogs & derivatives , Naphthalenes/chemistry , Polyurethanes/chemistry , Biocompatible Materials/chemistry , Isocyanates/chemistry , Lysine/administration & dosage , Lysine/chemistry , Microscopy, Electron, Scanning , Polyurethanes/administration & dosage , Solutions/chemistry
5.
Environ Sci Technol ; 44(21): 8264-9, 2010 Nov 01.
Article in English | MEDLINE | ID: mdl-20866068

ABSTRACT

This study evaluates the efficacy of green design principles such as the "12 Principles of Green Chemistry," and the "12 Principles of Green Engineering" with respect to environmental impacts found using life cycle assessment (LCA) methodology. A case study of 12 polymers is presented, seven derived from petroleum, four derived from biological sources, and one derived from both. The environmental impacts of each polymer's production are assessed using LCA methodology standardized by the International Organization for Standardization (ISO). Each polymer is also assessed for its adherence to green design principles using metrics generated specifically for this paper. Metrics include atom economy, mass from renewable sources, biodegradability, percent recycled, distance of furthest feedstock, price, life cycle health hazards and life cycle energy use. A decision matrix is used to generate single value metrics for each polymer evaluating either adherence to green design principles or life-cycle environmental impacts. Results from this study show a qualified positive correlation between adherence to green design principles and a reduction of the environmental impacts of production. The qualification results from a disparity between biopolymers and petroleum polymers. While biopolymers rank highly in terms of green design, they exhibit relatively large environmental impacts from production. Biopolymers rank 1, 2, 3, and 4 based on green design metrics; however they rank in the middle of the LCA rankings. Polyolefins rank 1, 2, and 3 in the LCA rankings, whereas complex polymers, such as PET, PVC, and PC place at the bottom of both ranking systems.


Subject(s)
Green Chemistry Technology/methods , Polymers/chemical synthesis , Biodegradation, Environmental , Conservation of Natural Resources , Environmental Pollution/prevention & control , Petroleum , Polyenes/chemical synthesis , Polyenes/chemistry , Polymers/chemistry
6.
Oral Maxillofac Surg Clin North Am ; 22(1): 195-9, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20159487

ABSTRACT

Presently, tissue adhesives and sealants have limited use in oral and maxillofacial surgical procedures. Skin closure occurs regularly with cyanoacrylate adhesives. Sealing of dural tears in conjunction with dural closure has been shown to be very successful. With the development of more head and neck reconstructive procedures and cosmetic procedures, demand will increase for better surgical adhesives. Clinical trials are beginning for newly developed adhesives with the chemical characterizations, the safe reabsorptive profile, and the adhesive strength necessary to benefit oral and maxillofacial surgery patients in the near future. Adhesives for bone fixation, while in early development, also show a promising chemical profile and will be of significant benefit to oral and maxillofacial surgical patients.


Subject(s)
Oral Surgical Procedures , Tissue Adhesives/therapeutic use , Biocompatible Materials/therapeutic use , Bone Cements/therapeutic use , Collagen/therapeutic use , Cyanoacrylates/therapeutic use , Dura Mater/injuries , Fibrin Tissue Adhesive/therapeutic use , Hemostatics/therapeutic use , Humans , Oral Surgical Procedures/methods , Polyurethanes/therapeutic use , Plastic Surgery Procedures/methods , Safety , Stress, Mechanical , Surface Properties , Tissue Adhesives/chemistry
7.
Acta Biomater ; 6(1): 144-53, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19524075

