Chemical Education Today
Reports from Other Journals
Research Advances by Angela G. King
Dendritic Macromer Replaces Sutures in Cataract Surgery Cataracts are characterized by the clouding of the eye’s lens, severely limiting vision. In a typical cataract removal procedure, physicians first cut an incision in the cornea and then after breaking up and removing the damaged lens using ultrasound, they replace it with a synthetic lens. The incision is either sealed with nylon sutures or allowed to “self-seal” on its own. Cataract surgery is one of the most commonly performed surgical procedures in the United States, with over 1.5 million procedures performed each year, according to the National Eye Institute. The number is expected to increase with the growth in the aging population. People who need cataract surgery, but don’t like the prospect of having their eyes sutured, may be in for some good news: A team of researchers has developed a novel, adhesive hydrogel that can be painted over incisions from cataract surgery affording faster, improved repair. (Hydrogels are colloidal gels in which water is the dispersion medium.) “Sutures can be difficult to care for and are hard on the eyes,” says study leader Mark W. Grinstaff, a chemist and biomedical engineer with Boston University. “Our hydrogel adhesive could ultimately replace the use of sutures for eye surgery altogether and go a long way toward improving patient care.” His co-leader on this project is Terry Kim of Duke University Medical Center in Durham, NC. In addition to cataracts, Grinstaff says that using a hydrogel adhesive instead of sutures shows promise for repairing eye wounds associated with LASIK surgery, ulcers, corneal and retinal injuries, and others. Although animal and human testing is still needed, he and Kim believe the hydrogel could be available to physicians in three to four years. Hydrogels have been used for several years in applications ranging from drug delivery to healing injured blood vessels, but Grinstaff says that using them to repair eye wounds is novel. In the current study, he and his associates crafted a transparent liquid hydrogel with optical properties similar to a human cornea. The transparent hydrogel is made from dendritic polymers derived from natural metabolites of small biocompatible molecules. Mixing a dendron polymer and poly(ethylene glycol dialdehyde), PEG-DA, at room temperature resulted in multiple thiazolidine linkages between the dendron’s cysteine residues and PEG-DA. The hydrogel produced in this manner gels within minutes. The linkage forms at neutral pH. In tests with a small number of eyes from human cadavers, the researchers demonstrated that treatment with the sealant was easier and much faster than the other procedures. The tests involved making 3-mm incisions in 17 cadaver eyes to simulate cataract surgery. Seven eyes were left unrepaired, representing the self-sealing surgery technique; two were repaired with sutures; and eight were repaired with the hydrogel sealant. The incision sealed with the hydrogel has a leaking pressure of 184 ± 79 mmHg, while self-sealed and sutured incisions have leaking pressures of 24 ± 8 mmHg and 54 ± 16 mmHg, respec346
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Figure 1. Photograph of a 3-mm corneal incision (between purple dots) sealed with a hydrogel (within the blue border). Reprinted with permission from J. Am. Chem. Soc. 2004, 126, 12744– 12745. Copyright 2004 American Chemical Society.
tively. Researchers hope to begin animal testing with the hydrogel in the near future.
More Information 1. Wathier, M.; Jung, P.; Carnahan, M.; Kim, T.; Grinstaff, M. Dendritic Macromers as in Situ Polymerizing Biomaterials for Securing Cataract Incisions, J. Am. Chem. Soc. 2004, 126, 12744–12745. 2. An online description of the hydrogel application is available at http://people.bu.edu/mgrin/projects.html (accessed Jan 2005).
Promising Polymer Therapy for Paralyzed Dogs Hydrophilic polymers are known to interact with cell membranes, both fusing transected cell processes and patching leaky defected membranes. The polymers’ ability to repair leaks in damaged axon membranes can be demonstrated using dye exclusion tests or following the migration of lactate dehydrogenase from the cytoplasm to the extracellular fluid, which occurs only if a membrane is compromised. In the past, scientists have utilized the ability of polyethylene glycol (PEG) and Poloxamer 188 (P 188) to repair damaged spinal axons to treat guinea pigs after severe spinal cord injury (SCI). Now a new study led by scientists at Purdue University demonstrates that intravenous administration of PEG or P 188 can help dogs who have severe, acute paraplegia resulting from naturally occurring intervertebrial disk herniation, exhibiting clinical signs of compressive SCI. Dogs admitted to the study were evaluated for superficial and deep pain, conscious hindlimb placement, load bearing and voluntary locomotion, and spinal reflex testing. All dogs were given two intravenous injections of the polymer solution (either ~3500 g/mol, 30% w/w PEG or P 188)
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Chemical Education Today
Reports from Other Journals
More Information 1. Laverty, P.; Leskovar, A.; Breur, G.; Coates, J.; Bergman, R.; Widmer, W.; Toombs, J.; Shapiro, S.; Borgens, R. A Preliminary Study of Intravenous Surfactants in Paraplegic Dogs: Polymer Therapy in Canine Clinical SCI. J. of Neurotrauma, 2004, 21, 1767–1777. 2. An online newsletter featuring a soap solution analogy for the PEG mechanism is available at http://www.vet.purdue.edu/ cpr/image/summer2003.pdf and more details on the study are available at http://www.vet.purdue.edu/cpr/research.html#fusion (both sites accessed Jan 2005). 3. Need to further excite your students about PEG? PEG was used in lava lamps; find a description of lava lamp science at http:// www.chemistry.org/portal/a/c/s/1/feature_ent.html?id= c373e9f6a713c8a98f6a4fd8fe800100 (accessed Jan 2005).