ABSTRACT

This study seeks to determine the effect of ionic ligands on the drug delivery characteristics of biodegradable polyurethane materials synthesized from lysine diisocyanate (LDI) and glycerol. Two naturally occurring, structurally related ionic species, choline chloride (CC) and isethionic acid (ISE), along with 3,3-dimethyl-butanol (DMB), their neutral carbon analog, were covalently incorporated into LDI-glycerol polyurethane materials. Selected organometallic and tertiary amine catalysts were used to fashion films and foams, respectively. The potent anticancer compound DB-67, a fluorescent camptothecin derivative, was also covalently linked to the polyurethane constructs. It was first determined that the sulfonate functional group on ISE does not react to a significant degree with isocyanate. The morphological characteristics of the polyurethane films and foams were assessed via scanning electron microscopy, showing significant differences related to the ionic ligands. The ionic materials displayed increased swelling in aqueous media over the neutral control materials. Differences in the distribution of DB-67 throughout the films and foams were then detected by fluorescence microscopy. The drug delivery characteristics of the materials were then evaluated in vitro, revealing accelerated release from ionic materials. The results of this study demonstrate the unique effects that incorporation of ionic ligands into LDI-glycerol polyurethanes have on the morphology and drug distribution of the materials. These differences have a significant impact on the drug delivery characteristics of the materials, and this information should prove useful in the design and synthesis of biodegradable controlled release systems.


Subject(s)
Antineoplastic Agents/pharmacology , Camptothecin/analogs & derivatives , Drug Delivery Systems , Isocyanates/chemistry , Lysine/analogs & derivatives , Organosilicon Compounds/pharmacology , Polyurethanes/chemistry , Biocompatible Materials , Camptothecin/pharmacology , Chemistry, Pharmaceutical/methods , Choline/pharmacology , Drug Carriers , Drug Design , Glycerol/chemistry , Humans , Ions , Isethionic Acid/chemistry , Ligands , Lysine/chemistry
8.
J Phys Chem B ; 113(45): 14971-80, 2009 Nov 12.
Article in English | MEDLINE | ID: mdl-19845375

ABSTRACT

Ab initio molecular modeling is used to design nonfluorous polymers that are potentially soluble in liquid CO2. We have used calculations to design three nonfluorous compounds meant to model the monomeric repeat units of polymers that exhibit multiple favorable binding sites for CO2. These compounds are methoxy isopropyl acetate, 2-methoxy ethoxy-propane, and 2-methoxy methoxy-propane. We have synthesized oligomers or polymers based on these small compounds and have tested their solubility in CO2. All three of these exhibit appreciable solubility in CO2. At 25 degrees C, oligo(3-acetoxy oxetane)6 is 5 wt % soluble at 25 MPa, the random copolymer (vinyl methoxymethyl ether30-co-vinyl acetate9) is 5 wt % soluble at 70 MPa and random copolymer (vinyl 1-methoxyethyl ether30-co-vinyl acetate9) is 3 wt % soluble at 120 MPa. These oligomers and polymers represent new additions to the very short list of nonfluorous CO2-soluble polymers. However, none of these are more soluble than poly(vinyl acetate), which exhibits the highest CO2 solubility of any known polymer containing only the elements C, H, and O.

9.
Acta Biomater ; 5(7): 2398-408, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19398389

ABSTRACT

In this study, we present an approach for the simultaneous release of multiple drug compounds at different rates from single-phase polyurethane foams constructed from lysine diisocyanate (LDI) and glycerol. The anti-cancer compounds DB-67 and doxorubicin were covalently incorporated into polyurethane foams, whereby drug release can then occur in concert with material degradation. To begin, the reactions of DB-67 and doxorubicin with LDI in the presence of a tertiary amine catalyst were monitored with infrared spectroscopy; each compound formed urethane linkages with LDI. Fluorescent spectra of DB-67 and doxorubicin were then recorded in phosphate-buffered saline, pH 7.4 (PBS), to ensure that each anti-cancer compound could be quantitatively detected alone and in combination. Doxorubicin and DB-67 were then incorporated into a series of degradable LDI-glycerol polyurethane foams alone and in combination with one another. The sol content, average porosity and drug distribution throughout each foam sample was measured and found to be similar amongst all foam samples. The stability of DB-67 and doxorubicin's fluorescent signal was then assessed over a 2-week period at 70 degrees C. Release rates of the compounds from the foams were assessed over a 10-week period at 4, 22, 37 and 70 degrees C by way of fluorescence spectroscopy. Release was found to be temperature-dependent, with rates related to the chemical structure of the incorporated drug. This study demonstrates that differential release of covalently bound drugs is possible from simple single-phase, degradable polyurethane foams.


Subject(s)
Absorbable Implants , Delayed-Action Preparations/chemistry , Glycerol/chemistry , Isocyanates/chemistry , Lysine/analogs & derivatives , Polyurethanes/chemistry , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Camptothecin/chemistry , Diffusion , Doxorubicin/administration & dosage , Doxorubicin/chemistry , Drug Compounding/methods , Gases/chemistry , Kinetics , Lysine/chemistry , Materials Testing , Organosilicon Compounds/administration & dosage , Organosilicon Compounds/chemistry
10.
Gastrointest Endosc ; 69(2): 289-96, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18657808

ABSTRACT

BACKGROUND: EMR is an accepted treatment for early esophageal cancer and high-grade dysplasia. One of the limitations of this technique is that extensive mucosal resection and endoscopic submucosal dissection may be required to obtain complete removal of the neoplasm, which may result in significant stricture formation. OBJECTIVE: The objective of the current study was to evaluate the efficacy of an endoscopically deployed extracellular matrix (ECM) scaffold material for prevention of esophageal stenosis after circumferential EMR. DESIGN: Ten mongrel dogs were subjected to surgical plane anesthesia and circumferential esophageal EMR by the cap technique. In 5 animals, an ECM scaffold material was endoscopically placed at the resection site; the remaining 5 animals were subjected to circumferential esophageal EMR without ECM placement. Follow-up endoscopy was performed at 4 and 8 weeks; necropsy with histologic assessment was performed at 8 weeks. SETTING: Animal laboratory. INTERVENTIONS: Circumferential esophageal EMR by the cap technique, followed by endoscopic placement of an ECM scaffold material. MAIN OUTCOME MEASUREMENTS: Degree of esophageal stricture and histologic assessment of remodeled esophageal tissue. RESULTS: All 5 control dogs had endoscopic evidence of esophageal stenosis. Three required early euthanasia because of inability to tolerate oral intake. Incomplete epithelialization and inflammation persisted at the EMR site in control animals. Endoscopic placement of an ECM scaffold material prevented clinically significant esophageal stenosis in all animals. Histologic assessment showed near-normal esophageal tissue with a lack of inflammation or scar tissue at 8 weeks. CONCLUSIONS: Endoscopic placement of an ECM scaffold material prevented esophageal stricture formation after circumferential EMR in this canine model during short-term observation.


Subject(s)
Digestive System Surgical Procedures/methods , Esophageal Neoplasms/surgery , Esophageal Stenosis/prevention & control , Extracellular Matrix , Tissue Scaffolds , Animals , Barrett Esophagus/surgery , Dogs , Esophagoscopy , Mucous Membrane/surgery , Postoperative Care
11.
Plast Reconstr Surg ; 122(1): 95-102, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18594391

ABSTRACT

BACKGROUND: Seroma formation is a common postoperative complication following many surgical procedures, including abdominoplasty. Several approaches have been investigated to prevent seroma formation by draining fluid or attempting to eliminate dead space, but these approaches have limited effectiveness. METHODS: A canine model of abdominoplasty was developed that reliably produced seroma formation. Bilateral subcutaneous pockets were created in the ventrolateral abdominal wall and additional tissue damage was inflicted using electrocautery. On one side, the tissue layers were treated with a lysine-derived urethane adhesive before closure, whereas the control side received no treatment before standard closure of the incision. RESULTS: Seroma formation (60 +/- 45 ml) was observed on the control side, whereas the treated side had adherence between the tissue layers and minimal if any fluid accumulation (1.7 +/- 1.4 ml) (p < 0.01) (n = 7). The adhesive invoked little or no cellular response, based on histologic examination of the tissue. CONCLUSION: The urethane surgical adhesive was effective in preventing the formation of seroma in this canine abdominoplasty model.