Compound in Smoke Provides the Spark for Germination In 1966, scientists isolated the compound (+)-strigol from the exudates of cotton roots, but it took six additional years for its structure to be assigned. Since (+)-strigol stimulates the germination of the parasitic weed Striga at nanomolar concentration, it has been the subject of many synthetic studies. A new report by a research team in Australia identifies a compound found in smoke that, like (+)-strigol, contains a
O
O
O OH
O O
O
O O
Figure 2. (+)-Strigol (left), and the compound recently found in smoke (right), both contain butenolide moieties and increase germination rates.
butenolide moiety. This new compound, 3-methyl-2Hfuro[2,3-c]pyran-2-one, increases germination rates of a variety of smoke-responsive plants including celery, parsley, and echinacea. Scientists have been trying to identify this compound for more than 15 years, since South African researchers demonstrated it was smoke—not heat or ash—that caused seeds to germinate after a fire. The compound was isolated by bioassay-guided fractionation of cellulose-derived smoke (produced from combusted filter paper). Successive fractions were assayed for germination induction against three plant species, including Grand Rapids lettuce. The structure of the isolated compound was obtained using a combination of mass spectrometry and NMR techniques and was confirmed by synthesis. The bioactivity of the newly identified butenolide in stimulating the germination of the plants that guided the fractionation was then compared to that of plant-derived smoke water. The results further confirm the butenolide as the naturally active compound present in smoke. This breakthrough could result in better horticultural and agricultural yields and improved forest restoration. It could also help farmers control weeds without having to wait for their seeds to germinate naturally, perhaps saving millions of dollars.
More Information 1. Flematti, G.; Ghisalberti, E.; Dixon, K.; Trengrove, R. A. Compound from Smoke That Promotes Seed Germination. Science 2004, 305, 977. 2. Online coverage of the butenolide discovery is at http:// www.abc.net.au/rn/science/ss/stories/s1177159.htm and http:// www.npr.org/templates/story/story.php?storyId=3253026 (both sites accessed Jan 2005).
Angela G. King is Senior Lecturer in Chemistry at Wake Forest University, P.O. Box 7486, Winston-Salem, NC 27109;
[email protected].
Structures for two of the molecules discussed in the section “Compound in Smoke Provides the Spark for Germination” are available in fully manipulable Chime format as JCE Featured Molecules in JCE Online (see page 488).
Featured Molecules
an interactive modeling feature, Only@JCE Online http://www.JCE.DivCHED.org/JCEWWW/Features/MonthlyMolecules
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Structures provided by A. King
within a 6-hour time frame. The molar mass and concentration of polymers administered were based on previous studies of guinea pigs and canines. After administration of the polymer solution, the dogs were anesthetized and underwent decompressive surgery. There were no complications to the administration of either polymer, nor any evidence of an increase in infection or bladder management. PEG administration resulted in a more rapid recovery as measured by the return of deep pain to hindlimbs and by the total neurological score (TNS) on standard neurological examination procedures. Of the canines enrolled in the study, 68% regained the use of their hindlimbs and could walk. By contrast, the selected control group, which did not receive the PEG or P 188 injections, had 62% of dogs remain paraplegic. Clinical paraplegia in dogs is a useful model for the development of emergent human clinical SCI therapies. Also, dogs with spinal cord injury, unlike rodents, do not have high rates of spontaneous recovery. The promising results obtained by this research team have catalyzed an application for a Phase one human clinical trial. In the meantime, scientists are working to image the interaction of polymers with membrane lesions in living neurons with atomic force microscopy.
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