Subject(s)
Abdominal Wall/surgery , Plastic Surgery Procedures/adverse effects , Seroma/prevention & control , Tissue Adhesives/administration & dosage , Animals , Disease Models, Animal , Dogs , Seroma/etiology
12.
Acta Biomater ; 4(4): 852-62, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18440882

ABSTRACT

The purpose of the present study was to develop a biodegradable and biocompatible polyurethane drug delivery system based on lysine diisocyanate (LDI) and glycerol for the controlled release of 7-tert-butyldimethylsilyl-10-hydroxy-camptothecin (DB-67). DB-67 has yet to be implemented in any clinical therapies due to the inability to delivered it in sufficient quantities to impact tumor growth and disease progression. To remedy this, DB-67 was covalently incorporated into our delivery system by way of an organometallic urethane catalyst and was found to be dispersed evenly throughout the LDI-glycerol polyurethane discs. Scanning electron micrographs indicate that the LDI-glycerol discs are uniform and possess a pore distribution typical of the non-solvent casting technique used to prepare them. The release rates of DB-67 from the LDI-glycerol discs were found to vary with both time and temperature and were shown capable of delivering therapeutic concentrations of DB-67 in vitro. Cellular proliferation assays demonstrate that empty LDI-glycerol discs alone do not significantly alter the growth of malignant human glioma cell lines (U87, T98G, LN229 and SG388). DB-67-loaded LDI-glycerol polyurethane discs were found to inhibit cellular proliferation by 50% on average in all the malignant glioma cell lines tested. These results clearly demonstrate the long-term, slow release of DB-67 from LDI-glycerol polyurethane discs and their potential for postoperative intracranial chemotherapy of cancers.


Subject(s)
Camptothecin/analogs & derivatives , Glioma/pathology , Glycerol/metabolism , Isocyanates/metabolism , Lysine/analogs & derivatives , Organosilicon Compounds/pharmacology , Polyurethanes/metabolism , Prostheses and Implants , Camptothecin/chemistry , Camptothecin/pharmacology , Cell Death/drug effects , Cell Line, Tumor , Delayed-Action Preparations , Drug Screening Assays, Antitumor , Glycerol/chemistry , Humans , Isocyanates/chemistry , Lysine/chemistry , Lysine/metabolism , Microscopy, Electron, Scanning , Organosilicon Compounds/chemistry , Solutions , Spectrometry, Fluorescence , Spectroscopy, Fourier Transform Infrared , Tablets
13.
Acta Biomater ; 4(5): 1263-74, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18440884

ABSTRACT

The purpose of the present study was to develop biodegradable and biocompatible polyurethane foams based on lysine diisocyanate (LDI) and glycerol to be used as drug-delivery systems for the controlled release of 7-tert-butyldimethylsilyl-10-hydroxy-camptothecin (DB-67). The impact of urethane catalysts on cellular proliferation was assessed in an attempt to enhance the biocompatibility of our polyurethane materials. DB-67, a potent camptothecin analog, was then incorporated into LDI-glycerol polyurethane foams with two different amine urethane catalysts: 1,4-diazobicyclo[2.2.2]-octane (DABCO) and 4,4'-(oxydi-2,1-ethane-diyl)bismorpholine (DMDEE). The material morphologies of the polyurethane foams were analyzed via scanning electron microscopy, and DB-67 distribution was assessed by way of fluorescence microscopy. Both foam morphology and drug distribution were found to correlate to the amine catalyst used. Hydrolytic release rates of DB-67 from the polyurethane foams were catalyst dependent and also demonstrated greater drug loads being released at higher temperatures. The foams were capable of delivering therapeutic concentrations of DB-67 in vitro over an 11week test period. Cellular proliferation assays demonstrate that empty LDI-glycerol foams did not significantly alter the growth of malignant human glioma cell lines (P<0.05). DB-67 loaded LDI-glycerol polyurethane foams were found to inhibit cellular proliferation by at least 75% in all the malignant glioma cell lines tested (P<1.0x10(-8)). These results clearly demonstrate the long-term, catalyst-dependent release of DB-67 from LDI-glycerol polyurethane foams, indicating their potential for use in implantable drug-delivery devices.


Subject(s)
Antineoplastic Agents/chemistry , Camptothecin/chemistry , Delayed-Action Preparations/chemistry , Drug Compounding/methods , Isocyanates/chemistry , Lysine/analogs & derivatives , Polyurethanes/chemistry , Antineoplastic Agents/administration & dosage , Camptothecin/administration & dosage , Catalysis , Delayed-Action Preparations/administration & dosage , Diffusion , Gases/chemistry , Lysine/chemistry , Materials Testing
15.
Biomaterials ; 27(24): 4304-14, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16635526

ABSTRACT

Wound healing is a complex and orchestrated process that re-establishes the barrier and other functions of the skin. While wound healing proceeds apace in healthy individual, bacterial overgrowth and infection disrupts this process with significant morbidity and mortality. As such, any artificial matrix to promote wound healing must also control infecting microbes. We had earlier developed a two-part space-conforming gel backbone based on polyethyleneglycol (PEG) or lactose, which used ionic silver as the catalyst for gelation. As silver is widely used as an in vitro antimicrobial, use of silver as a catalyst for gelation provided the opportunity to assess its function as an anti-microbial agent in the gels. We found that these gels show bacteriostatic and bactericidal activity for a range of Gram-negative and Gram-positive organisms, including aerobic as well as anaerobic bacteria. This activity lasted for days, as silver leached out of the formed gels over a day in the manner of second-order decay. Importantly the gels did not limit either cell growth or viability, though cell migration was affected. Adding collagen I fragments to the gels corrected this effect on cell migration. We also found that the PEG gel did not interfere with hemostasis. These observations provide the basis for use of the gel backbones for incorporation of anesthetic agents and factors that promote wound repair. In conclusion, silver ions can serve dual functions of catalyzing gelation and providing anti-microbial properties to a biocompatible polymer.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Silver/pharmacology , Wound Healing/physiology , Wounds and Injuries/microbiology , Bacterial Infections/prevention & control , Biocompatible Materials , Cells, Cultured , Humans , Mycoses/prevention & control , Wounds and Injuries/metabolism
16.
J Am Chem Soc ; 127(33): 11754-62, 2005 Aug 24.
Article in English | MEDLINE | ID: mdl-16104753

ABSTRACT

Several oxygenated hydrocarbons, including acetylated sugars, poly(propylene glycol), and oligo(vinyl acetate), have been used to generate CO2-soluble ionic surfactants. Surfactants with vinyl acetate tails yielded the most promising results, exhibiting levels of CO2 solubility comparable to those associated with fluorinated ionic surfactants. For example, a sodium sulfate with single, oligomeric vinyl acetate (VAc) tails consisting of 10 VAc repeat units was 7 wt % soluble in CO2 at 25 degrees C and 48 MPa. Upon introduction of water to these systems, only surfactants with the oligomeric vinyl acetate tails exhibited spectroscopic evidence of a polar environment that was capable of solubilizing the methyl orange into the CO2-rich phase. For example, a single-phase solution of CO2, 0.15 wt % sodium bis(vinyl acetate)8 sulfosuccinate, and water, at water loading (W) values ranging from 10 to 40 at 25 degrees C and 34.5 MPa, exhibited a methyl orange peak at 423 nm. This result indicated that the core of a reverse micelle provided a microenvironment with a polarity similar to that of methanol. Quantum chemical calculations indicate that the acetylated sugars may be too hydrophilic to readily form reverse micelles, whereas the VAc-based surfactants appear to have the correct balance of hydrophilic and hydrophobic forces necessary to form reverse micelles.


Subject(s)
Carbon Dioxide/chemistry , Hydrocarbons/chemistry , Surface-Active Agents/chemistry , Models, Chemical , Molecular Structure , Oxygen/chemistry , Solubility , Surface-Active Agents/chemical synthesis
17.
Acta Biomater ; 1(4): 471-84, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16701828

ABSTRACT

Many polyurethane elastomers display excellent mechanical properties and adequate biocompatibility. However, many medical-grade polyurethanes are prepared from aromatic diisocyanates and can degrade in vivo to carcinogenic aromatic diamines, although the question of whether the concentrations of these harmful degradation products attain physiologically relevant levels is currently unresolved and strongly debated. It is therefore desirable to synthesize new medical-grade polyurethanes from less toxic aliphatic diisocyanates. In this paper, biocompatible segmented polyurethane elastomers were synthesized from aliphatic diisocyanates (1,4-diisocyanatobutane (BDI) and lysine methyl ester diisocyanate (LDI)), novel diurea diol chain extenders based on tyrosine and tyramine, and a model poly(ethylene glycol) (PEG) diol soft segment. The objectives were to design a hard segment similar in structure to that of MDI-based polyurethanes and also investigate the effects of systematic changes in structure on mechanical and biological properties. The non-branched, symmetric polyurethane prepared from BDI and a tyramine-based chain extender had the highest modulus at 37 degrees C. Introduction of symmetric short-chain branches (SCBs) incorporated in the tyrosine-based chain extender lowered the modulus by an order of magnitude. Polyurethanes prepared from LDI were soft polymers that had a still lower modulus due to the asymmetric SCBs that hindered hard segment packing. Polyurethanes prepared from tyramine and tyrosine chain extenders thermally degraded at temperatures ranging from 110 to 150 degrees C, which are lower than that reported previously for phenyl urethanes. All four polyurethanes supported the attachment, proliferation, and high viability of MG-63 human osteoblast-like cells in vitro. Therefore, the non-cytotoxic chemistry of these polyurethanes make them good candidates for further development as biomedical implants.


Subject(s)
Biocompatible Materials/chemistry , Isocyanates/chemistry , Osteosarcoma/pathology , Osteosarcoma/physiopathology , Polyurethanes/chemistry , Tissue Engineering/methods , Urea/chemistry , Cell Culture Techniques/methods , Cell Line, Tumor , Cell Proliferation , Cell Survival , Cross-Linking Reagents/chemistry , Humans
18.
Biomaterials ; 25(1): 85-96, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14580912

ABSTRACT

Polymers with elastomeric mechanical properties, tunable biodegradation properties and cytocompatibility would be desirable for numerous biomedical applications. Toward this end a series of biodegradable poly(ether ester urethane)urea elastomers (PEEUUs) based on poly(ether ester) triblock copolymers were synthesized and characterized. Poly(ether ester) triblock copolymers were synthesized by ring-opening polymerization of epsilon-caprolactone with polyethylene glycol (PEG). PEEUUs were synthesized from these triblock copolymers and butyl diisocyanate, with putrescine as a chain extender. PEEUUs exhibited low glass transition temperatures and possessed tensile strengths ranging from 8 to 20MPa and breaking strains from 325% to 560%. Increasing PEG length or decreasing poly(caprolactone) length in the triblock segment increased PEEUU water absorption and biodegradation rate. Human umbilical vein endothelial cells cultured in a medium supplemented with PEEUU biodegradation solution suggested a lack of degradation product cytotoxicity. Endothelial cell adhesion to PEEUUs was less than 60% of tissue culture polystyrene and was inversely related to PEEUU hydrophilicity. Surface modification of PEEUUs with ammonia gas radio-frequency glow discharge and subsequent immobilization of the cell adhesion peptide Arg-Gly-Asp-Ser increased endothelial adhesion to a level equivalent to tissue culture polystyrene. These biodegradable PEEUUs thus possessed properties that would be amenable to applications where high strength and flexibility would be desirable and exhibited the potential for tuning with appropriate triblock segment selection and surface modification.


Subject(s)
Absorbable Implants , Biocompatible Materials/chemistry , Endothelial Cells/cytology , Endothelial Cells/physiology , Polyurethanes/chemistry , Putrescine/chemistry , Biocompatible Materials/chemical synthesis , Cell Adhesion/physiology , Cell Division/physiology , Cell Line , Cell Survival/physiology , Elasticity , Elastomers/chemical synthesis , Elastomers/chemistry , Humans , Materials Testing , Molecular Conformation , Polymers/chemical synthesis , Polymers/chemistry , Surface Properties , Temperature , Umbilical Veins/cytology , Umbilical Veins/physiology , Water/chemistry
19.
Tissue Eng ; 9(6): 1143-57, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14670102

ABSTRACT

A biodegradable, biocompatible, ascorbic acid-containing three-dimensional polyurethane matrix was developed for bone tissue-engineering scaffolds. This matrix was synthesized with lysine-di-isocyanate (LDI), ascorbic acid (AA), glycerol, and polyethylene glycol (PEG). LDI-glycerol-PEG-AA prepolymer when reacted with water foamed with the liberation of CO(2) to provide a pliable, spongy urethane polymer with pore diameters of 100 to 500 microm. The LDI-glycerol-PEG-AA matrix degraded in aqueous solution and yielded lysine, glycerol, PEG, and ascorbic acid as breakdown products. The degradation products did not significantly affect the solution pH. The LDI-glycerol-PEG-AA matrix can be fabricated into diverse scaffold dimensions and the physicochemical properties of the polymer network supported in vitro cell growth. Green fluorescent protein-transgenic mouse bone marrow cells (GFP-MBMCs) attached to the polymer matrix and remained viable, and the cells became confluent cultures. Furthermore, ascorbic acid released from LDI-glycerol-PEG-AA matrix stimulated cell proliferation, type I collagen, and alkaline phosphatase synthesis in vitro. Cells grown on LDI-glycerol-PEG-AA matrix did not differ phenotypically from cells grown on tissue culture polystyrene plates as assessed by cell growth, expression of mRNA for collagen type I, and transforming growth factor beta(1). These observations suggest that AA-containing polyurethane may be useful in bone tissue-engineering applications.


Subject(s)
Absorbable Implants , Ascorbic Acid/chemistry , Bone Marrow Cells/cytology , Bone Marrow Cells/physiology , Osteoblasts/cytology , Osteoblasts/physiology , Polyurethanes/chemistry , Tissue Engineering/methods , Animals , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Cell Differentiation/physiology , Cell Division/physiology , Cells, Cultured , Collagen Type I , Male , Materials Testing , Membranes, Artificial , Mice , Mice, Inbred C57BL , Surface Properties , Tissue Engineering/instrumentation
20.
J Biomed Mater Res A ; 67(2): 389-400, 2003 Nov 01.
Article in English | MEDLINE | ID: mdl-14566779

ABSTRACT

A novel, nontoxic, biodegradable, sponge-like polyurethane scaffold was synthesized from lysine-di-isocyanate (LDI) and glycerol. Ascorbic acid (AA) was copolymerized with LDI-glycerol. Our hypothesis was that the AA-containing polymer foam would enhance the biological activity of the osteoblastic precursor cell (OPCs). The LDI-glycerol-AA matrix degraded in aqueous solution to the nontoxic products of lysine, glycerol, and AA. The degradation products did not significantly affect the solution pH. The physical properties of the polymer network supported the cell growth in vitro. Mouse OPCs attached to the polymer matrix and remained viable. OPCs produced multilayered confluent cultures, a characteristic typical of bone cells. Furthermore, AA release stimulated cell proliferation, type I collagen, and alkaline phosphatase synthesis. Cells grown on the LDI-glycerol-AA matrix also showed an enhancement of mRNA expression for pro-alpha1 (I) collagen and transforming growth factor-alpha1 after 1 week. Data were tested for significance with an analysis of variance model and multiple comparison test (Fisher's Protected Least Significant Difference) at p < or = 0.05. The observations suggest that AA-containing polyurethane may be useful in bone tissue engineering applications.


Subject(s)
Ascorbic Acid/chemistry , Bone Substitutes/chemistry , Polyurethanes/chemistry , Alkaline Phosphatase/metabolism , Animals , Blotting, Western , Bone Substitutes/chemical synthesis , Cell Culture Techniques , Cell Division/physiology , Collagen Type I/metabolism , Glycerol/chemistry , Glycerol/metabolism , Lysine/chemistry , Lysine/metabolism , Mice , Polymers/chemical synthesis , Polymers/chemistry , Polymers/metabolism , Stem Cells/metabolism
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